Circulating hematopoietic progenitor cells in patients affected by Chornobyl accident.

PubMed

Bilko, N M; Dyagil, I S; Russu, I Z; Bilko, D I

2016-12-01

High radiation sensitivity of stem cells and their ability to accumulate sublethal radiation damage provides the basis for investigation of hematopoietic progenitors using in vivo culture methodology. Unique samples of peripheral blood and bone marrow were derived from the patients affected by Chornobyl accident during liquidation campaign. To investigate functional activity of circulating hematopoietic progenitor cells from peripheral blood and bone marrow of cleanup workers in early and remote periods after the accident at Chornobyl nuclear power plant (CNPP). The assessment of the functional activity of circulating hematopoietic progenitor cells was performed in samples of peripheral blood and bone marrow of 46 cleanup workers, who were treated in the National Scientific Center for Radiation Medicine of the Academy of Medical Sciences of Ukraine alongside with 35 non radiated patients, who served as a control. Work was performed by culturing peripheral blood and bone marrow mononuclear cells in the original gel diffusion capsules, implanted into the peritoneal cavity of CBA mice. It was shown that hematopoietic progenitor cells could be identified in the peripheral blood of liquidators of CNPP accident. At the same time the number of functionally active progenitor cells of the bone marrow was significantly decreased and during the next 10 years after the accident, counts of circulating progenitor cells in the peripheral blood as well as functionally active hematopoietic cells in bone marrow returned to normal levels. It was shown that hematopoietic progenitor cells are detected not only in the bone marrow but also in the peripheral blood of liquidators as a consequence of radiation exposure associated with CNPP accident. This article is a part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

Immune Humanization of Immunodeficient Mice Using Diagnostic Bone Marrow Aspirates from Carcinoma Patients

PubMed Central

Werner-Klein, Melanie; Proske, Judith; Werno, Christian; Schneider, Katharina; Hofmann, Hans-Stefan; Rack, Brigitte; Buchholz, Stefan; Ganzer, Roman; Blana, Andreas; Seelbach-Göbel, Birgit; Nitsche, Ulrich

2014-01-01

Tumor xenografts in immunodeficient mice, while routinely used in cancer research, preclude studying interactions of immune and cancer cells or, if humanized by allogeneic immune cells, are of limited use for tumor-immunological questions. Here, we explore a novel way to generate cancer models with an autologous humanized immune system. We demonstrate that hematopoietic stem and progenitor cells (HSPCs) from bone marrow aspirates of non-metastasized carcinoma patients, which are taken at specialized centers for diagnostic purposes, can be used to generate a human immune system in NOD-scid IL2rγ(null) (NSG) and HLA-I expressing NSG mice (NSG-HLA-A2/HHD) comprising both, lymphoid and myeloid cell lineages. Using NSG-HLA-A2/HHD mice, we show that responsive and self-tolerant human T cells develop and human antigen presenting cells can activate human T cells. As critical factors we identified the low potential of bone marrow HSPCs to engraft, generally low HSPC numbers in patient-derived bone marrow samples, cryopreservation and routes of cell administration. We provide here an optimized protocol that uses a minimum number of HSPCs, preselects high-quality bone marrow samples defined by the number of initially isolated leukocytes and intra-femoral or intra-venous injection. In conclusion, the use of diagnostic bone marrow aspirates from non-metastasized carcinoma patients for the immunological humanization of immunodeficient mice is feasible and opens the chance for individualized analyses of anti-tumoral T cell responses. PMID:24830425

Bone marrow adipocytes promote tumor growth in bone via FABP4-dependent mechanisms.

PubMed

Herroon, Mackenzie K; Rajagurubandara, Erandi; Hardaway, Aimalie L; Powell, Katelyn; Turchick, Audrey; Feldmann, Daniel; Podgorski, Izabela

2013-11-01

Incidence of skeletal metastases and death from prostate cancer greatly increases with age and obesity, conditions which increase marrow adiposity. Bone marrow adipocytes are metabolically active components of bone metastatic niche that modulate the function of neighboring cells; yet the mechanisms of their involvement in tumor behavior in bone have not been explored. In this study, using experimental models of intraosseous tumor growth and diet-induced obesity, we demonstrate the promoting effects of marrow fat on growth and progression of skeletal prostate tumors. We reveal that exposure to lipids supplied by marrow adipocytes induces expression of lipid chaperone FABP4, pro-inflammatory interleukin IL-1β, and oxidative stress protein HMOX-1 in metastatic tumor cells and stimulates their growth and invasiveness. We show that FABP4 is highly overexpressed in prostate skeletal tumors from obese mice and in bone metastasis samples from prostate cancer patients. In addition, we provide results suggestive of bi-directional interaction between FABP4 and PPARγ pathways that may be driving aggressive tumor cell behavior in bone. Together, our data provide evidence for functional relationship between bone marrow adiposity and metastatic prostate cancers and unravel the FABP4/IL-1β axis as a potential therapeutic target for this presently incurable disease.

Bone marrow adipocytes promote tumor growth in bone via FABP4-dependent mechanisms

PubMed Central

Herroon, Mackenzie K.; Rajagurubandara, Erandi; Hardaway, Aimalie L.; Powell, Katelyn; Turchick, Audrey; Feldmann, Daniel; Podgorski, Izabela

2013-01-01

Incidence of skeletal metastases and death from prostate cancer greatly increases with age and obesity, conditions which increase marrow adiposity. Bone marrow adipocytes are metabolically active components of bone metastatic niche that modulate the function of neighboring cells; yet the mechanisms of their involvement in tumor behavior in bone have not been explored. In this study, using experimental models of intraosseous tumor growth and diet-induced obesity, we demonstrate the promoting effects of marrow fat on growth and progression of skeletal prostate tumors. We reveal that exposure to lipids supplied by marrow adipocytes induces expression of lipid chaperone FABP4, pro-inflammatory interleukin IL-1β, and oxidative stress protein HMOX-1 in metastatic tumor cells and stimulates their growth and invasiveness. We show that FABP4 is highly overexpressed in prostate skeletal tumors from obese mice and in bone metastasis samples from prostate cancer patients. In addition, we provide results suggestive of bi-directional interaction between FABP4 and PPARγ pathways that may be driving aggressive tumor cell behavior in bone. Together, our data provide evidence for functional relationship between bone marrow adiposity and metastatic prostate cancers and unravel the FABP4/IL-1β axis as a potential therapeutic target for this presently incurable disease. PMID:24240026

Bone marrow (stem cell) donation

MedlinePlus

... medlineplus.gov/ency/patientinstructions/000839.htm Bone marrow (stem cell) donation To use the sharing features on this page, please enable ... cells are more likely to help patients than stem cells from older people. People who register must either: Use a cotton swab to take a sample of ...

A simple and sensitive method for determining plasma cell isotype and monoclonality in bone marrow using flowcytometry.

PubMed

van Zaanen, H C; Vet, R J; de Jong, C M; von dem Borne, A E; van Oers, M H

1995-09-01

In this paper we describe a new, rapid and sensitive method to determine plasma cell isotype and clonality in bone marrow using flowcytometry. With the use of a new fixation and permeabilization reagent (Permeafix), which preserves cell structure and morphology, and a monoclonal antibody (Mab) specific for plasma cells (B-B4), it has become possible to specifically select plasma cells and to determine the cytoplasmatic immunoglobulins by flowcytometry. Thirty successive bone marrow aspirates from multiple myeloma patients and patients with MGUS were studied as well as 10 bone marrow samples from patients with reactive plasmacytosis. Each sample was analysed both by immunofluorescence on cytospin smears and FACS analysis. There were no discrepancies between plasma cell isotype as determined by FACS and cytospin. Moreover, FACS analysis was shown to allow detection of very low numbers of plasma cells and to determine whether these plasma cells are mono- or polyclonal. Possible applications are discussed.

Karyotype of cryopreserved bone marrow cells.

PubMed

Chauffaille, M L L F; Pinheiro, R F; Stefano, J T; Kerbauy, J

2003-07-01

The analysis of chromosomal abnormalities is important for the study of hematological neoplastic disorders since it facilitates classification of the disease. The ability to perform chromosome analysis of cryopreserved malignant marrow or peripheral blast cells is important for retrospective studies. In the present study, we compared the karyotype of fresh bone marrow cells (20 metaphases) to that of cells stored with a simplified cryopreservation method, evaluated the effect of the use of granulocyte-macrophage colony-stimulating factor (GM-CSF) as an in vitro mitotic index stimulator, and compared the cell viability and chromosome morphology of fresh and cryopreserved cells whenever possible (sufficient metaphases for analysis). Twenty-five bone marrow samples from 24 patients with hematological disorders such as acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, chronic myeloid leukemia, megaloblastic anemia and lymphoma (8, 3, 3, 8, 1, and 1 patients, respectively) were selected at diagnosis, at relapse or during routine follow-up and one sample was obtained from a bone marrow donor after informed consent. Average cell viability before and after freezing was 98.8 and 78.5%, respectively (P < 0.05). Cytogenetic analysis was successful in 76% of fresh cell cultures, as opposed to 52% of cryopreserved samples (P < 0.05). GM-CSF had no proliferative effect before or after freezing. The morphological aspects of the chromosomes in fresh and cryopreserved cells were subjectively the same. The present study shows that cytogenetic analysis of cryopreserved bone marrow cells can be a reliable alternative when fresh cell analysis cannot be done, notwithstanding the reduced viability and lower percent of successful analysis that are associated with freezing.

CHARACTERIZATION OF FATTY ACID COMPOSITION IN BONE MARROW FLUID FROM POSTMENOPAUSAL WOMEN: MODIFICATION AFTER HIP FRACTURE

PubMed Central

Miranda, Melissa; Pino, Ana María; Fuenzalida, Karen; Rosen, Clifford J.; Seitz, Germán; Rodríguez, J. Pablo

2016-01-01

Bone marrow adipose tissue (BMAT) is associated with low bone mass, although the functional consequences for skeletal maintenance of increased BMAT are currently unclear. BMAT might have a role in systemic energy metabolism, and could be an energy source as well as an endocrine organ for neighboring bone cells, releasing cytokines, adipokines and free fatty acids into the bone marrow microenvironment. The aim of the present report was to compare the fatty acid composition in the bone marrow supernatant fluid (BMSF) and blood plasma of postmenopausal women women (65 to 80 years old). BMSF was obtained after spinning the aspirated bone marrow samples; donors were classified as control, osteopenic or osteoporotic after dual-energy X-ray absorptiometry. Total lipids from human bone marrow fluid and plasma were extracted, converted to the corresponding methyl esters, and finally analyzed by a gas chromatographer coupled with a mass spectrometer. Results showed that fatty acid composition in BMSF was dynamic and distinct from blood plasma, implying significance in the locally produced lipids. The fatty acid composition in the BMSF was enriched in saturated fatty acid and decreased in unsaturated fatty acids as compared to blood plasma, but this relationship switched in women who suffered a hip fracture. On the other hand, there was no relationship between BMSF and bone mineral density. In conclusion, lipid composition of BMSF is distinct from the circulatory compartment, most likely reflecting the energy needs of the marrow compartment. PMID:27416518

[THE COMPARISON OF RESULTS OF DETECTION OF MINIMAL RESIDUAL DISEASE IN PERIPHERAL BLOOD AND MARROW IN CHILDREN OF THE FIRST YEAR OF LIFE WITH ACUTE LYMPHOBLASTIC LEUCOSIS].

PubMed

Tsaur, G A; Riger, T O; Popov, A M; Nasedkina, T V; Kustanovich, A M; Solodovnikov, A G; Streneva, O V; Shorikov, E V; Tsvirenko, S V; Saveliev, L I; Fechina, L G

2015-04-01

The occurrence of minimal residual disease is an important prognostic factor under acute lymphoblastic leucosis in children and adults. In overwhelming majority of research studies bone marrow is used to detect minimal residual disease. The comparative characteristic of detection of minimal residual disease in peripheral blood and bone marrow was carried out. The prognostic role of occurrence of minimal residual disease in peripheral blood and bone marrow under therapy according protocol MLL-Baby was evaluated. The analysis embraced 142 pair samples from 53 patients with acute lymphoblastic leucosis and various displacements of gene MLL younger than 365 days. The minimal residual disease was detected by force of identification of chimeric transcripts using polymerase chain reaction in real-time mode in 7 sequential points of observation established by protocol of therapy. The comparability of results of qualitative detection of minimal residual disease in bone marrow and peripheral blood amounted to 84.5%. At that, in all 22 (15.5%) discordant samples minimal residual disease was detected only in bone marrow. Despite of high level of comparability of results of detection of minimal residual disease in peripheral blood and bone marrow the occurrence of minimal residual disease in peripheral blood at various stages of therapy demonstrated no independent prognostic significance. The established differences had no relationship with sensitivity of method determined by value of absolute expression of gene ABL. Most likely, these differences reflected real distribution of tumor cells. The results of study demonstrated that application of peripheral blood instead of bone marrow for monitoring of minimal residual disease under acute lymphoblastic leucosis in children of first year of life is inappropriate. At the same time, retention of minimal residual disease in TH4 in bone marrow was an independent and prognostic unfavorable factor under therapy of acute lymphoblastic leucosis of children of first year of life according protocol MLL-Baby (OO=7.326, confidence interval 2.378-22.565).

T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments.

PubMed

Hawkins, Edwin D; Duarte, Delfim; Akinduro, Olufolake; Khorshed, Reema A; Passaro, Diana; Nowicka, Malgorzata; Straszkowski, Lenny; Scott, Mark K; Rothery, Steve; Ruivo, Nicola; Foster, Katie; Waibel, Michaela; Johnstone, Ricky W; Harrison, Simon J; Westerman, David A; Quach, Hang; Gribben, John; Robinson, Mark D; Purton, Louise E; Bonnet, Dominique; Lo Celso, Cristina

2016-10-27

It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance. We observed highly dynamic cellular interactions and promiscuous distribution of leukaemia cells that migrated across the bone marrow, without showing any preferential association with bone marrow sub-compartments. Unexpectedly, this behaviour was maintained throughout disease development, from the earliest bone marrow seeding to response and resistance to chemotherapy. Our results reveal that T-ALL cells do not depend on specific bone marrow microenvironments for propagation of disease, nor for the selection of chemo-resistant clones, suggesting that a stochastic mechanism underlies these processes. Yet, although T-ALL infiltration and progression are independent of the stroma, accumulated disease burden leads to rapid, selective remodelling of the endosteal space, resulting in a complete loss of mature osteoblastic cells while perivascular cells are maintained. This outcome leads to a shift in the balance of endogenous bone marrow stroma, towards a composition associated with less efficient haematopoietic stem cell function. This novel, dynamic analysis of T-ALL interactions with the bone marrow microenvironment in vivo, supported by evidence from human T-ALL samples, highlights that future therapeutic interventions should target the migration and promiscuous interactions of cancer cells with the surrounding microenvironment, rather than specific bone marrow stroma, to combat the invasion by and survival of chemo-resistant T-ALL cells.

Trained nurses can obtain satisfactory bone marrow aspirates and trephine biopsies.

PubMed Central

Lawson, S; Aston, S; Baker, L; Fegan, C D; Milligan, D W

1999-01-01

AIMS: To assess the feasibility of training nurse practitioners to perform bone marrow aspiration and trephine biopsy, and to compare the quality of these samples with those obtained by medical staff. METHODS: A retrospective audit was undertaken of nurse practitioner and medical staff performance in bone marrow procedures in a busy haematology day unit. RESULTS: Nurse practitioners fared favourably in comparison with medical staff in performing bone marrow trephine biopsies, with mean biopsy lengths of 11 mm and 10.7 mm respectively. However, only 78% of the smears obtained by the nurses were judged technically satisfactory, compared with 91% prepared by doctors. This discrepancy was thought to be due largely to the quality of slide spreading. CONCLUSIONS: With motivated staff and a structured educational and training programme it is possible for nurse practitioners to perform the techniques of bone marrow aspiration and biopsy, and obtain specimens of satisfactory quality, thus improving efficiency of the haematology day unit and increasing quality of patient care. Images PMID:10396248

Isolation of circulating tumor cells in pancreatic cancer patients by immunocytochemical assay.

PubMed

Yang, Jing; Zhou, Ying; Zhao, Bin

2018-01-01

The patients diagnosed with pancreatic cancer have the possibilities of getting the cancer again even after resection. The tumor cells identified from blood can be related to different stages of tumor. In this study, we used an immunoassay to detect circulating tumor cells in blood and bone marrow samples. About 120 patients' blood and bone marrow samples were used in this study along with controls. The presence of tumor cells was evaluated with different stages of cancer classified by UICC. The survival rate at each stages of tumor was also analyzed. The tumor cells were isolated both in blood (29%) and bone marrow samples (25%). The prevalence of tumor cells increased with increase in stages of tumor in blood samples. The survival of the patients considerably related to different stages of tumor but it cannot be taken a parameter alone for the patients' survival. © 2017 Wiley Periodicals, Inc.

Bone marrow aspiration

MedlinePlus

Iliac crest tap; Sternal tap; Leukemia - bone marrow aspiration; Aplastic anemia - bone marrow aspiration; Myelodysplastic syndrome - bone marrow aspiration; Thrombocytopenia - bone marrow aspiration; Myelofibrosis - bone marrow aspiration

IL-8 as mediator in the microenvironment-leukaemia network in acute myeloid leukaemia.

PubMed

Kuett, Alexander; Rieger, Christina; Perathoner, Deborah; Herold, Tobias; Wagner, Michaela; Sironi, Silvia; Sotlar, Karl; Horny, Hans-Peter; Deniffel, Christian; Drolle, Heidrun; Fiegl, Michael

2015-12-17

The bone marrow microenvironment is physiologically hypoxic with areas being as low as 1% O2, e.g. the stem cell niche. Acute myeloid leukaemia (AML) blasts misuse these bone marrow niches for protection by the local microenvironment, but also might create their own microenvironment. Here we identify IL-8 as a hypoxia-regulated cytokine in both AML cell lines and primary AML samples that is induced within 48 hours of severe hypoxia (1% O2). IL-8 lacked effects on AML cells but induced migration in mesenchymal stromal cells (MSC), an integral part of the bone marrow. Accordingly, MSC were significantly increased in AML bone marrow as compared to healthy bone marrow. Interestingly, mononuclear cells obtained from healthy bone marrow displayed both significantly lower endogenous and hypoxia-induced production of IL-8. IL-8 mRNA expression in AML blasts from 533 patients differed between genetic subgroups with significantly lower expression of IL-8 in acute promyelocytic leukaemia (APL), while in non APL-AML patients with FLT ITD had the highest IL-8 expression. In this subgroup, high IL-8 expression was also prognostically unfavourable. In conclusion, hypoxia as encountered in the bone marrow specifically increases IL-8 expression of AML, which in turn impacts niche formation. High IL-8 expression might be correlated with poor prognosis in certain AML subsets.

The Molecular Prevalence of Viral Infections in Transplant Candidates with Bone Marrow Suppression, Shiraz, Southern Iran, 2010

PubMed Central

Mohammadi, B.; Yaghobi, R.; Dehghani, M.; Behzad Behbahani, A.

2013-01-01

Background: Transient bone marrow suppression, characterized by acute inability of the bone marrow to produce circulating blood cells, may strongly relate to the pathogenesis of some viral infections. Objective: To study the prevalence of some DNA and RNA viruses in patients with transient bone marrow suppression. Methods: EDTA-treated blood samples were collected from 27 patients with clinically- and laboratory-confirmed transient bone marrow suppression. The genomic DNA of hepatitis B virus, adenovirus, polyomavirus BK, and parvovirus B19, and genomic RNA of hepatitis C and G viruses were extracted and amplified by sensitive and specific in-house simple and nested PCR and RT-PCR protocols, respectively. The risk factors that might be related to the studied viral infections were analyzed. Results: Hepatitis B virus infection was diagnosed in 9 (33%) of 27 patients; adenovirus infection in 2 (7%); and parvovirus B19 infection in 7 (26%) of 27 patients. The genomic DNA of polyomovirus BK was not detected in any patients. Both hepatitis C and G viruses were found in 3 (11%) of 27 patients. Conclusion: Diagnosis of the high prevalence of hepatitis B virus, and parvovirus B19 in patients with transient bone marrow suppression, reflects the importance of these viral infections in introducing bone marrow suppression. This hypothesis should be confirmed in further studies. PMID:25013658

Perfluoroalkyl substances in human bone: concentrations in bones and effects on bone cell differentiation.

PubMed

Koskela, A; Koponen, J; Lehenkari, P; Viluksela, M; Korkalainen, M; Tuukkanen, J

2017-07-28

Perfluoroalkyl substances (PFAS), including two most commonly studied compounds perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are widely distributed environmental pollutants, used extensively earlier. Due to their toxicological effects the use of PFAS is now regulated. Based on earlier studies on PFOA's distribution in bone and bone marrow in mice, we investigated PFAS levels and their possible link to bone microarchitecture of human femoral bone samples (n = 18). Soft tissue and bone biopsies were also taken from a 49-year old female cadaver for PFAS analyses. We also studied how PFOA exposure affects differentiation of human osteoblasts and osteoclasts. PFAS were detectable from all dry bone and bone marrow samples, PFOS and PFOA being the most prominent. In cadaver biopsies, lungs and liver contained the highest concentrations of PFAS, whereas PFAS were absent in bone marrow. Perfluorononanoic acid (PFNA) was present in the bones, PFOA and PFOS were absent. In vitro results showed no disturbance in osteogenic differentiation after PFOA exposure, but in osteoclasts, lower concentrations led to increased resorption, which eventually dropped to zero after increase in PFOA concentration. In conclusion, PFAS are present in bone and have the potential to affect human bone cells partly at environmentally relevant concentrations.

Prolonged pancytopenia in a gene therapy patient with ADA-deficient SCID and trisomy 8 mosaicism: a case report.

PubMed

Engel, Barbara C; Podsakoff, Greg M; Ireland, Joanna L; Smogorzewska, E Monika; Carbonaro, Denise A; Wilson, Kathy; Shah, Ami; Kapoor, Neena; Sweeney, Mirna; Borchert, Mark; Crooks, Gay M; Weinberg, Kenneth I; Parkman, Robertson; Rosenblatt, Howard M; Wu, Shi-Qi; Hershfield, Michael S; Candotti, Fabio; Kohn, Donald B

2007-01-15

A patient with adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID) was enrolled in a study of retroviral-mediated ADA gene transfer to bone marrow hematopoietic stem cells. After the discontinuation of ADA enzyme replacement, busulfan (75 mg/m2) was administered for bone marrow cytoreduction, followed by infusion of autologous, gene-modified CD34+ cells. The expected myelosuppression developed after busulfan but then persisted, necessitating the administration of untransduced autologous bone marrow back-up at day 40. Because of sustained pancytopenia and negligible gene marking, diagnostic bone marrow biopsy and aspirate were performed at day 88. Analyses revealed hypocellular marrow and, unexpectedly, evidence of trisomy 8 in 21.6% of cells. Trisomy 8 mosaicism (T8M) was subsequently diagnosed by retrospective analysis of a pretreatment marrow sample that might have caused the lack of hematopoietic reconstitution. The confounding effects of this preexisting marrow cytogenetic abnormality on the response to gene transfer highlights another challenge of gene therapy with the use of autologous hematopoietic stem cells.

Prolonged pancytopenia in a gene therapy patient with ADA-deficient SCID and trisomy 8 mosaicism: a case report

PubMed Central

Engel, Barbara C.; Podsakoff, Greg M.; Ireland, Joanna L.; Smogorzewska, E. Monika; Carbonaro, Denise A.; Wilson, Kathy; Shah, Ami; Kapoor, Neena; Sweeney, Mirna; Borchert, Mark; Crooks, Gay M.; Weinberg, Kenneth I.; Parkman, Robertson; Rosenblatt, Howard M.; Wu, Shi-Qi; Hershfield, Michael S.; Candotti, Fabio; Kohn, Donald B.

2007-01-01

A patient with adenosine deaminase–deficient severe combined immune deficiency (ADA-SCID) was enrolled in a study of retroviral-mediated ADA gene transfer to bone marrow hematopoietic stem cells. After the discontinuation of ADA enzyme replacement, busulfan (75 mg/m2) was administered for bone marrow cytoreduction, followed by infusion of autologous, gene-modified CD34+ cells. The expected myelosuppression developed after busulfan but then persisted, necessitating the administration of untransduced autologous bone marrow back-up at day 40. Because of sustained pancytopenia and negligible gene marking, diagnostic bone marrow biopsy and aspirate were performed at day 88. Analyses revealed hypocellular marrow and, unexpectedly, evidence of trisomy 8 in 21.6% of cells. Trisomy 8 mosaicism (T8M) was subsequently diagnosed by retrospective analysis of a pretreatment marrow sample that might have caused the lack of hematopoietic reconstitution. The confounding effects of this preexisting marrow cytogenetic abnormality on the response to gene transfer highlights another challenge of gene therapy with the use of autologous hematopoietic stem cells. PMID:16973956

Analysis of bone marrow plasma cells in patients with solitary bone plasmacytoma.

PubMed

Bhaskar, Archana; Gupta, Ritu; Sharma, Atul; Kumar, Lalit; Jain, Paresh

Local radiotherapy is the treatment of choice for solitary bone plasmacytoma (SBP) and the role of adjuvant systemic chemotherapy in preventing progression to multiple myeloma (MM) is controversial. The purpose of this study was to examine the presence of systemic disease in the form of neoplastic plasma cells (PC) in bone marrow of patients with SBP. Flow cytometric immunophenotyping of PC was carried out on bone marrow aspirate of 7 patients using monoclonal antibodies: CD19 FITC, CD45 FITC, CD20 FITC, CD52 PE, CD117 PE, CD56 PE, CD38 PerCP-Cy5.5, CD138 APC, anti-kappa (κ) FITC and anti-lambda (λ) PE. The neoplastic as well as normal PC were identified in bone marrow aspirate of all the patients at the time of diagnosis; the neoplastic PC ranged from 0.1%to 0.7% of all BM cells and 33.5% to 89.7% of total BMPC. The κ:λ ratio was normal in all the samples ranging from 0.5% to 1.6%. The present work shows the presence of systemic disease in the form of neoplastic PC in bone marrow of patients with SBP. Prospective studies would be required to study if the levels of neoplastic PC in the bone marrow may help us identify patients who are likely to progress to overt MM and benefit from systemic chemotherapy.

Skeletal stem cell isolation: A review on the state-of-the-art microfluidic label-free sorting techniques.

PubMed

Xavier, Miguel; Oreffo, Richard O C; Morgan, Hywel

2016-01-01

Skeletal stem cells (SSC) are a sub-population of bone marrow stromal cells that reside in postnatal bone marrow with osteogenic, chondrogenic and adipogenic differentiation potential. SSCs reside only in the bone marrow and have organisational and regulatory functions in the bone marrow microenvironment and give rise to the haematopoiesis-supportive stroma. Their differentiation capacity is restricted to skeletal lineages and therefore the term SSC should be clearly distinguished from mesenchymal stem cells which are reported to exist in extra-skeletal tissues and, critically, do not contribute to skeletal development. SSCs are responsible for the unique regeneration capacity of bone and offer unlimited potential for application in bone regenerative therapies. A current unmet challenge is the isolation of homogeneous populations of SSCs, in vitro, with homogeneous regeneration and differentiation capacities. Challenges that limit SSC isolation include a) the scarcity of SSCs in bone marrow aspirates, estimated at between 1 in 10-100,000 mononuclear cells; b) the absence of specific markers and thus the phenotypic ambiguity of the SSC and c) the complexity of bone marrow tissue. Microfluidics provides innovative approaches for cell separation based on bio-physical features of single cells. Here we review the physical principles underlying label-free microfluidic sorting techniques and review their capacity for stem cell selection/sorting from complex (heterogeneous) samples. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization of Fatty Acid Composition in Bone Marrow Fluid From Postmenopausal Women: Modification After Hip Fracture.

PubMed

Miranda, Melissa; Pino, Ana María; Fuenzalida, Karen; Rosen, Clifford J; Seitz, Germán; Rodríguez, J Pablo

2016-10-01

Bone marrow adipose tissue (BMAT) is associated with low bone mass, although the functional consequences for skeletal maintenance of increased BMAT are currently unclear. BMAT might have a role in systemic energy metabolism, and could be an energy source as well as an endocrine organ for neighboring bone cells, releasing cytokines, adipokines and free fatty acids into the bone marrow microenvironment. The aim of the present report was to compare the fatty acid composition in the bone marrow supernatant fluid (BMSF) and blood plasma of postmenopausal women women (65-80 years old). BMSF was obtained after spinning the aspirated bone marrow samples; donors were classified as control, osteopenic or osteoporotic after dual-energy X-ray absorptiometry. Total lipids from human bone marrow fluid and plasma were extracted, converted to the corresponding methyl esters, and finally analyzed by a gas chromatographer coupled with a mass spectrometer. Results showed that fatty acid composition in BMSF was dynamic and distinct from blood plasma, implying significance in the locally produced lipids. The fatty acid composition in the BMSF was enriched in saturated fatty acid and decreased in unsaturated fatty acids as compared to blood plasma, but this relationship switched in women who suffered a hip fracture. On the other hand, there was no relationship between BMSF and bone mineral density. In conclusion, lipid composition of BMSF is distinct from the circulatory compartment, most likely reflecting the energy needs of the marrow compartment. J. Cell. Biochem. 117: 2370-2376, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A hyperboliod representation of the bone-marrow interface within 3D NMR images of trabecular bone: applications to skeletal dosimetry

NASA Astrophysics Data System (ADS)

Rajon, D. A.; Shah, A. P.; Watchman, C. J.; Brindle, J. M.; Bolch, W. E.

2003-06-01

Recent advances in physical models of skeletal dosimetry utilize high-resolution NMR microscopy images of trabecular bone. These images are coupled to radiation transport codes to assess energy deposition within active bone marrow irradiated by bone- or marrow-incorporated radionuclides. Recent studies have demonstrated that the rectangular shape of image voxels is responsible for cross-region (bone-to-marrow) absorbed fraction errors of up to 50% for very low-energy electrons (<50 keV). In this study, a new hyperboloid adaptation of the marching cube (MC) image-visualization algorithm is implemented within 3D digital images of trabecular bone to better define the bone-marrow interface, and thus reduce voxel effects in the assessment of cross-region absorbed fractions. To test the method, a mathematical sample of trabecular bone was constructed, composed of a random distribution of spherical marrow cavities, and subsequently coupled to the EGSnrc radiation code to generate reference values for the energy deposition in marrow or bone. Next, digital images of the bone model were constructed over a range of simulated image resolutions, and coupled to EGSnrc using the hyperboloid MC (HMC) algorithm. For the radionuclides 33P, 117mSn, 131I and 153Sm, values of S(marrow←bone) estimated using voxel models of trabecular bone were shown to have relative errors of 10%, 9%, <1% and <1% at a voxel size of 150 µm. At a voxel size of 60 µm, these errors were 6%, 5%, <1% and <1%, respectively. When the HMC model was applied during particle transport, the relative errors on S(marrow←bone) for these same radionuclides were reduced to 7%, 6%, <1% and <1% at a voxel size of 150 µm, and to 2%, 2%, <1% and <1% at a voxel size of 60 µm. The technique was also applied to a real NMR image of human trabecular bone with a similar demonstration of reductions in dosimetry errors.

Bone formation transcripts dominate the differential gene expression profile in an equine osteoporotic condition associated with pulmonary silicosis.

PubMed

Zavodovskaya, Regina; Stover, Susan M; Murphy, Brian G; Katzman, Scott; Durbin-Johnson, Blythe; Britton, Monica; Finno, Carrie J

2018-01-01

Osteoporosis has been associated with pulmonary silicosis in California horses exposed to soils rich in cytotoxic silica dioxide crystals, a syndrome termed silicate associated osteoporosis (SAO). The causal mechanism for the development of osteoporosis is unknown. Osteoporotic lesions are primarily located in bone marrow-rich sites such as ribs, scapula and pelvis. Gene transcription patterns within bone marrow and pulmonary lymph nodes of affected horses may offer clues to disease pathobiology. Bone marrow core and tracheobronchial lymph node tissue samples harvested postmortem from affected and unaffected horses were examined histologically and subjected to RNA sequencing (RNA-seq). Sequenced data were analyzed for differential gene expression and gene ontology. Metatranscriptomic and metagenomic assays evaluated samples for infectious agents. Thirteen of 17 differentially expressed transcripts in bone marrow were linked to bone and cartilage formation such as integrin binding bone sialoprotein (log2FC = 3.39, PFDR = 0.013) and chondroadherin (log2FC = 4.48, PFDR = 0.031). Equus caballus solute carrier family 9, subfamily A2 (log2FC = 3.77, PFDR = 0.0034) was one of the four differentially expressed transcripts linked to osteoclast activity. Osteoblasts were hyperplastic and hypertrophic in bone marrow from affected horses. Biological pathways associated with skeletal morphogenesis were significantly enriched in affected horses. The 30 differentially expressed genes in affected lymph nodes were associated with inflammatory responses. Evidence of infectious agents was not found. The SAO affected bone marrow molecular signature demonstrated increased transcription and heightened activation of osteoblasts. Increased osteoblastic activity could be part of the pathological mechanism for osteoporosis or a compensatory response to the accelerated osteolysis. Transcriptome data offer gene targets for inquiries into the role of osteocytes and osteoblasts in SAO pathogenesis. Viral or bacterial infectious etiology in SAO is less likely based on metatranscriptomic and metagenomic data but cannot be completely ruled out.

Osteoblasts Protect AML Cells from SDF-1-Induced Apoptosis

PubMed Central

Kremer, Kimberly N.; Dudakovic, Amel; McGee-Lawrence, Meghan E.; Philips, Rachael L.; Hess, Allan D.; Smith, B. Douglas; van Wijnen, Andre J.; Karp, Judith E.; Kaufmann, Scott H.; Westendorf, Jennifer J.; Hedin, Karen E.

2014-01-01

The bone marrow provides a protective environment for acute myeloid leukemia (AML) cells that often allows leukemic stem cells to survive standard chemotherapeutic regimens. Targeting these leukemic stem cells within the bone marrow is critical for preventing relapse. We recently demonstrated that SDF-1, a chemokine abundant in the bone marrow, induces apoptosis in AML cell lines and in patient samples expressing high levels of its receptor, CXCR4. Here we show that a subset of osteoblast lineage cells within the bone marrow can protect AML cells from undergoing apoptosis in response to the SDF-1 naturally present in that location. In co-culture systems, osteoblasts at various stages of differentiation protected AML cell lines and patient isolates from SDF-1-induced apoptosis. The differentiation of the osteoblast cell lines, MC3T3 and W-20-17, mediated this protection via a cell contact-independent mechanism. In contrast, bone marrow-derived mesenchymal cells, the precursors of osteoblasts, induced apoptosis in AML cells via a CXCR4-dependent mechanism and failed to protect AML cells from exogenously added SDF-1. These results indicate that osteoblasts in the process of differentiation potently inhibit the SDF-1-driven apoptotic pathway of CXCR4-expressing AML cells residing in the bone marrow. Drugs targeting this protective mechanism could potentially provide a new approach to treating AML by enhancing the SDF-1-induced apoptosis of AML cells residing within the bone marrow microenvironment. PMID:24851270

G-CSF-primed autologous and allogeneic bone marrow for transplantation in clinical oncology. Cell content and immunological characteristics

NASA Astrophysics Data System (ADS)

Grivtsova, L. Yu; Melkova, K. N.; Kupryshkina, N. A.; Vorotnikov, I. K.; Grigoryeva, T. A.; Selchuk, V. Yu; Grebennikova, O. P.; Titova, G. V.; Tupitsyn, N. N.

2018-01-01

60 samples of G-CSF-primed bone marrow (39 cancer patients and 21 healthy donors) to be used for transplantation to cancer patients were analyzed and compared by main characteristics with historical control and 13 bone marrow samples from control patient with mastopathy. Basing on morphological and multicolor flow cytometry findings certain characteristics of G-CSF-primed bone marrow were discovered, such as a significant increase in blast count in cancer patients as compared to donors and control patients (p<0.037), a higher neutrophil maturation index (p<0.001) and a lower percentage of mature lymphocytes (p<0.008) as compared to the control group. Among lymphocyte populations G-CSF-priming was associated with a significant increase in the total of mature CD3+ T-cells and CD8+ T-killers (p<0.0001) and a decrease in CD56+CD3- and/or CD16+CD3- NK-cells (p<0.006) both in cancer patients and healthy donors in comparison with the controls.

Genetic testing and counseling of a recipient after bone marrow transplant from a sibling harboring a germline BRCA1 pathogenic mutation.

PubMed

Škerl, Petra; Krajc, Mateja; Blatnik, Ana; Novaković, Srdjan

2017-07-01

Allogenic bone marrow transplant recipients represent a unique challenge, when they are referred for genetic testing and counseling. When performing genetic testing, it is extremely important to ensure that the detected DNA mutations originate from the patients own DNA, and therefore the most appropriate and reliable biological sample for DNA isolation must be obtained. The aim of the present study was to present the germline testing and counseling approach utilized in a rare case of a chimeric woman who received an allogenic bone marrow transplant from a sibling with a germline BRCA1 pathogenic mutation. According to our results, hairs with follicles are a reliable and ready source of DNA in a patient whose blood is of allogenic bone marrow transplant donor origin. Compared with a fibroblast culture, which is more difficult to obtain, the hair follicles are much more accessible and hair sampling is less invasive for the patient. Genetic testing based on the other sources of DNA, such as buccal swabs, is questionable due to the known risk of donor DNA contamination.

The healing effect of bone marrow-derived stem cells in acute radiation syndrome.

PubMed

Mortazavi, Seyed Mohammad Javad; Shekoohi-Shooli, Fatemeh; Aghamir, Seyed Mahmood Reza; Mehrabani, Davood; Dehghanian, Amirreza; Zare, Shahrokh; Mosleh-Shirazi, Mohammad Amin

2016-01-01

To determine the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on regeneration of bone marrow and intestinal tissue and survival rate in experimental mice with acute radiation syndrome (ARS). Forty mice were randomly divided into two equal groups of A receiving no BMSC transplantation and B receiving BMSCs. BMSCs were isolated from the bone marrow and cultured in DMEM media. Both groups were irradiated with 10 Gy (dose rate 0.28 Gy/ min) (60)CO during 35 minutes with a field size of 35×35 for all the body area. Twenty-four hours after γ irradiation, 150×10(3) cells of passage 5 in 150 µl medium were injected intravenously into the tail. Animals were euthanized one and two weeks after cell transplantation. They were evaluated histologically for any changes in bone marrow and intestinal tissues. The survival rate in mice were also determined. A significant increase for bone marrow cell count and survival rate were observed in group B in comparison to group A. Histological findings denoted to a healing in sample tissues. BMSCs could significantly reduce the side effects of ARS and increase the survival rate and healing in injured tissue. As such their transplantation may open a window in treatment of patients with ARS.

Automatic segmentation of Leishmania parasite in microscopic images using a modified CV level set method

NASA Astrophysics Data System (ADS)

Farahi, Maria; Rabbani, Hossein; Talebi, Ardeshir; Sarrafzadeh, Omid; Ensafi, Shahab

2015-12-01

Visceral Leishmaniasis is a parasitic disease that affects liver, spleen and bone marrow. According to World Health Organization report, definitive diagnosis is possible just by direct observation of the Leishman body in the microscopic image taken from bone marrow samples. We utilize morphological and CV level set method to segment Leishman bodies in digital color microscopic images captured from bone marrow samples. Linear contrast stretching method is used for image enhancement and morphological method is applied to determine the parasite regions and wipe up unwanted objects. Modified global and local CV level set methods are proposed for segmentation and a shape based stopping factor is used to hasten the algorithm. Manual segmentation is considered as ground truth to evaluate the proposed method. This method is tested on 28 samples and achieved 10.90% mean of segmentation error for global model and 9.76% for local model.

Highly sensitive MYD88L265P mutation detection by droplet digital PCR in Waldenström Macroglobulinemia.

PubMed

Drandi, Daniela; Genuardi, Elisa; Dogliotti, Irene; Ferrante, Martina; Jiménez, Cristina; Guerrini, Francesca; Lo Schirico, Mariella; Mantoan, Barbara; Muccio, Vittorio; Lia, Giuseppe; Zaccaria, Gian Maria; Omedè, Paola; Passera, Roberto; Orsucci, Lorella; Benevolo, Giulia; Cavallo, Federica; Galimberti, Sara; García-Sanz, Ramón; Boccadoro, Mario; Ladetto, Marco; Ferrero, Simone

2018-03-22

We here describe a novel method for MYD88 L265P mutation detection and minimal residual disease monitoring in Waldenström Macroglobulinemia, by droplet digital PCR, in bone marrow and peripheral blood cells, as well as in circulating cell free DNA. Our method shows a sensitivity of 5.00E-05, by far superior to the widely used allele-specific polymerase chain reaction (1.00E-03). Overall, 291 unsorted samples from 148 patients (133 Waldenstrom 11 IgG-lymphoplasmacytic lymphoma and 4 IgM-monoclonal gammopathy of undetermined significance), 194 baseline and 97 follow-up, were analyzed. 122/128 (95.3%) bone marrow and 47/66 (71.2%) baseline peripheral blood samples scored positive for MYD88 L265P Moreover, to investigate whether MYD88 L265P by droplet digital PCR could be used for minimal residual disease monitoring, mutation levels were compared with IGH-based minimal residual disease analysis in 10 patients, showing to be as informative as to the classical, standardized but not yet validated in Waldenström Macroglobulinemia, IGH-based minimal residual disease assay (r 2 =0.64). Finally, MYD88 L265P detection performed by droplet digital PCR on plasmatic circulating tumor DNA from 60 patients showed a good correlation with bone marrow (bone marrow median mutational value 1.92E-02, plasmatic circulating tumor DNA value: 1.4E-02, peripheral blood value: 1.03E-03). This study indicates that droplet digital PCR MYD88 L265P assay is a feasible and sensitive tool for mutational screening and minimal residual disease monitoring in Waldenström Macroglobulinemia. Both unsorted bone marrow and peripheral blood samples can be reliably tested, as well as circulating tumor DNA, that represents an attractive, less invasive alternative to bone marrow for MYD88 L265P detection. Copyright © 2018, Ferrata Storti Foundation.

Experiment K-6-23. Effect of spaceflight on levels and function of immune cells

NASA Technical Reports Server (NTRS)

Mandel, A. D.; Sonnenfeld, G.; Berry, W.; Taylor, G.; Wellhausen, S. R.; Konstantinova, I.; Lesnyak, A.; Fuchs, B.

1990-01-01

Two different immunology experiments were performed on samples received from rats flown on Cosmos 1887. In the first experiment, rat bone marrow cells were examined in Moscow for their response to colony stimulating factor-M. In the second experiment, rat spleen and bone marrow cells were stained in Moscow with a variety of antibodies directed against cell surface antigenic markers. These cells were preserved and shipped to the United States where they were subjected to analysis on a flow cytometer. The results of the studies indicate that bone marrow cells from flown rats showed a decreased response to colony stimulating factor than did bone marrow cells from control rats. There was a higher percentage of spleen cells from flown rats staining positively for pan-T-cell, suppressor-T-cell and innate interleukin-2 receptor antigens than from control animals. In addition, a higher percentage of cells that appeared to be part of the myelogenous population of bone marrow cells from flown rats stained positively for surface immunoglobulin than did equivalent cells from control rats.

WE-E-BRE-01: An Image-Based Skeletal Dosimetry Model for the ICRP Reference Adult Female - Internal Electron Sources

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Reilly, S; Maynard, M; Marshall, E

Purpose: Limitations seen in previous skeletal dosimetry models, which are still employed in commonly used software today, include the lack of consideration of electron escape and cross-fire from cortical bone, the modeling of infinite spongiosa, the disregard of the effect of varying cellularity on active marrow self-irradiation, and the lack of use of the more recent ICRP definition of a 50 micron surrogate tissue region for the osteoprogenitor cells - shallow marrow. These limitations were addressed in the present dosimetry model. Methods: Electron transport was completed to determine specific absorbed fractions to active marrow and shallow marrow of the skeletalmore » regions of the adult female. The bone macrostructure was obtained from the whole-body hybrid computational phantom of the UF series of reference phantoms, while the bone microstructure was derived from microCT images of skeletal region samples taken from a 45 year-old female cadaver. The target tissue regions were active marrow and shallow marrow. The source tissues were active marrow, inactive marrow, trabecular bone volume, trabecular bone surfaces, cortical bone volume and cortical bone surfaces. The marrow cellularity was varied from 10 to 100 percent for active marrow self-irradiation. A total of 33 discrete electron energies, ranging from 1 keV to 10 MeV, were either simulated or modeled analytically. Results: The method of combining macro- and microstructure absorbed fractions calculated using MCNPX electron transport was found to yield results similar to those determined with the PIRT model for the UF adult male in the Hough et al. study. Conclusion: The calculated skeletal averaged absorbed fractions for each source-target combination were found to follow similar trends of more recent dosimetry models (image-based models) and did not follow current models used in nuclear medicine dosimetry at high energies (due to that models use of an infinite expanse of trabecular spongiosa)« less

What Is a Bone Marrow Transplant?

MedlinePlus

... Print this page My Cart What is a bone marrow transplant? A bone marrow transplant is a ... blood.” – Edmund Waller, MD, PHD What is a bone marrow transplant? A bone marrow transplant is a ...

Isolation and hepatocyte differentiation of mesenchymal stem cells from porcine bone marrow--"surgical waste" as a novel MSC source.

PubMed

Brückner, S; Tautenhahn, H-M; Winkler, S; Stock, P; Jonas, S; Dollinger, M; Christ, B

2013-06-01

Mesenchymal stem cells (MSC) isolated from bone marrow and differentiated into hepatocyte-like cells have increasingly gained attention for clinical cell therapy of liver diseases because of their high regenerative capacity. They are available from bone marrow aspirates of the os coxae after puncture of the crista iliaca or from bone marrow "surgical waste" gained from amputations or knee and hip operations. Thus, the aim of the study was to demonstrate whether these pBM-MSC (porcine bone marrow-derived mesenchymal stem cells) displayed mesenchymal features and hepatocyte differentiation potential. MSC were isolated either from crista iliaca punctures or after sampling and collagenase digestion of bone marrow from the os femoris. Mesenchymal features were assessed by flow cytometry for specific surface antigens and their ability to differentiate into at least 3 lineages. Functional properties, such as urea or glycogen synthesis and cytochrome P450 activity, as well as the cell morphology were examined during hepatocyte differentiation. pBM-MSC from both sources lacked the hematopoietic markers CD14 and CD45 but expressed the typical mesenchymal markers CD44, CD29, CD90, and CD105. Both cell types could differentiate into adipocyte, osteocyte, and hepatocyte lineages. After hepatocyte differentiation, CD105 expression decreased significantly and cells changed morphology from fibroblastoid into polygonal, displaying significantly increased glycogen storage, urea synthesis, and cytochrome activity. pBM-MSC from various sources were identical in respect to their mesenchymal features and their hepatocyte differentiation potential. Hence, long bones might be a particularly useful resource to isolate bone marrow mesenchymal stem cells for transplantation. Copyright © 2013 Elsevier Inc. All rights reserved.

Dietary isoflavones act on bone marrow osteoprogenitor cells and stimulate ovary development before influencing bone mass in pre-pubertal piglets.

PubMed

De Wilde, Anne; Maria Rassi, Claudia; Cournot, Giulia; Colin, Colette; Lacroix, Herminie C; Chaumaz, Gilles; Coxam, Veronique; Bennetau-Pelissero, Catherine; Pointillart, Alain; Lieberherr, Michele

2007-07-01

Food containing soybeans provide isoflavone phytoestrogens that can preserve bone mass in postmenopausal women, and prevent bone loss in ovariectomized rats. But their effects on bone remain unclear, particularly on bone formation during growth. Two groups of eight pre-pubertal piglets were fed a basal or an isoflavone-enriched (S800) diet for 6 weeks. The S800 diet contained 800 mg SoyLifetrade mark/kg, providing 2.8 mg isoflavones/kg body weight/day. Several bones were collected and tested for bone strength and density. Bone marrow was collected from humeri together with blood samples and genital tracts. The plasma concentrations of isoflavones were increased in the pigs fed S800, but growth rate, body weight, plasma bone markers, bone mineral density, and strength were all unaffected. In contrast, cultured stromal cells from S800 pigs had more alkaline phosphatase-rich cells and mineralized nodules, secreted more osteocalcin, osteoprotegerin and RANK-L, synthesized more osteoprotegerin, and RANK-L. Cultured mononucleated nonadherent bone marrow cells from S800 pigs developed fewer tartrate-resistant acid phosphatase mononucleated cells (osteoclast progenitors) when cultured with 1,25(OH)(2)D(3), and resorbed a smaller area of dentine slices. Freshly isolated bone marrow osteoclast progenitors from S800 pigs had more caspase-3 cleavage activity, and synthesized less RANK. Both osteoclast and osteoblast progenitors had ERalpha and ERbeta, whose syntheses were stimulated by the S800 diet. The S800 piglets had heavier ovaries with more follicles, but their uterus weight was unaffected. We conclude that dietary isoflavones have no detectable effect on the bone mass of growing female piglets, but act on bone marrow osteoprogenitors via ERs--mainly ERbeta, and stimulate ovary development.

Hematologic effects of subcutaneous administration of recombinant human granulocyte colony-stimulating factor (filgrastim) in healthy alpacas.

PubMed

McKenzie, Erica C; Tornquist, Susan J; Gorman, M Elena; Cebra, Christopher K; Payton, Mark E

2008-06-01

To determine the effects of SC administration of filgrastim on cell counts in venous blood and bone marrow of healthy adult alpacas. 10 healthy alpacas. Alpacas were randomly assigned to receive treatment with filgrastim (5 microg/kg, SC; n=5) or an equivalent volume of physiologic saline (0.9% NaCl) solution (5) once a day for 3 days. Blood samples were obtained via jugular venipuncture 1 day prior to treatment and once a day for 5 days commencing 24 hours after the first dose was administered. Complete blood counts were performed for each blood sample. Bone marrow aspirates were obtained from the sternum of each alpaca 48 hours before the first treatment was administered and 72 hours after the third treatment was administered. Myeloid-to-erythroid cell (M:E) ratio was determined via cytologic evaluation of bone marrow aspirates. In filgrastim-treated alpacas, substantial increases in counts of WBCs and neutrophils were detected within 24 hours after the first dose was administered. Band cell count and percentage significantly increased 24 hours after the second dose. Counts of WBCs, neutrophils, and band cells remained high 48 hours after the third dose. Red blood cell counts and PCV were unaffected. The M:E ratio also increased significantly after treatment with filgrastim. Filgrastim induced rapid and substantial increases in numbers of circulating neutrophils and M:E ratios of bone marrow in healthy alpacas. Therefore, filgrastim may be useful in the treatment of camelids with impaired bone marrow function.

Release from quiescence of CD34+ CD38- human umbilical cord blood cells reveals their potentiality to engraft adults.

PubMed Central

Cardoso, A A; Li, M L; Batard, P; Hatzfeld, A; Brown, E L; Levesque, J P; Sookdeo, H; Panterne, B; Sansilvestri, P; Clark, S C

1993-01-01

Using optimal culture conditions in which the transforming growth factor beta 1 (TGF-beta 1) inhibitory loop has been interrupted by antisense TGF-beta 1 oligonucleotides or anti-TGF-beta serum, we have compared the proliferative capacities and the abilities of the CD34+ CD38- cell populations from bone marrow and umbilical cord blood to generate early progenitors in long-term cultures. The CD34+ CD38- fraction of umbilical cord blood accounts for 4% of the CD34+ fraction compared to only 1% in bone marrow, indicating that umbilical cord blood may be relatively enriched in stem cells. We estimate that the CD34+ CD38- cells from a typical umbilical cord blood sample produce equivalent numbers of colony-forming units (CFU)-granulocyte/erythrocyte/macrophage/megakaryocyte, twice as many CFU-granulocyte/macrophage (GM) and 3 times as many burst-forming units-erythroid as the same population from an average bone marrow sample used in adult transplantation. In addition, the colonies resulting from the umbilical cord blood samples were significantly larger than those from bone marrow, indicating a greater growth potential. However, the content of later progenitors, which may be important for short-term reconstitution, was less in umbilical cord blood-derived than in bone marrow-derived cell preparations, as estimated by a 4-fold lower production of CFU-GM in long-term cultures of CD34+ CD38+ cells. This deficit is partially compensated by the higher growth capacity of the resulting CFU-GM. These studies suggest that umbilical cord blood is a suitable source of cells for adult transplantation. PMID:7690969

The homing of bone marrow MSCs to non-osseous sites for ectopic bone formation induced by osteoinductive calcium phosphate

PubMed Central

Song, Guodong; Habibovic, Pamela; Bao, Chongyun; Hu, Jing; van Blitterswijk, Clemens A.; Yuan, Huipin; Chen, Wenchuan; Xu, Hockin H.K.

2013-01-01

Osteoinductive biomaterials are promising for bone repair. There is no direct proof that bone marrow mesenchymal stem cells (BMSCs) home to non-osseous sites and participate in ectopic bone formation induced by osteoinductive bioceramics. The objective of this study was to use a sex-mismatched beagle dog model to investigate BMSC homing via blood circulation to participate in ectopic bone formation via osteoinductive biomaterial. BMSCs of male dogs were injected into female femoral marrow cavity. The survival and stable chimerism of donor BMSCs in recipients were confirmed with polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH). Biphasic calcium phosphate (BCP) granules were implanted in dorsal muscles of female dogs. Y chromosomes were detected in samples harvested from female dogs which had received male BMSCs. At 4 weeks, cells with Y-chromosomes were distributed in the new bone matrix throughout the BCP granule implant. At 6 weeks, cells with Y chromosomes were present in newly mineralized woven bone. TRAP positive osteoclast-like cells were observed in 4-week implants, and the number of such cells decreased from 4 to 6 weeks. These results show that osteoprogenitors were recruited from bone marrow and homed to ectopic site to serve as a cell source for calcium phosphate-induced bone formation. In conclusion, BMSCs were demonstrated to migrate from bone marrow through blood circulation to non-osseous bioceramic implant site to contribute to ectopic bone formation in a canine model. BCP induced new bone in muscles without growth factor delivery, showing excellent osteoinductivity that could be useful for bone tissue engineering. PMID:23298780

An image-based skeletal dosimetry model for the ICRP reference adult female—internal electron sources

NASA Astrophysics Data System (ADS)

O'Reilly, Shannon E.; DeWeese, Lindsay S.; Maynard, Matthew R.; Rajon, Didier A.; Wayson, Michael B.; Marshall, Emily L.; Bolch, Wesley E.

2016-12-01

An image-based skeletal dosimetry model for internal electron sources was created for the ICRP-defined reference adult female. Many previous skeletal dosimetry models, which are still employed in commonly used internal dosimetry software, do not properly account for electron escape from trabecular spongiosa, electron cross-fire from cortical bone, and the impact of marrow cellularity on active marrow self-irradiation. Furthermore, these existing models do not employ the current ICRP definition of a 50 µm bone endosteum (or shallow marrow). Each of these limitations was addressed in the present study. Electron transport was completed to determine specific absorbed fractions to both active and shallow marrow of the skeletal regions of the University of Florida reference adult female. The skeletal macrostructure and microstructure were modeled separately. The bone macrostructure was based on the whole-body hybrid computational phantom of the UF series of reference models, while the bone microstructure was derived from microCT images of skeletal region samples taken from a 45 years-old female cadaver. The active and shallow marrow are typically adopted as surrogate tissue regions for the hematopoietic stem cells and osteoprogenitor cells, respectively. Source tissues included active marrow, inactive marrow, trabecular bone volume, trabecular bone surfaces, cortical bone volume, and cortical bone surfaces. Marrow cellularity was varied from 10 to 100 percent for active marrow self-irradiation. All other sources were run at the defined ICRP Publication 70 cellularity for each bone site. A total of 33 discrete electron energies, ranging from 1 keV to 10 MeV, were either simulated or analytically modeled. The method of combining skeletal macrostructure and microstructure absorbed fractions assessed using MCNPX electron transport was found to yield results similar to those determined with the PIRT model applied to the UF adult male skeletal dosimetry model. Calculated skeletal averaged absorbed fractions for each source-target combination were found to follow similar trends of more recent dosimetry models (image-based models) but did not follow results from skeletal models based upon assumptions of an infinite expanse of trabecular spongiosa.

Propionibacterium acnes infected intervertebral discs cause vertebral bone marrow lesions consistent with Modic changes.

PubMed

Dudli, Stefan; Liebenberg, Ellen; Magnitsky, Sergey; Miller, Steve; Demir-Deviren, Sibel; Lotz, Jeffrey C

2016-08-01

Modic type I change (MC1) are vertebral bone marrow lesions adjacent to degenerated discs that are specific for discogenic low back pain. The etiopathogenesis is unknown, but occult discitis, in particular with Propionibacteria acnes (P. acnes), has been suggested as a possible etiology. If true, antibiotic therapy should be considered for patients with MC1. However, this hypothesis is controversial. While some studies report up to 40% infection rate in herniated discs, others fail to detect infected discs and attribute reports of positive cultures to contamination during sampling procedure. Irrespective of the clinical controversy, whether it is biologically plausible for P. acnes to cause MC1 has never been investigated. Therefore, the objective of this study was to test if P. acnes can proliferate within discs and cause reactive changes in the adjacent bone marrow. P. acnes was aseptically isolated from a symptomatic human L4/5 disc with MC1 and injected into rat tail discs. We demonstrate proliferation of P. acnes and up-regulation of IL-1 and IL-6 within three days of inoculation. At day-7, disc degeneration was apparent along with fibrotic endplate erosion. TNF-α immunoreactivity was enhanced within the effected endplates along with cellular infiltrates. The bone marrow appeared normal. At day-14, endplates and trabecular bone close to the disc were almost completely resorbed and fibrotic tissue extended into the bone marrow. T-cells and TNF-α immunoreactivity were identified at the disc/marrow junction. On MRI, bone marrow showed MC1-like changes. In conclusion, P. acnes proliferate within the disc, induce degeneration, and cause MC1-like changes in the adjacent bone marrow. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1447-1455, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Bone marrow transplant

MedlinePlus

Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; Umbilical ...

Comparing different post-mortem human samples as DNA sources for downstream genotyping and identification.

PubMed

Calacal, Gayvelline C; Apaga, Dame Loveliness T; Salvador, Jazelyn M; Jimenez, Joseph Andrew D; Lagat, Ludivino J; Villacorta, Renato Pio F; Lim, Maria Cecilia F; Fortun, Raquel D R; Datar, Francisco A; De Ungria, Maria Corazon A

2015-11-01

The capability of DNA laboratories to perform genotyping procedures from post-mortem remains, including those that had undergone putrefaction, continues to be a challenge in the Philippines, a country characterized by very humid and warm conditions all year round. These environmental conditions accelerate the decomposition of human remains that were recovered after a disaster and those that were left abandoned after a crime. When considerable tissue decomposition of human remains has taken place, there is no other option but to extract DNA from bone and/or teeth samples. Routinely, femur shafts are obtained from recovered bodies for human identification because the calcium matrix protects the DNA contained in the osteocytes. In the Philippines, there is difficulty in collecting femur samples after natural disasters or even human-made disasters, because these events are usually characterized by a large number of fatalities. Identification of casualties is further delayed by limitation in human and material resources. Hence, it is imperative to test other types of biological samples that are easier to collect, transport, process and store. We analyzed DNA that were obtained from body fluid, bone marrow, muscle tissue, clavicle, femur, metatarsal, patella, rib and vertebral samples from five recently deceased untreated male cadavers and seven male human remains that were embalmed, buried for ∼ 1 month and then exhumed. The bodies had undergone different environmental conditions and were in various stages of putrefaction. A DNA extraction method utilizing a detergent-washing step followed by an organic procedure was used. The utility of bone marrow and vitreous fluid including bone marrow and vitreous fluid that was transferred on FTA(®) cards and subjected to autosomal STR and Y-STR DNA typing were also evaluated. DNA yield was measured and the presence or absence of PCR inhibitors in DNA extracts was assessed using Plexor(®)HY. All samples were amplified using PowerPlex(®)21 and PowerPlexY(®)23 systems and analyzed using the AB3500 Genetic Analyzer and the GeneMapper(®) ID-X v.1.2 software. PCR inhibitors were consistently detected in bone marrow, muscle tissue, rib and vertebra samples. Amplifiable DNA was obtained in a majority of the samples analyzed. DNA recovery from 0.1g biological material was adequate for successful genotyping of most of the non-bone and bone samples. Complete DNA profiles were generated from bone marrow, femur, metatarsal and patella with 0.1 ng DNA template. Using 0.5 ng DNA template resulted in increased allele recovery and improved intra- and inter-locus peak balance. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Identification of Suitable Reference Genes for mRNA Studies in Bone Marrow in a Mouse Model of Hematopoietic Stem Cell Transplantation.

PubMed

Li, H; Chen, C; Yao, H; Li, X; Yang, N; Qiao, J; Xu, K; Zeng, L

2016-10-01

Bone marrow micro-environment changes during hematopoietic stem cell transplantation (HSCT) with subsequent alteration of genes expression. Quantitative polymerase chain reaction (q-PCR) is a reliable and reproducible technique for the analysis of gene expression. To obtain more accurate results, it is essential to find a reference during HSCT. However, which gene is suitable during HSCT remains unclear. This study aimed to identify suitable reference genes for mRNA studies in bone marrow after HSCT. C57BL/6 mice were treated with either total body irradiation (group T) or busulfan/cyclophosphamide (BU/CY) (group B) followed by infusion of bone marrow cells. Normal mice without treatments were served as a control. All samples (group T + group B + control) were defined as group G. On days 7, 14, and 21 after transplantation, transcription levels of 7 candidate genes, ACTB, B2M, GAPDH, HMBS, HPRT, SDHA, and YWHAZ, in bone marrow cells were measured by use of real-time quantitative PCR. The expression stability of these 7 candidate reference genes were analyzed by 2 statistical software programs, GeNorm and NormFinder. Our results showed that ACTB displayed the highest expression in group G, with lowest expression of PSDHA in group T and HPRT in groups B and G. Analysis of expression stability by use of GeNorm or NormFinder demonstrated that expression of B2M in bone marrow were much more stable during HSCT, compared with other candidate genes including commonly used reference genes GAPDH and ACTB. ACTB could be used as a suitable reference gene for mRNA studies in bone marrow after HSCT. Copyright © 2016 Elsevier Inc. All rights reserved.

Bone marrow hypoplasia associated with fenbendazole administration in a dog.

PubMed

Gary, Anthony T; Kerl, Marie E; Wiedmeyer, Charles E; Turnquist, Susan E; Cohn, Leah A

2004-01-01

A 1.5-year-old Doberman pinscher was presented with sudden-onset of fever and malaise. Twelve days prior to presentation, fenbendazole therapy was initiated for a suspected lungworm infection. Results of a complete blood count on presentation showed pancytopenia, while histopathological evaluation of a bone marrow core sample revealed bone marrow hypoplasia of undetermined etiology. Bactericidal antibiotics and fluid therapy, as well as discontinuation of fenbendazole administration, led to a complete resolution of clinical and hematological abnormalities within 15 days. An idiosyncratic reaction to fenbendazole was suspected based on the absence of infectious, neoplastic, autoimmune, and toxic etiologies, as well as resolution of clinical signs and pancytopenia upon drug withdrawal.

Molecular Detection of Breast Cancer

DTIC Science & Technology

1998-02-01

treatment-resistant cancer cells. Clearly new approaches are needed to treat these diseases. This project is designed to develop novel approaches to...detect breast cancer cells that contaminate peripheral blood and bone marrow, and to remove such contaminating cells. An RT-PCR assay has been developed ...to detect breast cancer cells, and a novel gene therapy vector has been developed to kill contaminating cancer cells. Blood and bone marrow samples

Following damage, the majority of bone marrow-derived airway cells express an epithelial marker.

PubMed

MacPherson, Heather; Keir, Pamela A; Edwards, Carol J; Webb, Sheila; Dorin, Julia R

2006-12-19

Adult-derived bone marrow stem cells are capable of reconstituting the haematopoietic system. However there is ongoing debate in the literature as to whether bone marrow derived cells have the ability to populate other tissues and express tissue specific markers. The airway has been an organ of major interest and was one of the first where this was demonstrated. We have previously demonstrated that the mouse airway can be repopulated by side population bone marrow transplanted cells. Here we investigate the frequency and phenotypic nature of these bone marrow derived cells. Female mice were engrafted with male whole bone marrow or side population (SP) cells and subjected to detergent-induced damage after 3 months. Donor cells were identified by Y chromosome fluorescence in situ hybridisation and their phenotype was assessed by immunohistochemistry on the same sections. Slides were visualised by a combination of widefield and deconvolved microscopy and whole cells were analysed on cytospin preparations. The frequencies of engraftment of male cells in the airway of mice that show this (9/10), range from 1.0-1.6% with whole marrow and 0.6-1.5% with SP cells. Undamaged controls have only between 0.1 and 0.2% male cells in the trachea. By widefield microscopy analysis we find 60.2% (53/88) of male donor derived cells express cytokeratins as a marker of epithelial cells. These results were reinforced using deconvolved microscopy and scored by two independent investigators. In addition cytospin analysis of cells dissociated from the damaged trachea of engrafted mice also reveals donor derived Y chromosome positive cells that are immunopositive for cytokeratin. Using cytokeratin and the universal haematopoietic marker CD45 immunohistochemistry, we find the donor derived cells fall into four phenotypic classes. We do not detect cytokeratin positive cells in whole bone marrow using cytokeratin immunostaining and we do not detect any cytokeratin mRNA in SP or bone marrow samples by RT-PCR. The appearance of bone marrow derived cells in the tracheal epithelium is enriched by detergent-induced tissue damage and the majority of these cells express an epithelial marker. The cytokeratin positive donor derived cells in the tracheal epithelium are not present in the injected donor cells and must have acquired this novel phenotype in vivo.

Following damage, the majority of bone marrow-derived airway cells express an epithelial marker

PubMed Central

MacPherson, Heather; Keir, Pamela A; Edwards, Carol J; Webb, Sheila; Dorin, Julia R

2006-01-01

Background Adult-derived bone marrow stem cells are capable of reconstituting the haematopoietic system. However there is ongoing debate in the literature as to whether bone marrow derived cells have the ability to populate other tissues and express tissue specific markers. The airway has been an organ of major interest and was one of the first where this was demonstrated. We have previously demonstrated that the mouse airway can be repopulated by side population bone marrow transplanted cells. Here we investigate the frequency and phenotypic nature of these bone marrow derived cells. Methods Female mice were engrafted with male whole bone marrow or side population (SP) cells and subjected to detergent-induced damage after 3 months. Donor cells were identified by Y chromosome fluorescence in situ hybridisation and their phenotype was assessed by immunohistochemistry on the same sections. Slides were visualised by a combination of widefield and deconvolved microscopy and whole cells were analysed on cytospin preparations. Results The frequencies of engraftment of male cells in the airway of mice that show this (9/10), range from 1.0 – 1.6% with whole marrow and 0.6 – 1.5% with SP cells. Undamaged controls have only between 0.1 and 0.2% male cells in the trachea. By widefield microscopy analysis we find 60.2% (53/88) of male donor derived cells express cytokeratins as a marker of epithelial cells. These results were reinforced using deconvolved microscopy and scored by two independent investigators. In addition cytospin analysis of cells dissociated from the damaged trachea of engrafted mice also reveals donor derived Y chromosome positive cells that are immunopositive for cytokeratin. Using cytokeratin and the universal haematopoietic marker CD45 immunohistochemistry, we find the donor derived cells fall into four phenotypic classes. We do not detect cytokeratin positive cells in whole bone marrow using cytokeratin immunostaining and we do not detect any cytokeratin mRNA in SP or bone marrow samples by RT-PCR. Conclusion The appearance of bone marrow derived cells in the tracheal epithelium is enriched by detergent-induced tissue damage and the majority of these cells express an epithelial marker. The cytokeratin positive donor derived cells in the tracheal epithelium are not present in the injected donor cells and must have acquired this novel phenotype in vivo. PMID:17177981

Good, Bad, or Ugly: the Biological Roles of Bone Marrow Fat.

PubMed

Singh, Lakshman; Tyagi, Sonia; Myers, Damian; Duque, Gustavo

2018-04-01

Bone marrow fat expresses mixed characteristics, which could correspond to white, brown, and beige types of fat. Marrow fat could act as either energy storing and adipokine secreting white fat or as a source of energy for hematopoiesis and bone metabolism, thus acting as brown fat. However, there is also a negative interaction between marrow fat and other elements of the bone marrow milieu, which is known as lipotoxicity. In this review, we will describe the good and bad roles of marrow fat in the bone, while focusing on the specific components of the negative effect of marrow fat on bone metabolism. Lipotoxicity in the bone is exerted by bone marrow fat through the secretion of adipokines and free fatty acids (FFA) (predominantly palmitate). High levels of FFA found in the bone marrow of aged and osteoporotic bone are associated with decreased osteoblastogenesis and bone formation, decreased hematopoiesis, and increased osteoclastogenesis. In addition, FFA such as palmitate and stearate induce apoptosis and dysfunctional autophagy in the osteoblasts, thus affecting their differentiation and function. Regulation of marrow fat could become a therapeutic target for osteoporosis. Inhibition of the synthesis of FFA by marrow fat could facilitate osteoblastogenesis and bone formation while affecting osteoclastogenesis. However, further studies testing this hypothesis are still required.

Growth of erythroid burst-forming units (BFU-E) in cultures of canine bone marrow and peripheral blood cells: effect of serum from irradiated dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kreja, L.; Baltschukat, K.; Nothdurft, W.

1988-08-01

Erythroid burst-forming units (BFU-E) from canine bone marrow and peripheral blood could be grown in methylcellulose in the presence of an appropriate batch of fetal calf serum (FCS), transferrin, and erythropoietin (Epo). However, improved colony formation (size and number of bursts) was obtained when serum from total body irradiated dogs was present in the culture. This serum, obtained from dogs at day 9 after total body irradiation with a dose of 3.9 Gy, reduced markedly the Epo requirement of BFU-E. Furthermore, it allowed the omission of FCS from the culture medium if cholesterol and bovine serum albumin (BSA) were usedmore » as FCS substitutes. BFU-E concentrations were found to be rather different in the peripheral blood and in bone marrow samples from different sites (i.e., iliac crest, sternum, and humerus) of normal beagles. The studies further show that canine bone marrow BFU-E can be cryopreserved in liquid nitrogen.« less

Training echo state networks for rotation-invariant bone marrow cell classification.

PubMed

Kainz, Philipp; Burgsteiner, Harald; Asslaber, Martin; Ahammer, Helmut

2017-01-01

The main principle of diagnostic pathology is the reliable interpretation of individual cells in context of the tissue architecture. Especially a confident examination of bone marrow specimen is dependent on a valid classification of myeloid cells. In this work, we propose a novel rotation-invariant learning scheme for multi-class echo state networks (ESNs), which achieves very high performance in automated bone marrow cell classification. Based on representing static images as temporal sequence of rotations, we show how ESNs robustly recognize cells of arbitrary rotations by taking advantage of their short-term memory capacity. The performance of our approach is compared to a classification random forest that learns rotation-invariance in a conventional way by exhaustively training on multiple rotations of individual samples. The methods were evaluated on a human bone marrow image database consisting of granulopoietic and erythropoietic cells in different maturation stages. Our ESN approach to cell classification does not rely on segmentation of cells or manual feature extraction and can therefore directly be applied to image data.

Hypoxia-Activated Prodrug TH-302 Targets Hypoxic Bone Marrow Niches in Preclinical Leukemia Models.

PubMed

Benito, Juliana; Ramirez, Marc S; Millward, Niki Zacharias; Velez, Juliana; Harutyunyan, Karine G; Lu, Hongbo; Shi, Yue-Xi; Matre, Polina; Jacamo, Rodrigo; Ma, Helen; Konoplev, Sergej; McQueen, Teresa; Volgin, Andrei; Protopopova, Marina; Mu, Hong; Lee, Jaehyuk; Bhattacharya, Pratip K; Marszalek, Joseph R; Davis, R Eric; Bankson, James A; Cortes, Jorge E; Hart, Charles P; Andreeff, Michael; Konopleva, Marina

2016-04-01

To characterize the prevalence of hypoxia in the leukemic bone marrow, its association with metabolic and transcriptional changes in the leukemic blasts and the utility of hypoxia-activated prodrug TH-302 in leukemia models. Hyperpolarized magnetic resonance spectroscopy was utilized to interrogate the pyruvate metabolism of the bone marrow in the murine acute myeloid leukemia (AML) model. Nanostring technology was used to evaluate a gene set defining a hypoxia signature in leukemic blasts and normal donors. The efficacy of the hypoxia-activated prodrug TH-302 was examined in the in vitro and in vivo leukemia models. Metabolic imaging has demonstrated increased glycolysis in the femur of leukemic mice compared with healthy control mice, suggesting metabolic reprogramming of hypoxic bone marrow niches. Primary leukemic blasts in samples from AML patients overexpressed genes defining a "hypoxia index" compared with samples from normal donors. TH-302 depleted hypoxic cells, prolonged survival of xenograft leukemia models, and reduced the leukemia stem cell pool in vivo In the aggressive FLT3/ITD MOLM-13 model, combination of TH-302 with tyrosine kinase inhibitor sorafenib had greater antileukemia effects than either drug alone. Importantly, residual leukemic bone marrow cells in a syngeneic AML model remain hypoxic after chemotherapy. In turn, administration of TH-302 following chemotherapy treatment to mice with residual disease prolonged survival, suggesting that this approach may be suitable for eliminating chemotherapy-resistant leukemia cells. These findings implicate a pathogenic role of hypoxia in leukemia maintenance and chemoresistance and demonstrate the feasibility of targeting hypoxic cells by hypoxia cytotoxins. ©2015 American Association for Cancer Research.

Assessment of bone marrow plasma cell infiltrates in multiple myeloma: the added value of CD138 immunohistochemistry

PubMed Central

Al-Quran, Samer Z.; Yang, Lijun; Magill, James M.; Braylan, Raul C.; Douglas-Nikitin, Vonda K.

2012-01-01

Summary Assessment of bone marrow involvement by malignant plasma cells is an important element in the diagnosis and follow-up of patients with multiple myeloma and other plasma cell dyscrasias. Microscope-based differential counts of bone marrow aspirates are used as the primary method to evaluate bone marrow plasma cell percentages. However, multiple myeloma is often a focal process, a fact that impacts the accuracy and reliability of the results of bone marrow plasma cell percentages obtained by differential counts of bone marrow aspirate smears. Moreover, the interobserver and intraobserver reproducibility of counting bone marrow plasma cells microscopically has not been adequately tested. CD138 allows excellent assessment of plasma cell numbers and distribution in bone marrow biopsies. We compared estimates of plasma cell percentages in bone marrow aspirates and in hematoxylin-eosin– and CD138-stained bone marrow biopsy sections (CD138 sections) in 79 bone marrows from patients with multiple myeloma. There was a notable discrepancy in bone marrow plasma cell percentages using the different methods of observation. In particular, there was a relatively poor concordance of plasma cell percentage estimation between aspirate smears and CD138 sections. Estimates of plasma cell percentage using CD138 sections demonstrated the highest interobserver concordance. This observation was supported by computer-assisted image analysis. In addition, CD138 expression highlighted patterns of plasma cell infiltration indicative of neoplasia even in the absence of plasmacytosis. We conclude that examination of CD138 sections should be considered for routine use in the estimation of plasma cell load in the bone marrow. PMID:17714757

Incorporation of Bone Marrow Cells in Pancreatic Pseudoislets Improves Posttransplant Vascularization and Endocrine Function

PubMed Central

Wittig, Christine; Laschke, Matthias W.; Scheuer, Claudia; Menger, Michael D.

2013-01-01

Failure of revascularization is known to be the major reason for the poor outcome of pancreatic islet transplantation. In this study, we analyzed whether pseudoislets composed of islet cells and bone marrow cells can improve vascularization and function of islet transplants. Pancreatic islets isolated from Syrian golden hamsters were dispersed into single cells for the generation of pseudoislets containing 4×103 cells. To create bone marrow cell-enriched pseudoislets 2×103 islet cells were co-cultured with 2×103 bone marrow cells. Pseudoislets and bone marrow cell-enriched pseudoislets were transplanted syngeneically into skinfold chambers to study graft vascularization by intravital fluorescence microscopy. Native islet transplants served as controls. Bone marrow cell-enriched pseudoislets showed a significantly improved vascularization compared to native islets and pseudoislets. Moreover, bone marrow cell-enriched pseudoislets but not pseudoislets normalized blood glucose levels after transplantation of 1000 islet equivalents under the kidney capsule of streptozotocin-induced diabetic animals, although the bone marrow cell-enriched pseudoislets contained only 50% of islet cells compared to pseudoislets and native islets. Fluorescence microscopy of bone marrow cell-enriched pseudoislets composed of bone marrow cells from GFP-expressing mice showed a distinct fraction of cells expressing both GFP and insulin, indicating a differentiation of bone marrow-derived cells to an insulin-producing cell-type. Thus, enrichment of pseudoislets by bone marrow cells enhances vascularization after transplantation and increases the amount of insulin-producing tissue. Accordingly, bone marrow cell-enriched pseudoislets may represent a novel approach to increase the success rate of islet transplantation. PMID:23875013

Association of plasma cell subsets in the bone marrow and free light chain concentrations in the serum of monoclonal gammopathy patients.

PubMed

Ayliffe, Michael John; Behrens, Judith; Stern, Simon; Sumar, Nazira

2012-08-01

This study investigated bone marrow plasma cell subsets and monoclonal free light chain concentrations in blood of monoclonal gammopathy patients. 54 bone marrow samples were stained by double immunofluorescence to enumerate cellular subsets making either intact monoclonal immunoglobulin or free light chains only. Blood taken at the same time was assayed for free light chains by an automated immunoassay. Patients were assigned to three cellular population categories: single intact monoclonal immunoglobulin (59%), dual monoclonal immunoglobulin and free light chain only (31%), or single free light chain only (9%). The median affected free light chain concentration of each group was 75 mg/l, 903 mg/l and 3320 mg/l, respectively, but with substantial overlap. In myeloma patients the difference in serum free light chain concentrations between patients with free light chain only marrow cells and those without was statistically significant. Serum free light chain levels >600 mg/l result mostly from marrow cells restricted to free light chain production.

Consequences of irradiation on bone and marrow phenotypes, and its relation to disruption of hematopoietic precursors

PubMed Central

Green, Danielle E.; Rubin, Clinton T.

2014-01-01

The rising levels of radiation exposure, specifically for medical treatments and accidental exposures, have added great concern for the long term risks of bone fractures. Both the bone marrow and bone architecture are devastated following radiation exposure. Even sub-lethal doses cause a deficit to the bone marrow microenvironment, including a decline in hematopoietic cells, and this deficit occurs in a dose dependent fashion. Certain cell phenotypes though are more susceptible to radiation damage, with mesenchymal stem cells being more resilient than the hematopoietic stem cells. The decline in total bone marrow hematopoietic cells is accompanied with elevated adipocytes into the marrow cavity, thereby inhibiting hematopoiesis and recovery of the bone marrow microenvironment. Poor bone marrow is also associated with a decline in bone architectural quality. Therefore, the ability to maintain the bone marrow microenvironment would hinder much of the trabecular bone loss caused by radiation exposure, ultimately decreasing some comorbidities in patients exposed to radiation. PMID:24607941

MR-Based Assessment of Bone Marrow Fat in Osteoporosis, Diabetes, and Obesity

PubMed Central

Cordes, Christian; Baum, Thomas; Dieckmeyer, Michael; Ruschke, Stefan; Diefenbach, Maximilian N.; Hauner, Hans; Kirschke, Jan S.; Karampinos, Dimitrios C.

2016-01-01

Bone consists of the mineralized component (i.e., cortex and trabeculae) and the non-mineralized component (i.e., bone marrow). Most of the routine clinical bone imaging uses X-ray-based techniques and focuses on the mineralized component. However, bone marrow adiposity has been also shown to have a strong linkage with bone health. Specifically, multiple previous studies have demonstrated a negative association between bone marrow fat fraction (BMFF) and bone mineral density. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are ideal imaging techniques for non-invasively investigating the properties of bone marrow fat. In the present work, we first review the most important MRI and MRS methods for assessing properties of bone marrow fat, including methodologies for measuring BMFF and bone marrow fatty acid composition parameters. Previous MRI and MRS studies measuring BMFF and fat unsaturation in the context of osteoporosis are then reviewed. Finally, previous studies investigating the relationship between bone marrow fat, other fat depots, and bone health in patients with obesity and type 2 diabetes are presented. In summary, MRI and MRS are powerful non-invasive techniques for measuring properties of bone marrow fat in osteoporosis, obesity, and type 2 diabetes and can assist in future studies investigating the pathophysiology of bone changes in the above clinical scenarios. PMID:27445977

Blood and Bone Marrow Donation

MedlinePlus

... who's waiting for a stem cell transplant. Risks Bone marrow donation The most serious risk associated with ... or her health insurance. What you can expect Bone marrow donation Collecting stem cells from bone marrow ...

Multipotent Mesenchymal Stromal Stem Cell Expansion by Plating Whole Bone Marrow at a Low Cellular Density: A More Advantageous Method for Clinical Use

PubMed Central

Mareschi, Katia; Rustichelli, Deborah; Calabrese, Roberto; Gunetti, Monica; Sanavio, Fiorella; Castiglia, Sara; Risso, Alessandra; Ferrero, Ivana; Tarella, Corrado; Fagioli, Franca

2012-01-01

Mesenchymal stem cells (MSCs) are a promising source for cell therapy due to their pluripotency and immunomodulant proprieties. As the identification of “optimal” conditions is important to identify a standard procedure for clinical use. Percoll, Ficoll and whole bone marrow directly plated were tested from the same sample as separation methods. The cells were seeded at the following densities: 100 000, 10 000, 1000, 100, 10 cells/cm2. After reaching confluence, the cells were detached, pooled and re-plated at 1000, 500, 100, and 10 cells/cm2. Statistical analyses were performed. Cumulative Population Doublings (PD) did not show significant differences for the separation methods and seeding densities but only for the plating density. Some small quantity samples plated in T25 flasks at plating densities of 10 and 100 cells/cm2 did not produce any expansion. However, directly plated whole bone marrow resulted in a more advantageous method in terms of CFU-F number, cellular growth and minimal manipulation. No differences were observed in terms of gross morphology, differentiation potential or immunophenotype. These data suggest that plating whole bone marrow at a low cellular density may represent a good procedure for MSC expansion for clinical use. PMID:23715383

Meeting report of the 2016 bone marrow adiposity meeting.

PubMed

van der Eerden, Bram; van Wijnen, André

2017-10-02

There is considerable interest in the physiology and pathology, as well as the cellular and molecular biology, of bone marrow adipose tissue (BMAT). Because bone marrow adiposity is linked not only to systemic energy metabolism, but also to both bone marrow and musculoskeletal disorders, this biologic compartment has become of major interest to investigators from diverse disciplines. Bone marrow adiposity represents a virtual multi-tissue endocrine organ, which encompasses cells from multiple developmental lineages (e.g., mesenchymal, myeloid, lymphoid) and occupies all the non-osseous and non-cartilaginous space within long bones. A number of research groups are now focusing on bone marrow adiposity to understand a range of clinical afflictions associated with bone marrow disorders and to consider mechanisms-based strategies for future therapies.

Study of Imaging Pattern in Bone Marrow Oedema in MRI in Recent Knee Injuries and its Correlation with Type of Knee Injury.

PubMed

Sahoo, Kulamani; Garg, Ashish; Saha, Pramod; Dodia, Jainesh Valjibhai; Raj, Vinay Rajappa; Bhairagond, Shweta Jagadish

2016-04-01

The knee is a major weight bearing joint that provides mobility and stability during physical activity as well as balance while standing. If the knee is exposed to forces beyond its physiologic range, risk of injury to bone or soft tissue structures increases. A thorough understanding of knee injury patterns and their mechanisms may help in achieving more accurate assessment of injuries. To identify imaging pattern in bone marrow oedema and to correlate the pattern of bone marrow oedema retrospectively with type of knee injury from clinical history. A cross-sectional study was done on all patients referred to Krishna Hospital, Karad for MRI knee with history of recent (< 6 weeks) knee injury. Study was conducted between May 2014 to September 2015 with a sample size of 200 patients. Plain radiograph of knee was done in all patients and they were scanned using 1.5 Tesla Seimens Avanto (Tim + Dot) with Tx/Rx 15 channel knee coil # Tim. Among the 200 cases, bone marrow contusion was noted in 138 cases (69%) and absent contusion in 62 cases (31%). Bone marrow contusion showed five patterns (according to Sanders classification) i.e., Clip injury in 39 cases (28.3%), Pivot shift injury in 78 cases (56.5%), Dashboard injury in eight cases (5.8%), Hyperextension injury in four cases (2.9%), Lateral patellar dislocation in three cases (2.2%). In six cases (4.3%) no pattern of bone marrow contusion could be explained and was categorized as unclassified pattern. Pivot shift pattern is most common contusion pattern and the most common type/mode of sports related injury. By analysing bone marrow contusion pattern, type/mode can be determined in most of the cases. By applying a biomechanical approach in MR interpretation, it is possible to detect lesions like ligament rupture and osseous contusion, to predict subtle but it might overlook important abnormalities.

Investigating the Abscopal Effects of Radioablation on Shielded Bone Marrow in Rodent Models Using Multimodality Imaging.

PubMed

Afshar, Solmaz F; Zawaski, Janice A; Inoue, Taeko; Rendon, David A; Zieske, Arthur W; Punia, Jyotinder N; Sabek, Omaima M; Gaber, M Waleed

2017-07-01

The abscopal effect is the response to radiation at sites that are distant from the irradiated site of an organism, and it is thought to play a role in bone marrow (BM) recovery by initiating responses in the unirradiated bone marrow. Understanding the mechanism of this effect has applications in treating BM failure (BMF) and BM transplantation (BMT), and improving survival of nuclear disaster victims. Here, we investigated the use of multimodality imaging as a translational tool to longitudinally assess bone marrow recovery. We used positron emission tomography/computed tomography (PET/CT), magnetic resonance imaging (MRI) and optical imaging to quantify bone marrow activity, vascular response and marrow repopulation in fully and partially irradiated rodent models. We further measured the effects of radiation on serum cytokine levels, hematopoietic cell counts and histology. PET/CT imaging revealed a radiation-induced increase in proliferation in the shielded bone marrow (SBM) compared to exposed bone marrow (EBM) and sham controls. T 2 -weighted MRI showed radiation-induced hemorrhaging in the EBM and unirradiated SBM. In the EBM and SBM groups, we found alterations in serum cytokine and hormone levels and in hematopoietic cell population proportions, and histological evidence of osteoblast activation at the bone marrow interface. Importantly, we generated a BMT mouse model using fluorescent-labeled bone marrow donor cells and performed fluorescent imaging to reveal the migration of bone marrow cells from shielded to radioablated sites. Our study validates the use of multimodality imaging to monitor bone marrow recovery and provides evidence for the abscopal response in promoting bone marrow recovery after irradiation.

Failure to generate bone marrow adipocytes does not protect mice from ovariectomy-induced osteopenia.

PubMed

Iwaniec, Urszula T; Turner, Russell T

2013-03-01

A reciprocal association between bone marrow fat and bone mass has been reported in ovariectomized rodents, suggesting that bone marrow adipogenesis has a negative effect on bone growth and turnover balance. Mice with loss of function mutations in kit receptor (kit(W/W-v)) have no bone marrow adipocytes in tibia or lumbar vertebra. We therefore tested the hypothesis that marrow fat contributes to the development of osteopenia by comparing the skeletal response to ovariectomy (ovx) in growing wild type (WT) and bone marrow adipocyte-deficient kit(W/W-v) mice. Mice were ovx at 4 weeks of age and sacrificed 4 or 10 weeks post-surgery. Body composition was measured at necropsy by dual-energy X-ray absorptiometry. Cortical (tibia) and cancellous (tibia and lumbar vertebra) bone architecture were evaluated by microcomputed tomography. Bone marrow adipocyte size and density, osteoblast- and osteoclast-lined bone perimeters, and bone formation were determined by histomorphometry. Ovx resulted in an increase in total body fat mass at 10 weeks post-ovx in both genotypes, but the response was attenuated in the in kit(W/W-v) mice. Adipocytes were present in bone marrow of tibia and lumbar vertebra in WT mice and bone marrow adiposity increased following ovx. In contrast, marrow adipocytes were not detected in either intact or ovx kit(W/W-v) mice. However, ovx in WT and kit(W/W-v) mice resulted in statistically indistinguishable changes in cortical and cancellous bone mass, cortical and cancellous bone formation rate, and cancellous osteoblast and osteoclast-lined bone perimeters. In conclusion, our findings do not support a causal role for increased bone marrow fat as a mediator of ovx-induced osteopenia in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

Bone Marrow Test: MedlinePlus Lab Test Information

MedlinePlus

... this page: https://medlineplus.gov/labtests/bonemarrowtest.html Bone Marrow Test To use the sharing features on this page, please enable JavaScript. What Are Bone Marrow Tests? Bone marrow is a soft, spongy ...

PERFORMANCE OF CONVENTIONAL PCRs BASED ON PRIMERS DIRECTED TO NUCLEAR AND MITOCHONDRIAL GENES FOR THE DETECTION AND IDENTIFICATION OF Leishmania spp.

PubMed Central

LOPES, Estela Gallucci; GERALDO, Carlos Alberto; MARCILI, Arlei; SILVA, Ricardo Duarte; KEID, Lara Borges; OLIVEIRA, Trícia Maria Ferreira da Silva; SOARES, Rodrigo Martins

2016-01-01

In visceral leishmaniasis, the detection of the agent is of paramount importance to identify reservoirs of infection. Here, we evaluated the diagnostic attributes of PCRs based on primers directed to cytochrome-B (cytB), cytochrome-oxidase-subunit II (coxII), cytochrome-C (cytC), and the minicircle-kDNA. Although PCRs directed to cytB, coxII, cytC were able to detect different species of Leishmania, and the nucleotide sequence of their amplicons allowed the unequivocal differentiation of species, the analytical and diagnostic sensitivity of these PCRs were much lower than the analytical and diagnostic sensitivity of the kDNA-PCR. Among the 73 seropositive animals, the asymptomatic dogs had spleen and bone marrow samples collected and tested; only two animals were positive by PCRs based on cytB, coxII, and cytC, whereas 18 were positive by the kDNA-PCR. Considering the kDNA-PCR results, six dogs had positive spleen and bone marrow samples, eight dogs had positive bone marrow results but negative results in spleen samples and, in four dogs, the reverse situation occurred. We concluded that PCRs based on cytB, coxII, and cytC can be useful tools to identify Leishmania species when used in combination with automated sequencing. The discordance between the results of the kDNA-PCR in bone marrow and spleen samples may indicate that conventional PCR lacks sensitivity for the detection of infected dogs. Thus, primers based on the kDNA should be preferred for the screening of infected dogs. PMID:27253743

Meeting report of the 2016 bone marrow adiposity meeting

PubMed Central

van der Eerden, Bram; van Wijnen, André

2017-01-01

Abstract There is considerable interest in the physiology and pathology, as well as the cellular and molecular biology, of bone marrow adipose tissue (BMAT). Because bone marrow adiposity is linked not only to systemic energy metabolism, but also to both bone marrow and musculoskeletal disorders, this biologic compartment has become of major interest to investigators from diverse disciplines. Bone marrow adiposity represents a virtual multi-tissue endocrine organ, which encompasses cells from multiple developmental lineages (e.g., mesenchymal, myeloid, lymphoid) and occupies all the non-osseous and non-cartilaginous space within long bones. A number of research groups are now focusing on bone marrow adiposity to understand a range of clinical afflictions associated with bone marrow disorders and to consider mechanisms-based strategies for future therapies. PMID:28410005

The role of bone marrow-derived cells during the bone healing process in the GFP mouse bone marrow transplantation model.

PubMed

Tsujigiwa, Hidetsugu; Hirata, Yasuhisa; Katase, Naoki; Buery, Rosario Rivera; Tamamura, Ryo; Ito, Satoshi; Takagi, Shin; Iida, Seiji; Nagatsuka, Hitoshi

2013-03-01

Bone healing is a complex and multistep process in which the origin of the cells participating in bone repair is still unknown. The involvement of bone marrow-derived cells in tissue repair has been the subject of recent studies. In the present study, bone marrow-derived cells in bone healing were traced using the GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) were transplanted into C57BL/6 J wild mice. After transplantation, bone injury was created using a 1.0-mm drill. Bone healing was histologically assessed at 3, 7, 14, and 28 postoperative days. Immunohistochemistry for GFP; double-fluorescent immunohistochemistry for GFP-F4/80, GFP-CD34, and GFP-osteocalcin; and double-staining for GFP and tartrate-resistant acid phosphatase were performed. Bone marrow transplantation successfully replaced the hematopoietic cells into GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts or osteocytes in the repair stage were GFP-negative, whereas osteoclasts in the repair and remodeling stages and hematopoietic cells were GFP-positive. The results indicated that bone marrow-derived cells might not differentiate into osteoblasts. The role of bone marrow-derived cells might be limited to adjustment of the microenvironment by differentiating into inflammatory cells, osteoclasts, or endothelial cells in immature blood vessels.

Indoleamine 2,3-dioxygenase and regulatory T cells in acute myeloid leukemia.

PubMed

Mansour, Iman; Zayed, Rania A; Said, Fadwa; Latif, Lamyaa Abdel

2016-09-01

The microenvironment of acute myeloid leukemia (AML) is suppressive for immune cells. Regulatory T cells (Tregs) have been recognized to play a role in helping leukemic cells to evade immunesurveillance. The mesenchymal stem cells (MSCs) are essential contributors in immunomodulation of the microenvironment as they can promote differentiation of Tregs via the indoleamine 2,3-dioxygenase (IDO) pathway. The aim of the present work was to evaluate the expression of IDO in bone marrow derived MSCs and to study its correlation to percentage of Tregs. Thirty-seven adult bone marrow samples were cultured in appropriate culture medium to isolate MSCs. Successful harvest of MSCs was determined by plastic adherence, morphology, and positive expression of CD271 and CD105; negative expression of CD34 and CD45 using flowcytometry. MSCs were examined for IDO expression by immunocytochemistry using anti-IDO monoclonal antibody. CD4+ CD25+ cells (Tregs) were measured in bone marrow samples by flowcytometry. MSCs were successfully isolated from 20 of the 37 bone marrow samples cultured. MSCs showed higher expression of IDO and Tregs percentage was higher in AML patients compared to control subjects (P = 0.002 and P < 0.001, respectively). A positive correlation was found between IDO expression and Tregs percentage (P value = 0.012, r = 0.5). In this study, we revealed an association between high IDO expression in MSCs and elevated levels of Tregs which could have an important role in the pathogenesis of AML, providing immunosuppressive microenvironment.

Monte Carlo simulation of age-dependent radiation dose from alpha- and beta-emitting radionuclides to critical trabecular bone and bone marrow targets

NASA Astrophysics Data System (ADS)

Dant, James T.; Richardson, Richard B.; Nie, Linda H.

2013-05-01

Alpha (α) particles and low-energy beta (β) particles present minimal risk for external exposure. While these particles can induce leukemia and bone cancer due to internal exposure, they can also be beneficial for targeted radiation therapies. In this paper, a trabecular bone model is presented to investigate the radiation dose from bone- and marrow-seeking α and β emitters to different critical compartments (targets) of trabecular bone for different age groups. Two main issues are addressed with Monte Carlo simulations. The first is the absorption fractions (AFs) from bone and marrow to critical targets within the bone for different age groups. The other issue is the application of 223Ra for the radiotherapy treatment of bone metastases. Both a static model and a simulated bone remodeling process are established for trabecular bone. The results show significantly lower AFs from radionuclide sources in the bone volume to the peripheral marrow and the haematopoietic marrow for adults than for newborns and children. The AFs from sources on the bone surface and in the bone marrow to peripheral marrow and haematopoietic marrow also varies for adults and children depending on the energy of the particles. Regarding the use of 223Ra as a radionuclide for the radiotherapy of bone metastases, the simulations show a significantly higher dose from 223Ra and its progeny in forming bone to the target compartment of bone metastases than that from two other more commonly used β-emitting radiopharmaceuticals, 153Sm and 89Sr. There is also a slightly lower dose from 223Ra in forming bone to haematopoietic marrow than that from 153Sm and 89Sr. These results indicate a higher therapy efficiency and lower marrow toxicity from 223Ra and its progeny. In conclusion, age-related changes in bone dimension and cellularity seem to significantly affect the internal dose from α and β emitters in the bone and marrow to critical targets, and 223Ra may be a more efficient radiopharmaceutical for the treatment of bone metastases than 153Sm and 89Sr, if the diffusion of 219Rn to the bone marrow is insignificant.

Clonal Architecture of Secondary Acute Myeloid Leukemia

PubMed Central

Walter, Matthew J.; Shen, Dong; Ding, Li; Shao, Jin; Koboldt, Daniel C.; Chen, Ken; Larson, David E.; McLellan, Michael D.; Dooling, David; Abbott, Rachel; Fulton, Robert; Magrini, Vincent; Schmidt, Heather; Kalicki-Veizer, Joelle; O’Laughlin, Michelle; Fan, Xian; Grillot, Marcus; Witowski, Sarah; Heath, Sharon; Frater, John L.; Eades, William; Tomasson, Michael; Westervelt, Peter; DiPersio, John F.; Link, Daniel C.; Mardis, Elaine R.; Ley, Timothy J.; Wilson, Richard K.; Graubert, Timothy A.

2012-01-01

BACKGROUND The myelodysplastic syndromes are a group of hematologic disorders that often evolve into secondary acute myeloid leukemia (AML). The genetic changes that underlie progression from the myelodysplastic syndromes to secondary AML are not well understood. METHODS We performed whole-genome sequencing of seven paired samples of skin and bone marrow in seven subjects with secondary AML to identify somatic mutations specific to secondary AML. We then genotyped a bone marrow sample obtained during the antecedent myelodysplastic-syndrome stage from each subject to determine the presence or absence of the specific somatic mutations. We identified recurrent mutations in coding genes and defined the clonal architecture of each pair of samples from the myelodysplastic-syndrome stage and the secondary-AML stage, using the allele burden of hundreds of mutations. RESULTS Approximately 85% of bone marrow cells were clonal in the myelodysplastic-syndrome and secondary-AML samples, regardless of the myeloblast count. The secondary-AML samples contained mutations in 11 recurrently mutated genes, including 4 genes that have not been previously implicated in the myelodysplastic syndromes or AML. In every case, progression to acute leukemia was defined by the persistence of an antecedent founding clone containing 182 to 660 somatic mutations and the outgrowth or emergence of at least one subclone, harboring dozens to hundreds of new mutations. All founding clones and subclones contained at least one mutation in a coding gene. CONCLUSIONS Nearly all the bone marrow cells in patients with myelodysplastic syndromes and secondary AML are clonally derived. Genetic evolution of secondary AML is a dynamic process shaped by multiple cycles of mutation acquisition and clonal selection. Recurrent gene mutations are found in both founding clones and daughter subclones. (Funded by the National Institutes of Health and others.) PMID:22417201

viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia.

PubMed

Amir, El-ad David; Davis, Kara L; Tadmor, Michelle D; Simonds, Erin F; Levine, Jacob H; Bendall, Sean C; Shenfeld, Daniel K; Krishnaswamy, Smita; Nolan, Garry P; Pe'er, Dana

2013-06-01

New high-dimensional, single-cell technologies offer unprecedented resolution in the analysis of heterogeneous tissues. However, because these technologies can measure dozens of parameters simultaneously in individual cells, data interpretation can be challenging. Here we present viSNE, a tool that allows one to map high-dimensional cytometry data onto two dimensions, yet conserve the high-dimensional structure of the data. viSNE plots individual cells in a visual similar to a scatter plot, while using all pairwise distances in high dimension to determine each cell's location in the plot. We integrated mass cytometry with viSNE to map healthy and cancerous bone marrow samples. Healthy bone marrow automatically maps into a consistent shape, whereas leukemia samples map into malformed shapes that are distinct from healthy bone marrow and from each other. We also use viSNE and mass cytometry to compare leukemia diagnosis and relapse samples, and to identify a rare leukemia population reminiscent of minimal residual disease. viSNE can be applied to any multi-dimensional single-cell technology.

Genetic features of myelodysplastic syndrome and aplastic anemia in pediatric and young adult patients

PubMed Central

Keel, Siobán B.; Scott, Angela; Sanchez-Bonilla, Marilyn; Ho, Phoenix A.; Gulsuner, Suleyman; Pritchard, Colin C.; Abkowitz, Janis L.; King, Mary-Claire; Walsh, Tom; Shimamura, Akiko

2016-01-01

The clinical and histopathological distinctions between inherited versus acquired bone marrow failure and myelodysplastic syndromes are challenging. The identification of inherited bone marrow failure/myelodysplastic syndromes is critical to inform appropriate clinical management. To investigate whether a subset of pediatric and young adults undergoing transplant for aplastic anemia or myelodysplastic syndrome have germline mutations in bone marrow failure/myelodysplastic syndrome genes, we performed a targeted genetic screen of samples obtained between 1990–2012 from children and young adults with aplastic anemia or myelodysplastic syndrome transplanted at the Fred Hutchinson Cancer Research Center. Mutations in inherited bone marrow failure/myelodysplastic syndrome genes were found in 5.1% (5/98) of aplastic anemia patients and 13.6% (15/110) of myelodysplastic syndrome patients. While the majority of mutations were constitutional, a RUNX1 mutation present in the peripheral blood at a 51% variant allele fraction was confirmed to be somatically acquired in one myelodysplastic syndrome patient. This highlights the importance of distinguishing germline versus somatic mutations by sequencing DNA from a second tissue or from parents. Pathological mutations were present in DKC1, MPL, and TP53 among the aplastic anemia cohort, and in FANCA, GATA2, MPL, RTEL1, RUNX1, SBDS, TERT, TINF2, and TP53 among the myelodysplastic syndrome cohort. Family history or physical examination failed to reliably predict the presence of germline mutations. This study shows that while any single specific bone marrow failure/myelodysplastic syndrome genetic disorder is rare, screening for these disorders in aggregate identifies a significant subset of patients with inherited bone marrow failure/myelodysplastic syndrome. PMID:27418648

Comparison of collagen matrix treatment impregnated with platelet rich plasma vs bone marrow.

PubMed

Minamimura, Ai; Ichioka, Shigeru; Sano, Hitomi; Sekiya, Naomi

2014-02-01

This study has reported the efficacy of an autologous bone marrow-impregnated collagen matrix experimentally and clinically. Then, it reflected that platelet rich plasma (PRP) was as good a source of growth factors as bone marrow and available in a less invasive procedure. This study aimed to compare the efficacy of a PRP-impregnated collagen matrix with that of a bone marrow-impregnated collagen matrix by quantifying wound size and capillary density using genetically diabetic db/db mice. Bone marrow cells were obtained from femurs of ddy mice. Then, a small amount of collagen matrix was immersed in bone marrow suspension. This is called a bone marrow-impregnated collagen matrix. PRP was obtained from healthy human blood and a small amount of collagen matrix was immersed in PRP. This is called a PRP-impregnated collagen matrix. A bone marrow-impregnated collagen matrix and PRP-impregnated collagen matrix were applied to excisional skin wounds on a genetically healing-impaired mouse (n = 6) and wounds were evaluated 6 days after the procedure. Wounds were divided into two groups: PRP (n = 6), in which a PRP-impregnated collagen matrix was applied; and bone marrow (n = 6), in which collagen immersed in a bone marrow suspension was applied. There was no significant difference between the PRP and bone-marrow groups in the rate of vascular density increase or wound size decrease. The present study suggested that the PRP-impregnated collagen matrix promotes repair processes at least as strongly as the bone marrow-impregnated collagen matrix. Given lower invasiveness, the PRP-impregnated collagen matrix would have advantages in clinical use.

Aspiration and Biopsy: Bone Marrow

MedlinePlus

... Print What It Is Bone marrow aspirations and biopsies are performed to examine bone marrow, the spongy liquid part of the bone where blood cells are ... you might also feel the pressure of the biopsy needle pushing in. Some ... sharp cramp as the liquid bone marrow is withdrawn for the aspiration or ...

Quantitative MRI and spectroscopy of bone marrow

PubMed Central

Ruschke, Stefan; Dieckmeyer, Michael; Diefenbach, Maximilian; Franz, Daniela; Gersing, Alexandra S.; Krug, Roland; Baum, Thomas

2017-01-01

Bone marrow is one of the largest organs in the human body, enclosing adipocytes, hematopoietic stem cells, which are responsible for blood cell production, and mesenchymal stem cells, which are responsible for the production of adipocytes and bone cells. Magnetic resonance imaging (MRI) is the ideal imaging modality to monitor bone marrow changes in healthy and pathological states, thanks to its inherent rich soft‐tissue contrast. Quantitative bone marrow MRI and magnetic resonance spectroscopy (MRS) techniques have been also developed in order to quantify changes in bone marrow water–fat composition, cellularity and perfusion in different pathologies, and to assist in understanding the role of bone marrow in the pathophysiology of systemic diseases (e.g. osteoporosis). The present review summarizes a large selection of studies published until March 2017 in proton‐based quantitative MRI and MRS of bone marrow. Some basic knowledge about bone marrow anatomy and physiology is first reviewed. The most important technical aspects of quantitative MR methods measuring bone marrow water–fat composition, fatty acid composition, perfusion, and diffusion are then described. Finally, previous MR studies are reviewed on the application of quantitative MR techniques in both healthy aging and diseased bone marrow affected by osteoporosis, fractures, metabolic diseases, multiple myeloma, and bone metastases. Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:332–353. PMID:28570033

Bone marrow vascular endothelial growth factor level per platelet count might be a significant predictor for the treatment outcomes of patients with diffuse large B-cell lymphomas.

PubMed

Kim, Jung Sun; Gang, Ga Won; Lee, Se Ryun; Sung, Hwa Jung; Park, Young; Kim, Dae Sik; Choi, Chul Won; Kim, Byung Soo

2015-10-01

Developing a parameter to predict bone marrow invasion by non-Hodgkin's lymphoma is an important unmet medical need for treatment decisions. This study aimed to confirm the validity of the hypothesis that bone marrow plasma vascular endothelial growth factor level might be correlated with the risk of bone marrow involvement and the prognosis of patients with diffuse large B-cell non-Hodgkin's lymphoma. Forty-nine diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone regimen were enrolled. Vascular endothelial growth factor level was measured with enzyme-linked immunosorbent assay. The validity of bone marrow plasma vascular endothelial growth factor level and bone marrow vascular endothelial growth factor level per platelet count for predicting treatment response and survival after initial rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone combined chemotherapy was assessed. Bone marrow plasma vascular endothelial growth factor level per platelet count was significantly associated with old age (≥ 65 years), poor performance score (≥ 2), high International prognosis index (≥ 3) and bone marrow invasion. The patients with high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) showed a significantly lower complete response rate than the others. On Kaplan-Meier survival curves, the patients with high bone marrow plasma vascular endothelial growth factor levels (≥ 655 pg/ml) or high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) demonstrated a significantly shorter overall survival and progression-free survival than the others. In the patients without bone marrow involvement, bone marrow plasma vascular endothelial growth factor level per platelet count had a significant relationship with overall survival and progression-free survival. Multivariate analysis revealed that the patients without BM invasion showing high level of bone marrow plasma vascular endothelial growth factor per platelet count had significantly shorter progression-free survival and overall survival. Bone marrow plasma vascular endothelial growth factor level per platelet count might be associated with bone marrow invasion by diffuse large B-cell lymphoma and is correlated with clinical outcomes after treatment. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Skeletal dosimetry: A hyperboloid representation of the bone-marrow interface to reduce voxel effects in three-dimensional images of trabecular bone

NASA Astrophysics Data System (ADS)

Rajon, Didier Alain

Radiation damage to the hematopoietic bone marrow is clearly defined as the limiting factor to the development of internal emitter therapies. Current dosimetry models rely on chord-length distributions measured through the complex microstructure of the trabecular bone regions of the skeleton in which most of the active marrow is located. Recently, Nuclear Magnetic Resonance (NMR) has been used to obtain high-resolution three-dimensional (3D) images of small trabecular bone samples. These images have been coupled with computer programs to estimate dosimetric parameters such as chord-length distributions, and energy depositions by monoenergetic electrons. This new technique is based on the assumption that each voxel of the image is assigned either to bone tissue or to marrow tissue after application of a threshold value. Previous studies showed that this assumption had important consequences on the outcome of the computer calculations. Both the chord-length distribution measurements and the energy deposition calculations are subject to voxel effects that are responsible for large discrepancies when applied to mathematical models of trabecular bone. The work presented in this dissertation proposes first a quantitative study of the voxel effects. Consensus is that the voxelized representation of surfaces should not be used as direct input to dosimetry computer programs. Instead we need a new technique to transform the interfaces into smooth surfaces. The Marching Cube (MC) algorithm was used and adapted to do this transformation. The initial image was used to generate a continuous gray-level field throughout the image. The interface between bone and marrow was then simulated by the iso-gray-level surface that corresponds to a predetermined threshold value. Calculations were then performed using this new representation. Excellent results were obtained for both the chord-length distribution and the energy deposition measurements. Voxel effects were reduced to an acceptable level and the discrepancies found when using the voxelized representation of the interface were reduced to a few percent. We conclude that this new model should be used every time one performs dosimetry estimates using NMR images of trabecular bone samples.

Identification of resident and inflammatory bone marrow derived cells in the sclera by bone marrow and haematopoietic stem cell transplantation

PubMed Central

Hisatomi, Toshio; Sonoda, Koh‐hei; Ishikawa, Fumihiko; Qiao, Hong; Nakamura, Takahiro; Fukata, Mitsuhiro; Nakazawa, Toru; Noda, Kousuke; Miyahara, Shinsuke; Harada, Mine; Kinoshita, Shigeru; Hafezi‐Moghadam, Ali; Ishibashi, Tatsuro; Miller, Joan W

2007-01-01

Aims To characterise bone marrow derived cells in the sclera under normal and inflammatory conditions, we examined their differentiation after transplantation from two different sources, bone marrow and haematopoietic stem cells (HSC). Methods Bone marrow and HSC from green fluorescent protein (GFP) transgenic mice were transplanted into irradiated wild‐type mice. At 1 month after transplantation, mice were sacrificed and their sclera examined by histology, immunohistochemistry (CD11b, CD11c, CD45), and transmission and scanning electron microscopy. To investigate bone marrow derived cell recruitment under inflammatory conditions, experimental autoimmune uveitis (EAU) was induced in transplanted mice. Results GFP positive cells were distributed in the entire sclera and comprised 22.4 (2.8)% (bone marrow) and 28.4 (10.9)% (HSC) of the total cells in the limbal zone and 18.1 (6.7)% (bone marrow) and 26.3 (3.4)% (HSC) in the peripapillary zone. Immunohistochemistry showed that GFP (+) CD11c (+), GFP (+) CD11b (+) cells migrated in the sclera after bone marrow and HSC transplantation. Transmission and scanning electron microscopy revealed antigen presenting cells among the scleral fibroblasts. In EAU mice, vast infiltration of GFP (+) cells developed into the sclera. Conclusion We have provided direct and novel evidence for the migration of bone marrow and HSC cells into the sclera differentiating into macrophages and dendritic cells. Vast infiltration of bone marrow and HSC cells was found to be part of the inflammatory process in EAU. PMID:17035278

SU-E-J-250: A Methodology for Active Bone Marrow Protection for Cervical Cancer Intensity-Modulated Radiotherapy Using 18F-FLT PET/CT Image

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, C; Yin, Y

Purpose: The purpose of this study was to compare a radiation therapy treatment planning that would spare active bone marrow and whole pelvic bone marrow using 18F FLT PET/CT image. Methods: We have developed an IMRT planning methodology to incorporate functional PET imaging using 18F FLT/CT scans. Plans were generated for two cervical cancer patients, where pelvicactive bone marrow region was incorporated as avoidance regions based on the range: SUV>2., another region was whole pelvic bone marrow. Dose objectives were set to reduce the volume of active bone marrow and whole bone marraw. The volumes of received 10 (V10) andmore » 20 (V20) Gy for active bone marrow were evaluated. Results: Active bone marrow regions identified by 18F FLT with an SUV>2 represented an average of 48.0% of the total osseous pelvis for the two cases studied. Improved dose volume histograms for identified bone marrow SUV volumes and decreases in V10(average 18%), and V20(average 14%) were achieved without clinically significant changes to PTV or OAR doses. Conclusion: Incorporation of 18F FLT/CT PET in IMRT planning provides a methodology to reduce radiation dose to active bone marrow without compromising PTV or OAR dose objectives in cervical cancer.« less

Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro.

PubMed

Torisawa, Yu-suke; Spina, Catherine S; Mammoto, Tadanori; Mammoto, Akiko; Weaver, James C; Tat, Tracy; Collins, James J; Ingber, Donald E

2014-06-01

Current in vitro hematopoiesis models fail to demonstrate the cellular diversity and complex functions of living bone marrow; hence, most translational studies relevant to the hematologic system are conducted in live animals. Here we describe a method for fabricating 'bone marrow-on-a-chip' that permits culture of living marrow with a functional hematopoietic niche in vitro by first engineering new bone in vivo, removing it whole and perfusing it with culture medium in a microfluidic device. The engineered bone marrow (eBM) retains hematopoietic stem and progenitor cells in normal in vivo-like proportions for at least 1 week in culture. eBM models organ-level marrow toxicity responses and protective effects of radiation countermeasure drugs, whereas conventional bone marrow culture methods do not. This biomimetic microdevice offers a new approach for analysis of drug responses and toxicities in bone marrow as well as for study of hematopoiesis and hematologic diseases in vitro.

Bone marrow lesions in hip osteoarthritis are characterized by increased bone turnover and enhanced angiogenesis.

PubMed

Shabestari, M; Vik, J; Reseland, J E; Eriksen, E F

2016-10-01

Bone marrow lesions (BML), previously denoted bone marrow edema, are detected as water signals by magnetic resonance imaging (MRI). Previous histologic studies were unable to demonstrate any edematous changes at the tissue level. Therefore, our aim was to investigate the underlying biological mechanisms of the water signal in MRI scans of bone affected by BML. Tetracycline labeling in addition to water sensitive MRI scans of 30 patients planned for total hip replacement surgery was undertaken. Twenty-one femoral heads revealed BML on MRI, while nine were negative and used as controls (CON). Guided by the MRI images cylindrical biopsies were extracted from areas with BML in the femoral heads. Tissue sections from the biopsies were subjected to histomorphometric image analyses of the cancellous bone envelope. Patients with BML exhibited an average 40- and 18-fold increase of bone formation rate and mineralizing surface, respectively. Additionally, samples with BML demonstrated 2-fold reduction of marrow fat and 28-fold increase of woven bone. Immunohistochemical analysis showed a 4-fold increase of angiogenesis markers CD31 and von Willebrand Factor (vWF) in the BML-group compared to CON. This study indicates that BML are characterized by increased bone turnover, vascularity and angiogenesis in keeping with it being a reparatory process. Thus, the water signal, which is the hallmark of BML on MRI, is most probably reflecting increased tissue vascularity accompanying increased remodeling activity. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

A STUDY OF PREDICTED BONE MARROW DISTRIBUTION ON CALCULATED MARROW DOSE FROM EXTERNAL RADIATION EXPOSURES USING TWO SETS OF IMAGE DATA FOR THE SAME INDIVIDUAL

PubMed Central

Caracappa, Peter F.; Chao, T. C. Ephraim; Xu, X. George

2010-01-01

Red bone marrow is among the tissues of the human body that are most sensitive to ionizing radiation, but red bone marrow cannot be distinguished from yellow bone marrow by normal radiographic means. When using a computational model of the body constructed from computed tomography (CT) images for radiation dose, assumptions must be applied to calculate the dose to the red bone marrow. This paper presents an analysis of two methods of calculating red bone marrow distribution: 1) a homogeneous mixture of red and yellow bone marrow throughout the skeleton, and 2) International Commission on Radiological Protection cellularity factors applied to each bone segment. A computational dose model was constructed from the CT image set of the Visible Human Project and compared to the VIP-Man model, which was derived from color photographs of the same individual. These two data sets for the same individual provide the unique opportunity to compare the methods applied to the CT-based model against the observed distribution of red bone marrow for that individual. The mass of red bone marrow in each bone segment was calculated using both methods. The effect of the different red bone marrow distributions was analyzed by calculating the red bone marrow dose using the EGS4 Monte Carlo code for parallel beams of monoenergetic photons over an energy range of 30 keV to 6 MeV, cylindrical (simplified CT) sources centered about the head and abdomen over an energy range of 30 keV to 1 MeV, and a whole-body electron irradiation treatment protocol for 3.9 MeV electrons. Applying the method with cellularity factors improves the average difference in the estimation of mass in each bone segment as compared to the mass in VIP-Man by 45% over the homogenous mixture method. Red bone marrow doses calculated by the two methods are similar for parallel photon beams at high energy (above about 200 keV), but differ by as much as 40% at lower energies. The calculated red bone marrow doses differ significantly for simplified CT and electron beam irradiation, since the computed red bone marrow dose is a strong function of the cellularity factor applied to bone segments within the primary radiation beam. These results demonstrate the importance of properly applying realistic cellularity factors to computation dose models of the human body. PMID:19430219

A study of predicted bone marrow distribution on calculated marrow dose from external radiation exposures using two sets of image data for the same individual.

PubMed

Caracappa, Peter F; Chao, T C Ephraim; Xu, X George

2009-06-01

Red bone marrow is among the tissues of the human body that are most sensitive to ionizing radiation, but red bone marrow cannot be distinguished from yellow bone marrow by normal radiographic means. When using a computational model of the body constructed from computed tomography (CT) images for radiation dose, assumptions must be applied to calculate the dose to the red bone marrow. This paper presents an analysis of two methods of calculating red bone marrow distribution: 1) a homogeneous mixture of red and yellow bone marrow throughout the skeleton, and 2) International Commission on Radiological Protection cellularity factors applied to each bone segment. A computational dose model was constructed from the CT image set of the Visible Human Project and compared to the VIP-Man model, which was derived from color photographs of the same individual. These two data sets for the same individual provide the unique opportunity to compare the methods applied to the CT-based model against the observed distribution of red bone marrow for that individual. The mass of red bone marrow in each bone segment was calculated using both methods. The effect of the different red bone marrow distributions was analyzed by calculating the red bone marrow dose using the EGS4 Monte Carlo code for parallel beams of monoenergetic photons over an energy range of 30 keV to 6 MeV, cylindrical (simplified CT) sources centered about the head and abdomen over an energy range of 30 keV to 1 MeV, and a whole-body electron irradiation treatment protocol for 3.9 MeV electrons. Applying the method with cellularity factors improves the average difference in the estimation of mass in each bone segment as compared to the mass in VIP-Man by 45% over the homogenous mixture method. Red bone marrow doses calculated by the two methods are similar for parallel photon beams at high energy (above about 200 keV), but differ by as much as 40% at lower energies. The calculated red bone marrow doses differ significantly for simplified CT and electron beam irradiation, since the computed red bone marrow dose is a strong function of the cellularity factor applied to bone segments within the primary radiation beam. These results demonstrate the importance of properly applying realistic cellularity factors to computation dose models of the human body.

Automated Quantification of Hematopoietic Cell – Stromal Cell Interactions in Histological Images of Undecalcified Bone

PubMed Central

Zehentmeier, Sandra; Cseresnyes, Zoltan; Escribano Navarro, Juan; Niesner, Raluca A.; Hauser, Anja E.

2015-01-01

Confocal microscopy is the method of choice for the analysis of localization of multiple cell types within complex tissues such as the bone marrow. However, the analysis and quantification of cellular localization is difficult, as in many cases it relies on manual counting, thus bearing the risk of introducing a rater-dependent bias and reducing interrater reliability. Moreover, it is often difficult to judge whether the co-localization between two cells results from random positioning, especially when cell types differ strongly in the frequency of their occurrence. Here, a method for unbiased quantification of cellular co-localization in the bone marrow is introduced. The protocol describes the sample preparation used to obtain histological sections of whole murine long bones including the bone marrow, as well as the staining protocol and the acquisition of high-resolution images. An analysis workflow spanning from the recognition of hematopoietic and non-hematopoietic cell types in 2-dimensional (2D) bone marrow images to the quantification of the direct contacts between those cells is presented. This also includes a neighborhood analysis, to obtain information about the cellular microenvironment surrounding a certain cell type. In order to evaluate whether co-localization of two cell types is the mere result of random cell positioning or reflects preferential associations between the cells, a simulation tool which is suitable for testing this hypothesis in the case of hematopoietic as well as stromal cells, is used. This approach is not limited to the bone marrow, and can be extended to other tissues to permit reproducible, quantitative analysis of histological data. PMID:25938636

The effects of the CXCR2 antagonist, MK-7123, on bone marrow functions in healthy subjects.

PubMed

Hastrup, Nina; Khalilieh, Sauzanne; Dale, David C; Hanson, Lars G; Magnusson, Peter; Tzontcheva, Anjela; Tseng, Jack; Huyck, Susan; Rosenberg, Elizabeth; Krogsgaard, Kim

2015-04-01

The CXCR2 antagonist MK-7123 causes dose-dependent reductions in absolute neutrophil counts (ANC) and decreases neutrophil tissue responses, but its effects on bone marrow functions are not yet known. We conducted a double-blind, randomized study in 18 healthy subjects comparing the effects of either MK-7123 (30mg, po, daily for 28days) or placebo on peripheral blood counts and bone marrow myeloid cell populations. MK-7123 caused a reversible decrease (approximately 50%) in the ANC as demonstrated on days 1 and 28, the first and last days of the treatment period. Bone marrow aspirate smears and biopsy imprints did not differ in the proportion of mature neutrophils in pretreatment, day 28, day 56 or placebo samples. There were no treatment effects on biopsy or aspirate clot cellularity, myeloid to erythroid or myeloid post-mitotic to mitotic ratios; flow-cytometric analyses of aspirate cells; or bone marrow fat to cell balance as assessed by MRI. MK-7123 was generally well tolerated with neutropenia being the most common adverse event; however, there were no clinical symptoms associated with decreased ANCs. These findings indicate that the CXCR2 antagonist MK-7123 causes rapidly reversible decrease in the ANC without measurable myelosuppressive effects. The results support the development of CXCR2 antagonists as potentially useful anti-inflammatory agents, primarily interrupting neutrophil trafficking. Copyright © 2015. Published by Elsevier Ltd.

Erythropoietic bone marrow in the pigeon: Development of its distribution and volume during growth and pneumatization of bones

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schepelmann, K.

1990-01-01

During postnatal development of the pigeon, a large portion of the skeleton becomes pneumatized, displacing the hemopoietic bone marrow. The consequences of pneumatization on distribution and quantity of bone marrow as well as the availability of other sites for hemopoiesis have been investigated. Hemopoietic marrow of differently aged pigeons divided into five groups from 1 week posthatching (p.h.) up to 6 months p.h. was labeled with Fe-59 and examined by serial whole-body sections. Autoradiography and morphometry as well as scintillation counts of single bones and organs were also carried out. No sign of a reactivation of embryonic sites of erythropoiesismore » was found. Bone marrow weight and its proportion of whole-body weight increased during the first 4 weeks p.h. from 0.54% to 2.44% and decreased in the following months to about 1.0%. The developing bone marrow showed a progressive distribution during the first months of life, eventually being distributed proportionally over the entire skeleton, except for the skull. At the age of 6 months p.h. bone marrow had been displaced, its volume decreasing in correlation to increasing pneumaticity and conversion to fatty marrow. This generates the characteristic pattern of bone marrow distribution in adult pigeons, which shows hemopoietic bone marrow in ulna, radius, femur, tibiotarsus, scapula, furcula, and the caudal vertebrae.« less

The X-ray attenuation characteristics and density of human calcaneal marrow do not change significantly during adulthood

NASA Technical Reports Server (NTRS)

Les, C. M.; Whalen, R. T.; Beaupre, G. S.; Yan, C. H.; Cleek, T. M.; Wills, J. S.

2002-01-01

Changes in the material characteristics of bone marrow with aging can be a significant source of error in measurements of bone density when using X-ray and ultrasound imaging modalities. In the context of computed tomography, dual-energy computed techniques have been used to correct for changes in marrow composition. However, dual-energy quantitative computed tomography (DE-QCT) protocols, while increasing the accuracy of the measurement, reduce the precision and increase the radiation dose to the patient in comparison to single-energy quantitative computed tomography (SE-QCT) protocols. If the attenuation properties of the marrow for a particular bone can be shown to be relatively constant with age, it should be possible to use single-energy techniques without experiencing errors caused by unknown marrow composition. Marrow was extracted by centrifugation from 10 mm thick frontal sections of 34 adult cadaver calcanei (28 males, 6 females, ages 17-65 years). The density and energy-dependent linear X-ray attenuation coefficient of each marrow sample were determined. For purposes of comparing our results, we then computed an effective CT number at two GE CT/i scan voltages (80 and 120 kVp) for each specimen. The coefficients of variation for the density, CT number at 80 kVp and CT number at 120 kVp were each less than 1%, and the parameters did not change significantly with age (p > 0.2, r2 < 0.02, power > 0.8 where the minimum acceptable r2 = 0.216). We could demonstrate no significant gender-associated differences in these relationships. These data suggest that calcaneal bone marrow X-ray attenuation properties and marrow density are essentially constant from the third through sixth decades of life.

The Application of Bone Marrow Transplantation to the Treatment of Genetic Diseases

NASA Astrophysics Data System (ADS)

Parkman, Robertson

1986-06-01

Genetic diseases can be treated by transplantation of either normal allogeneic bone marrow or, potentially, autologous bone marrow into which the normal gene has been inserted in vitro (gene therapy). Histocompatible allogeneic bone marrow transplantation is used for the treatment of genetic diseases whose clinical expression is restricted to lymphoid or hematopoietic cells. The therapeutic role of bone marrow transplantation in the treatment of generalized genetic diseases, especially those affecting the central nervous system, is under investigation. The response of a generalized genetic disease to allogeneic bone marrow transplantation may be predicted by experiments in vitro. Gene therapy can be used only when the gene responsible for the disease has been characterized. Success of gene therapy for a specific genetic disease may be predicted by its clinical response to allogeneic bone marrow transplantation.

Computational modelling of the mechanics of trabecular bone and marrow using fluid structure interaction techniques.

PubMed

Birmingham, E; Grogan, J A; Niebur, G L; McNamara, L M; McHugh, P E

2013-04-01

Bone marrow found within the porous structure of trabecular bone provides a specialized environment for numerous cell types, including mesenchymal stem cells (MSCs). Studies have sought to characterize the mechanical environment imposed on MSCs, however, a particular challenge is that marrow displays the characteristics of a fluid, while surrounded by bone that is subject to deformation, and previous experimental and computational studies have been unable to fully capture the resulting complex mechanical environment. The objective of this study was to develop a fluid structure interaction (FSI) model of trabecular bone and marrow to predict the mechanical environment of MSCs in vivo and to examine how this environment changes during osteoporosis. An idealized repeating unit was used to compare FSI techniques to a computational fluid dynamics only approach. These techniques were used to determine the effect of lower bone mass and different marrow viscosities, representative of osteoporosis, on the shear stress generated within bone marrow. Results report that shear stresses generated within bone marrow under physiological loading conditions are within the range known to stimulate a mechanobiological response in MSCs in vitro. Additionally, lower bone mass leads to an increase in the shear stress generated within the marrow, while a decrease in bone marrow viscosity reduces this generated shear stress.

Bone marrow concentrate and platelet-rich plasma differ in cell distribution and interleukin 1 receptor antagonist protein concentration.

PubMed

Cassano, Jennifer M; Kennedy, John G; Ross, Keir A; Fraser, Ethan J; Goodale, Margaret B; Fortier, Lisa A

2018-01-01

Bone marrow concentrate (BMC) and platelet-rich plasma (PRP) are used extensively in regenerative medicine. The aim of this study was to determine differences in the cellular composition and cytokine concentrations of BMC and PRP and to compare two commercial BMC systems in the same patient cohort. Patients (29) undergoing orthopaedic surgery were enrolled. Bone marrow aspirate (BMA) was processed to generate BMC from two commercial systems (BMC-A and BMC-B). Blood was obtained to make PRP utilizing the same system as BMC-A. Bone marrow-derived samples were cultured to measure colony-forming units, and flow cytometry was performed to assess mesenchymal stem cell (MSC) markers. Cellular concentrations were assessed for all samples. Catabolic cytokines and growth factors important for cartilage repair were measured using multiplex ELISA. Colony-forming units were increased in both BMCs compared to BMA (p < 0.0001). Surface markers were consistent with MSCs. Platelet counts were not significantly different between BMC-A and PRP, but there were differences in leucocyte concentrations. TGF-β1 and PDGF were not different between BMC-A and PRP. IL-1ra concentrations were greater (p = 0.0018) in BMC-A samples (13,432 pg/mL) than in PRP (588 pg/mL). The IL-1ra/IL-1β ratio in all BMC samples was above the value reported to inhibit IL-1β. The bioactive factors examined in this study have differing clinical effects on musculoskeletal tissue. Differences in the cellular and cytokine composition between PRP and BMC and between BMC systems should be taken into consideration by the clinician when choosing a biologic for therapeutic application. Clinical, Level II.

Bone Marrow Diseases

MedlinePlus

Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. It contains stem cells. The stem cells can ... the platelets that help with blood clotting. With bone marrow disease, there are problems with the stem ...

Bone Marrow Transplantation

MedlinePlus

Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. It contains immature cells, called stem cells. The ... platelets, which help the blood to clot. A bone marrow transplant is a procedure that replaces a ...

[Hypoplastic acute promyelocytic leukemia with continuous hypocellular bone marrow after remission].

PubMed

Nakamura, Toshiki; Makiyama, Junya; Matsuura, Ayumi; Kurohama, Hirokazu; Kitanosono, Hideaki; Ito, Masahiro; Yoshida, Shinichiro; Miyazaki, Yasushi

2018-01-01

An 87-year old female presented with unsteady gait and occasional subcutaneous hematomas. Blood examination findings revealed pancytopenia and mild coagulopathy. Both the histopathological evaluation of bone marrow smears and bone marrow biopsy revealed a hypocellular bone marrow. However, APL cells were observed and PML-RARA fusion gene was detected. On the basis of these findings, the patient was diagnosed with hypoplastic acute promyelocytic leukemia. She received ATRA treatment and achieved complete remission (CR) 29 days from the commencement of therapy. After the first CR, she received two courses of ATO as a consolidation therapy. Following the latter treatments, she maintained CR, but a hypoplastic bone marrow was still observed. Hypoplastic AML is defined as AML with a low bone marrow cellularity. It is clinically important to distinguish it from aplastic anemia and hypoplastic MDS. It has been suggested that both cytogenetic and morphological diagnosis are imperative to the differential diagnosis of hypocellular bone marrow.

Three dimensional de novo micro bone marrow and its versatile application in drug screening and regenerative medicine.

PubMed

Li, Guanqun; Liu, Xujun; Du, Qian; Gao, Mei; An, Jing

2015-08-01

The finding that bone marrow hosts several types of multipotent stem cell has prompted extensive research aimed at regenerating organs and building models to elucidate the mechanisms of diseases. Conventional research depends on the use of two-dimensional (2D) bone marrow systems, which imposes several obstacles. The development of 3D bone marrow systems with appropriate molecules and materials however, is now showing promising results. In this review, we discuss the advantages of 3D bone marrow systems over 2D systems and then point out various factors that can enhance the 3D systems. The intensive research on 3D bone marrow systems has revealed multiple important clinical applications including disease modeling, drug screening, regenerative medicine, etc. We also discuss some possible future directions in the 3D bone marrow research field. © 2015 by the Society for Experimental Biology and Medicine.

Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats

PubMed Central

Zhang, Qing; Miller, Christopher; Bible, Jesse; Li, Jiliang; Xu, Xiaoqing; Mehta, Nozer; Gilligan, James; Vignery, Agnès; Scholz, Jodi A Carlson

2012-01-01

Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH). Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH or vehicle for four weeks. Both femurs from each rat were analyzed by X-ray and pQCT, then analyzed either by microCT, histology or biomechanical testing. Marrow ablation alone induced transient bone formation of low abundance that persisted over four weeks, while marrow ablation followed by PTH induced bone formation of high abundance that also persisted over four weeks. Our data confirms that the osteo-inducive effect of marrow ablation and the additive effect of marrow ablation, followed by PTH, occurs in aged rats. Our observations open new avenues of investigations in the field of tissue regeneration. Local marrow ablation, in conjunction with an anabolic agent, might provide a new platform for rapid site-directed bone growth in areas of high bone loss, such as in the hip and wrist, which are subject to fracture. PMID:24710549

Use of various diagnostic methods in a patient with Gaucher disease type I.

PubMed

Farahati, J; Trenn, G; John-Mikolajewski, V; Zander, C; Pastores, G M; Sciuk, J; Reiners, C

1996-08-01

A series of plain radiographs, bone scans, bone marrow scans, and MRIs is reported in a patient with Gaucher disease type I, in whom two episodes of acute bone crisis developed during a 6-year period of follow-up. Acute bone crisis and global indolent bone marrow displacement could both be assessed by bone marrow scintigraphy, whereas MRI could better clarify the corti-comedullary alteration after bone infarction. Thus, MRI and bone marrow scintigraphy could be used as complementary imaging methods in the management of patients with Gaucher disease.

Mature adipocytes in bone marrow protect myeloma cells against chemotherapy through autophagy activation

USDA-ARS?s Scientific Manuscript database

A major problem in patients with multiple myeloma is chemotherapy resistance, which develops in myeloma cells upon interaction with bone marrow stromal cells. However, few studies have determined the role of bone marrow adipocytes, a major component of stromal cells in the bone marrow, in myeloma ch...

Human blood and marrow side population stem cell and Stro-1 positive bone marrow stromal cell numbers decline with age, with an increase in quality of surviving stem cells: Correlation with cytokines

PubMed Central

Brusnahan, S.K.; McGuire, T.R.; Jackson, J.D.; Lane, J.T.; Garvin, K.L.; O’Kane, B.J.; Berger, A.M.; Tuljapurkar, S.R.; Kessinger, M.A.; Sharp, J.G.

2010-01-01

Hematological deficiencies increase with aging leading to anemias, reduced hematopoietic stress responses and myelodysplasias. This study tested the hypothesis that side population hematopoietic stem cells (SP-HSC) would decrease with aging, correlating with IGF-1 and IL-6 levels and increases in bone marrow fat. Marrow was obtained from the femoral head and trochanteric region of the femur at surgery for total hip replacement (N = 100). Whole trabecular marrow samples were ground in a sterile mortar and pestle and cellularity and fat content determined. Marrow and blood mononuclear cells were stained with Hoechst dye and the SP-HSC profiles acquired. Marrow stromal cells (MSC) were enumerated flow cytometrically employing the Stro-1 antibody, and clonally in the colony forming unit fibroblast (CFU-F) assay. Plasma levels of IGF-1 (ng/ml) and IL-6 (pg/ml) were measured by ELISA. SP-HSC in blood and bone marrow decreased with age but the quality of the surviving stem cells increased. MSC decreased non-significantly. IGF-1 levels (mean = 30.7, SEM = 2) decreased and IL-6 levels (mean = 4.4, SEM = 1) increased with age as did marrow fat (mean = 1.2 mm fat/g, SEM = 0.04). There were no significant correlations between cytokine levels or fat and SP-HSC numbers. Stem cells appear to be progressively lost with aging and only the highest quality stem cells survive. PMID:21035480

A method to generate enhanced GFP+ chimeric mice to study the role of bone marrow-derived cells in the eye.

PubMed

Singh, Vivek; Jaini, Ritika; Torricelli, André A M; Tuohy, Vincent K; Wilson, Steven E

2013-11-01

GFP-chimeric mice are important tools to study the role of bone marrow-derived cells in eye physiology. A method is described to generate GFP-chimeric mice using whole-body, sub-lethal radiation (600 rad) of wild-type C57BL/6 recipients followed by tail vein injection of bone marrow cells derived from GFP+ (GFP-transgenic C57/BL/6-Tg(UBC-GFP)30 Scha/J) mice. This method yields stable GFP+ chimeras with greater than 95% chimerism (range 95-99%), achieved within one month of bone marrow transfer confirmed by microscopy and fluorescence-assisted cell sorting (FACS) analysis, with lower mortality after irradiation than prior methods. To demonstrate the efficacy of GFP+ bone marrow chimeric mice, the role of circulating GFP+ bone marrow-derived cells in myofibroblast generation after irregular photo-therapeutic keratectomy (PTK) was analyzed. Many SMA+ myofibroblasts that were generated at one month after PTK were derived from GFP+ bone marrow-derived cells. The GFP+ bone marrow chimeric mouse provides an excellent model for studying the role of bone marrow-derived cells in corneal wound healing, glaucoma surgery, optic nerve head pathology and retinal pathophysiology and wound healing. Copyright © 2013 Elsevier Ltd. All rights reserved.

Role of whole bone marrow, whole bone marrow cultured cells, and mesenchymal stem cells in chronic wound healing.

PubMed

Rodriguez-Menocal, Luis; Shareef, Shahjahan; Salgado, Marcela; Shabbir, Arsalan; Van Badiavas, Evangelos

2015-03-13

Recent evidence has shown that bone marrow cells play critical roles during the inflammatory, proliferative and remodeling phases of cutaneous wound healing. Among the bone marrow cells delivered to wounds are stem cells, which can differentiate into multiple tissue-forming cell lineages to effect, healing. Gaining insight into which lineages are most important in accelerating wound healing would be quite valuable in designing therapeutic approaches for difficult to heal wounds. In this report we compared the effect of different bone marrow preparations on established in vitro wound healing assays. The preparations examined were whole bone marrow (WBM), whole bone marrow (long term initiating/hematopoietic based) cultured cells (BMC), and bone marrow derived mesenchymal stem cells (BM-MSC). We also applied these bone marrow preparations in two murine models of radiation induced delayed wound healing to determine which had a greater effect on healing. Angiogenesis assays demonstrated that tube formation was stimulated by both WBM and BMC, with WBM having the greatest effect. Scratch wound assays showed higher fibroblast migration at 24, 48, and 72 hours in presence of WBM as compared to BM-MSC. WBM also appeared to stimulate a greater healing response than BMC and BM-MSC in a radiation induced delayed wound healing animal model. These studies promise to help elucidate the role of stem cells during repair of chronic wounds and reveal which cells present in bone marrow might contribute most to the wound healing process.

The dynamics of adult haematopoiesis in the bone and bone marrow environment.

PubMed

Ho, Miriel S H; Medcalf, Robert L; Livesey, Stephen A; Traianedes, Kathy

2015-08-01

This review explores the dynamic relationship between bone and bone marrow in the genesis and regulation of adult haematopoiesis and will provide an overview of the haematopoietic hierarchical system. This will include the haematopoietic stem cell (HSC) and its niches, as well as discuss emerging evidence of the reciprocal interplay between bone and bone marrow, and support of the pleiotropic role played by bone cells in the regulation of HSC proliferation, differentiation and function. In addition, this review will present demineralized bone matrix as a unique acellular matrix platform that permits the generation of ectopic de novo bone and bone marrow and provides a means of investigating the temporal sequence of bone and bone marrow regeneration. It is anticipated that the utilization of this matrix-based approach will help researchers in gaining deeper insights into the major events leading to adult haematopoiesis in the bone marrow. Furthermore, this model may potentially offer new avenues to manipulate the HSC niche and hence influence the functional output of the haematopoietic system. © 2015 John Wiley & Sons Ltd.

Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras

PubMed Central

Das, Anusuya; Segar, Claire E.; Chu, Yihsuan; Wang, Tiffany W.; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C.; Cui, Quanjun; Botchwey, Edward A.

2015-01-01

Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects. PMID:26125501

Persistent injury-associated anemia: the role of the bone marrow microenvironment.

PubMed

Millar, Jessica K; Kannan, Kolenkode B; Loftus, Tyler J; Alamo, Ines G; Plazas, Jessica; Efron, Philip A; Mohr, Alicia M

2017-06-15

The regulation of erythropoiesis involves hematopoietic progenitor cells, bone marrow stroma, and the microenvironment. Following severe injury, a hypercatecholamine state develops that is associated with increased mobilization of hematopoietic progenitor cells to peripheral blood and decreased growth of bone marrow erythroid progenitor cells that manifests clinically as a persistent injury-associated anemia. Changes within the bone marrow microenvironment influence the development of erythroid progenitor cells. Therefore, we sought to determine the effects of lung contusion, hemorrhagic shock, and chronic stress on the hematopoietic cytokine response. Bone marrow was obtained from male Sprague-Dawley rats (n = 6/group) killed 7 d after lung contusion followed by hemorrhagic shock (LCHS) or LCHS followed by daily chronic restraint stress (LCHS/CS). End point polymerase chain reaction was performed for interleukin-1β, interleukin-10, stem cell factor, transforming growth factor-β, high-mobility group box-1 (HMGB-1), and B-cell lymphoma-extra large. Seven days following LCHS and LCHS/CS, bone marrow expression of prohematopoietic cytokines (interleukin-1β, interleukin-10, stem cell factor, and transforming growth factor-β) was significantly decreased, and bone marrow expression of HMGB-1 was significantly increased. B-cell lymphoma-extra large bone marrow expression was not affected by LCHS or LCHS/CS (naïve: 44 ± 12, LCHS: 44 ± 12, LCHS/CS: 37 ± 1, all P > 0.05). The bone marrow microenvironment was significantly altered following severe trauma in a rodent model. Prohematopoietic cytokines were downregulated, and the proinflammatory cytokine HMGB-1 had increased bone marrow expression. Modulation of the bone marrow microenvironment may represent a therapeutic strategy following severe trauma to alleviate persistent injury-associated anemia. Copyright © 2017 Elsevier Inc. All rights reserved.

SU-E-T-13: A Comparative Dosimetric Study On Radio-Dynamic Therapy for Pelvic Cancer Treatment: Strategies for Bone Marrow Dose and Volume Reduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, C; Renmin Hospital of Wuhan University, Wuhan, Hubei Province; Wang, B

Purpose: Radio-dynamic therapy (RDT) is a potentially effective modality for local and systemic cancer treatment. Using RDT, the administration of a radio-sensitizer enhances the biological effect of high-energy photons. Although the sensitizer uptake ratio of tumor to normal tissue is normally high, one cannot simply neglect its effect on critical structures. In this study, we aim to explore planning strategies to improve bone marrow sparing without compromising the plan quality for RDT treatment of pelvic cancers. Methods: Ten cervical and ten prostate cancer patients who previously received radiotherapy at our institution were selected for this study. For each patient, ninemore » plans were created using the Varian Eclipse treatmentplanning-system (TPS) with 3D-CRT, IMRT, and VMAT delivery techniques containing various gantry angle combinations and optimization parameters (dose constraints to the bone marrow). To evaluate the plans for bone marrow sparing, the dose-volume parameters V5, V10, V15, V20, V30, and V40 for bone marrow were examined. Effective doseenhancement factors for the sensitizer were used to weigh the dose-volume histograms for various tissues from individual fractions. Results: The planning strategies had different impacts on bone marrow sparing for the cervical and prostate cases. For the cervical cases, provided the bone marrow constraints were properly set during optimization, the dose to bone marrow sparing was found to be comparable between different IMRT and VMAT plans regardless of the gantry angle selection. For the prostate cases, however, careful selection of gantry angles could dramatically improve the bone marrow sparing, although the dose distribution in bone marrow was clinically acceptable for all prostate plans that we created. Conclusion: For intensity-modulated RDT planning for cervical cancer, planners should set bone marrow constraints properly to avoid any adverse damage, while for prostate cancer one can carefully select gantry angles to improve bone marrow sparing when necessary.« less

[Study of migration and distribution of bone marrow cells transplanted animals with B16 melanoma ].

PubMed

Poveshchenko, A F; Solovieva, A O; Zubareva, K E; Strunkin, D N; Gricyk, O B; Poveshchenko, O V; Shurlygina, A V; Konenkov, V I

2017-01-01

Purpose. Reveal features migration and distribution of syngeneic bone marrow cells (BMC) and subpopulations (MSC) after transplantation into the recipient carrier B16 melanoma bodies. Methods. We used mouse male and female C57BL/6 mice. Induction of Tumor Growth: B16 melanoma cells implanted subcutaneously into right hind paw of female C57BL/6 mice at a dose of 2.5 x 105 cells / mouse. migration study in vivo distribution and BMC and MSC was performed using genetic markers - Y-chromosome specific sequence line male C57Bl/6 syngeneic intravenous transplantation in females using the polymerase chain reaction (PCR) in real time on Authorized Termal Cycler - Light Cycler 480 II / 96 (Roche). Introduction suspension of unseparated bone marrow cells, mesenchymal stem cells from donor to recipient male mice (syngeneic recipient female C57BL/6), followed by isolation of recipients of organs was performed at regular intervals, then of organ recipients isolated DNA. Results. It was shown that bone marrow cells positive for Y-chromosome in migrate lymphoid (lymph nodes, spleen, bone marrow) or in non-lymphoid organs (liver, heart, brain, skin) syngeneic recipients. In addition to the migration of cells from the bone marrow to other organs, there is a way back migration of cells from the circulation to the bone marrow. B16 melanoma stimulates the migration of transplanted MSCs and BMC in bone marrow. It is found that tumor growth enhanced migration of transplanted bone marrow cells, including populations of MSCs in the bone marrow. In the early stages of tumor formation MSC migration activity higher than the BMC. In the later stages of tumor formation undivided population of bone marrow cells migrate to the intense swelling compared with a population of MSCs. Conclusion. The possibility of using bone marrow MSCs for targeted therapy of tumor diseases, because migration of MSCs in tumor tissue can be used to effectively deliver anticancer drugs.

PPARγ antagonist attenuates mouse immune-mediated bone marrow failure by inhibition of T cell function

PubMed Central

Sato, Kazuya; Feng, Xingmin; Chen, Jichun; Li, Jungang; Muranski, Pawel; Desierto, Marie J.; Keyvanfar, Keyvan; Malide, Daniela; Kajigaya, Sachiko; Young, Neal S.

2016-01-01

Acquired aplastic anemia is an immune-mediated disease, in which T cells target hematopoietic cells; at presentation, the bone marrow is replaced by fat. It was reported that bone marrow adipocytes were negative regulators of hematopoietic microenvironment. To examine the role of adipocytes in bone marrow failure, we investigated peroxisomal proliferator-activated receptor gamma, a key transcription factor in adipogenesis, utilizing an antagonist of this factor called bisphenol-A-diglycidyl-ether. While bisphenol-A-diglycidyl-ether inhibited adipogenesis as expected, it also suppressed T cell infiltration of bone marrow, reduced plasma inflammatory cytokines, decreased expression of multiple inflammasome genes, and ameliorated marrow failure. In vitro, bisphenol-A-diglycidyl-ether suppressed activation and proliferation, and reduced phospholipase C gamma 1 and nuclear factor of activated T-cells 1 expression, as well as inhibiting calcium flux in T cells. The in vivo effect of bisphenol-A-diglycidyl-ether on T cells was confirmed in a second immune-mediated bone marrow failure model, using different strains and non-major histocompatibility antigen mismatched: bisphenol-A-diglycidyl-ether ameliorated marrow failure by inhibition of T cell infiltration of bone marrow. Our data indicate that peroxisomal proliferator-activated receptor gamma antagonists may attenuate murine immune-mediated bone marrow failure, at least in part, by suppression of T cell activation, which might hold implications in the application of peroxisomal proliferator-activated receptor gamma antagonists in immune-mediated pathophysiologies, both in the laboratory and in the clinic. Genetically “fatless” mice developed bone marrow failure with accumulation of marrow adipocytes in our model, even in the absence of body fat, suggesting different mechanisms of systematic and marrow adipogenesis and physiologic versus pathophysiologic fat accumulation. PMID:26589913

Antifungal susceptibility and pathogenic potential of environmental isolated filamentous fungi compared with colonizing agents in immunocompromised patients.

PubMed

Teixeira, A B A; Silva, M; Lyra, L; Luz, E A; Uno, J; Takada, H; Miyaji, M; Nishimura, K; Schreiber, A Z

2005-09-01

Infection is a major cause of morbidity and mortality in bone marrow transplant recipients and in patients with hematological malignancies. The source of infection is almost always endogenous flora or the hospital environment. The present study evaluated bone marrow transplant recipients and patients with hematological malignancies colonized and/or infected with filamentous fungi. During 1 year, environmental air samples were also taken from the bone marrow transplant unit by a modification of gravity air-setting plate (GASP) methodology. Fusarium spp. were the most prevalent genus in the fall and Cladosporium spp. in the winter. Clinically isolated strains grew better at 37 degrees C than environmental strains. According to NCCLS M-38P methods, environmental Aspergillus strains showed higher MICs to miconazol and itraconazol, and clinical Fusarium strains were less susceptible to fluconazole.

Peri-implant bone density in senile osteoporosis-changes from implant placement to osseointegration.

PubMed

Beppu, Kensuke; Kido, Hirofumi; Watazu, Akira; Teraoka, Kay; Matsuura, Masaro

2013-04-01

The aim of this study was to examine healing over time after implant body placement in a senile osteoporosis model and a control group. In this study, 16-week-old male mice were used. The senile osteoporosis model consisted of senescence-accelerated prone 6 mice and the control group consisted of senescence-accelerated resistant 1 mice. Titanium-coated plastic implants were used as experimental implants whose dimensions were 3.0 mm in length, 1.1 mm in apical diameter, and 1.2 mm in coronal diameter. Bone samples were collected at 5, 7, 14, 21, and 28 days after implant placement. A micro-quantitative computed tomography (QCT) system was used to scan these samples and a phantom in order to quantitate bone mineral measurements. Bone mineral density (BMD) of each sample was measured. Each sample was also examined by light microscopy after QCT imaging. At 14 and 28 days after implant placement, the bone-implant contact (BIC) ratios were calculated from light microscopy images and were divided into cortical bone and bone marrow regions. When BMD was compared between the osteoporosis and control groups using micro-QCT, the osteoporosis group had a significantly lower BMD in the region 0-20 µm from the implant surface in the bone marrow region at 14 days onward after implant placement. Compared with the control group, the osteoporosis model also had significantly lower BMD in all regions 0-100 µm from the implant surface in the bone marrow region at 14 days after placement. However, in the cortical bone region, no statistically significant difference was observed in the regions at the bone-implant interface. Light microscopy revealed osseointegration for all implants 28 days after implant placement. The osteoporosis model tended to have lower BICs compared with that of the control group, although this did not reach statistical significance. Our results showed that osseointegration was achieved in the osteoporosis model. However, the BMD was 30-40% lower than that of the control group in the region closest to the implant surface in bone marrow region. Peri-implant BMD was lower in a relatively large area in the osteoporosis model during an important time for osseointegration. Therefore, this result suggests that osteoporosis might be considered as a risk factor in implant therapy. The osteoporosis model had a lower BMD than the control group in the region closest to the implant during an important time for osseointegration. This result suggests that senile osteoporosis might be a risk factor in implant therapy. However, the osteoporosis model and the control group had no difference in peri-implant BMD in the cortical bone region. This suggests that risk might be avoided by implant placement that effectively uses the cortical bone. © 2011 Wiley Periodicals, Inc.

Bone marrow transplant - discharge

MedlinePlus

Transplant - bone marrow - discharge; Stem cell transplant - discharge; Hematopoietic stem cell transplant - discharge; Reduced intensity; Non-myeloablative transplant - discharge; Mini transplant - discharge; Allogenic bone marrow transplant - discharge; ...

A patient with familial bone marrow failure and an inversion of chromosome 8.

PubMed

Buchbinder, David Kyle; Zadeh, Touran; Nugent, Diane

2011-12-01

Familial bone marrow failure has been associated with a variety of chromosomal aberrations. Chromosome 8 abnormalities have been described in association with neoplastic and hematologic disorders; however, to our knowledge, inversion of the long arm of chromosome 8 has not been described in the context of familial bone marrow failure. We describe a 9-year-old female with familial bone marrow failure and an inversion of chromosome 8 [inv (8) (q22, q24.3)]. Given the importance of considering the genetic determinants of familial bone marrow failure, the potential role of chromosome 8 abnormalities in the development of marrow failure is discussed.

Is fatty acid composition of human bone marrow significant to bone health?

PubMed

Pino, Ana María; Rodríguez, J Pablo

2017-12-16

The bone marrow adipose tissue (BMAT) is a conserved component of the marrow microenvironment, providing storage and release of energy and stabilizing the marrow extent. Also, it is recognized both the amount and quality of BMAT are relevant to preserve the functional relationships between BMAT, bone, and blood cell production. In this article we ponder the information supporting the tenet that the quality of BMAT is relevant to bone health. In the human adult the distribution of BMAT is heterogeneous over the entire skeleton, and both BMAT accumulation and bone loss come about with aging in healthy populations. But some pathological conditions which increase BMAT formation lead to bone impairment and fragility. Analysis in vivo of the relative content of saturated and unsaturated fatty acids (FA) in BMAT indicates site-related bone marrow fat composition and an association between increased unsaturation index (UI) and bone health. With aging some impairment ensues in the regulation of bone marrow cells and systemic signals leading to local chronic inflammation. Most of the bone loss diseases which evolve altered BMAT composition have as common factors aging and/or chronic inflammation. Both saturated and unsaturated FAs originate lipid species which are active mediators in the inflammation process. Increased free saturated FAs may lead to lipotoxicity of bone marrow cells. The pro-inflammatory, anti-inflammatory or resolving actions of compounds derived from long chain poly unsaturated FAs (PUFA) on bone cells is varied, and depending on the metabolism of the parent n:3 or n:6 PUFAs series. Taking together the evidence substantiate that marrow adipocyte function is fundamental for an efficient link between systemic and marrow fatty acids to accomplish specific energy or regulatory needs of skeletal and marrow cells. Further, they reveal marrow requirements of PUFAs. Copyright © 2017 Elsevier Inc. All rights reserved.

Bone and fat connection in aging bone.

PubMed

Duque, Gustavo

2008-07-01

The fat and bone connection plays an important role in the pathophysiology of age-related bone loss. This review will focus on the age-induced mechanisms regulating the predominant differentiation of mesenchymal stem cells into adipocytes. Additionally, bone marrow fat will be considered as a diagnostic and therapeutic approach to osteoporosis. There are two types of bone and fat connection. The 'systemic connection', usually seen in obese patients, is hormonally regulated and associated with high bone mass and strength. The 'local connection' happens inside the bone marrow. Increasing amounts of bone marrow fat affect bone turnover through the inhibition of osteoblast function and survival and the promotion of osteoclast differentiation and activation. This interaction is regulated by paracrine secretion of fatty acids and adipokines. Additionally, bone marrow fat could be quantified using noninvasive methods and could be used as a therapeutic approach due to its capacity to transdifferentiate into bone without affecting other types of fat in the body. The bone and fat connection within the bone marrow constitutes a typical example of lipotoxicity. Additionally, bone marrow fat could be used as a new diagnostic and therapeutic approach for osteoporosis in older persons.

Cocaine-contaminated allogeneic bone marrow transplantation.

PubMed

Keung, Y K; Morgan, D; Cobos, E

2001-01-01

Should a person with history of drug addiction be categorically denied as a bone marrow donor? The answer to the question is controversial. We report a case of allogeneic bone marrow transplantation for refractory acute myeloid leukemia preceded by essential thrombocythemia. The donor used cocaine and marijuana the night before the bone marrow harvest. Copyright 2001 S. Karger AG, Basel

A study of 23 unicameral bone cysts of the calcaneus: open chip allogeneic bone graft versus percutaneous injection of bone powder with autogenous bone marrow.

PubMed

Park, Il-Hyung; Micic, Ivan Dragoljub; Jeon, In-Ho

2008-02-01

The treatment of unicameral bone cyst varies from percutaneous needle biopsy, aspiration and local injection of steroid, autologous bone marrow, or demineralized bone matrix to curettage and open bone-grafting. The purpose of this study was to compare the results of open chip allogeneic bone graft versus percutaneous injection of demineralized bone powder with autogenous bone marrow in management of calcaneal cysts. Twenty-three calcaneal unicameral cysts in 20 patients were treated. Lyophilized irradiated chip allogeneic bone (CAB) and autogenous bone marrow were used for treatment of 13 cysts in 11 patients, and 10 cysts in 9 patients were treated with percutaneous injection of irradiated allogeneic demineralized bone powder (DBP) and autogenous bone marrow. There were 11 males and 9 female patients with mean age of 17 years. The patients were followed for an average of 49.4 months. Complete healing was achieved in 9 cysts treated with chip allogeneic bone and in 5 cysts treated with powdered bone. Four cysts treated with CAB and 3 cysts treated with DBP healed with a defect. Two cysts treated with powdered bone and autogenous bone marrow were classified as persistent. No infections or pathological fractures were observed during the followup period. Percutaneous injection of a mixture of allogeneic bone powder with autogenous bone marrow is a minimal invasive method and could be an effective alternative in the treatment of unicameral calcaneal bone cysts. The postoperative morbidity was low, the hospital stay was brief, and patient's comfort for unrestricted activity was enhanced.

Lipid determination in bone marrow and mineralized bone tissue: From sample preparation to improved high-performance thin-layer and liquid chromatographic approaches.

PubMed

During, Alexandrine

2017-09-15

In view of their key roles in the bone physiology (e.g., in the biomineralization process) and their potential implication in bone pathologies, an approach to study lipids in situ is needed. The aim of the present paper is to propose an original procedure to characterize lipids in both bone marrow (BM) and mineralized tissue (MT) compartments, taking into consideration sample preparation, lipid extraction and analytical issues, when using small sample size (≤ 0.5g of rat femurs). The potential contamination of the MT by marrow lipids and the poor accessibility of certain lipids from the MT - two major issues in bone handling - were taking care, respectively by performing two cleaning steps after BM removal and by adding a demineralization step to the overall lipid extraction protocol. For lipid analyses, a multi-one-dimensional HP-TLC method was developed to analyze the major neutral and polar lipids at once and showed an excellent resolution (for 15 standards) and a good precision (inter-day RSD<13%). When subjected to the entire "lipid extraction-HP-TLC" protocol, spike recoveries of the standards ranged between 76 and 122%. This HP-TLC method was suitable for lipid determination in both BM and MT [e.g., the MT had 5-times lesser lipids and a lower TG/phospholipid ratio than the BM (P <0.05)], and was quite reliable in term of lipid quantification. The demineralization step allowed to extract additional phosphatidylserine and esterified cholesterol from the MT, suggesting that these two species were associated to the mineralized matrix possibly in relation to their physiological role in the bone. Moreover, a reverse phase HPLC method for fatty acid determination as naphthacyl esters was set up to study fatty acids in bone samples and was used to validate the HP-TLC data. The fatty acid profile of the MT exhibited lower linoleic acid (18:2 n-6) and linolenic acid (18:3 n-3+n-6) levels and higher arachidonic acid (20:4 n-6) and docosahexaenoic acid (22:6 n-3) levels (P<0.05, compared to BM), suggesting that the MT is more metabolically active than the BM in term of long chain fatty acid production. In sum, the present work should contribute to facilitate future studies in the bone lipid field in view to understand better their implication in the marrow fat expansion-associated bone pathologies, such as osteoporosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Experiment K-7-23: Effect of Spaceflight on Level and Function of Immune Cells. Part 1; Immunology Studies

NASA Technical Reports Server (NTRS)

Sonnenfeld, G.; Mandel, A.; Konstantinova, I. V.; Berry, W. D.; Taylor, G. R.; Lesnyak, A. T.; Fuchs, B. B.; Rakhmilevich, A. L.

1994-01-01

Two different experiments were carried out in this segment of the immunology protocol for samples received from rats flown on Cosmos 2044. Control groups included vivarium, synchronous and antiorthostatically suspended rats. In the first experiment, rat bone marrow cells were examined in Moscow for their response to recombinant murine colony stimulating factor-granulocyte / monocyte (CSF-GM). In the second experiment, rat spleen and bone marrow cells were stained in Moscow with a variety of antibodies directed against cell surface antigenic markers. These cells were preserved and shipped to the United States for analysis on a flow cytometer. The results of the studies indicated that bone marrow cells from flown and suspended rats showed a decreased response to CSF-GM as compared to bone marrow cells from control rats. Spleen cells from flown rats showed increased percentages of suppressor-cytotoxic-T and helper-T cells amongst the entire cell population. Bone marrow cells showed an increase in the percentage of helper-T cells in the myelogenous population and increased percentages of anti-asialo GM-1 bearing, interleukin-2 receptor bearing, pan-T and helper-T cells in the lymphocytic population. Cell populations from rats suspended antiorthostatically did not follow the same pattern of distribution of leukocytes as cell populations for flown rats. These results are similar, but not identical to, earlier results from Cosmos 1887, and confirm that space flight can have profound effects on immune system components and activities.

Increased megakaryocytic proliferation, pro-platelet deposition and expression of fibrosis-associated factors in children with chronic myeloid leukaemia with bone marrow fibrosis.

PubMed

Hussein, K; Stucki-Koch, A; Göhring, G; Kreipe, H; Suttorp, M

2017-07-01

Paediatric chronic myeloid leukaemia (ped-CML) is rare and ped-CML with fibre accumulation in the bone marrow (MF) is thought to be even rarer. In adults (ad-CML), fibrosis represents an adverse prognostic factor. So far, the pro-fibrotic changes in the bone marrow microenvironment have not been investigated in detail in ped-CML. From a total of 66 ped-CML in chronic phase, biopsies were analysable and 10 had MF1/2 (MF1, n=8/10; MF2, n=2/10). We randomly selected 16 ped-CML and 16 ad-CML cases with and without fibrosis (each n=8) as well as 18 non-neoplastic controls. Bone marrow samples were analysed with a real-time PCR-based assay (including 127 genes for paediatric cases) and by immunohistochemistry. We found increased expression of megakaryocytic genes in ped-CML. The number of megakaryocytes and pro-platelets are increased in CML patients, but the most significant increase was noted for ped-CML-MF1/2. Anti-fibrotic MMP9 expression was lower in children than in adults. Cell mobilisation-related CXCL12 was decreased in young and adult patients with CML but not the corresponding receptor CXCR4. In summary, fibre accumulation in ped-CML-MF1/2 is associated with increased megakaryocytic proliferation and increased interstitial pro-platelet deposition. Deregulated expression of matrix-modulating factors shifts the bone marrow microenvironment towards fibrosis.

The role of bone marrow evaluation in the staging of patients with otherwise localized, low-risk neuroblastoma.

PubMed

Russell, Heidi V; Golding, Laurie A; Suell, Mary Nell; Nuchtern, Jed G; Strother, Douglas R

2005-12-01

Bone marrow aspirations and biopsies are standard staging procedures for neuroblastoma because the tumor frequently metastasizes to the bone marrow. The presence of bone marrow metastases indicates stage 4 or 4S neuroblastoma by International Neuroblastoma Staging System (INSS) criteria; these stages are also associated with other metastatic sites of disease. We questioned whether bone marrow studies changed the staging or treatment of children with localized, completely resected tumors if there was no other evidence of metastatic spread. If stage of disease rarely changed with bone marrow results, it might be possible to avoid this procedure in a subset of patients with neuroblastoma. The staging studies of patients with INSS stage 1 (n = 29), 4 (n = 60), and 4S (n = 13) neuroblastoma from two institutions were reviewed. There were no patients upstaged from stage 1 to 4 or 4S by bone marrow metastases alone. Fifty-nine of 60 stage 4 patients had other sites of metastases on imaging studies, the remaining patient had an unresectable primary tumor and marrow disease. All subjects with stage 4S disease had liver metastases. Bone marrow studies did not contribute data that changed the stage of patients who had surgically resectable tumors and no evidence of metastatic spread on imaging studies. When present, metastatic spread to the marrow was associated with advanced local tumors or other sites of metastatic disease. Given the relatively small size of our study population, further studies are warranted that investigate the utility of bone marrow studies for patients who otherwise have INSS stage 1 neuroblastoma. 2005 Wiley-Liss, Inc.

Bone marrow mesenchymal stem cells from patients with aplastic anemia maintain functional and immune properties and do not contribute to the pathogenesis of the disease.

PubMed

Bueno, Clara; Roldan, Mar; Anguita, Eduardo; Romero-Moya, Damia; Martín-Antonio, Beatriz; Rosu-Myles, Michael; del Cañizo, Consuelo; Campos, Francisco; García, Regina; Gómez-Casares, Maite; Fuster, Jose Luis; Jurado, Manuel; Delgado, Mario; Menendez, Pablo

2014-07-01

Aplastic anemia is a life-threatening bone marrow failure disorder characterized by peripheral pancytopenia and marrow hypoplasia. The majority of cases of aplastic anemia remain idiopathic, although hematopoietic stem cell deficiency and impaired immune responses are hallmarks underlying the bone marrow failure in this condition. Mesenchymal stem/stromal cells constitute an essential component of the bone marrow hematopoietic microenvironment because of their immunomodulatory properties and their ability to support hematopoiesis, and they have been involved in the pathogenesis of several hematologic malignancies. We investigated whether bone marrow mesenchymal stem cells contribute, directly or indirectly, to the pathogenesis of aplastic anemia. We found that mesenchymal stem cell cultures can be established from the bone marrow of aplastic anemia patients and display the same phenotype and differentiation potential as their counterparts from normal bone marrow. Mesenchymal stem cells from aplastic anemia patients support the in vitro homeostasis and the in vivo repopulating function of CD34(+) cells, and maintain their immunosuppressive and anti-inflammatory properties. These data demonstrate that bone marrow mesenchymal stem cells from patients with aplastic anemia do not have impaired functional and immunological properties, suggesting that they do not contribute to the pathogenesis of the disease. Copyright© Ferrata Storti Foundation.

Copper-64 Labeled Liposomes for Imaging Bone Marrow

PubMed Central

Lee, Sang-gyu; Gangangari, Kishore; Kalidindi, Teja Muralidhar; Punzalan, Blesida; Larson, Steven M.; Pillarsetty, Naga Vara Kishore

2016-01-01

Introduction Bone marrow is the soft tissue compartment inside the bones made up of hematopoietic cells, adipocytes, stromal cells, phagocytic cells, stem cells, and sinusoids. While [18F]-FLT has been utilized to image proliferative marrow, to date, there are no reports of particle based positron emission tomography (PET) imaging agents for imaging bone marrow. We have developed copper-64 labeled liposomal formulation that selectively targets bone marrow and therefore serves as an efficient PET probe for imaging bone marrow. Methods Optimized liposomal formulations were prepared with succinyl PE, DSPC, cholesterol, and mPEG-DSPE (69:39:1:10:0.1) with diameters of 90 and 140 nm, and were doped with DOTA-Bn-DSPE for stable 64Cu incorporation into liposomes. Results PET imaging and biodistribution studies with 64Cu-labeled liposomes indicate that accumulation in bone marrow was as high as 15.18 ± 3.69 %ID/g for 90 nm liposomes and 7.01 ± 0.92 %ID/g for 140 nm liposomes at 24 h post-administration. In vivo biodistribution studies in tumor-bearing mice indicate that the uptake of 90 nm particles is approximately 0.89 ± 0.48 %ID/g in tumor and 14.22 ± 8.07 %ID/g in bone marrow, but respective values for Doxil® like liposomes are 0.83 ± 0.49 %ID/g and 2.23 ± 1.00 %ID/g. Conclusion Our results indicate that our novel PET labeled liposomes target bone marrow with very high efficiency and therefore can function as efficient bone marrow imaging agents. PMID:27694056

Hematoxylin Bodies in Pediatric Bone Marrow Aspirates and Their Utility in the Diagnosis of Systemic Lupus Erythematosus.

PubMed

Xu, Min; Chisholm, Karen M; Fan, Guang; Stevens, Anne M; Rutledge, Joe C

2017-01-01

In our recent case report, the finding of lupus erythematosus (LE) cells in a bone marrow aspirate led to the diagnosis of systemic lupus erythematosus (SLE) and appropriate treatment, although the patient was not clinically suspected to have SLE. To determine whether LE cells are present in the bone marrow aspirates of SLE patients, but overlooked in routine bone marrow morphology review, bone marrow aspirates from 30 pediatric patients (15 with SLE and 15 with other diagnoses) evaluated by rheumatologists were reviewed. LE cells were found in the bone marrow aspirates of only 1 SLE patient and none in non-SLE patients. However, hematoxylin bodies were identified in 53% (8/15) of SLE patients. Neither hematoxylin bodies nor LE cells were found in the aspirates from patients with other disorders. Three additional pediatric patients identified prospectively were found to have hematoxylin bodies in the bone marrow aspirates. Although the diagnosis was not initially suspected, 2 of the 3 patients were subsequently diagnosed with SLE. All patients with hematoxylin bodies and SLE had antinuclear antibody titers ≥1:640 with a homogeneous staining pattern. In addition, bone marrow aspirates of 9 adult patients were reviewed, and neither LE cells nor hematoxylin bodies were identified. In summary, hematoxylin bodies were present in the bone marrow aspirates of many pediatric SLE patients, while LE cells were rare. The finding of hematoxylin bodies in pediatric bone marrow aspirates is a helpful and specific diagnostic clue that may lead to the diagnosis of SLE when other clinical features are nonspecific.

Development and characterization of a lung-protective method of bone marrow transplantation in the mouse.

PubMed

Janssen, William J; Muldrow, Alaina; Kearns, Mark T; Barthel, Lea; Henson, Peter M

2010-05-31

Allogeneic bone marrow transplantation is a common method used to study the contribution of myeloid and lymphoid cell populations in murine models of disease. The method requires lethal doses of radiation to ablate the bone marrow. Unintended consequences of radiation include organ injury and inflammatory cell activation. The goal of our study was to determine the degree to which bone marrow transplantation alters lungs and to develop a system to protect the lungs during radiation. C57BL/6 mice were subjected to total body irradiation with 900cGy and then transplanted with bone marrow from green fluorescent protein (GFP) expressing mice. Resultant chimeras exhibited a significant decline in alveolar macrophage numbers within 72h, modest influx of neutrophils in the lungs at 14days, and repopulation of the lungs by alveolar macrophages of bone marrow origin by 28days. Neutrophil influx and alveolar macrophage turnover were prevented when 1cm thick lead shields were used to protect the lungs during radiation, such that 8weeks after transplantation less than 30% of alveolar macrophages were of donor origin. Lung-shielded mice achieved a high level of bone marrow engraftment with greater than 95% of circulating leukocytes expressing GFP. In addition, their response to intratracheal lipopolysaccharide was similar to non-transplanted mice. We describe a model whereby lead shields protect resident cell populations in the lungs from radiation during bone marrow transplantation but permit full bone marrow engraftment. This system may be applicable to other organ systems in which protection from radiation during bone marrow transplantation is desired.

Comparison among T1-weighted magnetic resonance imaging, modified dixon method, and magnetic resonance spectroscopy in measuring bone marrow fat.

PubMed

Shen, Wei; Gong, Xiuqun; Weiss, Jessica; Jin, Ye

2013-01-01

An increasing number of studies are utilizing different magnetic resonance (MR) methods to quantify bone marrow fat due to its potential role in osteoporosis. Our aim is to compare the measurements of bone marrow fat among T1-weighted magnetic resonance imaging (MRI), modified Dixon method (also called fat fraction MRI (FFMRI)), and magnetic resonance spectroscopy (MRS). Contiguous MRI scans were acquired in 27 Caucasian postmenopausal women with a modified Dixon method (i.e., FFMRI). Bone marrow adipose tissue (BMAT) of T1-weighted MRI and bone marrow fat fraction of the L3 vertebra and femoral necks were quantified using SliceOmatic and Matlab. MRS was also acquired at the L3 vertebra. Correlation among the three MR methods measured bone marrow fat fraction and BMAT ranges from 0.78 to 0.88 (P < 0.001) in the L3 vertebra. Correlation between BMAT measured by T1-weighted MRI and bone marrow fat fraction measured by modified FFMRI is 0.86 (P < 0.001) in femoral necks. There are good correlations among T1-weighted MRI, FFMRI, and MRS for bone marrow fat quantification. The inhomogeneous distribution of bone marrow fat, the threshold segmentation of the T1-weighted MRI, and the ambiguity of the FFMRI may partially explain the difference among the three methods.

Comparison among T1-Weighted Magnetic Resonance Imaging, Modified Dixon Method, and Magnetic Resonance Spectroscopy in Measuring Bone Marrow Fat

PubMed Central

Shen, Wei; Gong, Xiuqun; Weiss, Jessica; Jin, Ye

2013-01-01

Introduction. An increasing number of studies are utilizing different magnetic resonance (MR) methods to quantify bone marrow fat due to its potential role in osteoporosis. Our aim is to compare the measurements of bone marrow fat among T1-weighted magnetic resonance imaging (MRI), modified Dixon method (also called fat fraction MRI (FFMRI)), and magnetic resonance spectroscopy (MRS). Methods. Contiguous MRI scans were acquired in 27 Caucasian postmenopausal women with a modified Dixon method (i.e., FFMRI). Bone marrow adipose tissue (BMAT) of T1-weighted MRI and bone marrow fat fraction of the L3 vertebra and femoral necks were quantified using SliceOmatic and Matlab. MRS was also acquired at the L3 vertebra. Results. Correlation among the three MR methods measured bone marrow fat fraction and BMAT ranges from 0.78 to 0.88 (P < 0.001) in the L3 vertebra. Correlation between BMAT measured by T1-weighted MRI and bone marrow fat fraction measured by modified FFMRI is 0.86 (P < 0.001) in femoral necks. Conclusion. There are good correlations among T1-weighted MRI, FFMRI, and MRS for bone marrow fat quantification. The inhomogeneous distribution of bone marrow fat, the threshold segmentation of the T1-weighted MRI, and the ambiguity of the FFMRI may partially explain the difference among the three methods. PMID:23606951

Marrow donor registry and cord blood bank in Taiwan.

PubMed

Lee, Tsung Dao

2002-08-01

Unrelated Bone marrow transplant was initiated thirty years ago. Though there are over millions of donors registered with the bone marrow registries worldwide, Asian patients rarely find a match with all these donors. Tzu Chi Marrow Donor Registry was established to meet this need. It has become the largest Asian marrow donor registry in the world. With the introduction of high technology to test the HLA of the donors and recipients, the success rate of bone marrow transplant is greatly improved among Asian countries. 50% of blood disease Asian patients who cannot find a bone marrow matched donor will be complemented by the establishment of cord blood banks in Taiwan.

An Association between BK Virus Replication in Bone Marrow and Cytopenia in Kidney-Transplant Recipients

PubMed Central

Pambrun, Emilie; Mengelle, Catherine; Fillola, Geneviève; Laharrague, Patrick; Esposito, Laure; Cardeau-Desangles, Isabelle; Del Bello, Arnaud; Izopet, Jacques; Rostaing, Lionel; Kamar, Nassim

2014-01-01

The human polyomavirus BK (BKV) is associated with severe complications, such as ureteric stenosis and polyomavirus-associated nephropathy (PVAN), which often occur in kidney-transplant patients. However, it is unknown if BKV can replicate within bone marrow. The aim of this study was to search for BKV replication within the bone marrow of kidney-transplant patients presenting with a hematological disorder. Seventy-two kidney-transplant patients underwent bone-marrow aspiration for cytopenia. At least one virus was detected in the bone marrow of 25/72 patients (35%), that is, parvovirus B19 alone (n = 8), parvovirus plus Epstein-Barr virus (EBV) (n = 3), cytomegalovirus (n = 4), EBV (n = 2), BKV alone (n = 7), and BKV plus EBV (n = 1). Three of the eight patients who had BKV replication within the bone marrow had no detectable BKV replication in the blood. Neutropenia was observed in all patients with BKV replication in the bone marrow, and blockade of granulocyte maturation was observed. Hematological disorders disappeared in all patients after doses of immunosuppressants were reduced. In conclusion, an association between BKV replication in bone marrow and hematological disorders, especially neutropenia, was observed. Further studies are needed to confirm these findings. PMID:24868448

Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell Fate.

PubMed

Fan, Yi; Hanai, Jun-Ichi; Le, Phuong T; Bi, Ruiye; Maridas, David; DeMambro, Victoria; Figueroa, Carolina A; Kir, Serkan; Zhou, Xuedong; Mannstadt, Michael; Baron, Roland; Bronson, Roderick T; Horowitz, Mark C; Wu, Joy Y; Bilezikian, John P; Dempster, David W; Rosen, Clifford J; Lanske, Beate

2017-03-07

Intermittent PTH administration builds bone mass and prevents fractures, but its mechanism of action is unclear. We genetically deleted the PTH/PTHrP receptor (PTH1R) in mesenchymal stem cells using Prx1Cre and found low bone formation, increased bone resorption, and high bone marrow adipose tissue (BMAT). Bone marrow adipocytes traced to Prx1 and expressed classic adipogenic markers and high receptor activator of nuclear factor kappa B ligand (Rankl) expression. RANKL levels were also elevated in bone marrow supernatant and serum, but undetectable in other adipose depots. By cell sorting, Pref1 + RANKL + marrow progenitors were twice as great in mutant versus control marrow. Intermittent PTH administration to control mice reduced BMAT significantly. A similar finding was noted in male osteoporotic patients. Thus, marrow adipocytes exhibit osteogenic and adipogenic characteristics, are uniquely responsive to PTH, and secrete RANKL. These studies reveal an important mechanism for PTH's therapeutic action through its ability to direct mesenchymal cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.

Sequencing analysis of mutations induced by N-ethyl-N-nitrosourea at different sampling times in mouse bone marrow.

PubMed

Wang, Jianyong; Chen, Tao

2010-03-01

In our previous study (Wang et al., 2004, Toxicol. Sci. 82: 124-128), we observed that the cII gene mutant frequency (MF) in the bone marrow of Big Blue mice showed significant increase as early as day 1, reached the maximum at day 3 and then decreased to a plateau by day 15 after a single dose of carcinogen N-ethyl-N-nitrosourea (ENU) treatment, which is different from the longer mutation manifestation time and the constancy of MFs after reaching their maximum in some other tissues. To determine the mechanism underlying the quick increase in MF and the peak formation in the mutant manifestation, we examined the mutation frequencies and spectra of the ENU-induced mutants collected from different sampling times in this study. The cII mutants from days 1, 3 and 120 after ENU treatment were randomly selected from different animals. The mutation frequencies were 33, 217, 305 and 144 x 10(-6) for control, days 1, 3, and 120, respectively. The mutation spectra at days 1 and 3 were significantly different from that at day 120. Considering that stem cells are responsible for the ultimate MF plateau (day 120) and transit cells are accountable for the earlier MF induction (days 1 or 3) in mouse bone marrow, we conclude that transit cells are much more sensitive to mutation induction than stem cells in mouse bone marrow, which resulted in the specific mutation manifestation induced by ENU.

Purification of Bone Marrow Clonal Cells from Patients with Myelodysplastic Syndrome via IGF-IR

PubMed Central

He, Qi; Chang, Chun-Kang; Xu, Feng; Zhang, Qing-Xia; Shi, Wen-Hui; Li, Xiao

2015-01-01

Malignant clonal cells purification can greatly benefit basic and clinical studies in myelodysplastic syndrome (MDS). In this study, we investigated the potential of using type 1 insulin-like growth factor receptor (IGF-IR) as a marker for purification of malignant bone marrow clonal cells from patients with MDS. The average percentage of IGF-IR expression in CD34+ bone marrow cells among 15 normal controls was 4.5%, 70% of which also express the erythroid lineage marker CD235a. This indicates that IGF-IR mainly express in erythropoiesis. The expression of IGF-IR in CD34+ cells of 55 MDS patients was significantly higher than that of cells from the normal controls (54.0 vs. 4.5%). Based on the pattern of IGF-IR expression in MDS patients and normal controls, sorting of IGF-IR-positive and removal of CD235a-positive erythroid lineage cells with combination of FISH detection were performed on MDS samples with chromosomal abnormalities. The percentage of malignant clonal cells significantly increased after sorting. The enrichment effect was more significant in clonal cells with a previous percentage lower than 50%. This enrichment effect was present in samples from patients with +8, 5q-/-5, 20q-/-20 or 7q-/-7 chromosomal abnormalities. These data suggest that IGF-IR can be used as a marker for MDS bone marrow clonal cells and using flow cytometry for positive IGF-IR sorting may effectively purify MDS clonal cells. PMID:26469401

Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras.

PubMed

Das, Anusuya; Segar, Claire E; Chu, Yihsuan; Wang, Tiffany W; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C; Cui, Quanjun; Botchwey, Edward A

2015-09-01

Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bone Marrow Adipose Tissue and Skeletal Health.

PubMed

Muruganandan, Shanmugam; Govindarajan, Rajgopal; Sinal, Christopher J

2018-05-31

To summarize and discuss recent progress and novel signaling mechanisms relevant to bone marrow adipocyte formation and its physiological/pathophysiological implications for bone remodeling. Skeletal remodeling is a coordinated process entailing removal of old bone and formation of new bone. Several bone loss disorders such as osteoporosis are commonly associated with increased bone marrow adipose tissue. Experimental and clinical evidence supports that a reduction in osteoblastogenesis from mesenchymal stem cells at the expense of adipogenesis, as well as the deleterious effects of adipocyte-derived signaling, contributes to the etiology of osteoporosis as well as bone loss associated with aging, diabetes mellitus, post-menopause, and chronic drug therapy. However, this view is challenged by findings indicating that, in some contexts, bone marrow adipose tissue may have a beneficial impact on skeletal health. Further research is needed to better define the role of marrow adipocytes in bone physiology/pathophysiology and to determine the therapeutic potential of manipulating mesenchymal stem cell differentiation.

A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow.

PubMed

Wynn, Robert F; Hart, Claire A; Corradi-Perini, Carla; O'Neill, Liam; Evans, Caroline A; Wraith, J Ed; Fairbairn, Leslie J; Bellantuono, Ilaria

2004-11-01

Homing of bone marrow stromal cells (MSCs) to bone and bone marrow after transplantation, important for the correction of conditions such as metabolic storage disorders, can occur but with poor efficiency. Substantial improvements in engraftment will be required in order to derive a clinical benefit from MSC transplantation. Chemokines are the most important factors controlling cellular migration. Stromal-derived factor-1 (SDF-1) has been shown to be critical in promoting the migration of cells to the bone marrow, via its specific receptor CXCR4. The aim of our study was to investigate CXCR4 expression on MSCs and its role in mediating migration to bone marrow. We show that CXCR4, although present at the surface of a small subset of MSCs, is important for mediating specific migration of these cells to bone marrow.

Autologous bone marrow purging with LAK cells.

PubMed

Giuliodori, L; Moretti, L; Stramigioli, S; Luchetti, F; Annibali, G M; Baldi, A

1993-12-01

In this study we will demonstrate that LAK cells, in vitro, can lyse hematologic neoplastic cells with a minor toxicity of the staminal autologous marrow cells. In fact, after bone marrow and LAK co-culture at a ratio of 1/1 for 8 hours, the inhibition on the GEMM colonies resulted to be 20% less compared to the untreated marrow. These data made LAK an inviting agent for marrow purging in autologous bone marrow transplantation.

Graft-versus-host disease

MedlinePlus

GVHD; Bone marrow transplant - graft-versus-host disease; Stem cell transplant - graft-versus-host disease; Allogeneic transplant - ... GVHD may occur after a bone marrow, or stem cell, transplant in which someone receives bone marrow ...

Bone Marrow Failure Secondary to Cytokinesis Failure

DTIC Science & Technology

2015-12-01

SUPPLEMENTARY NOTES 14. ABSTRACT Fanconi anemia (FA) is a human genetic disease characterized by a progressive bone marrow failure and heightened...Fanconi anemia (FA) is the most commonly inherited bone marrow failure syndrome. FA patients develop bone marrow failure during the first decade of...experiments proposed in specific aims 1- 3 (Tasks 1-3). Task 1: To determine whether HSCs from Fanconi anemia mouse models have increased cytokinesis

Combination of BMP-2-releasing gelatin/β-TCP sponges with autologous bone marrow for bone regeneration of X-ray-irradiated rabbit ulnar defects.

PubMed

Yamamoto, Masaya; Hokugo, Akishige; Takahashi, Yoshitake; Nakano, Takayoshi; Hiraoka, Masahiro; Tabata, Yasuhiko

2015-07-01

The objective of this study is to evaluate the feasibility of gelatin sponges incorporating β-tricalcium phosphate (β-TCP) granules (gelatin/β-TCP sponges) to enhance bone regeneration at a segmental ulnar defect of rabbits with X-ray irradiation. After X-ray irradiation of the ulnar bone, segmental critical-sized defects of 20-mm length were created, and bone morphogenetic protein-2 (BMP-2)-releasing gelatin/β-TCP sponges with or without autologous bone marrow were applied to the defects to evaluate bone regeneration. Both gelatin/β-TCP sponges containing autologous bone marrow and BMP-2-releasing sponges enhanced bone regeneration at the ulna defect to a significantly greater extent than the empty sponges (control). However, in the X-ray-irradiated bone, the bone regeneration either by autologous bone marrow or BMP-2 was inhibited. When combined with autologous bone marrow, the BMP-2 exhibited significantly high osteoinductivity, irrespective of the X-ray irradiation. The bone mineral content at the ulna defect was similar to that of the intact bone. It is concluded that the combination of bone marrow with the BMP-2-releasing gelatin/β-TCP sponge is a promising technique to induce bone regeneration at segmental bone defects after X-ray irradiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chondrogenic Differentiation Processes in Human Bone Marrow Aspirates Seeded in Three-Dimensional Woven Poly(ε-Caprolactone) Scaffolds Enhanced by rAAV-Mediated SOX9 Gene Transfer.

PubMed

Venkatesan, Jagadeesh Kumar; Moutos, Franklin T; Rey-Rico, Ana; Estes, Bradley T; Frisch, Janina; Schmitt, Gertrud; Madry, Henning; Guilak, Farshid; Cucchiarini, Magali

2018-05-02

Combining gene therapy approaches with tissue engineering procedures is an active area of translational research for the effective treatment of articular cartilage lesions, especially to target chondrogenic progenitor cells such as those derived from the bone marrow. Here, we evaluated the effect of genetically modifying concentrated human mesenchymal stem cells from bone marrow to induce chondrogenesis by recombinant adeno-associated viral (rAAV) vector gene transfer of the sex-determining region Y-type high-mobility group box 9 (SOX9) factor upon seeding in three-dimensional (3D) woven poly(ε-caprolactone) (PCL) scaffolds that provide mechanical properties mimicking those of native articular cartilage. Prolonged, effective SOX9 expression was reported in the constructs for at least 21 days, the longest time point evaluated, leading to enhanced metabolic and chondrogenic activities relative to the control conditions (reporter lacZ gene transfer or absence of vector treatment) but without affecting the proliferative activities in the samples. The application of the rAAV SOX9 vector also prevented undesirable hypertrophic and terminal differentiation in the seeded concentrates. As bone marrow is readily accessible during surgery, such findings reveal the therapeutic potential of providing rAAV-modified marrow concentrates within 3D woven PCL scaffolds for repair of focal cartilage lesions.

FLOCK cluster analysis of plasma cell flow cytometry data predicts bone marrow involvement by plasma cell neoplasia.

PubMed

Dorfman, David M; LaPlante, Charlotte D; Li, Betty

2016-09-01

We analyzed plasma cell populations in bone marrow samples from 353 patients with possible bone marrow involvement by a plasma cell neoplasm, using FLOCK (FLOw Clustering without K), an unbiased, automated, computational approach to identify cell subsets in multidimensional flow cytometry data. FLOCK identified discrete plasma cell populations in the majority of bone marrow specimens found by standard histologic and immunophenotypic criteria to be involved by a plasma cell neoplasm (202/208 cases; 97%), including 34 cases that were negative by standard flow cytometric analysis that included clonality assessment. FLOCK identified discrete plasma cell populations in only a minority of cases negative for involvement by a plasma cell neoplasm by standard histologic and immunophenotypic criteria (38/145 cases; 26%). Interestingly, 55% of the cases negative by standard analysis, but containing a FLOCK-identified discrete plasma cell population, were positive for monoclonal gammopathy by serum protein electrophoresis and immunofixation. FLOCK-identified and quantitated plasma cell populations accounted for 3.05% of total cells on average in cases positive for involvement by a plasma cell neoplasm by standard histologic and immunophenotypic criteria, and 0.27% of total cells on average in cases negative for involvement by a plasma cell neoplasm by standard histologic and immunophenotypic criteria (p<0.0001; area under the curve by ROC analysis=0.96). The presence of a FLOCK-identified discrete plasma cell population was predictive of the presence of plasma cell neoplasia with a sensitivity of 97%, compared with only 81% for standard flow cytometric analysis, and had specificity of 74%, PPV of 84% and NPV of 95%. FLOCK analysis, which has been shown to provide useful diagnostic information for evaluating patients with suspected systemic mastocytosis, is able to identify neoplastic plasma cell populations analyzed by flow cytometry, and may be helpful in the diagnostic evaluation of bone marrow samples for involvement by plasma cell neoplasia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Level of selected toxic elements in meat, liver, tallow and bone marrow of young semi-domesticated reindeer (Rangifer tarandus tarandus L.) from Northern Norway

PubMed Central

Hassan, Ammar Ali; Rylander, Charlotta; Brustad, Magritt; Sandanger, Torkjel M.

2012-01-01

Objectives To gain knowledge on toxic elements in semi-domesticated reindeer and their distribution in meat, liver, tallow and bone marrow. The correlations between concentrations in meat and liver, as well as the use of the latter as an indicator for toxic elements in meat, were also investigated. Study design Cross-sectional study on population of semi-domesticated reindeer from 2 northern Norwegian counties (Finnmark and Nordland). Methods Semi-domesticated reindeer carcasses (n=31) were randomly selected, from which meat, liver, tallow and bone marrow samples were collected. Selected toxic elements (cadmium, lead, arsenic, nickel and vanadium) were studied. Results Liver was the organ with the highest level of all elements except for nickel, which was highest in bone marrow. Meat had the lowest levels, whereas levels in tallow and bone marrow were between those of meat and liver. Concentrations of cadmium, lead and arsenic were significantly different (p<0.05) between meat and liver, while only arsenic and cadmium were significantly correlated in meat (rs=0.71, p<0.01) and liver (rs=0.72, p<0.01). The cadmium level exceeded the European Commission's (EC) maximum level set for bovine meat and live in 52% of the liver samples (n=29). Nevertheless, the estimated monthly cadmium intake from liver of 2.29 µg/kg body weight was well below the provisional tolerable monthly intake of 25 µg/kg body weight set by the FAO/WHO Joint Expert Committee on Food Additives. Conclusions Based on the measured levels and their relation to the maximum level and to the provisional tolerable weekly/monthly intake limits, it could be inferred that consumption of reindeer meat is not associated with any health risk related to the studied toxic elements for consumers. PMID:22564461

Human blood and marrow side population stem cell and Stro-1 positive bone marrow stromal cell numbers decline with age, with an increase in quality of surviving stem cells: correlation with cytokines.

PubMed

Brusnahan, S K; McGuire, T R; Jackson, J D; Lane, J T; Garvin, K L; O'Kane, B J; Berger, A M; Tuljapurkar, S R; Kessinger, M A; Sharp, J G

2010-01-01

Hematological deficiencies increase with aging leading to anemias, reduced hematopoietic stress responses and myelodysplasias. This study tested the hypothesis that side population hematopoietic stem cells (SP-HSC) would decrease with aging, correlating with IGF-1 and IL-6 levels and increases in bone marrow fat. Marrow was obtained from the femoral head and trochanteric region of the femur at surgery for total hip replacement (N=100). Whole trabecular marrow samples were ground in a sterile mortar and pestle and cellularity and fat content determined. Marrow and blood mononuclear cells were stained with Hoechst dye and the SP-HSC profiles acquired. Marrow stromal cells (MSC) were enumerated flow cytometrically employing the Stro-1 antibody, and clonally in the colony forming unit fibroblast (CFU-F) assay. Plasma levels of IGF-1 (ng/ml) and IL-6 (pg/ml) were measured by ELISA. SP-HSC in blood and bone marrow decreased with age but the quality of the surviving stem cells increased. MSC decreased non-significantly. IGF-1 levels (mean=30.7, SEM=2) decreased and IL-6 levels (mean=4.4, SEM=1) increased with age as did marrow fat (mean=1.2mmfat/g, SEM=0.04). There were no significant correlations between cytokine levels or fat and SP-HSC numbers. Stem cells appear to be progressively lost with aging and only the highest quality stem cells survive. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Evaluation of Functional Marrow Irradiation Based on Skeletal Marrow Composition Obtained Using Dual-Energy Computed Tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Magome, Taiki; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota; Department of Radiology, The University of Tokyo Hospital, Tokyo

Purpose: To develop an imaging method to characterize and map marrow composition in the entire skeletal system, and to simulate differential targeted marrow irradiation based on marrow composition. Methods and Materials: Whole-body dual energy computed tomography (DECT) images of cadavers and leukemia patients were acquired, segmented to separate bone marrow components, namely, bone, red marrow (RM), and yellow marrow (YM). DECT-derived marrow fat fraction was validated using histology of lumbar vertebrae obtained from cadavers. The fractions of RM (RMF = RM/total marrow) and YMF were calculated in each skeletal region to assess the correlation of marrow composition with sites and ages. Treatmentmore » planning was simulated to target irradiation differentially at a higher dose (18 Gy) to either RM or YM and a lower dose (12 Gy) to the rest of the skeleton. Results: A significant correlation between fat fractions obtained from DECT and cadaver histology samples was observed (r=0.861, P<.0001, Pearson). The RMF decreased in the head, neck, and chest was significantly inversely correlated with age but did not show any significant age-related changes in the abdomen and pelvis regions. Conformity of radiation to targets (RM, YM) was significantly dependent on skeletal sites. The radiation exposure was significantly reduced (P<.05, t test) to organs at risk (OARs) in RM and YM irradiation compared with standard total marrow irradiation (TMI). Conclusions: Whole-body DECT offers a new imaging technique to visualize and measure skeletal-wide marrow composition. The DECT-based treatment planning offers volumetric and site-specific precise radiation dosimetry of RM and YM, which varies with aging. Our proposed method could be used as a functional compartment of TMI for further targeted radiation to specific bone marrow environment, dose escalation, reduction of doses to OARs, or a combination of these factors.« less

Unicameral bone cysts treated by injection of bone marrow or methylprednisolone.

PubMed

Chang, C H; Stanton, R P; Glutting, J

2002-04-01

In 79 consecutive patients with unicameral bone cysts we compared the results of aspiration and injection of bone marrow with those of aspiration and injection of steroid. All were treated by the same protocol. The only difference was the substance injected into the cysts. The mean radiological follow-up to detect activity in the cyst was 44 months (12 to 108). Of the 79 patients, 14 received a total of 27 injections of bone marrow and 65 a total of 99 injections of steroid. Repeated injections were required in 57% of patients after bone marrow had been used and in 49% after steroid. No complications were noted in either group. In this series no advantage could be shown for the use of autogenous injection of bone marrow compared with injection of steroid in the management of unicameral bone cysts.

Immune response

MedlinePlus Videos and Cool Tools

... These cells develop into two groups in the bone marrow. From the bone marrow, one group of lymphocytes migrates to a ... or B cells, mature and develop within the bone marrow itself. In that process, they achieve the ...

[Bone marrow stromal damage mediated by immune response activity].

PubMed

Vojinović, J; Kamenov, B; Najman, S; Branković, Lj; Dimitrijević, H

1994-01-01

The aim of this work was to estimate influence of activated immune response on hematopoiesis in vitro, using the experimental model of BCG immunized BALB/c mice and in patients with chronic immunoactivation: long-lasting infections, autoimmunity or malignancy. We correlated changes in long term bone marrow cultures (Dexter) and NBT reduction with appearance of anemia in patients and experimental model of immunization by BCG. Increased spontaneous NBT reduction pointed out role of macrophage activation in bone marrow stroma damage. Long-term bone marrow cultures showed reduced number of hematopoietic cells, with predomination of fibroblasts and loss of fat cells. This results correlated with anemia and leucocytosis with stimulated myelopoiesis in peripheral blood. Activation of immune response, or acting of any agent that directly changes extracellular matrix and cellularity of bone marrow, may result in microenviroment bone marrow damage that modify hematopoiesis.

Survival and endogenous colony formation in irradiated mice grafted with normal or infectious mononucleosis bone marrow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Louwagie, A. C.; Verwilghen, R. L.

1973-07-01

Mice were exposed to 850 or 975 rad of whole-body radiation; three hr later mice were given normal human bone marrow, infectious mononucleosis bone marrow, or cells from malignant blood diseases. The surviving mice were killed at day 9 and the spleen nodules were counted. Some mice were also given antihuman antilymphocytic serum (ALS). In mice exposed to 975 rad, the highest survival was observed in mice grafted with infectious mononucleosis bone marrow, while none of the animals grafted with cells from malignant blood diseases survived 9 days. In mice exposed to 850 rad, grafting of normal or infectious mononucleosismore » bone marrow markedly decreased the survival. Endogenous spleen colonies were induced in all animals grafted with normal or infectious mononucleosis bone marrow. (HLW)« less

Genomic analysis of bone marrow failure and myelodysplastic syndromes reveals phenotypic and diagnostic complexity

PubMed Central

Zhang, Michael Y.; Keel, Siobán B.; Walsh, Tom; Lee, Ming K.; Gulsuner, Suleyman; Watts, Amanda C.; Pritchard, Colin C.; Salipante, Stephen J.; Jeng, Michael R.; Hofmann, Inga; Williams, David A.; Fleming, Mark D.; Abkowitz, Janis L.; King, Mary-Claire; Shimamura, Akiko

2015-01-01

Accurate and timely diagnosis of inherited bone marrow failure and inherited myelodysplastic syndromes is essential to guide clinical management. Distinguishing inherited from acquired bone marrow failure/myelodysplastic syndrome poses a significant clinical challenge. At present, diagnostic genetic testing for inherited bone marrow failure/myelodysplastic syndrome is performed gene-by-gene, guided by clinical and laboratory evaluation. We hypothesized that standard clinically-directed genetic testing misses patients with cryptic or atypical presentations of inherited bone marrow failure/myelodysplastic syndrome. In order to screen simultaneously for mutations of all classes in bone marrow failure/myelodysplastic syndrome genes, we developed and validated a panel of 85 genes for targeted capture and multiplexed massively parallel sequencing. In patients with clinical diagnoses of Fanconi anemia, genomic analysis resolved subtype assignment, including those of patients with inconclusive complementation test results. Eight out of 71 patients with idiopathic bone marrow failure or myelodysplastic syndrome were found to harbor damaging germline mutations in GATA2, RUNX1, DKC1, or LIG4. All 8 of these patients lacked classical clinical stigmata or laboratory findings of these syndromes and only 4 had a family history suggestive of inherited disease. These results reflect the extensive genetic heterogeneity and phenotypic complexity of bone marrow failure/myelodysplastic syndrome phenotypes. This study supports the integration of broad unbiased genetic screening into the diagnostic workup of children and young adults with bone marrow failure and myelodysplastic syndromes. PMID:25239263

[Histologic assessment of tissue healing of hyaline cartilage by use of semiquantitative evaluation scale].

PubMed

Vukasović, Andreja; Ivković, Alan; Jezek, Davor; Cerovecki, Ivan; Vnuk, Drazen; Kreszinger, Mario; Hudetz, Damir; Pećina, Marko

2011-01-01

Articular cartilage is an avascular and aneural tissue lacking lymph drainage, hence its inability of spontaneous repair following injury. Thus, it offers an interesting model for scientific research. A number of methods have been suggested to enhance cartilage repair, but none has yet produced significant success. The possible application of the aforementioned methods has brought about the necessity to evaluate their results. The objective of this study was to analyze results of a study of the effects of the use of TGF-beta gene transduced bone marrow clot on articular cartilage defects using ICRS visual histological assessment scale. The research was conducted on 28 skeletally mature sheep that were randomly assigned to four groups and surgically inflicted femoral chondral defects. The articular surfaces were then treated with TGF-beta1 gene transduced bone marrow clot (TGF group), GFP transduced bone marrow clot (GFP group), untransduced bone marrow clot (BM group) or left untreated (NC group). The analysis was performed by visual examination of cartilage samples and results were obtained using ICRS visual histological assessment scale. The results were subsequently subjected to statistical assessment using Kruskal-Wallis and Mann-Whitney tests. Kruskal-Wallis test yielded statistically significant difference with respect to cell distribution. Mann-Whitney test showed statistically significant difference between TGF and NC groups (P = 0.002), as well as between BM and NC groups (P = 0.002 with Bonferroni correction). Twenty-six of the twenty-eight samples were subjected to histologic and subsequent statistical analysis; two were discarded due to faulty histology technique. Our results indicated a level of certainty as to the positive effect of TGF-beta1 gene transduced bone marrow clot in restoration of articular cartilage defects. However, additional research is necessary in the field. One of the significant drawbacks on histologic assessment of cartilage samples were the errors in histologic preparation, for which some samples had to be discarded and significantly impaired the analytical quality of the others. Defects of structures surrounding the articular cartilage, e.g., subchondral bone or connective tissue, might also impair the quality of histologic analysis. Additional analyses, i.e. polarizing microscopy should be performed to determine the degree of integration of the newly formed tissue with the surrounding cartilage. The semiquantitative ICRS scale, although of great practical value, has limitations as to the objectivity of the assessment, taking into account the analytical ability of the evaluator, as well as the accuracy of semiquantitative analysis in comparison to the methods of quantitative analysis. Overall results of histologic analysis indicated that the application of TGF-beta1 gene transduced bone marrow clot could have measurable clinical effects on articular cartilage repair. The ICRS visual histological assessment scale is a valuable analytical method for cartilage repair evaluation. In this respect, further analyses of the method value would be of great importance.

Bone marrow biopsy in monoclonal gammopathies: correlations between pathological findings and clinical data. The Cooperative Group for Study and Treatment of Multiple Myeloma.

PubMed Central

Riccardi, A; Ucci, G; Luoni, R; Castello, A; Coci, A; Magrini, U; Ascari, E

1990-01-01

Between January 1987 and October 1989, 561 consecutive untreated patients with monoclonal gammopathy of undetermined clinical importance (MGUS) (n = 295) or with multiple myeloma (n = 266) were evaluated in a multicentre trial. Both bone marrow biopsy and aspiration (performed at different anatomical sites) were required at presentation. Bone marrow biopsy data indicated that changes in bone marrow composition from MGUS to early multiple myeloma and to advanced multiple myeloma followed a precise pattern, including an increased percentage of bone marrow plasma cells (BMPC%), a shift from plasmocytic to plasmoblastic cytology, an increase in bone marrow cellularity and fibrosis, a change in bone marrow infiltration (becoming diffuse rather than interstitial), a decrease in residual haemopoiesis and an increase in osteoclasts. In multiple myeloma the BMPC% of biopsy specimens and aspirate were closely related, although in 5% of cases the difference between the two values was greater than 20%. Some histological features were remarkably associated with each other. For example, BMPC% was higher in cases with plasmoblastic cytology, heavy fibrosis, or reduced residual haemopoiesis. Anaemia was the clinical characteristic most influenced by bone marrow histology. The BMPC% was the only histological variable which affected the greatest number of clinical and laboratory characteristics, including, besides haemoglobin concentration, erythrocyte sedimentation rate, radiographic skeletal bone disease, and serum concentrations of monoclonal component, calcium, beta 2-microglobulin and thymidine kinase activity. These data indicate that comparative bone marrow histology in monoclonal gammopathies has clinical importance. Images PMID:2199532

Getting to the Heart of Being the Match: A Qualitative Analysis of Bone Marrow Donor Recruitment and Retention among College Students

ERIC Educational Resources Information Center

Kaster, Elizabeth C.; Rogers, Charles R.; Jeon, Kwon Chan; Rosen, Brittany

2014-01-01

Introduction: For those with certain blood or bone cancers, bone marrow donation can mean the difference between life and death. The National Marrow Donor Program® (NMDP) operates the largest bone marrow registry of potential donors; however, at times when potential matches are identified, many donors opt not to donate. The purpose of this study…

The bone marrow is not only a primary lymphoid organ: The critical role for T lymphocyte migration and housing of long-term memory plasma cells.

PubMed

Pabst, Reinhard

2018-05-22

In immunology and anatomy textbooks the bone marrow is described as a typical "primary lymphoid organ" producing lymphoid cells independent of antigens. The hematopoietic bone marrow is largely age-dependent organ with great anatomical and functional differences among various species. There are estimates that about 12% of all lymphoid cells in the human body are found in the bone marrow at any given time (2% in the peripheral blood). Enormous numbers of T lymphocytes migrate to the bone marrow and partly return later to the blood. Many of these lymphocytes are memory CD4 + and CD8 + T cells. A few days after immunization a wave of plasma cells and their precursors migrate to the bone marrow where they lose their migratory response to CXCL-12 and CXCL9. There is a relative enrichment of CD19 + B cells in the bone marrow outnumbering those in the blood and secondary lymphoid organs. This is not due to local production. The proliferation and migration kinetics of these lymphoid cells in the bone marrow have to be studied in more detail as this is of major clinical relevance. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Automated classification of bone marrow cells in microscopic images for diagnosis of leukemia: a comparison of two classification schemes with respect to the segmentation quality

NASA Astrophysics Data System (ADS)

Krappe, Sebastian; Benz, Michaela; Wittenberg, Thomas; Haferlach, Torsten; Münzenmayer, Christian

2015-03-01

The morphological analysis of bone marrow smears is fundamental for the diagnosis of leukemia. Currently, the counting and classification of the different types of bone marrow cells is done manually with the use of bright field microscope. This is a time consuming, partly subjective and tedious process. Furthermore, repeated examinations of a slide yield intra- and inter-observer variances. For this reason an automation of morphological bone marrow analysis is pursued. This analysis comprises several steps: image acquisition and smear detection, cell localization and segmentation, feature extraction and cell classification. The automated classification of bone marrow cells is depending on the automated cell segmentation and the choice of adequate features extracted from different parts of the cell. In this work we focus on the evaluation of support vector machines (SVMs) and random forests (RFs) for the differentiation of bone marrow cells in 16 different classes, including immature and abnormal cell classes. Data sets of different segmentation quality are used to test the two approaches. Automated solutions for the morphological analysis for bone marrow smears could use such a classifier to pre-classify bone marrow cells and thereby shortening the examination duration.

Bone marrow involvement is rare in superficial gastric mucosa-associated lymphoid tissue lymphoma.

PubMed

Park, Jae Yong; Kim, Sang Gyun; Kim, Joo Sung; Jung, Hyun Chae

2016-01-01

The initial staging work-up of gastric mucosa-associated lymphoid tissue (MALT) lymphoma includes bone marrow examination. Since gastric MALT lymphoma is mostly detected in early stages with the national cancer screening programme in Korea, bone marrow is rarely involved. To investigate the incidence of bone marrow involvement in gastric MALT lymphomas and the role of bone marrow examination for an initial staging work-up. Patients diagnosed with gastric MALT lymphoma at Seoul National University Hospital from January 2005 to July 2014 were enrolled. Clinical databases of the patients were retrospectively reviewed. Out of 105 patients, 91 (86.7%) were classified as stage IE1. Among these patients, 78 patients with Helicobacter pylori infection underwent eradication therapy, and complete remission was achieved in 74 cases (94.9%). Twelve out of 13 patients (92.3%) without H. pylori infection underwent radiotherapy or surgery and all achieved complete remission. Bone marrow involvement was proven in only one patient (1.0%). Bone marrow involvement was rare in patients with only superficial gastric MALT lymphoma without extragastric invasion. Further studies are warranted to identify the risk factors of bone marrow involvement in gastric MALT lymphoma. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Reduced immune responses in chimeric mice engrafted with bone marrow cells from mice with airways inflammation.

PubMed

Scott, Naomi M; Ng, Royce L X; McGonigle, Terence A; Gorman, Shelley; Hart, Prue H

2015-11-01

During respiratory inflammation, it is generally assumed that dendritic cells differentiating from the bone marrow are immunogenic rather than immunoregulatory. Using chimeric mice, the outcomes of airways inflammation on bone marrow progenitor cells were studied. Immune responses were analyzed in chimeric mice engrafted for >16 weeks with bone marrow cells from mice with experimental allergic airways disease (EAAD). Responses to sensitization and challenge with the allergen causing inflammation in the bone marrow-donor mice were significantly reduced in the chimeric mice engrafted with bone marrow cells from mice with EAAD (EAAD-chimeric). Responses to intranasal LPS and topical fluorescein isothiocyanate (non-specific challenges) were significantly attenuated. Fewer activated dendritic cells from the airways and skin of the EAAD-chimeric mice could be tracked to the draining lymph nodes, and may contribute to the significantly reduced antigen/chemical-induced hypertrophy in the draining nodes, and the reduced immune responses to sensitizing allergens. Dendritic cells differentiating in vitro from the bone marrow of >16 weeks reconstituted EAAD-chimeric mice retained an ability to poorly prime immune responses when transferred into naïve mice. Dendritic cells developing from bone marrow progenitors during airways inflammation are altered such that daughter cells have reduced antigen priming capabilities.

Relative importance of the bone marrow and spleen in the production and dissemination of B lymphocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosse, C.; Cole, S.B.; Appleton, C.

1978-04-01

The relative importance of the bone marrow and spleen in the production of B lymphocytes was investigated in guinea pigs by the combined use of (/sup 3/H)TdR radioautography and fluorescent microscopy after the staining of B cells by FITC-F (ab')/sub 2/-goat-anti-guinea pig Ig. Large and small lymphoid cells possess sIg in the marrow and spleen but B cell turnover in the marrow exceeds that in the spleen. That newly generated bone marrow B cells are not derived from an extramyeloid bursa equivalent was demonstrated by the absence of (/sup 3/H)TdR labeled B cells in tibial marrow 72 hr after (/supmore » 3/H)TdR was administered systemically, while the circulation to the hind limbs was occluded. Pulse and chase studies with (/sup 3/H)TdR showed that large marrow B cells are derived from sIg-negative, proliferating precursors resident in the bone marrow and not from the enlargement of activated small B lymphocytes. The acquisition of (/sup 3/H)TdR by splenic B cells lagged behind that observed in the marrow. Three days after topical labeling of tibial and femoral bone marrow with (/sup 3/H)TdR, a substantial proportion of splenic B cells were replaced by cells that had seeded there from the labeled marrow. The studies unequivocally identify the bone marrow as the organ of primary importance in B cell generation, and indicate that in the guinea pig rapidly renewed B lymphocytes of the spleen are replaced by lymphocytes recently generated in bone marrow. The rate of replacement of B lymphocytes in the lymph node by cells newly generated in the bone marrow takes place at a slower tempo than in the spleen.« less

Characterization of bone marrow mononuclear cells on biomaterials for bone tissue engineering in vitro.

PubMed

Henrich, Dirk; Verboket, René; Schaible, Alexander; Kontradowitz, Kerstin; Oppermann, Elsie; Brune, Jan C; Nau, Christoph; Meier, Simon; Bonig, Halvard; Marzi, Ingo; Seebach, Caroline

2015-01-01

Bone marrow mononuclear cells (BMCs) are suitable for bone tissue engineering. Comparative data regarding the needs of BMC for the adhesion on biomaterials and biocompatibility to various biomaterials are lacking to a large extent. Therefore, we evaluated whether a surface coating would enhance BMC adhesion and analyze the biocompatibility of three different kinds of biomaterials. BMCs were purified from human bone marrow aspirate samples. Beta tricalcium phosphate (β-TCP, without coating or coated with fibronectin or human plasma), demineralized bone matrix (DBM), and bovine cancellous bone (BS) were assessed. Seeding efficacy on β-TCP was 95% regardless of the surface coating. BMC demonstrated a significantly increased initial adhesion on DBM and β-TCP compared to BS. On day 14, metabolic activity was significantly increased in BMC seeded on DBM in comparison to BMC seeded on BS. Likewise increased VEGF-synthesis was observed on day 2 in BMC seeded on DBM when compared to BMC seeded on BS. The seeding efficacy of BMC on uncoated biomaterials is generally high although there are differences between these biomaterials. Beta-TCP and DBM were similar and both superior to BS, suggesting either as suitable materials for spatial restriction of BMC used for regenerative medicine purposes in vivo.

Characterization of Bone Marrow Mononuclear Cells on Biomaterials for Bone Tissue Engineering In Vitro

PubMed Central

Verboket, René; Kontradowitz, Kerstin; Oppermann, Elsie; Brune, Jan C.; Nau, Christoph; Meier, Simon; Bonig, Halvard; Marzi, Ingo; Seebach, Caroline

2015-01-01

Bone marrow mononuclear cells (BMCs) are suitable for bone tissue engineering. Comparative data regarding the needs of BMC for the adhesion on biomaterials and biocompatibility to various biomaterials are lacking to a large extent. Therefore, we evaluated whether a surface coating would enhance BMC adhesion and analyze the biocompatibility of three different kinds of biomaterials. BMCs were purified from human bone marrow aspirate samples. Beta tricalcium phosphate (β-TCP, without coating or coated with fibronectin or human plasma), demineralized bone matrix (DBM), and bovine cancellous bone (BS) were assessed. Seeding efficacy on β-TCP was 95% regardless of the surface coating. BMC demonstrated a significantly increased initial adhesion on DBM and β-TCP compared to BS. On day 14, metabolic activity was significantly increased in BMC seeded on DBM in comparison to BMC seeded on BS. Likewise increased VEGF-synthesis was observed on day 2 in BMC seeded on DBM when compared to BMC seeded on BS. The seeding efficacy of BMC on uncoated biomaterials is generally high although there are differences between these biomaterials. Beta-TCP and DBM were similar and both superior to BS, suggesting either as suitable materials for spatial restriction of BMC used for regenerative medicine purposes in vivo. PMID:25802865

Enhancement of the repair of dog alveolar cleft by an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture.

PubMed

Yuanzheng, Chen; Yan, Gao; Ting, Li; Yanjie, Fu; Peng, Wu; Nan, Bai

2015-05-01

Autologous bone graft has been regarded as the criterion standard for the repair of alveolar cleft. However, the most prominent issue in alveolar cleft treatment is the high absorption rate of the bone graft. The authors' objective was to investigate the effects of an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture on the repair of dog alveolar cleft. Twenty beagle dogs with unilateral alveolar clefts created by surgery were divided randomly into four groups: group A underwent repair with an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture; group B underwent repair with autologous iliac bone and bone marrow-derived mesenchymal stem cells; group C underwent repair with autologous iliac bone and platelet-rich fibrin; and group D underwent repair with autologous iliac bone as the control. One day and 6 months after transplantation, the transplant volumes and bone mineral density were assessed by quantitative computed tomography. All of the transplants were harvested for hematoxylin and eosin staining 6 months later. Bone marrow-derived mesenchymal stem cells and platelet-rich fibrin transplants formed the greatest amounts of new bone among the four groups. The new bone formed an extensive union with the underlying maxilla in groups A, B, and C. Transplants with the bone marrow-derived mesenchymal stem cells, platelet-rich fibrin, and their mixture retained the majority of their initial volume, whereas the transplants in the control group showed the highest absorption rate. Bone mineral density of transplants with the bone marrow-derived mesenchymal stem cells, platelet-rich fibrin, and their mixture 6 months later was significantly higher than in the control group (p < 0.05), and was the highest in bone marrow-derived mesenchymal stem cells and platelet-rich fibrin mixed transplants. Hematoxylin and eosin staining showed that the structure of new bones formed the best in group A. Both bone marrow-derived mesenchymal stem cells and platelet-rich fibrin are capable of improving the repair of dog alveolar cleft, and the mixture of them is more potent than each one of them used singly for enhancing new bone regeneration.

Evaluation of Bone Marrow Processing Protocol for Therapeutic Applications via Culture and Characterization of Mesenchymal Stem Cells.

PubMed

Verma, Poonam; Bansal, Himanshu; Agrawal, Anupama; Leon, Jerry; Sundell, I Birgitta; Koka, Prasad S

Human mesenchymal stem cells from bone marrow (hMSCs) have broad therapeutic potential. These cells can be are readily isolated from bone marrow by their property to adhere to tissue culture treated culture wares. However, the proliferation rates and other properties of the cells gradually change during expansion. This study aims to validate the protocol of isolation and differentiation of hMSCs from bone marrow for therapeutic applications. Sixty ml of bone marrow was extracted from 5 patients and MSCs were isolated. These were characterized by Flow Cytometry, CFU assay and were differentiated into bone, fat cells and neurocytes. The cells were having healthy morphology. These were positive for the markers CD105, CD90 and CD73 and negative for CD45, CD34 and HLA-DR. The cells could differentiate into fat, bone and neural cells. MSCs from the bone marrow were isolated and differentiated. These cells were morphologically healthy and passed CFU assay. The cells exhibited differentiation potential into bone, fat and neural tissue. These cells can be used in therapeutic applications.

Improved bone marrow stromal cell adhesion on micropatterned titanium surfaces.

PubMed

Iskandar, Maria E; Cipriano, Aaron F; Lock, Jaclyn; Gott, Shannon C; Rao, Masaru P; Liu, Huinan

2012-01-01

Implant longevity is desired for all bone replacements and fixatives. Titanium (Ti) implants fail due to lack of juxtaposed bone formation, resulting in implant loosening. Implant surface modifications have shown to affect the interactions between the implant and bone. In clinical applications, it is crucial to improve osseointegration and implant fixation at the implant and bone interface. Moreover, bone marrow derived cells play a significant role for implant and tissue integration. Therefore, the objective of this study is to investigate how surface micropatterning on Ti influences its interactions with bone marrow derived cells containing mesenchymal and hematopoietic stem cells. Bone marrow derived mesenchymal stem cells (BMSC) have the capability of differentiating into osteoblasts that contribute to bone growth, and therefore implant/bone integration. Hematopoietic stem cell derivatives are precursor cells that contribute to inflammatory response. By using all three cells naturally contained within bone marrow, we mimic the physiological environment to which an implant is exposed. Primary rat bone marrow derived cells were seeded onto Ti with surfaces composed of arrays of grooves of equal width and spacing ranging from 0.5 to 50 µm, fabricated using a novel plasma-based dry etching technique. Results demonstrated enhanced total cell adhesion on smaller micrometer-scale Ti patterns compared with larger micrometer-scale Ti patterns, after 24-hr culture. Further studies are needed to determine bone marrow derived cell proliferation and osteogenic differentiation potential on micropatterned Ti, and eventually nanopatterned Ti.

Bone-marrow transplant - series (image)

MedlinePlus

Bone-marrow transplants are performed for: deficiencies in red blood cells (aplastic anemia) and white blood cells (leukemia or ... Bone-marrow transplants prolong the life of patients who might otherwise die. As with all major organ transplants, however, ...

Canine Skin and Conjunctival Swab Samples for the Detection and Quantification of Leishmania infantum DNA in an Endemic Urban Area in Brazil

PubMed Central

de Almeida Ferreira, Sidney; Leite, Rodrigo Souza; Ituassu, Leonardo Trindade; Almeida, Gregório Guilherme; Souza, Daniel Menezes; Fujiwara, Ricardo Toshio; de Andrade, Antero Silva Ribeiro; Melo, Maria Norma

2012-01-01

Background We evaluated kDNA PCR/hybridization and quantitative real-time PCR (qPCR) targeting the gene of DNA polymerase of Leishmania infantum for CVL diagnosis and assessment of parasite load in clinical samples obtained invasively and non-invasively. Methodology/Principal Findings Eighty naturally infected dogs from an endemic urban area in Brazil were used. Animals were divided into two groups based on the presence or absence of CVL clinical sings. Skin biopsies, bone marrow, blood and conjunctival swabs samples were collected and submitted to L. infantum DNA detection. In addition, anti-Leishmania antibody titers were measured by Immunofluorescence antibody test. The symptomatic dogs had increased titers compared to asymptomatic dogs (P = 0.025). The frequencies of positive results obtained by kDNA PCR/hybridization for asymptomatic and symptomatic dogs, respectively, were as follows: right conjunctiva, 77.5% and 95.0%; left conjunctiva, 75.0% and 87.5%; skin, 45.0% and 75.0%; bone marrow, 50.0% and 77.5%; and blood, 27.5% and 22.5%. In both groups, the parasite load in the skin samples was the highest (P<0.0001). The parasite loads in the conjunctival swab and bone marrow samples were statistically equivalent within each group. The parasite burden in conjunctival swabs was higher in the dogs with clinical signs than in asymptomatic dogs (P = 0.028). This same relationship was also observed in the bone marrow samples (P = 0.002). No differences in amastigotes load in the skin were detected between the groups. Conclusions The conjunctival swab is a suitable clinical sample for qualitative molecular diagnosis of CVL. The highest parasite burdens were detected in skin regardless of the presence of VL-associated clinical signs. The qPCR results emphasized the role of dogs, particularly asymptomatic dogs, as reservoirs for CVL because of the high cutaneous parasite loads. These results may help to explain the maintenance of high transmission rates and numbers of CVL cases in endemic urban regions. PMID:22506084

[Effect of intravenous treatment with OK-432 on the bone marrow in patients with lung cancer].

PubMed

Fujii, M; Ishikawa, M; Toki, H

1984-03-01

We studied effects of OK-432 on the bone marrow and peripheral blood cells of lung cancer patients. The nuclear cell count of bone marrow increased in 5 to 7 patients upon intravenous treatment with OK-432 compared with 3 of 6 patients who were intramuscularly treated with OK-432. Serial neutrophil counts of bone marrow increased in all 7 patients treated intravenously compared with 3 of 6 patients treated intramuscularly. The mean nuclear cell count or the serial neutrophil count of bone marrow in intravenously treated patients was significantly higher than the pretreatment values (p less than 0.001). In the peripheral blood picture, the difference in white blood cells or neutrophils before and after intravenous treatment was also statistically significant (p less than 0.01). There was no change in the erythrocytic series count of bone marrow and the hemoglobin count. Our results support the superiority of intravenous OK-432 treatment over intramuscular treatment in the growth-accelerating effect on bone marrow cells, especially regarding the neutrophil series.

Bone Marrow Aspirate Concentrate-Enhanced Marrow Stimulation of Chondral Defects

PubMed Central

Eichler, Hermann; Orth, Patrick

2017-01-01

Mesenchymal stem cells (MSCs) from bone marrow play a critical role in osteochondral repair. A bone marrow clot forms within the cartilage defect either as a result of marrow stimulation or during the course of the spontaneous repair of osteochondral defects. Mobilized pluripotent MSCs from the subchondral bone migrate into the defect filled with the clot, differentiate into chondrocytes and osteoblasts, and form a repair tissue over time. The additional application of a bone marrow aspirate (BMA) to the procedure of marrow stimulation is thought to enhance cartilage repair as it may provide both an additional cell population capable of chondrogenesis and a source of growth factors stimulating cartilage repair. Moreover, the BMA clot provides a three-dimensional environment, possibly further supporting chondrogenesis and protecting the subchondral bone from structural alterations. The purpose of this review is to bridge the gap in our understanding between the basic science knowledge on MSCs and BMA and the clinical and technical aspects of marrow stimulation-based cartilage repair by examining available data on the role and mechanisms of MSCs and BMA in osteochondral repair. Implications of findings from both translational and clinical studies using BMA concentrate-enhanced marrow stimulation are discussed. PMID:28607559

Reciprocal Relation between Marrow Adiposity and the Amount of Bone in the Axial and Appendicular Skeleton of Young Adults

PubMed Central

Di Iorgi, Natascia; Rosol, Michael; Mittelman, Steven D.; Gilsanz, Vicente

2008-01-01

Background: Studies in the elderly suggest a reciprocal relation between increased marrow adiposity and bone loss, supporting basic research data indicating that osteoblasts and adipocytes share a common progenitor cell. However, whether this relation represents a preferential differentiation of stromal cells from osteoblasts to adipocytes or whether a passive accumulation of fat as bone is lost and marrow space increases with aging is unknown. To address this question and avoid the confounding effect of bone loss, we examined teenagers and young adults. Methods: Using computed tomography, we obtained measurements of bone density and cross-sectional area of the lumbar vertebral bodies and cortical bone area, cross-sectional area, marrow canal area, and fat density in the marrow of the femurs in 255 sexually mature subjects (126 females, 129 males; 15–24.9 yr of age). Additionally, values for total body fat were obtained with dual-energy x-ray absorptiometry. Results: Regardless of gender, reciprocal relations were found between fat density and measures of vertebral bone density and femoral cortical bone area (r = 0.19–0.39; all P values ≤ .03). In contrast, there was no relation between marrow canal area and cortical bone area in the femurs, neither between fat density and the cross-sectional dimensions of the bones. We also found no relation between anthropometric or dual-energy x-ray absorptiometry fat values and measures for marrow fat density. Conclusions: Our results indicate an inverse relation between bone marrow adiposity and the amount of bone in the axial and appendicular skeleton and support the notion of a common progenitor cell capable of mutually exclusive differentiation into the cell lineages responsible for bone and fat formation. PMID:18381577

Pulmonary Embolization of Fat and Bone Marrow in Cynomolgus Macaques (Macaca fascicularis)

PubMed Central

Fong, Derek L.; Murnane, Robert D.; Hotchkiss, Charlotte E.; Green, Damian J.; Hukkanen, Renee R.

2011-01-01

Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma. PMID:21819686

Pulmonary embolization of fat and bone marrow in cynomolgus Macaques (Macaca fascicularis).

PubMed

Fong, Derek L; Murnane, Robert D; Hotchkiss, Charlotte E; Green, Damian J; Hukkanen, Renee R

2011-02-01

Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma.

The emerging role of bone marrow adipose tissue in bone health and dysfunction.

PubMed

Ambrosi, Thomas H; Schulz, Tim J

2017-12-01

Replacement of red hematopoietic bone marrow with yellow adipocyte-rich marrow is a conserved physiological process among mammals. The extent of this conversion is influenced by a wide array of pathological and non-pathological conditions. Of particular interest is the observation that some marrow adipocyte-inducing factors seem to oppose each other, for instance obesity and caloric restriction. Intriguingly, several important molecular characteristics of bone marrow adipose tissue (BMAT) are distinct from the classical depots of white and brown fat tissue. This depot of fat has recently emerged as an active part of the bone marrow niche that exerts paracrine and endocrine functions thereby controlling osteogenesis and hematopoiesis. While some functions of BMAT may be beneficial for metabolic adaptation and bone homeostasis, respectively, most findings assign bone fat a detrimental role during regenerative processes, such as hematopoiesis and osteogenesis. Thus, an improved understanding of the biological mechanisms leading to formation of BMAT, its molecular characteristics, and its physiological role in the bone marrow niche is warranted. Here we review the current understanding of BMAT biology and its potential implications for health and the development of pathological conditions.

Spread of Pseudomonas fluorescens due to contaminated drinking water in a bone marrow transplant unit.

PubMed

Wong, Vanessa; Levi, Katrina; Baddal, Buket; Turton, Jane; Boswell, Tim C

2011-06-01

Pseudomonas infections are an important cause of morbidity and mortality in immunocompromised patients. We present here data for the spread of Pseudomonas fluorescens caused by a contaminated drinking water dispenser in a bone marrow transplant unit. Over a 1-month period we observed a sharp increase in the isolation of P. fluorescens from weekly pharyngeal surveillance swabs. Environmental samples were taken from a variety of water sources throughout the unit. These samples were cultured on cetrimide agar medium, and isolates were epidemiologically characterized by antibiotic susceptibility patterns and molecular typing methods. Nine patients became colonized with P. fluorescens, and six out of the nine developed febrile neutropenia. P. fluorescens was cultured after the filtration of 100 ml of drinking water from one of two stand-alone chiller units supplying cooled bottled water to the bone marrow transplant unit. All other environmental samples were negative. There were no further cases of P. fluorescens colonization after the contaminated dispenser was removed. Molecular typing showed that all P. fluorescens isolates were identical by both random amplification of polymorphic DNA PCR and pulsed-field gel electrophoresis. We recommend that such bottled water supplies not be used in high-risk areas or be subject to regular microbiological monitoring.

Percutaneous osteoplasty with a bone marrow nail for fractures of long bones: experimental study.

PubMed

Nakata, Kouhei; Kawai, Nobuyuki; Sato, Morio; Cao, Guang; Sahara, Shinya; Tanihata, Hirohiko; Takasaka, Isao; Minamiguchi, Hiroyuki; Nakai, Tomoki

2010-09-01

To develop percutaneous osteoplasty with the use of a bone marrow nail for fixation of long-bone fractures, and to evaluate its feasibility and safety in vivo and in vitro. Six long bones in three healthy swine were used in the in vivo study. Acrylic cement was injected through an 11-gauge bone biopsy needle and a catheter into a covered metallic stent placed within the long bone, creating a bone marrow nail. In the in vitro study, we determined the bending, tug, and compression strengths of the acrylic cement nails 9 cm long and 8 mm in diameter (N = 10). The bending strength of the artificially fractured bones (N = 6) restored with the bone marrow nail and cement augmentation was then compared with that of normal long bones (N = 6). Percutaneous osteoplasty with a bone marrow nail was successfully achieved within 1 hour for all swine. After osteoplasty, all swine regained the ability to run until they were euthanized. Blood tests and pathologic findings showed no adverse effects. The mean bending, tug, and compression strengths of the nail were 91.4 N/mm(2) (range, 75.0-114.1 N/mm(2)), 20.9 N/mm(2) (range, 6.6-30.4 N/mm(2)), and 103.0 N/mm(2) (range, 96.3-110.0 N/mm(2)), respectively. The bending strength ratio of artificially fractured bones restored with bone marrow nail and cement augmentation to normal long bone was 0.32. Percutaneous osteoplasty with use of a bone marrow nail and cement augmentation appears to have potential in treating fractures of non-weight-bearing long bones. Copyright 2010 SIR. Published by Elsevier Inc. All rights reserved.

Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases

PubMed Central

Hardaway, Aimalie L.; Herroon, Mackenzie K.; Rajagurubandara, Erandi

2014-01-01

Adipocytes are important but underappreciated components of bone marrow microenvironment, and their numbers greatly increase with age, obesity, and associated metabolic pathologies. Age and obesity are also significant risk factors for development of metastatic prostate cancer. Adipocytes are metabolically active cells that secrete adipokines, growth factors, and inflammatory mediators; influence behavior and function of neighboring cells; and have a potential to disturb local milleu and dysregulate normal bone homeostasis. Increased marrow adiposity has been linked to bone marrow inflammation and osteoporosis of the bone, but its effects on growth and progression of prostate tumors that have metastasized to the skeleton are currently not known. This review focuses on fat-bone relationship in a context of normal bone homeostasis and metastatic tumor growth in bone. We discuss effects of marrow fat cells on bone metabolism, hematopoiesis, and inflammation. Special attention is given to CCL2- and COX-2-driven pathways and their potential as therapeutic targets for bone metastatic disease. PMID:24398857

Disruption of Annexin II /p11 Interaction Suppresses Leukemia Cell Binding, Homing and Engraftment, and Sensitizes the Leukemia Cells to Chemotherapy.

PubMed

Gopalakrishnapillai, Anilkumar; Kolb, E Anders; Dhanan, Priyanka; Mason, Robert W; Napper, Andrew; Barwe, Sonali P

2015-01-01

The bone marrow microenvironment plays an important role in acute lymphoblastic leukemia (ALL) cell proliferation, maintenance, and resistance to chemotherapy. Annexin II (ANX2) is abundantly expressed on bone marrow cells and complexes with p11 to form ANX2/p11-hetero-tetramer (ANX2T). We present evidence that p11 is upregulated in refractory ALL cell lines and patient samples. A small molecule inhibitor that disrupts ANX2/p11 interaction (ANX2T inhibitor), an anti-ANX2 antibody, and knockdown of p11, abrogated ALL cell adhesion to osteoblasts, indicating that ANX2/p11 interaction facilitates binding and retention of ALL cells in the bone marrow. Furthermore, ANX2T inhibitor increased the sensitivity of primary ALL cells co-cultured with osteoblasts to dexamethasone and vincristine induced cell death. Finally, in an orthotopic leukemia xenograft mouse model, the number of ALL cells homing to the bone marrow was reduced by 40-50% in mice injected with anti-ANX2 antibody, anti-p11 antibody or ANX2T inhibitor compared to respective controls. In a long-term engraftment assay, the percentage of ALL cells in mouse blood, bone marrow and spleen was reduced in mice treated with agents that disrupt ANX2/p11 interaction. These data show that disruption of ANX2/p11 interaction results in reduced ALL cell adhesion to osteoblasts, increased ALL cell sensitization to chemotherapy, and suppression of ALL cell homing and engraftment.

Immunophenotyping in systemic mastocytosis diagnosis: 'CD25 positive' alone is more informative than the 'CD25 and/or CD2' WHO criterion.

PubMed

Morgado, José Mário T; Sánchez-Muñoz, Laura; Teodósio, Cristina G; Jara-Acevedo, Maria; Alvarez-Twose, Iván; Matito, Almudena; Fernández-Nuñez, Elisa; García-Montero, Andrés; Orfao, Alberto; Escribano, Luís

2012-04-01

Aberrant expression of CD2 and/or CD25 by bone marrow, peripheral blood or other extracutaneous tissue mast cells is currently used as a minor World Health Organization diagnostic criterion for systemic mastocytosis. However, the diagnostic utility of CD2 versus CD25 expression by mast cells has not been prospectively evaluated in a large series of systemic mastocytosis. Here we evaluate the sensitivity and specificity of CD2 versus CD25 expression in the diagnosis of systemic mastocytosis. Mast cells from a total of 886 bone marrow and 153 other non-bone marrow extracutaneous tissue samples were analysed by multiparameter flow cytometry following the guidelines of the Spanish Network on Mastocytosis at two different laboratories. The 'CD25+ and/or CD2+ bone marrow mast cells' World Health Organization criterion showed an overall sensitivity of 100% with 99.0% specificity for the diagnosis of systemic mastocytosis whereas CD25 expression alone presented a similar sensitivity (100%) with a slightly higher specificity (99.2%). Inclusion of CD2 did not improve the sensitivity of the test and it decreased its specificity. In tissues other than bone marrow, the mast cell phenotypic criterion revealed to be less sensitive. In summary, CD2 expression does not contribute to improve the diagnosis of systemic mastocytosis when compared with aberrant CD25 expression alone, which supports the need to update and replace the minor World Health Organization 'CD25+ and/or CD2+' mast cell phenotypic diagnostic criterion by a major criterion based exclusively on CD25 expression.

The Analysis of the Adverse Reaction of Traditional Chinese Medicine Tumor Bone Marrow Suppression

NASA Astrophysics Data System (ADS)

Wei, Zhenzhen; Fang, Xiaoyan; Miao, Mingsan

2018-01-01

With the rapid increase of cancer patients, chemotherapy is the main method for the clinical treatment of cancer, but also in the treatment of the adverse reactions--bone marrow suppression is often a serious infection caused by patients after chemotherapy and the important cause of mortality. Chinese medicine has obvious advantages in the prevention and treatment of bone marrow depression after chemotherapy. According to tumor bone marrow suppression after chemotherapy of etiology and pathogenesis of traditional Chinese medicine and China national knowledge internet nearly 10 years of traditional Chinese medicine in the prevention and control of the status of clinical and laboratory research of tumor bone marrow suppression, the author analyzed and summarized its characteristics, so as to provide the basis for treating bone marrow suppression of drug research and development, and promote small adverse reactions of the development and utilization of natural medicine and its preparations.

High-fidelity organic preservation of bone marrow in ca. 10 Ma amphibians

NASA Astrophysics Data System (ADS)

McNamara, Maria E.; Orr, Patrick J.; Kearns, Stuart L.; Alcalá, Luis; Anadón, Pere; Peñalver-Mollá, Enrique

2006-08-01

Bone marrow in ca. 10 Ma frogs and salamanders from the Miocene of Libros, Spain, represents the first fossilized example of this extremely decay-prone tissue. The bone marrow, preserved in three dimensions as an organic residue, retains the original texture and red and yellow color of hematopoietic and fatty marrow, respectively; moldic osteoclasts and vascular structures are also present. We attribute exceptional preservation of the fossilized bone marrow to cryptic preservation: the bones of the amphibians formed protective microenvironments, and inhibited microbial infiltration. Specimens in which bone marrow is preserved vary in their completeness and articulation and in the extent to which the body outline is preserved as a thin film of organically preserved bacteria. Cryptic preservation of these labile tissues is thus to a large extent independent of, and cannot be predicted by, the taphonomic history of the remainder of the specimen.

Stem cells rejuvenate radiation-impaired vasculogenesis in murine distraction osteogenesis.

PubMed

Deshpande, Sagar S; Gallagher, Kathleen K; Donneys, Alexis; Nelson, Noah S; Guys, Nicholas P; Felice, Peter A; Page, Erin E; Sun, Hongli; Krebsbach, Paul H; Buchman, Steven R

2015-03-01

Radiotherapy is known to be detrimental to bone and soft-tissue repair. Bone marrow stromal cells have been shown to enhance bone regeneration during distraction osteogenesis following radiation therapy. The authors posit that transplanted bone marrow stromal cells will significantly augment the mandibular vascularity devastated by radiation therapy. Nineteen male Lewis rats were split randomly into three groups: distraction osteogenesis only (n = 5), radiation therapy plus distraction osteogenesis (n = 7), and radiation therapy plus distraction osteogenesis with intraoperative placement of 2 million bone marrow stromal cells (n = 7). A mandibular osteotomy was performed, and an external fixator device was installed. From postoperative days 4 through 12, rats underwent a gradual 5.1-mm distraction followed by a 28-day consolidation period. On postoperative day 40, Microfil was perfused into the vasculature and imaging commenced. Vascular radiomorphometric values were calculated for regions of interest. An analysis of variance with post hoc Tukey or Games-Howell tests was used, dependent on data homogeneity. Stereologic analysis indicated significant remediation in vasculature in the bone marrow stromal cell group compared with the radiation therapy/distraction osteogenesis group. Each of five metrics idicated significant improvements from radiation therapy/distraction osteogenesis to the bone marrow stromal cell group, with no difference between the bone marrow stromal cell group and the distraction osteogenesis group. Bone marrow stromal cells used together with distraction osteogenesis can rejuvenate radiation-impaired vasculogenesis in the mandible, reversing radiation therapy-induced isotropy and creating a robust vascular network. Bone marrow stromal cells may offer clinicians an alternative reconstructive modality that could improve the lifestyle of patients with hypovascular bone.

Isolation of Circulating Plasma Cells in Multiple Myeloma Using CD138 Antibody-Based Capture in a Microfluidic Device

NASA Astrophysics Data System (ADS)

Qasaimeh, Mohammad A.; Wu, Yichao C.; Bose, Suman; Menachery, Anoop; Talluri, Srikanth; Gonzalez, Gabriel; Fulciniti, Mariateresa; Karp, Jeffrey M.; Prabhala, Rao H.; Karnik, Rohit

2017-04-01

The necessity for bone marrow aspiration and the lack of highly sensitive assays to detect residual disease present challenges for effective management of multiple myeloma (MM), a plasma cell cancer. We show that a microfluidic cell capture based on CD138 antigen, which is highly expressed on plasma cells, permits quantitation of rare circulating plasma cells (CPCs) in blood and subsequent fluorescence-based assays. The microfluidic device is based on a herringbone channel design, and exhibits an estimated cell capture efficiency of ~40-70%, permitting detection of <10 CPCs/mL using 1-mL sample volumes, which is difficult using existing techniques. In bone marrow samples, the microfluidic-based plasma cell counts exhibited excellent correlation with flow cytometry analysis. In peripheral blood samples, the device detected a baseline of 2-5 CD138+ cells/mL in healthy donor blood, with significantly higher numbers in blood samples of MM patients in remission (20-24 CD138+ cells/mL), and yet higher numbers in MM patients exhibiting disease (45-184 CD138+ cells/mL). Analysis of CPCs isolated using the device was consistent with serum immunoglobulin assays that are commonly used in MM diagnostics. These results indicate the potential of CD138-based microfluidic CPC capture as a useful ‘liquid biopsy’ that may complement or partially replace bone marrow aspiration.

Question of bone marrow stromal fibroblast traffic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maloney, M.A.; Lamela, R.A.; Patt, H.M.

Bone marrow stromal fibroblasts (CFU-F) normally do not exchange bone marrow sites in vivo. Restitution of the CFU-F after radiation damage is primarily recovery by the local fibroblasts from potentially lethal damage. Migration of stromal fibroblasts from shielded sites to an irradiated site makes a minimal contribution, if any, to CFU-F recovery. Determination of the relative contribution of donor stromal cells in bone marrow transplants by karyotyping the proliferating bone marrow stromal cells in vitro may not reflect the relative distribution of fibroblasts in the marrow. If there is residual damage to the host stromal fibroblasts from treatment before transplantation,more » these cells may not be able to proliferate in vitro. Therefore, an occasional transplanted fibroblast may contribute most of the metaphase figures scored for karyotype.« less

Histological features of bone marrow in paediatric patients during the asymptomatic phase of early-stage Black African sickle cell anaemia.

PubMed

Mauriello, Alessandro; Giacobbi, Erica; Saggini, Andrea; Isgrò, Antonella; Facchetti, Simone; Anemona, Lucia

2017-04-01

Bone marrow histological features of sickle cell anaemia (SCA) patients during early stages and in the asymptomatic phase of the disease appear an interesting area of study, representing early-stage consequences of SCA with a close relation to its pathophysiology. Unfortunately, this field of research has never been specifically addressed before. Bone marrow biopsies from 26 consecutive Black African SCA patients (M:F=1.6:1; age 2-17 years), free of clinical signs of chronic bone marrow damage, with no recent history of symptomatic vaso-occlusive episodes, and waiting for haematopoietic stem cell transplantation (HSCT), underwent morphological, immunohistochemical and electron microscopy evaluation. Additional comparison with three bone marrow specimens from post-HSCT SCA patients and 10 bone marrow specimens from AS healthy carriers was performed. Bone marrow of SCA patients was normocellular or slighly hypercellular in all cases. Erythroid hyperplasia was a common feature. Myeloid lineage was slightly decreased with normal to slightly diminished neutrophilic granulocytes; CD68 positive monocytic-macrophagic cells appeared slightly increased, with a predominant CD163 positive M2/M(Hb) phenotype. A positive correlation was found between haemoglobin values and number of bone marrow erythroid cells (R 2 =0.15, p=0.05). Intravascular and interstitial clusters of erythroid sickle cells were found in bone marrow of pre-HSCT homozygous SS SCA patients, as well as heterozygous AS healthy carriers, and the single post-HSCT patient matched to an AS health carrier donor. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Asthma progression to airway remodeling and bone marrow eosinophil responses in genetically distinct strains of mice.

PubMed

Hogan, Mary Beth; Piktel, Debra; Hubbs, Ann F; McPherson, Leslie E; Landreth, Kenneth S

2008-12-01

Patient factors that cause long-term airway remodeling are largely unidentified. This suggests that genetic differences may determine which asthmatic patients develop airway remodeling. A murine model with repeated allergen exposure leading to peribronchial fibrosis in complement factor 5 (C5)-deficient A/J mice has been used to study asthma progression. No studies have addressed the systemic effects of allergen sensitization or chronic allergen exposure on bone marrow eosinophilopoiesis in this mouse strain. To investigate bone marrow eosinophil responses during acute sensitization and chronic allergen exposure using genetically distinct mouse strains differing in persistent airway reactivity and remodeling. The C5-sufficient BALB/c and C5-deficient A/J mice were repetitively exposed to intranasal ovalbumin for 12 weeks. Subsequently, the mice were evaluated for airway eosinophilia, mucus-containing goblet cells, and peribronchial fibrosis. Both strains of mice were also acutely sensitized to ovalbumin. Bone marrow eosinophil progenitor cells and mature eosinophils were enumerated. BALB/c and A/J mice have similar bone marrow responses after acute allergen exposure, with elevations in bone marrow eosinophil progenitor cell and eosinophil numbers. After chronic allergen exposure, only C5-deficient A/J mice that developed peribronchial fibrosis exhibited bone marrow eosinophilia. BALB/c mice lacked peribronchial fibrosis and extinguished accelerated eosinophil production after long-term allergen challenge. Chronic airway remodeling after repeated allergen exposure in genetically different mice correlated with differences in long-term bone marrow eosinophilopoiesis. Preventing asthma from progressing to chronic airway remodeling with fibrosis may involve identifying genetically determined influences on bone marrow responses to chronic allergen exposure.

Granulocyte-mobilized bone marrow.

PubMed

Arcese, William; De Angelis, Gottardo; Cerretti, Raffaella

2012-11-01

In the last few years, mobilized peripheral blood has overcome bone marrow as a graft source, but, despite the evidence of a more rapid engraftment, the incidence of chronic graft-versus-host disease is significantly higher with, consequently, more transplant-related mortality on the long follow-up. Overall, the posttransplant outcome of mobilized peripheral blood recipients is similar to that of patients who are bone marrow grafted. More recently, the use of bone marrow after granulocyte colony-stimulating factor (G-CSF) donor priming has been introduced in the transplant practice. Herein, we review biological acquisitions and clinical results on the use of G-CSF-primed bone marrow as a source of hematopoietic stem cells (HSC) for allogeneic stem cell transplantation. G-CSF the increases the HSC compartment and exerts an intense immunoregulatory effect on marrow T-cells resulting in the shift from Th1 to Th2 phenotype with higher production of anti-inflammatory cytokines. The potential advantages of these biological effects have been translated in the clinical practice by using G-CSF primed unmanipulated bone marrow in the setting of transplant from human leukocyte antigen (HLA)-haploidentical donor with highly encouraging results. For patients lacking an HLA-identical sibling, the transplant of G-CSF primed unmanipulated bone marrow from a haploidentical donor combined with an intense in-vivo immunosuppression is a valid alternative achieving results that are well comparable with those reported for umbilical cord blood, HLA-matched unrelated peripheral blood/bone marrow or T-cell-depleted haploidentical transplant.

[Assessment of therapeutic results for simple bone cyst with percutaneous injection of autogenous bone marrow].

PubMed

Wang, Enbo; Zhao, Qun; Zhang, Lijun

2006-09-01

To evaluate the therapeutic results of percutaneous injection of autogenous bone marrow for simple bone cyst and to analyze the prognostic factors of the treatment. From March 2000 to June 2005, 31 patients with simple bone cysts were treated by percutaneous injection of autogenous bone marrow. Of 31 patients, there were 18 males and 13 females, aged 5 years and 7 months to 15 years. The locations were proximal humerus in 18 cases, proximal femur in 7 cases and other sites in 6 cases. Two cases were treated with repeated injections. The operative process included percutaneous aspiration of fluid in the bone cysts and injection of autogenous bone marrow aspirated from posterior superior iliac spine. The mean volume of marrow injected was 40 ml (30-70 ml). No complications were noted during treatment. Thirty patients were followed for an average of 2.2 years (1-5 years) with 2 cases out of follow-up. After one injection of bone marrow, 9 cysts (29.0%) were healed up completely, 7 cysts (22.6%) basically healed up, 13 cysts (41.9%) healed up partially and 2 (6.5%) had no response. The satisfactory and effective rates were 67.7% and 93.5% respectively. There was significant difference between active stage group and resting stage group(P<0.05). There were no statistically significant difference in therapeutic results between groups of different ages, lesion sites or bone marrow hyperplasia(P>0.05). Percutaneous injection of autogenous bone marrow is a safe and effective method to treat simple bone cyst, but repeated injections is necessary for some patients. The therapeutic results are better in cysts at resting stage than those at active stage.

Primary Hyperparathyroidism: The Influence of Bone Marrow Adipose Tissue on Bone Loss and of Osteocalcin on Insulin Resistance

PubMed Central

Mendonça, Maira L.; Batista, Sérgio L.; Nogueira-Barbosa, Marcello H.; Salmon, Carlos E.G.; de Paula, Francisco J.A.

2016-01-01

OBJECTIVES: Bone marrow adipose tissue has been associated with low bone mineral density. However, no data exist regarding marrow adipose tissue in primary hyperparathyroidism, a disorder associated with bone loss in conditions of high bone turnover. The objective of the present study was to investigate the relationship between marrow adipose tissue, bone mass and parathyroid hormone. The influence of osteocalcin on the homeostasis model assessment of insulin resistance was also evaluated. METHODS: This was a cross-sectional study conducted at a university hospital, involving 18 patients with primary hyperparathyroidism (PHPT) and 21 controls (CG). Bone mass was assessed by dual-energy x-ray absorptiometry and marrow adipose tissue was assessed by 1H magnetic resonance spectroscopy. The biochemical evaluation included the determination of parathyroid hormone, osteocalcin, glucose and insulin levels. RESULTS: A negative association was found between the bone mass at the 1/3 radius and parathyroid hormone levels (r = -0.69; p<0.01). Marrow adipose tissue was not significantly increased in patients (CG = 32.8±11.2% vs PHPT = 38.6±12%). The serum levels of osteocalcin were higher in patients (CG = 8.6±3.6 ng/mL vs PHPT = 36.5±38.4 ng/mL; p<0.005), but no associations were observed between osteocalcin and insulin or between insulin and both marrow adipose tissue and bone mass. CONCLUSION: These results suggest that the increment of adipogenesis in the bone marrow microenvironment under conditions of high bone turnover due to primary hyperparathyroidism is limited. Despite the increased serum levels of osteocalcin due to primary hyperparathyroidism, these patients tend to have impaired insulin sensitivity. PMID:27626477

Prognostic value of angiogenesis in solitary bone plasmacytoma.

PubMed

Kumar, Shaji; Fonseca, Rafael; Dispenzieri, Angela; Lacy, Martha Q; Lust, John A; Wellik, Linda; Witzig, Thomas E; Gertz, Morie A; Kyle, Robert A; Greipp, Philip R; Rajkumar, S Vincent

2003-03-01

Angiogenesis plays an important role in the biology of multiple myeloma (MM) and has prognostic importance in this disease. Solitary plasmacytoma is a localized plasma cell malignancy that progresses to MM in a significant number of patients. We examined if angiogenesis is increased in solitary plasmacytoma and if it can help identify patients likely to progress to myeloma. We studied angiogenesis in plasmacytoma biopsy samples and bone marrow biopsies from 25 patients. High-grade angiogenesis was present in 64% of plasmacytomas. In contrast, bone marrow angiogenesis was low in all patients. Patients with high-grade angiogenesis in the plasmacytoma sample were more likely to progress to myeloma and had a shorter progression-free survival compared with patients with low-grade angiogenesis (P =.02). Angiogenesis is increased in solitary plasmacytoma and is a significant predictor of progression to myeloma and provides further evidence of its importance in the pathogenesis of myeloma.

Benzene-induced myelotoxicity: application of flow cytofluorometry for the evaluation of early proliferative change in bone marrow.

PubMed Central

Irons, R D

1981-01-01

A detailed description of flow cytofluorometric DNA cell cycle analysis is presented. A number of studies by the author and other investigators are reviewed in which a method is developed for the analysis of cell cycle phase in bone marrow of experimental animals. Bone marrow cell cycle analysis is a sensitive indicator of changes in bone marrow proliferative activity occurring early in chemically-induced myelotoxicity. Cell cycle analysis, used together with other hematologic methods, has revealed benzene-induced toxicity in proliferating bone marrow cells to be cycle specific, appearing to affect a population in late S phase which then accumulate in G2/M. PMID:7016521

The diagnostic utility of bone marrow aspiration and biopsy in patients with acquired immunodeficiency syndrome.

PubMed

Gluckman, R J; Rosner, F; Guarneri, J J

1989-02-01

Diagnostic bone marrow aspiration, biopsy, and culture are useful procedures in the evaluation of patients with suspected or proven acquired immunodeficiency syndrome (AIDS) who are febrile. In as many as one fourth of these patients, the information provided by the bone marrow examination may establish a diagnosis of a disseminated opportunistic infection when other studies are not informative. We have also discovered a previously unreported association between thrombocytopenia and the presence of bone marrow granulomas in our patients with AIDS and suggest that thrombocytopenia may be a clue to enable the clinician to predict a positive bone marrow result more accurately. The explanation for this apparent association remains to be elucidated.

Mixed donor chimerism in non-malignant haematological diseases after allogeneic bone marrow transplantation.

PubMed

Shamshad, Ghassan Umair; Ahmed, Suhaib; Bhatti, Farhat Abbas; Ali, Nadir

2012-12-01

To determine the frequency of mixed donor chimerism in patients of non-malignant haematological diseases after allogeneic bone marrow transplant. A cross-sectional, observational study. Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from July 2010 to June 2011. Donor chimerism was assessed in patients of aplastic anaemia and beta-thalassaemia major who underwent allogeneic bone marrow transplantation (BMT). Peripheral blood samples were used to assess chimerism status by analysis of short tandem repeats (STR). In patients where pre-transplant blood sample was not available, swab of buccal mucosa was used for pre-transplant STR profile. A standard set of primers for STR markers were used and the amplified DNA was resolved by gel electrophoresis and stained with silver nitrate. The percentage of donor origin DNA was estimated by densitometer. Out of 84 patients, 52 (62%) were males, while 32 (38%) were females. In patients of beta-thalassaemia major, 31 (62%) developed mixed donor chimerism (MC), 13 (26%) developed complete donor chimerism (CC) and 6 (12%) had graft failure. In aplastic anaemia, 17 patients (50%) achieved MC, 13 (38.2%) had CC and 4 (11.8%) developed graft failure. The combined frequency of mixed donor chimerism for both the diseases was 58.3%. D3S1358 was the most informative STR marker in these patients. Majority of the studied patients developed mixed donor chimerism following bone marrow transplantation, whereas only a minor percentage of the patients had graft failure. Analysis of D3S1358 was the most informative in assessing donor chimerism in patients who underwent BMT.

Digital image analysis agrees with visual estimates of adult bone marrow trephine biopsy cellularity.

PubMed

Hagiya, A S; Etman, A; Siddiqi, I N; Cen, S; Matcuk, G R; Brynes, R K; Salama, M E

2018-04-01

Evaluation of cellularity is an essential component of bone marrow trephine biopsy examination. The standard practice is to report the results as visual estimates (VE). Digital image analysis (DIA) offers the promise of more objective measurements of cellularity. Adult bone marrow trephine biopsy sections were assessed for cellularity by VE. Sections were scanned using an Aperio AT2 Scanscope and analyzed using a Cytonuclear (version 1.4) algorithm on halo software. Intraclass correlation (ICC) was used to assess relatedness between VE and DIA, and between MRI and DIA for a separate subset of patients. Trephine biopsy sections from a subset of patients with bone marrow biopsies uninvolved by malignancy were assessed for age-related changes. Interobserver VE agreement was good to excellent. The ICC value was 0.81 for VE and DIA, and 0.50 for MRI and DIA. Linearity studies showed no statistically significant trend for age-related changes in cellularity in our cohort (r = -.29, P = .06). Agreement was good between VE and DIA. It may be possible to use DIA or VE to measure cellularity in the appropriate clinical scenario. The limited sample size precludes similar determinations for MRI calculations. Further studies examining healthy donors are necessary before making definitive conclusions regarding age and cellularity. © 2017 John Wiley & Sons Ltd.

Automated morphological analysis of bone marrow cells in microscopic images for diagnosis of leukemia: nucleus-plasma separation and cell classification using a hierarchical tree model of hematopoesis

NASA Astrophysics Data System (ADS)

Krappe, Sebastian; Wittenberg, Thomas; Haferlach, Torsten; Münzenmayer, Christian

2016-03-01

The morphological differentiation of bone marrow is fundamental for the diagnosis of leukemia. Currently, the counting and classification of the different types of bone marrow cells is done manually under the use of bright field microscopy. This is a time-consuming, subjective, tedious and error-prone process. Furthermore, repeated examinations of a slide may yield intra- and inter-observer variances. For that reason a computer assisted diagnosis system for bone marrow differentiation is pursued. In this work we focus (a) on a new method for the separation of nucleus and plasma parts and (b) on a knowledge-based hierarchical tree classifier for the differentiation of bone marrow cells in 16 different classes. Classification trees are easily interpretable and understandable and provide a classification together with an explanation. Using classification trees, expert knowledge (i.e. knowledge about similar classes and cell lines in the tree model of hematopoiesis) is integrated in the structure of the tree. The proposed segmentation method is evaluated with more than 10,000 manually segmented cells. For the evaluation of the proposed hierarchical classifier more than 140,000 automatically segmented bone marrow cells are used. Future automated solutions for the morphological analysis of bone marrow smears could potentially apply such an approach for the pre-classification of bone marrow cells and thereby shortening the examination time.

The chemokine receptor CXCR6 contributes to recruitment of bone marrow-derived fibroblast precursors in renal fibrosis

PubMed Central

Xia, Yunfeng; Yan, Jingyin; Jin, Xiaogao; Entman, Mark L.; Wang, Yanlin

2014-01-01

Bone marrow-derived fibroblasts in circulation are of hematopoietic origin, proliferate, differentiate into myofibroblasts, and express the chemokine receptor CXCR6. Since chemokines mediate the trafficking of circulating cells to sites of injury, we studied the role of CXCR6 in mouse models of renal injury. Significantly fewer bone marrow-derived fibroblasts accumulated in the kidney of CXCR6 knockout mice in response to injury, expressed less profibrotic chemokines and cytokines, displayed fewer myofibroblasts, and expressed less α-smooth muscle actin in the obstructed kidneys compared with wild-type mice. CXCR6 deficiency inhibited total collagen deposition and suppressed expression of collagen I and fibronectin in the obstructed kidneys. Furthermore, wild type mice engrafted with CXCR6−/− bone marrow cells displayed fewer bone marrow-derived fibroblasts in the kidneys with obstructive injury and showed less severe renal fibrosis compared with wild-type mice engrafted with CXCR6+/+ bone marrow cells. Transplant of wild type bone marrow into CXCR6−/− recipients restored recruitment of myeloid fibroblasts and susceptibility to fibrosis. Hematopoietic fibroblasts migrate into injured kidney and proliferate and differentiate into myofibroblasts. Thus, CXCR6, together with other chemokines and their receptors, may play important roles in the recruitment of bone marrow-derived fibroblast precursors into the kidney and contribute to the pathogenesis of renal fibrosis. PMID:24646857

The chemokine receptor CXCR6 contributes to recruitment of bone marrow-derived fibroblast precursors in renal fibrosis.

PubMed

Xia, Yunfeng; Yan, Jingyin; Jin, Xiaogao; Entman, Mark L; Wang, Yanlin

2014-08-01

Bone marrow-derived fibroblasts in circulation are of hematopoietic origin, and they proliferate, differentiate into myofibroblasts, and express the chemokine receptor CXCR6. As chemokines mediate the trafficking of circulating cells to sites of injury, we studied the role of CXCR6 in mouse models of renal injury. Significantly, the kidney of CXCR6 knockout mice accumulated fewer bone marrow-derived fibroblasts in response to injury, expressed less profibrotic chemokines and cytokines, displayed fewer myofibroblasts, and expressed less α-smooth muscle actin in the obstructed kidneys compared with wild-type (WT) mice. CXCR6 deficiency inhibited total collagen deposition and suppressed the expression of collagen I and fibronectin in the obstructed kidneys. Furthermore, WT mice engrafted with CXCR6(-/-) bone marrow cells displayed fewer bone marrow-derived fibroblasts in the kidneys with obstructive injury and showed less severe renal fibrosis compared with WT mice engrafted with CXCR6(+/+) bone marrow cells. Transplant of WT bone marrow into CXCR6(-/-) recipients restored recruitment of myeloid fibroblasts and susceptibility to fibrosis. Hematopoietic fibroblasts migrate into injured kidney and proliferate and differentiate into myofibroblasts. Thus, CXCR6, together with other chemokines and their receptors, may have important roles in the recruitment of bone marrow-derived fibroblast precursors into the kidney and contribute to the pathogenesis of renal fibrosis.

[Effects of recombinant human alpha-2b and gamma interferons on bone marrow megakaryocyte progenitors (CFU-Meg) from patients with chronic myelocytic leukemia].

PubMed

Tanabe, Y; Dan, K; Kuriya, S; Nomura, T

1989-10-01

The effects of recombinant human interferon (IFN) alpha-2b and gamma on the bone marrow megakaryocyte progenitors (CFU-Meg) were compared between eight patients in the chronic phase of Ph1-positive chronic myelocytic leukemia (CML) and five hematologically normal patients. CFU-Meg was assayed in plasma clot culture added with phytohemagglutinin-stimulated leukocyte-conditioned medium as a source of colony stimulating activity. The average count of CFU-Meg colonies formed from the bone marrow of CML patients was 5.5 times that of normal controls. Spontaneous CFU-Meg colonies were grown in seven of eight CML patients, but in none of five controls. Colony formation by CFU-Meg in CML as well as normal bone marrow was suppressed by the two preparations of IFN in a dose dependent fashion. Their suppressive influence on colonies from CFU-Meg was comparable between CML and normal bone marrow at lower concentrations, but was less marked for CML than normal bone marrow at higher concentrations. The formation of CFU-Meg colonies from CML bone marrow was more severely suppressed by IFN-gamma than IFN-alpha-2b. Depletion of either T lymphocytes or adherent cells from the CML bone marrow cells diminished the suppressive effects of IFN-gamma, but had no influence on the effects of IFN-alpha-2b.

Early loss of subchondral bone following microfracture is counteracted by bone marrow aspirate in a translational model of osteochondral repair

PubMed Central

Gao, Liang; Orth, Patrick; Müller-Brandt, Kathrin; Goebel, Lars K. H.; Cucchiarini, Magali; Madry, Henning

2017-01-01

Microfracture of cartilage defects may induce alterations of the subchondral bone in the mid- and long-term, yet very little is known about their onset. Possibly, these changes may be avoided by an enhanced microfracture technique with additional application of bone marrow aspirate. In this study, full-thickness chondral defects in the knee joints of minipigs were either treated with (1) debridement down to the subchondral bone plate alone, (2) debridement with microfracture, or (3) microfracture with additional application of bone marrow aspirate. At 4 weeks after microfracture, the loss of subchondral bone below the defects largely exceeded the original microfracture holes. Of note, a significant increase of osteoclast density was identified in defects treated with microfracture alone compared with debridement only. Both changes were significantly counteracted by the adjunct treatment with bone marrow. Debridement and microfracture without or with bone marrow were equivalent regarding the early cartilage repair. These data suggest that microfracture induced a substantial early resorption of the subchondral bone and also highlight the potential value of bone marrow aspirate as an adjunct to counteract these alterations. Clinical studies are warranted to further elucidate early events of osteochondral repair and the effect of enhanced microfracture techniques. PMID:28345610

Can bone marrow differentiate into renal cells?

PubMed

Imai, Enyu; Ito, Takahito

2002-10-01

A considerable plasticity of adult stem cells has been confirmed in a wide variety of tissues. In particular, the pluripotency of bone marrow-derived stem cells may influence the regeneration of injured tissues and may provide novel avenues in regenerative medicine. Bone marrow contains at least hematopoietic and mesenchymal stem cells, and both can differentiate into a wide range of differentiated cells. Side population (SP) cells, which are originally defined in bone marrow cells by high efflux of DNA-binding dye, seem to be a new class of multipotent stem cells. Irrespective of the approach used to obtain stem cells, the fates of marrow-derived cells following bone marrow transplantation can be traced by labeling donor cells with green fluorescence protein or by identifying donor Y chromosome in female recipients. So far, bone marrow-derived cells have been reported to differentiate into renal cells, including mesangial cells, endothelial cells, podocytes, and tubular cells in the kidney, although controversy exists. Further studies are required to address this issue. Cell therapy will be promising when we learn to control stem cells such as bone marrow-derived stem cells, embryonic stem cells, and resident stem cells in the kidney. Identification of factors that support stem cells or promote their differentiation should provide a relevant step towards cell therapy.

Morphological study of bone marrow to assess the effects of lead acetate on haemopoiesis and aplasia and the ameliorating role of Carica papaya extract

PubMed Central

THAM, CHING S.; CHAKRAVARTHI, SRIKUMAR; HALEAGRAHARA, NAGARAJA; DE ALWIS, RANJIT

2013-01-01

Lead causes damage to the body by inducing oxidative stress. The sites of damage include the bone marrow, where marrow hypoplasia and osteosclerosis may be observed. Leaves of Carica papaya, which have antioxidant and haemopoietic properties, were tested against the effect of lead acetate in experimental rats. The rats were divided into 8 groups; control, lead acetate only, Carica papaya (50 mg and 200 mg), post-treatment with Carica papaya (50 mg and 200 mg) following lead acetate administration and pre-treatment with Carica papaya (50 mg and 200 mg) followed by lead acetate administration. The substances were administered for 14 days. The effects were evaluated by measuring protein carbonyl content (PCC) and glutathione content (GC) in the bone marrow. Histological changes in the bone marrow were also observed. The results showed that Carica papaya induced a significant reduction in the PCC activity and significantly increased the GC in the bone marrow. Carica papaya also improved the histology of the bone marrow compared with that of the lead acetate-treated group. In summary, Carica papaya was effective against the oxidative damage caused by lead acetate in the bone marrow and had a stimulatory effect on haemopoiesis. PMID:23403524

Morphological study of bone marrow to assess the effects of lead acetate on haemopoiesis and aplasia and the ameliorating role of Carica papaya extract.

PubMed

Tham, Ching S; Chakravarthi, Srikumar; Haleagrahara, Nagaraja; DE Alwis, Ranjit

2013-02-01

Lead causes damage to the body by inducing oxidative stress. The sites of damage include the bone marrow, where marrow hypoplasia and osteosclerosis may be observed. Leaves of Carica papaya, which have antioxidant and haemopoietic properties, were tested against the effect of lead acetate in experimental rats. The rats were divided into 8 groups; control, lead acetate only, Carica papaya (50 mg and 200 mg), post-treatment with Carica papaya (50 mg and 200 mg) following lead acetate administration and pre-treatment with Carica papaya (50 mg and 200 mg) followed by lead acetate administration. The substances were administered for 14 days. The effects were evaluated by measuring protein carbonyl content (PCC) and glutathione content (GC) in the bone marrow. Histological changes in the bone marrow were also observed. The results showed that Carica papaya induced a significant reduction in the PCC activity and significantly increased the GC in the bone marrow. Carica papaya also improved the histology of the bone marrow compared with that of the lead acetate-treated group. In summary, Carica papaya was effective against the oxidative damage caused by lead acetate in the bone marrow and had a stimulatory effect on haemopoiesis.

Association of murine lupus and thymic full-length endogenous retroviral expression maps to a bone marrow stem cell

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krieg, A.M.; Gourley, M.F.; Steinberg, A.D.

1991-05-01

Recent studies of thymic gene expression in murine lupus have demonstrated 8.4-kb (full-length size) modified polytropic (Mpmv) endogenous retroviral RNA. In contrast, normal control mouse strains do not produce detectable amounts of such RNA in their thymuses. Prior studies have attributed a defect in experimental tolerance in murine lupus to a bone marrow stem cell rather than to the thymic epithelium; in contrast, infectious retroviral expression has been associated with the thymic epithelium, rather than with the bone marrow stem cell. The present study was designed to determine whether the abnormal Mpmv expression associated with murine lupus mapped to thymicmore » epithelium or to a marrow precursor. Lethally irradiated control and lupus-prone mice were reconstituted with T cell depleted bone marrow; one month later their thymuses were studied for endogenous retroviral RNA and protein expression. Recipients of bone marrow from nonautoimmune donors expressed neither 8.4-kb Mpmv RNA nor surface MCF gp70 in their thymuses. In contrast, recipients of bone marrow from autoimmune NZB or BXSB donors expressed thymic 8.4-kb Mpmv RNA and mink cell focus-forming gp70. These studies demonstrate that lupus-associated 8.4-kb Mpmv endogenous retroviral expression is determined by bone marrow stem cells.« less

Mesenchymal Progenitors Residing Close to the Bone Surface Are Functionally Distinct from Those in the Central Bone Marrow

PubMed Central

Siclari, Valerie A.; Zhu, Ji; Akiyama, Kentaro; Liu, Fei; Zhang, Xianrong; Chandra, Abhishek; Nah-Cederquist, Hyun-Duck; Shi, Songtao; Qin, Ling

2013-01-01

Long bone is an anatomically complicated tissue with trabecular-rich metaphyses at two ends and cortical-rich diaphysis at the center. The traditional flushing method only isolates mesenchymal progenitor cells from the central region of long bones and these cells are distant from the bone surface. We propose that mesenchymal progenitors residing in endosteal bone marrow that is close to the sites of bone formation, such as trabecular bone and endosteum, behave differently from those in the central bone marrow. In this report, we separately isolated endosteal bone marrow using a unique enzymatic digestion approach and demonstrated that it contained a much higher frequency of mesenchymal progenitors than the central bone marrow. Endosteal mesenchymal progenitors express traditional mesenchymal stem cell markers and are capable of multi-lineage differentiation. However, we found that mesenchymal progenitors isolated from different anatomical regions of the marrow did exhibit important functional differences. Compared to their central marrow counterparts, endosteal mesenchymal progenitors have superior proliferative ability with reduced expression of cell cycle inhibitors. They showed greater immunosuppressive activity in culture and in a mouse model of inflammatory bowel disease. Aging is a major contributing factor for trabecular bone loss. We found that old mice have a dramatically decreased number of endosteal mesenchymal progenitors compared to young mice. Parathyroid hormone (PTH) treatment potently stimulates bone formation. A single PTH injection greatly increased the number of endosteal mesenchymal progenitors, particularly those located at the metaphyseal bone, but had no effect on their central counterparts. In summary, endosteal mesenchymal progenitors are more metabolically active and relevant to physiological bone formation than central mesenchymal progenitors. Hence, they represent a biologically important target for future mesenchymal stem cell studies. PMID:23274348

Influence of different modifications of a calcium phosphate bone cement on adhesion, proliferation, and osteogenic differentiation of human bone marrow stromal cells.

PubMed

Vater, Corina; Lode, Anja; Bernhardt, Anne; Reinstorf, Antje; Heinemann, Christiane; Gelinsky, Michael

2010-03-15

Collagen and noncollagenous proteins of the extracellular bone matrix are able to stimulate bone cell activities and bone healing. The modification of calcium phosphate bone cements used as temporary bone replacement materials with these proteins seems to be a promising approach to accelerate new bone formation. In this study, we investigated adhesion, proliferation, and osteogenic differentiation of human bone marrow stromal cells (hBMSC) on Biocement D/collagen composites which have been modified with osteocalcin and O-phospho-L-serine. Modification with osteocalcin was carried out by its addition to the cement precursor before setting as well as by functionalization of the cement samples after setting and sterilization. hBMSC were cultured on these samples for 28 days with and without osteogenic supplements. We found a positive impact especially of the phosphoserine-modifications but also of both osteocalcin-modifications on differentiation of hBMSC indicated by higher expression of the osteoblastic markers matrix metalloproteinase-13 and bone sialo protein II. For hBMSC cultured on phosphoserine-containing composites, an increased proliferation has been observed. However, in case of the osteocalcin-modified samples, only osteocalcin adsorbed after setting and sterilization of the cement samples was able to promote initial adhesion and proliferation of hBMSC. The addition of osteocalcin before setting results in a finer microstructure but the biological activity of osteocalcin might be impaired due to the sterilization process. Thus, our data indicate that the initial adhesion and proliferation of hBMSC is enhanced rather by the biological activity of osteocalcin than by the finer microstructure. (c) 2009 Wiley Periodicals, Inc.

Isolated juvenile xanthogranuloma in the bone marrow: report of a case and review of the literature.

PubMed

Kesserwan, Chimen; Boué, Daniel R; Kahwash, Samir B

2007-01-01

We report a case of juvenile xanthogranuloma limited to involvement of the bone marrow in a 6-week-old male infant. Evaluation of the bone marrow was a part of the workup for peripheral blood cytopenia. Examination showed hypercellular marrow with paratrabecular clusters of lipidized histiocytes positive for CD68, CD4, and factor XIII(a) and negative for S100 and CD1a. Clinical and radiological workup showed no associated skin lesions or osseous or visceral involvement. The patient was started on chemotherapy with clinical improvement and gradual decreased bone marrow involvement. The child is alive and well at 16 months of age. This case represents, to the best of our knowledge, the 1st documented case of juvenile xanthogranuloma with isolated bone marrow involvement sparing skin and viscera.

Recommendations for the standardization of bone marrow disease assessment and reporting in children with neuroblastoma on behalf of the International Neuroblastoma Response Criteria Bone Marrow Working Group.

PubMed

Burchill, Susan A; Beiske, Klaus; Shimada, Hiroyuki; Ambros, Peter F; Seeger, Robert; Tytgat, Godelieve A M; Brock, Penelope R; Haber, Michelle; Park, Julie R; Berthold, Frank

2017-04-01

The current study was conducted to expedite international standardized reporting of bone marrow disease in children with neuroblastoma and to improve equivalence of care. A multidisciplinary International Neuroblastoma Response Criteria Bone Marrow Working Group was convened by the US National Cancer Institute in January 2012 with representation from Europe, North America, and Australia. Practical transferable recommendations to standardize the reporting of bone marrow disease were developed. To the authors' knowledge, the current study is the first to comprehensively present consensus criteria for the collection, analysis, and reporting of the percentage area of bone marrow parenchyma occupied by tumor cells in trephine-biopsies. The quantitative analysis of neuroblastoma content in bone marrow aspirates by immunocytology and reverse transcriptase-quantitative polymerase chain reaction are revised. The inclusion of paired-like homeobox 2b (PHOX2B) for immunohistochemistry and reverse transcriptase-quantitative polymerase chain reaction is recommended. Recommendations for recording bone marrow response are provided. The authors endorse the quantitative assessment of neuroblastoma cell content in bilateral core needle biopsies-trephines and aspirates in all children with neuroblastoma, with the exception of infants, in whom the evaluation of aspirates alone is advised. It is interesting to note that 5% disease is accepted as an internationally achievable level for disease assessment. The quantitative assessment of neuroblastoma cells is recommended to provide data from which evidence-based numerical criteria for the reporting of bone marrow response can be realized. This is particularly important in the minimal disease setting and when neuroblastoma detection in bone marrow is intermittent, where clinical impact has yet to be validated. The wide adoption of these harmonized criteria will enhance the ability to compare outcomes from different trials and facilitate collaborative trial design. Cancer 2017;123:1095-1105. © 2016 American Cancer Society. © 2016 American Cancer Society.

Influence of clinical status and parasite load on erythropoiesis and leucopoiesis in dogs naturally infected with leishmania (Leishmania) chagasi.

PubMed

Trópia de Abreu, Raquel; Carvalho, Maria das Graças; Carneiro, Cláudia Martins; Giunchetti, Rodolfo Cordeiro; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Coura-Vital, Wendel; Corrêa-Oliveira, Rodrigo; Reis, Alexandre Barbosa

2011-05-10

The bone marrow is considered to be an important storage of parasites in Leishmania-infected dogs, although little is known about cellular genesis in this organ during canine visceral leishmaniasis (CVL). The aim of the present study was to evaluate changes in erythropoiesis and leucopoiesis in bone marrow aspirates from dogs naturally infected with Leishmania chagasi and presenting different clinical statuses and bone marrow parasite densities. The evolution of CVL from asymptomatic to symptomatic status was accompanied by increasing parasite density in the bone marrow. The impact of bone marrow parasite density on cellularity was similar in dogs at different clinical stages, with animals in the high parasite density group. Erythroid and eosinophilic hypoplasia, proliferation of neutrophilic precursor cells and significant increases in lymphocytes and plasma cell numbers were the major alterations observed. Differential bone marrow cell counts revealed increases in the myeloid:erythroid ratio associated to increased numbers of granulopoietic cells in the different clinical groups compared with non-infected dogs. Analysis of the data obtained indicated that the assessment of bone marrow constitutes an additional and useful tool by which to elaborate a prognosis for CVL.

Influence of Clinical Status and Parasite Load on Erythropoiesis and Leucopoiesis in Dogs Naturally Infected with Leishmania (Leishmania) chagasi

PubMed Central

Trópia de Abreu, Raquel; Carvalho, Maria das Graças; Carneiro, Cláudia Martins; Giunchetti, Rodolfo Cordeiro; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Coura-Vital, Wendel; Corrêa-Oliveira, Rodrigo; Reis, Alexandre Barbosa

2011-01-01

Background The bone marrow is considered to be an important storage of parasites in Leishmania-infected dogs, although little is known about cellular genesis in this organ during canine visceral leishmaniasis (CVL). Methodology/Principal Findings The aim of the present study was to evaluate changes in erythropoiesis and leucopoiesis in bone marrow aspirates from dogs naturally infected with Leishmania chagasi and presenting different clinical statuses and bone marrow parasite densities. The evolution of CVL from asymptomatic to symptomatic status was accompanied by increasing parasite density in the bone marrow. The impact of bone marrow parasite density on cellularity was similar in dogs at different clinical stages, with animals in the high parasite density group. Erythroid and eosinophilic hypoplasia, proliferation of neutrophilic precursor cells and significant increases in lymphocytes and plasma cell numbers were the major alterations observed. Differential bone marrow cell counts revealed increases in the myeloid:erythroid ratio associated to increased numbers of granulopoietic cells in the different clinical groups compared with non-infected dogs. Conclusions Analysis of the data obtained indicated that the assessment of bone marrow constitutes an additional and useful tool by which to elaborate a prognosis for CVL. PMID:21572995

Secretome within the bone marrow microenvironment: A basis for mesenchymal stem cell treatment and role in cancer dormancy.

PubMed

Eltoukhy, Hussam S; Sinha, Garima; Moore, Caitlyn; Gergues, Marina; Rameshwar, Pranela

2018-05-31

The secretome produced by cells within the bone marrow is significant to homeostasis. The bone marrow, a well-studied organ, has multiple niches with distinct roles for supporting stem cell functions. Thus, an understanding of mediators involved in the regulation of stem cells could serve as a model for clinical problems and solutions such as tissue repair and regeneration. The exosome secretome of bone marrow stem cells is a developing area of research with respect to the regenerative potential by bone marrow cell, particularly the mesenchymal stem cells. The bone marrow niche regulates endogenous processes such as hematopoiesis but could also support the survival of tumors such as facilitating the cancer stem cells to exist in dormancy for decades. The bone marrow-derived secretome will be critical to future development of therapeutic strategies for oncologic diseases, in addition to regenerative medicine. This article discusses the importance for parallel studies to determine how the same secretome may compromise safety during the use of stem cells in regenerative medicine. Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Human bone marrow harbors cells with neural crest-associated characteristics like human adipose and dermis tissues

PubMed Central

Coste, Cécile; Neirinckx, Virginie; Sharma, Anil; Agirman, Gulistan; Rogister, Bernard; Foguenne, Jacques; Lallemend, François

2017-01-01

Adult neural crest stem-derived cells (NCSC) are of extraordinary high plasticity and promising candidates for use in regenerative medicine. Several locations such as skin, adipose tissue, dental pulp or bone marrow have been described in rodent, as sources of NCSC. However, very little information is available concerning their correspondence in human tissues, and more precisely for human bone marrow. The main objective of this study was therefore to characterize NCSC from adult human bone marrow. In this purpose, we compared human bone marrow stromal cells to human adipose tissue and dermis, already described for containing NCSC. We performed comparative analyses in terms of gene and protein expression as well as functional characterizations. It appeared that human bone marrow, similarly to adipose tissue and dermis, contains NESTIN+ / SOX9+ / TWIST+ / SLUG+ / P75NTR+ / BRN3A+/ MSI1+/ SNAIL1+ cells and were able to differentiate into melanocytes, Schwann cells and neurons. Moreover, when injected into chicken embryos, all those cells were able to migrate and follow endogenous neural crest migration pathways. Altogether, the phenotypic characterization and migration abilities strongly suggest the presence of neural crest-derived cells in human adult bone marrow. PMID:28683107

Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve Repair and Functional Outcomes

DTIC Science & Technology

2017-07-01

AWARD NUMBER: W81XWH-15-2-0026 TITLE: Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve...of Decellularized Nerve Allograft with 5a. CONTRACT NUMBER Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve 5b. GRANT NUMBER W81XWH...commercially available decellularized processed peripheral nerve allograft scaffold (Avance® Nerve Graft, AxoGen, Alachua FL) with autologous bone marrow

MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation.

PubMed

Li, Chang-Jun; Cheng, Peng; Liang, Meng-Ke; Chen, Yu-Si; Lu, Qiong; Wang, Jin-Yu; Xia, Zhu-Ying; Zhou, Hou-De; Cao, Xu; Xie, Hui; Liao, Er-Yuan; Luo, Xiang-Hang

2015-04-01

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in osteogenesis that is accompanied by an increased propensity toward adipocyte differentiation. This switch increases adipocyte numbers and decreases the number of osteoblasts, contributing to age-related bone loss. Here, we found that the level of microRNA-188 (miR-188) is markedly higher in BMSCs from aged compared with young mice and humans. Compared with control mice, animals lacking miR-188 showed a substantial reduction of age-associated bone loss and fat accumulation in bone marrow. Conversely, mice with transgenic overexpression of miR-188 in osterix+ osteoprogenitors had greater age-associated bone loss and fat accumulation in bone marrow relative to WT mice. Moreover, using an aptamer delivery system, we found that BMSC-specific overexpression of miR-188 in mice reduced bone formation and increased bone marrow fat accumulation. We identified histone deacetylase 9 (HDAC9) and RPTOR-independent companion of MTOR complex 2 (RICTOR) as the direct targets of miR-188. Notably, BMSC-specific inhibition of miR-188 by intra-bone marrow injection of aptamer-antagomiR-188 increased bone formation and decreased bone marrow fat accumulation in aged mice. Together, our results indicate that miR-188 is a key regulator of the age-related switch between osteogenesis and adipogenesis of BMSCs and may represent a potential therapeutic target for age-related bone loss.

The Analysis of Fixed Final State Optimal Control in Bilinear System Applied to Bone Marrow by Cell-Cycle Specific (CCS) Chemotherapy

NASA Astrophysics Data System (ADS)

Rainarli, E.; E Dewi, K.

2017-04-01

The research conducted by Fister & Panetta shown an optimal control model of bone marrow cells against Cell Cycle Specific chemotherapy drugs. The model used was a bilinear system model. Fister & Panetta research has proved existence, uniqueness, and characteristics of optimal control (the chemotherapy effect). However, by using this model, the amount of bone marrow at the final time could achieve less than 50 percent from the amount of bone marrow before given treatment. This could harm patients because the lack of bone marrow cells made the number of leukocytes declining and patients will experience leukemia. This research would examine the optimal control of a bilinear system that applied to fixed final state. It will be used to determine the length of optimal time in administering chemotherapy and kept bone marrow cells on the allowed level at the same time. Before simulation conducted, this paper shows that the system could be controlled by using a theory of Lie Algebra. Afterward, it shows the characteristics of optimal control. Based on the simulation, it indicates that strong chemotherapy drug given in a short time frame is the most optimal condition to keep bone marrow cells spine on the allowed level but still could put playing an effective treatment. It gives preference of the weight of treatment for keeping bone marrow cells. The result of chemotherapy’s effect (u) is not able to reach the maximum value. On the other words, it needs to make adjustments of medicine’s dosage to satisfy the final treatment condition e.g. the number of bone marrow cells should be at the allowed level.

Gamma Radiation Induces Micronucleated Reticulocytes in 3-D Bone Marrow Bioreactors in Vitro

PubMed Central

Sun, Hongliang; Dertinger, Stephen D.; Hyrien, Ollivier; David Wu, J. H.; Chen, Yuhchyau

2009-01-01

Radiation injury to the bone marrow is potentially lethal due to the potent DNA-damaging effects on cells of the hematopoietic system, including bone marrow stem cell, progenitor, and the precursor cell populations. Investigation of radiation genotoxic effects on bone marrow progenitor/precursor cells has been challenged by the lack of optimal in vitro surrogate organ culture systems, and the overall difficulty to sustain lineage-specific proliferation and differentiation of hematopoiesis in vitro. We report the investigation of radiation genotoxic effects in bone marrow cultures of C57Bl/6 mice established in 3-D bioreactors, which sustain long-term bone marrow cultures. For these studies, genotoxicity is measured by the induction of micronucleated reticulocytes (MN-RET). The kinetics and dose-response relationship of MN-RET induction in response to gamma-radiation of bioreactor-maintained bone marrow cultures are presented. Our data showed that 3-D long-term bone marrow cultures had sustained erythropoiesis capable of generating reticulocytes up to 8 weeks. The peak time-interval of viable cell output and percentage of reticulocytes increased steadily and reached the initial peak between the 14th to 21st days after inoculations. This was followed by a rebound or staying relatively constant until week 8. The percentage of MN-RET reached the maximum between 24 and 32 hours post 1 Gy gamma-ray. There was a near linear MN-RET induction by gamma radiation from 0 Gy to 1.0 Gy, followed by an attenuated increase to 1.5 – 2.0 Gy. The MN-RET response showed a downtrend beyond 2 Gy. Our data suggest that bone marrow culture in the 3-D bioreactor may be a useful organ culture system for the investigation of radiation genotoxic effect in vitro. PMID:19786117

Selective Shielding of Bone Marrow: An Approach to Protecting Humans from External Gamma Radiation.

PubMed

Waterman, Gideon; Kase, Kenneth; Orion, Itzhak; Broisman, Andrey; Milstein, Oren

2017-09-01

The current feasibility of protecting emergency responders through bone marrow selective shielding is highlighted in the recent OECD/NEA report on severe accident management. Until recently, there was no effective personal protection from externally penetrating gamma radiation. In Chernobyl, first-responders wore makeshift lead sheeting, whereas in Fukushima protective equipment from gamma radiation was not available. Older protective solutions that use thin layers of shielding over large body surfaces are ineffective for energetic gamma radiation. Acute exposures may result in Acute Radiation Syndrome where the survival-limiting factor up to 10 Gy uniform, homogeneous exposure is irreversible bone marrow damage. Protracted, lower exposures may result in malignancies of which bone marrow is especially susceptible, being compounded by leukemia's short latency time. This highlights the importance of shielding bone marrow for preventing both deterministic and stochastic effects. Due to the extraordinary regenerative potential of hematopoietic stem cells, to effectively prevent the deterministic effects of bone marrow exposure, it is sufficient to protect only a small fraction of this tissue. This biological principle allows for a new class of equipment providing unprecedented attenuation of radiation to select marrow-rich regions, deferring the hematopoietic sub-syndrome of Acute Radiation Syndrome to much higher doses. As approximately half of the body's active bone marrow resides within the pelvis region, shielding this area holds great promise for preventing the deterministic effects of bone marrow exposure and concomitantly reducing stochastic effects. The efficacy of a device that selectively shields this region and other radiosensitive organs in the abdominal area is shown here.

Missing Cells: Pathophysiology, Diagnosis, and Management of (Pan)Cytopenia in Childhood

PubMed Central

Erlacher, Miriam; Strahm, Brigitte

2015-01-01

Peripheral blood cytopenia in children can be due to a variety of acquired or inherited diseases. Genetic disorders affecting a single hematopoietic lineage are frequently characterized by typical bone marrow findings, such as lack of progenitors or maturation arrest in congenital neutropenia or a lack of megakaryocytes in congenital amegakaryocytic thrombocytopenia, whereas antibody-mediated diseases such as autoimmune neutropenia are associated with a rather unremarkable bone marrow morphology. By contrast, pancytopenia is frequently associated with a hypocellular bone marrow, and the differential diagnosis includes acquired aplastic anemia, myelodysplastic syndrome, inherited bone marrow failure syndromes such as Fanconi anemia and dyskeratosis congenita, and a variety of immunological disorders including hemophagocytic lymphohistiocytosis. Thorough bone marrow analysis is of special importance for the diagnostic work-up of most patients. Cellularity, cellular composition, and dysplastic signs are the cornerstones of the differential diagnosis. Pancytopenia in the presence of a normo- or hypercellular marrow with dysplastic changes may indicate myelodysplastic syndrome. More challenging for the hematologist is the evaluation of the hypocellular bone marrow. Although aplastic anemia and hypocellular refractory cytopenia of childhood (RCC) can reliably be differentiated on a morphological level, the overlapping pathophysiology remains a significant challenge for the choice of the therapeutic strategy. Furthermore, inherited bone marrow failure syndromes are usually associated with the morphological picture of RCC, and the recognition of these entities is essential as they often present a multisystem disease requiring different diagnostic and therapeutic approaches. This paper gives an overview over the different disease entities presenting with (pan)cytopenia, their pathophysiology, characteristic bone marrow findings, and therapeutic approaches. PMID:26217651

Transplantation of neurotrophin-3-transfected bone marrow mesenchymal stem cells for the repair of spinal cord injury.

PubMed

Dong, Yuzhen; Yang, Libin; Yang, Lin; Zhao, Hongxing; Zhang, Chao; Wu, Dapeng

2014-08-15

Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal cord injury. These results indicate that neurotrophin-3 can promote the survival of bone marrow mesenchymal stem cells transplanted into the region of spinal cord injury and potentially enhance the therapeutic effect in the repair of spinal cord injury.

The diagnostic utility of bone marrow aspiration and biopsy in patients with acquired immunodeficiency syndrome.

PubMed Central

Gluckman, R. J.; Rosner, F.; Guarneri, J. J.

1989-01-01

Diagnostic bone marrow aspiration, biopsy, and culture are useful procedures in the evaluation of patients with suspected or proven acquired immunodeficiency syndrome (AIDS) who are febrile. In as many as one fourth of these patients, the information provided by the bone marrow examination may establish a diagnosis of a disseminated opportunistic infection when other studies are not informative. We have also discovered a previously unreported association between thrombocytopenia and the presence of bone marrow granulomas in our patients with AIDS and suggest that thrombocytopenia may be a clue to enable the clinician to predict a positive bone marrow result more accurately. The explanation for this apparent association remains to be elucidated. PMID:2733050

Value of molecular monitoring during the treatment of chronic myeloid leukemia: a Cancer and Leukemia Group B study.

PubMed

Stock, W; Westbrook, C A; Peterson, B; Arthur, D C; Szatrowski, T P; Silver, R T; Sher, D A; Wu, D; Le Beau, M M; Schiffer, C A; Bloomfield, C D

1997-01-01

Disappearance of the Philadelphia chromosome during treatment for chronic myeloid leukemia (CML) has become an important therapeutic end point. To determine the additional value of molecular monitoring during treatment for CML, we performed a prospective, sequential analysis using quantitative Southern blot monitoring of BCR gene rearrangements of blood and marrow samples from Cancer and Leukemia Group B (CALGB) study 8761. Sixty-four previously untreated adults with chronic-phase CML who were enrolled onto CALGB 8761, a molecular-monitoring companion study to a treatment study for adults with chronic-phase CML (CALGB 9013). Treatment consisted of repetitive cycles of interferon alfa and low-dose subcutaneous cytarabine. Blood and marrow Southern blot quantitation of BCR gene rearrangements was compared with marrow cytogenetic analysis before the initiation of treatment and of specified points during therapy. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis was performed to detect residual disease in patients who achieved a complete response by Southern blot or cytogenetic analysis. Quantitative molecular monitoring by Southern blot analysis of blood samples was found to be equivalent to marrow monitoring at all time points. Twelve of 62 (19%) follow-up samples studied by Southern blot analysis had a complete loss of BCR gene rearrangement in matched marrow and blood specimens. Southern blot monitoring of blood samples was also found to be highly correlated to marrow cytogenetic evaluation at all points, although there were four discordant cases in which Southern blot analysis of blood showed no BCR gene rearrangement, yet demonstrated from 12% to 20% Philadelphia chromosome-positive metaphase cells in the marrow. RT-PCR analysis detected residual disease in five of six patients in whom no malignant cells were detected using Southern blot or cytogenetic analyses. Quantitative Southern blot analysis of blood samples may be substituted for bone marrow to monitor the response to therapy in CML and results in the need for fewer bone marrow examinations. To avoid overestimating the degree of response, marrow cytogenetic analysis should be performed when patients achieve a complete response by Southern blot monitoring. This approach provides a rational, cost-effective strategy to monitor the effect of treatment of individual patients, as well as to analyze large clinical trials in CML.

The Effect of Different Bone Marrow Stimulation Techniques on Human Talar Subchondral Bone: A Micro-Computed Tomography Evaluation.

PubMed

Gianakos, Arianna L; Yasui, Youichi; Fraser, Ethan J; Ross, Keir A; Prado, Marcelo P; Fortier, Lisa A; Kennedy, John G

2016-10-01

To evaluate morphological alterations, microarchitectural disturbances, and the extent of bone marrow access to the subchondral bone marrow compartment using micro-computed tomography analysis in different bone marrow stimulation (BMS) techniques. Nine zones in a 3 × 3 grid pattern were assigned to 5 cadaveric talar dome articular surfaces. A 1.00-mm microfracture awl (s.MFX), a 2.00-mm standard microfracture awl (l.MFX), or a 1.25-mm Kirschner wire (K-wire) drill hole was used to penetrate the subchondral bone in each grid zone. Subchondral bone holes and adjacent tissue areas were assessed by micro-computed tomography to analyze adjacent bone area destruction and communicating channels to the bone marrow. Grades 1 to 3 were assigned, where 1 = minimal compression/sclerosis; 2 = moderate compression/sclerosis; 3 = severe compression/sclerosis. Bone volume/total tissue volume, bone surface area/bone volume, trabecular thickness, and trabecular number were calculated in the region of interest. Visual assessment revealed that the s.MFX had significantly more grade 1 holes (P < .001) and that the l.MFX had significantly more poor/grade 3 holes (P = .002). Bone marrow channel assessment showed a statistically significant increase in the number of channels in the s.MFX when compared with both K-wire and l.MFX holes (P < .001). Bone volume fraction for the s.MFX was significantly less than that of the l.MFX (P = .029). BMS techniques using instruments with larger diameters resulted in increased trabecular compaction and sclerosis in areas adjacent to the defect. K-wire and l.MFX techniques resulted in less open communicating bone marrow channels, denoting a reduction in bone marrow access. The results of this study indicate that BMS using larger diameter devices results in greater microarchitecture disturbances. The current study suggests that the choice of a BMS technique should be carefully considered as the results indicate that smaller diameter hole sizes may diminish the amount of microarchitectural disturbances in the subchondral bone. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Bone-marrow densitometry: Assessment of marrow space of human vertebrae by single energy high resolution-quantitative computed tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peña, Jaime A.; Damm, Timo; Bastgen, Jan

Purpose: Accurate noninvasive assessment of vertebral bone marrow fat fraction is important for diagnostic assessment of a variety of disorders and therapies known to affect marrow composition. Moreover, it provides a means to correct fat-induced bias of single energy quantitative computed tomography (QCT) based bone mineral density (BMD) measurements. The authors developed new segmentation and calibration methods to obtain quantitative surrogate measures of marrow-fat density in the axial skeleton. Methods: The authors developed and tested two high resolution-QCT (HR-QCT) based methods which permit segmentation of bone voids in between trabeculae hypothesizing that they are representative of bone marrow space. Themore » methods permit calculation of marrow content in units of mineral equivalent marrow density (MeMD). The first method is based on global thresholding and peeling (GTP) to define a volume of interest away from the transition between trabecular bone and marrow. The second method, morphological filtering (MF), uses spherical elements of different radii (0.1–1.2 mm) and automatically places them in between trabeculae to identify regions with large trabecular interspace, the bone-void space. To determine their performance, data were compared ex vivo to high-resolution peripheral CT (HR-pQCT) images as the gold-standard. The performance of the methods was tested on a set of excised human vertebrae with intact bone marrow tissue representative of an elderly population with low BMD. Results: 86% (GTP) and 87% (MF) of the voxels identified as true marrow space on HR-pQCT images were correctly identified on HR-QCT images and thus these volumes of interest can be considered to be representative of true marrow space. Within this volume, MeMD was estimated with residual errors of 4.8 mg/cm{sup 3} corresponding to accuracy errors in fat fraction on the order of 5% both for GTP and MF methods. Conclusions: The GTP and MF methods on HR-QCT images permit noninvasive localization and densitometric assessment of marrow fat with residual accuracy errors sufficient to study disorders and therapies known to affect bone marrow composition. Additionally, the methods can be used to correct BMD for fat induced bias. Application and testing in vivo and in longitudinal studies are warranted to determine the clinical performance and value of these methods.« less

Radionuclide imaging of bone marrow disorders

PubMed Central

Agool, Ali; Glaudemans, Andor W. J. M.; Boersma, Hendrikus H.; Dierckx, Rudi A. J. O.; Vellenga, Edo

2010-01-01

Noninvasive imaging techniques have been used in the past for visualization the functional activity of the bone marrow compartment. Imaging with radiolabelled compounds may allow different bone marrow disorders to be distinguished. These imaging techniques, almost all of which use radionuclide-labelled tracers, such as 99mTc-nanocolloid, 99mTc-sulphur colloid, 111In-chloride, and radiolabelled white blood cells, have been used in nuclear medicine for several decades. With these techniques three separate compartments can be recognized including the reticuloendothelial system, the erythroid compartment and the myeloid compartment. Recent developments in research and the clinical use of PET tracers have made possible the analysis of additional properties such as cellular metabolism and proliferative activity, using 18F-FDG and 18F-FLT. These tracers may lead to better quantification and targeting of different cell systems in the bone marrow. In this review the imaging of different bone marrow targets with radionuclides including PET tracers in various bone marrow diseases are discussed. PMID:20625724

Removing financial barriers to organ and bone marrow donation: the effect of leave and tax legislation in the U.S.

PubMed

Lacetera, Nicola; Macis, Mario; Stith, Sarah S

2014-01-01

Many U.S. states have passed legislation providing leave to organ and bone marrow donors and/or tax benefits for live and deceased organ and bone marrow donations and to employers of donors. We exploit cross-state variation in the timing of such legislation to analyze its impact on organ donations by living and deceased persons, on measures of the quality of the transplants, and on the number of bone marrow donations. We find that these provisions do not have a significant impact on the quantity of organs donated. The leave laws, however, do have a positive impact on bone marrow donations, and the effect increases with the size of the population of beneficiaries and with the generosity of the legislative provisions. Our results suggest that this legislation works for moderately invasive procedures such as bone marrow donation, but these incentives may be too low for organ donation, which is riskier and more burdensome. Copyright © 2013 Elsevier B.V. All rights reserved.

Tolerance to MHC class II disparate allografts through genetic modification of bone marrow

PubMed Central

Jindra, Peter T.; Tripathi, Sudipta; Tian, Chaorui; Iacomini, John; Bagley, Jessamyn

2012-01-01

Induction of molecular chimerism through genetic modification of bone marrow is a powerful tool for the induction of tolerance. Here we demonstrate for the first time that expression of an allogeneic MHC class II gene in autologous bone marrow cells, resulting in a state of molecular chimerism, induces tolerance to MHC class II mismatched skin grafts, a stringent test of transplant tolerance. Reconstitution of recipients with syngeneic bone marrow transduced with retrovirus encoding H-2I-Ab (I-Ab) resulted the long-term expression of the retroviral gene product on the surface of MHC class II-expressing bone marrow derived cell types. Mechanistically, tolerance was maintained by the presence of regulatory T cells, which prevented proliferation and cytokine production by alloreactive host T cells. Thus, the introduction of MHC class II genes into bone marrow derived cells through genetic engineering results in tolerance. These results have the potential to extend the clinical applicability of molecular chimerism for tolerance induction. PMID:22833118

CELLS INVOLVED IN THE IMMUNE RESPONSE

PubMed Central

Abdou, Nabih I.; Richter, Maxwell

1969-01-01

Rabbits were made immunologically tolerant to either human serum albumin or bovine gamma globulin by the neonatal administration of antigen. At 10 wk of age, they were challenged with the tolerogenic antigen and found to be non-responsive. However, these tolerant rabbits could respond with humoral antibody formation directed toward the tolerogenic antigen if they were treated with normal, allogeneic bone marrow or bone marrow obtained from a rabbit made tolerant toward a different antigen. They were incapable of responding if they were given bone marrow obtained from a rabbit previously made tolerant to the tolerogenic antigen. Irradiated rabbits were unable to respond if treated with tolerant bone marrow, but could respond well if given normal bone marrow. Since it has previously been demonstrated that the antibody-forming cell, in an irradiated recipient of allogeneic bone marrow, is of recipient and not donor origin, the data presented strongly indicate that the unresponsive cell in the immunologically tolerant rabbit is the antigen-reactive cell. PMID:4183777

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis.

PubMed

Cheung, Laurence C; Strickland, Deborah H; Howlett, Meegan; Ford, Jette; Charles, Adrian K; Lyons, Karen M; Brigstock, David R; Goldschmeding, Roel; Cole, Catherine H; Alexander, Warren S; Kees, Ursula R

2014-07-01

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells. While connective tissue growth factor has been implicated in hematopoietic malignancies, and is known to play critical roles in skeletogenesis and regulation of bone marrow stromal cells, its role in hematopoiesis has not been described. Here we demonstrate that the absence of connective tissue growth factor in mice results in impaired hematopoiesis. Using a chimeric fetal liver transplantation model, we show that absence of connective tissue growth factor has an impact on B-cell development, in particular from pro-B to more mature stages, which is linked to a requirement for connective tissue growth factor in bone marrow stromal cells. Using in vitro culture systems, we demonstrate that connective tissue growth factor potentiates B-cell proliferation and promotes pro-B to pre-B differentiation in the presence of interleukin-7. This study provides a better understanding of the functions of connective tissue growth factor within the bone marrow, showing the dual regulatory role of the growth factor in skeletogenesis and in stage-specific B lymphopoiesis. Copyright© Ferrata Storti Foundation.

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis

PubMed Central

Cheung, Laurence C.; Strickland, Deborah H.; Howlett, Meegan; Ford, Jette; Charles, Adrian K.; Lyons, Karen M.; Brigstock, David R.; Goldschmeding, Roel; Cole, Catherine H.; Alexander, Warren S.; Kees, Ursula R.

2014-01-01

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells. While connective tissue growth factor has been implicated in hematopoietic malignancies, and is known to play critical roles in skeletogenesis and regulation of bone marrow stromal cells, its role in hematopoiesis has not been described. Here we demonstrate that the absence of connective tissue growth factor in mice results in impaired hematopoiesis. Using a chimeric fetal liver transplantation model, we show that absence of connective tissue growth factor has an impact on B-cell development, in particular from pro-B to more mature stages, which is linked to a requirement for connective tissue growth factor in bone marrow stromal cells. Using in vitro culture systems, we demonstrate that connective tissue growth factor potentiates B-cell proliferation and promotes pro-B to pre-B differentiation in the presence of interleukin-7. This study provides a better understanding of the functions of connective tissue growth factor within the bone marrow, showing the dual regulatory role of the growth factor in skeletogenesis and in stage-specific B lymphopoiesis. PMID:24727816

Bone marrow solid core biopsy needle: a critical assessment of the utility, benefits and limitations of the instruments employed in current day haematology and oncology.

PubMed

Islam, Anwarul

2018-06-01

The optimal clinical evaluation of the bone marrow requires an examination of air-dried and well-stained films of the aspirated tissue along with a histopathological evaluation of adequately processed and properly stained core biopsy specimens. A bone marrow evaluation can be essential in establishing a diagnosis, determining the efficacy of treatment in haematological disorders and to monitor haematological status of patients following bone marrow/stem cell transplantation. It is also an essential component of the staging process for newly diagnosed malignancies. Currently available bone marrow aspiration needles are quite satisfactory and if properly used provide good-quality specimens for morphological evaluation. However, if a bone marrow core biopsy is concerned, several needles are currently in use but not all of them provide good-quality biopsy specimens for histological evaluation or are user friendly. We have compared the recently introduced Moeller Medical single use bone marrow core biopsy needle with the Jamshidi needle with marrow acquisition cradle (CareFusion), J-needle (Cardinal Health) and OnControl device (Vidacare). It is concluded that the Moeller Medical needle system has definite advantages over others and is recommended for routine use. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Histologic and cytologic bone marrow findings in dogs with suspected precursor-targeted immune-mediated anemia and associated phagocytosis of erythroid precursors.

PubMed

Lucidi, Cynthia de A; de Rezende, Christian L E; Jutkowitz, L Ari; Scott, Michael A

2017-09-01

Precursor-targeted immune-mediated anemia (PIMA) has been suspected in dogs with nonregenerative anemia and bone marrow findings varying from erythroid hyperplasia to pure red cell aplasia. Phagocytosis of erythroid precursors/rubriphagocytosis (RP) reported in some affected dogs suggests a destructive component to the pathogenesis of PIMA. The purpose of the study was to characterize laboratory and clinical findings in dogs with suspected PIMA and RP, with emphasis on cytologic and histologic bone marrow findings. Dogs with PIMA and RP were identified by review of paired bone marrow aspirate and core biopsy slides collected over a 4-year period. Samples were systematically assessed and characterized along with other pertinent laboratory data and clinical findings. Twenty-five dogs met criteria for PIMA and had RP that was relatively stage-selective. Erythropoiesis was expanded to the stage of erythroid precursors undergoing most prominent phagocytosis, yielding patterns characterized by a hypo-, normo-, or hypercellular erythroid lineage. A 4 th pattern involved severe collagen myelofibrosis, and there was a spectrum of mild to severe collagen myelofibrosis overall. Evidence of immune-mediated hemolysis was rare. Immunosuppressive therapy was associated with remission in 77% of dogs treated for at least the median response time of 2 months. Bone marrow patterns in dogs fulfilling criteria for PIMA were aligned with stage-selective phagocytosis of erythroid precursors and the development of collagen myelofibrosis, common in dogs with PIMA. Recognition of these patterns and detection of RP facilitates diagnosis of PIMA, and slow response to immunosuppressive therapy warrants further investigation into its pathogenesis. © 2017 American Society for Veterinary Clinical Pathology.

High-sensitivity virus and mycoplasma screening test reveals high prevalence of parvovirus B19 infection in human synovial tissues and bone marrow.

PubMed

Watanabe, Ken; Otabe, Koji; Shimizu, Norio; Komori, Keiichirou; Mizuno, Mitsuru; Katano, Hisako; Koga, Hideyuki; Sekiya, Ichiro

2018-03-27

Latent microorganism infection is a safety concern for the clinical application of mesenchymal stem cells (MSCs). The aim of this study is to investigate the frequencies and sensitivities of the latent virus and mycoplasma infections in synovium, bone marrow, peripheral blood cells, and blood plasma and cultured synovial MSCs. Total DNA and RNA of the synovium (n = 124), bone marrow (n = 123), peripheral blood cells (n = 121), plasma (n = 121), and 14-day cultured synovial MSCs (n = 63) were collected from patients who underwent total knee arthroplasty or anterior ligament reconstruction after written informed consents were obtained. The multiplex polymerase chain reaction (PCR) primers were designed to quantitatively measure the representative genomes of 13 DNA viruses, 6 RNA viruses, and 9 mycoplasmas. Multi-spliced mRNA detection and virus spike test were also performed to demonstrate the sensitivity of synovial MSCs to the candidate pathogens. In synovium and bone marrow, the positive rates of parvovirus B19 genome were significantly higher than in peripheral blood cells (18.7% and 22% vs. 0.8%, respectively). Multi-alignment analysis of amplified and sequenced viral target genes showed the proximity of the parvovirus B19 gene from different tissue in the same patients. Synovial MSCs cultured for 14 days were positive for virus infection only in two patients (2/62 = 3%). Parvovirus B19 multi-spliced mRNAs were not detected in these two samples. Virus spike test demonstrated the sensitivity of synovial MSCs to herpes simplex virus (HSV)1 and cytomegalovirus (CMV), but not to parvovirus B19. This study revealed a relatively high incidence of latent parvovirus B19 in synovium and bone marrow tissue.

Concurrence of B-lymphoblastic leukemia and myeloproliferative neoplasm with copy neutral loss of heterozygosity at chromosome 1p harboring a MPL W515S mutation.

PubMed

Tao, Jiangchuan; Zhang, Xiaohui; Lancet, Jeffrey; Bennett, John M; Cai, Li; Papenhausen, Peter; Moscinski, Lynn; Zhang, Ling

2014-01-01

B-lymphoblastic leukemia (B-ALL) is a neoplasm of precursors committed to B-cell lineage, whereas myeloproliferative neoplasm (MPN) is a clonal proliferation derived from myeloid stem cells. Concurrent B-ALL with MPN is uncommon except in the presence of abnormalities of the PDGFRA, PDGFRB, or FGFR1 genes or the BCR-ABL1 fusion gene. Herein, we describe a rare concurrence, B-ALL with MPN without the aforementioned genetic aberrations, in a 64-year-old male patient. The patient was initially diagnosed with B-ALL with normal karyotype and responded well to aggressive chemotherapy but had sustained leukocytosis and splenomegaly. The posttreatment restaging bone marrow was free of B-ALL but remained hypercellular with myeloid predominance. Using a single nucleotide polymorphism microarray study, we identified a copy neutral loss of heterozygosity at the terminus of 1p in the bone marrow samples taken at diagnosis and again at remission, 49% and 100%, respectively. Several additional genetic abnormalities were present in the initial marrow sample but not in the remission marrow samples. Retrospective molecular studies detected a MPL W515S homozygous mutation in both the initial and remission marrows for B-ALL, at 30-40% and 80% dosage effect, respectively. In summary, we present a case of concurrent B-ALL and MPN and demonstrate a stepwise cytogenetic and molecular approach to the final diagnosis. Copyright © 2014 Elsevier Inc. All rights reserved.

(18)F-FDG dynamic PET/CT in patients with multiple myeloma: patterns of tracer uptake and correlation with bone marrow plasma cell infiltration rate.

PubMed

Sachpekidis, Christos; Mai, Elias K; Goldschmidt, Hartmut; Hillengass, Jens; Hose, Dirk; Pan, Leyun; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2015-06-01

The value of F-FDG PET in the diagnostic approach of multiple myeloma (MM) remains incompletely elicited. Little is known about the kinetics of F-FDG in the bone marrow and extramedullary sites in MM. This study aimed to evaluate quantitative data on kinetics and distribution patterns of F-FDG in MM patients with regard to pelvic bone marrow plasma cell infiltration. The study included 40 patients with primary MM. Dynamic PET/CT scanning of the lower lumbar spine and pelvis was performed after the administration of F-FDG. Whole-body PET/CT studies were performed. Sites of focal increased tracer uptake were considered as highly suggestive of myelomatous involvement after taking into account the patient history and CT findings. Bone marrow of the os ilium without pathologic tracer accumulation served as reference. The evaluation of dynamic PET/CT studies was based in addition to the conventional visual (qualitative) assessment, on semiquantitative (SUV) calculations, as well as on absolute quantitative estimations after application of a 2-tissue compartment model and a noncompartmental approach. F-FDG quantitative information and corresponding distribution patterns were correlated with pelvic bone marrow plasma cell infiltration. Fifty-two myelomatous lesions were detected in the pelvis. All parameters in suspected MM lesions ranged in significantly higher levels than in reference tissue (P < 0.01). Correlative analyses revealed that bone marrow plasma cell infiltration rate correlated significantly with SUVaverage, SUVmax, and the parameters K1, influx, and fractal dimension of F-FDG in reference bone marrow (P < 0.01). In addition, whole-body static PET/CT imaging demonstrated 4 patterns of tracer uptake; these are as follows: negative, focal, diffuse, and mixed (focal/diffuse) tracer uptake. Patients with a mixed pattern of radiotracer uptake had the highest mean plasma cell infiltration rate in their bone marrow, whereas those with negative PET/CT scans demonstrated the lowest bone marrow plasma cell infiltration. In total, 265 focal myeloma-indicative F-FDG-avid lesions were detected, 129 of which correlated with low-dose CT osteolytic findings. No significant correlation between the number of focal lesions detected in PET/CT and bone marrow infiltration was detected. The F-FDG kinetic parameters K1, influx, and fractal dimension as well as SUVaverage from reference tissue correlated significantly with bone marrow malignant plasma cell infiltration rate. Patients with negative PET/CT demonstrated the lowest bone marrow infiltration by malignant plasma cells, whereas those with a mixed pattern of tracer uptake had the highest infiltration.

Periodontal regeneration with stem cells-seeded collagen-hydroxyapatite scaffold.

PubMed

Liu, Zeping; Yin, Xing; Ye, Qingsong; He, Wulin; Ge, Mengke; Zhou, Xiaofu; Hu, Jing; Zou, Shujuan

2016-07-01

Re-establishing compromised periodontium to its original structure, properties and function is demanding, but also challenging, for successful orthodontic treatment. In this study, the periodontal regeneration capability of collagen-hydroxyapatite scaffolds, seeded with bone marrow stem cells, was investigated in a canine labial alveolar bone defect model. Bone marrow stem cells were isolated, expanded and characterized. Porous collagen-hydroxyapatite scaffold and cross-linked collagen-hydroxyapatite scaffold were prepared. Attachment, migration, proliferation and morphology of bone marrow stem cells, co-cultured with porous collagen-hydroxyapatite or cross-linked collagen-hydroxyapatite, were evaluated in vitro. The periodontal regeneration capability of collagen-hydroxyapatite scaffold with or without bone marrow stem cells was tested in six beagle dogs, with each dog carrying one sham-operated site as healthy control, and three labial alveolar bone defects untreated to allow natural healing, treated with bone marrow stem cells - collagen-hydroxyapatite scaffold implant or collagen-hydroxyapatite scaffold implant, respectively. Animals were euthanized at 3 and 6 months (3 animals per group) after implantation and the resected maxillary and mandibular segments were examined using micro-computed tomography scan, H&E staining, Masson's staining and histometric evaluation. Bone marrow stem cells were successfully isolated and demonstrated self-renewal and multi-potency in vitro. The porous collagen-hydroxyapatite and cross-linked collagen-hydroxyapatite had average pore sizes of 415 ± 20 µm and 203 ± 18 µm and porosity of 69 ± 0.5% and 50 ± 0.2%, respectively. The attachment, proliferation and migration of bone marrow stem cells were satisfactory on both porous collagen-hydroxyapatite and cross-linked collagen-hydroxyapatite scaffolds. Implantation of bone marrow stem cells - collagen-hydroxyapatite or collagen-hydroxyapatite scaffold in beagle dogs with experimental periodontal defects resulted in significantly enhanced periodontal regeneration characterized by formation of new bone, periodontal ligament and cementum, compared with the untreated defects, as evidenced by histological and micro-computed tomography examinations. The prepared collagen-hydroxyapatite scaffolds possess favorable bio-compatibility. The bone marrow stem cells - collagen-hydroxyapatite and collagen-hydroxyapatite scaffold - induced periodontal regeneration, with no aberrant events complicating the regenerative process. Further research is necessary to improve the bone marrow stem cells behavior in collagen-hydroxyapatite scaffolds after implantation. © The Author(s) 2016.

Evaluation of centrifuged bone marrow on bone regeneration around implants in rabbit tibia.

PubMed

Betoni, Walter; Queiroz, Thallita P; Luvizuto, Eloá R; Valentini-Neto, Rodolpho; Garcia-Júnior, Idelmo R; Bernabé, Pedro F E

2012-12-01

To evaluate the bone regeneration of cervical defects produced around titanium implants filled with blood clot and filled with centrifuged bone marrow (CBM) by means of histomorphometric analysis. Twelve rabbits received 2 titanium implants in each right tibia, with the upper cortical prepared with a 5-mm drill and the lower cortex with a 3-mm-diameter drill. Euthanasia was performed to allow analysis at 7, 21, and 60 days after operation. The samples were embedded in light curing resin, cut and stained with alizarin red and Stevenel blue for a histomorphometric analysis of the bone-to-implant contact (BIC) and the bone area around implant (BA). The values obtained were statistically analyzed using the nonparametric Kruskal-Wallis test (P = 0.05). At 60 days postoperation, the groups had their cervical defects completely filled by neoformed bone tissue. There was no statistically significant difference between the groups regarding BIC and BA during the analyzed periods. There was no difference in the bone repair of periimplant cervical defects with or without the use of CBM.

Acute Exposure to High Dose γ-Radiation Results in Transient Activation of Bone Lining Cells

PubMed Central

Turner, Russell T.; Iwaniec, Urszula T.; Wong, Carmen P.; Lindenmaier, Laurence B.; Wagner, Lindsay A.; Branscum, Adam J.; Menn, Scott A.; Taylor, James; Zhang, Ye; Wu, Honglu; Sibonga, Jean D.

2014-01-01

The present studies investigated the cellular mechanisms for the detrimental effects of high dose whole body γ-irradiation on bone. In addition, radioadaptation and bone marrow transplantation were assessed as interventions to mitigate the skeletal complications of irradiation. Increased trabecular thickness and separation and reduced fractional cancellous bone volume, connectivity density, and trabecular number were detected in proximal tibia and lumbar vertebra 14 days following γ-irradiation with 6 Gy. To establish the cellular mechanism for the architectural changes, vertebrae were analyzed by histomorphometry 1, 3, and 14 days following irradiation. Marrow cell density decreased within 1 day (67% reduction, p<0.0001), reached a minimum value after 3 days (86% reduction, p<0.0001), and partially rebounded by 14 days (30% reduction, p=0.0025) following irradiation. In contrast, osteoblast-lined bone perimeter was increased by 290% (1 day, p=0.04), 1230% (3 days, p<0.0001), and 530% (14 days, p=0.003), respectively. There was a strong association between radiation-induced marrow cell death and activation of bone lining cells to express the osteoblast phenotype (Pearson correlation −0.85, p<0.0001). An increase (p=0.004) in osteoclast-lined bone perimeter was also detected with irradiation. A priming dose of γ-radiation (0.5 mGy), previously shown to reduce mortality, had minimal effect on the cellular responses to radiation and did not prevent detrimental changes in bone architecture. Bone marrow transplantation normalized marrow cell density, bone turnover, and most indices of bone architecture following irradiation. In summary, radiation-induced death of marrow cells is associated with 1) a transient increase in bone formation due, at least in part, to activation of bone lining cells, and 2) an increase in bone resorption due to increased osteoclast perimeter. Bone marrow transplantation is effective in mitigating the detrimental effects of acute exposure to high dose whole body γ-radiation on bone turnover. PMID:23954507

PET/CT versus bone marrow biopsy in the initial evaluation of bone marrow infiltration in various pediatric malignancies.

PubMed

Zapata, Claudia P; Cuglievan, Branko; Zapata, Catalina M; Olavarrieta, Raquel; Raskin, Scott; Desai, Kavita; De Angulo, Guillermo

2018-02-01

Accurate staging is essential in the prognosis and management of pediatric malignancies. Current protocols require screening for marrow infiltration with bone marrow biopsy (BMB) as the gold standard. Positron emission tomography-computed tomography (PET-CT) is commonly used to complete the staging process and can also be used to evaluate marrow infiltration. To compare PET-CT and BMB in the initial evaluation of bone marrow infiltration in pediatric cancers. We retrospectively reviewed new cases of EWS, rhabdomyosarcoma, neuroblastoma, and lymphoma diagnosed between January 2009 and October 2014. Each case had undergone both PET-CT and BMB within 4 weeks without treatment in the interval between screening modalities. We reviewed 69 cases. Bone marrow infiltration was demonstrated in 34 cases by PET-CT and in 18 cases by BMB. The sensitivity and negative predictive value of PET-CT were both 100%. Interestingly, the cases in which infiltration was not detected on BMB had an abnormal marrow signal on PET-CT focal or distant to iliac crest. PET-CT has a high sensitivity when assessing marrow infiltration in pediatric malignancies. Advances in radiologic modalities may obviate the use of invasive, painful, and costly procedures like BMB. Furthermore, biopsy results are limited by insufficient tissue or the degree of marrow infiltration (diffuse vs. focal disease). PET-CT can improve the precision of biopsy when used as a guiding tool. This study proposes the use of PET-CT as first-line screening for bone marrow infiltration to improve the accuracy of staging in new diagnoses. © 2017 Wiley Periodicals, Inc.

Transforming growth factor-{beta} inhibits CCAAT/enhancer-binding protein expression and PPAR{gamma} activity in unloaded bone marrow stromal cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahdjoudj, S.; Kaabeche, K.; Holy, X.

2005-02-01

The molecular mechanisms regulating the adipogenic differentiation of bone marrow stromal cells in vivo remain largely unknown. In this study, we investigated the regulatory effects of transforming growth factor beta-2 (TGF-{beta}2) on transcription factors involved in adipogenic differentiation induced by hind limb suspension in rat bone marrow stromal cells in vivo. Time course real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis of gene expression showed that skeletal unloading progressively increases the expression of CCAAT/enhancer-binding protein (C/EBP){alpha} and C/EBP{beta} {alpha} at 5 days in bone marrow stromal cells resulting in increased peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}2) transcripts at 7 days. TGF-{beta}2more » administration in unloaded rats corrected the rise in C/EBP{alpha} and C/EBP{beta} transcripts induced by unloading in bone marrow stromal cells. This resulted in inhibition of PPAR{gamma}2 expression that was associated with increased Runx2 expression. Additionally, the inhibition of C/EBP{alpha} and C/EBP{beta} expression by TGF-{beta}2 was associated with increased PPAR{gamma} serine phosphorylation in bone marrow stromal cells, a mechanism that inhibits PPAR{gamma} transactivating activity. The sequential inhibitory effect of TGF-{beta}2 on C/EBP{alpha}, C/EBP{beta}, and PPAR{gamma}2 resulted in reduced LPL expression and abolition of bone marrow stromal cell adipogenic differentiation, which contributed to prevent bone loss induced by skeletal unloading. We conclude that TGF-{beta}2 inhibits the excessive adipogenic differentiation of bone marrow stromal cells induced by skeletal unloading by inhibiting C/EBP{alpha}, C/EBP{beta}, and PPAR{gamma} expression and activity, which provides a sequential mechanism by which TGF-{beta}2 regulates adipogenic differentiation of bone marrow stromal cells in vivo.« less

40 CFR 798.5385 - In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis.

Code of Federal Regulations, 2014 CFR

2014-07-01

... cytogenetics tests: Chromosomal analysis. 798.5385 Section 798.5385 Protection of Environment ENVIRONMENTAL... Genetic Toxicity § 798.5385 In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis. (a) Purpose. The in vivo bone marrow cytogenetic test is a mutagenicity test for the detection of structural...

40 CFR 798.5385 - In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis.

Code of Federal Regulations, 2011 CFR

2011-07-01

... cytogenetics tests: Chromosomal analysis. 798.5385 Section 798.5385 Protection of Environment ENVIRONMENTAL... Genetic Toxicity § 798.5385 In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis. (a) Purpose. The in vivo bone marrow cytogenetic test is a mutagenicity test for the detection of structural...

78 FR 76507 - Revised Medical Criteria for Evaluating Cancer (Malignant Neoplastic Diseases)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-17

... blast (immature) cells in the peripheral blood or bone marrow is 10 percent or greater. We propose this... evaluate cancer treatment by bone marrow or stem cell transplantation, including transplantation using stem... evaluate cancers treated with bone marrow or stem cell transplantation, including transplantation using...

40 CFR 798.5385 - In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis.

Code of Federal Regulations, 2010 CFR

2010-07-01

... cytogenetics tests: Chromosomal analysis. 798.5385 Section 798.5385 Protection of Environment ENVIRONMENTAL... Genetic Toxicity § 798.5385 In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis. (a) Purpose. The in vivo bone marrow cytogenetic test is a mutagenicity test for the detection of structural...

40 CFR 798.5385 - In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis.

Code of Federal Regulations, 2012 CFR

2012-07-01

... cytogenetics tests: Chromosomal analysis. 798.5385 Section 798.5385 Protection of Environment ENVIRONMENTAL... Genetic Toxicity § 798.5385 In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis. (a) Purpose. The in vivo bone marrow cytogenetic test is a mutagenicity test for the detection of structural...

40 CFR 798.5385 - In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis.

Code of Federal Regulations, 2013 CFR

2013-07-01

... cytogenetics tests: Chromosomal analysis. 798.5385 Section 798.5385 Protection of Environment ENVIRONMENTAL... Genetic Toxicity § 798.5385 In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis. (a) Purpose. The in vivo bone marrow cytogenetic test is a mutagenicity test for the detection of structural...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Urman, M.; O'Sullivan, R.A.; Nugent, R.A.

This case concerns a patient with intracranial extramedullary hematopoiesis (EH) suspected on a CT scan and subsequently confirmed with In-111 chloride and Tc-99m SC bone marrow scans. The bone marrow scans also provided additional information by demonstrating other sites of EH in the paravertebral tissues and bone marrow expansion into the distal extremities.

Intrasinusoidal pattern of bone marrow infiltration by hepatosplenic T-cell lymphoma.

PubMed

Butler, Liesl Ann; Juneja, Surender

2018-04-01

Hepatosplenic T-cell lymphoma is a rare, aggressive form of extranodal lymphoma, which frequently involves the bone marrow. An intrasinusoidal pattern of infiltration is characteristic of the disease and is often best appreciated on immunohistochemical staining. Bone marrow biopsy can be a useful diagnostic tool.

Survival of Free and Encapsulated Human and Rat Islet Xenografts Transplanted into the Mouse Bone Marrow

PubMed Central

Meier, Raphael P. H.; Seebach, Jörg D.; Morel, Philippe; Mahou, Redouan; Borot, Sophie; Giovannoni, Laurianne; Parnaud, Geraldine; Montanari, Elisa; Bosco, Domenico; Wandrey, Christine; Berney, Thierry; Bühler, Leo H.; Muller, Yannick D.

2014-01-01

Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow) and 10 days (kidney capsule). Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation. PMID:24625569

Selective differentiation and proliferation of hematopoietic cells induced by recombinant human interleukins.

PubMed Central

Saito, H; Hatake, K; Dvorak, A M; Leiferman, K M; Donnenberg, A D; Arai, N; Ishizaka, K; Ishizaka, T

1988-01-01

Effects of recombinant human interleukins on hematopoiesis were explored by using suspension cultures of mononuclear cells of human umbilical-cord blood and bone marrow. The results showed that interleukin 5 induced the selective differentiation and proliferation of eosinophils. After 3 weeks in culture with interleukin 5, essentially all nonadherent cells in both bone marrow and cord blood cell cultures became eosinophilic myelocytes. Culture of the same cells with interleukin 4 resulted in the selective growth of OKT3+ lymphocytes. However, OKT3+ cells did not develop if the bone marrow cells were depleted of OKT3+/OKT11+ cells prior to the culture, indicating that interleukin 4 induced the proliferation of a subpopulation of resting T cells present in cord blood and bone marrow cell preparations. In suspension cultures of bone marrow cells and cord blood cells grown in the presence of interleukin 3, basophilic, eosinophilic, and neutrophilic myelocytes and macrophages developed within 2 weeks. By 3 weeks, however, the majority of nonadherent cells became eosinophilic myelocytes. In contrast to mouse bone marrow cell cultures, neither interleukin 3 nor a combination of interleukins 3 and 4 induced the differentiation of mast cells in human bone marrow or cord blood cell cultures. Images PMID:3258425

X-Ray Crystal Structure of Bone Marrow Kinase in the X Chromosome: A Tec Family Kinase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muckelbauer, Jodi; Sack, John S.; Ahmed, Nazia

Bone marrow kinase in the X chromosome, a member of the Tec family of tyrosine kinases, plays a role in both monocyte/macrophage trafficking as well as cytokine secretion. Although the structures of Tec family kinases Bruton's tyrosine kinase and IL-2-inducible T-cell kinase are known, the crystal structures of other Tec family kinases have remained elusive. We report the X-ray crystal structures of bone marrow kinase in the X chromosome in complex with dasatinib at 2.4 {angstrom} resolution and PP2 at 1.9 {angstrom} resolution. The bone marrow kinase in the X chromosome structures reveal a typical kinase protein fold; with well-orderedmore » protein conformation that includes an open/extended activation loop and a stabilized DFG-motif rendering the kinase in an inactive conformation. Dasatinib and PP2 bind to bone marrow kinase in the X chromosome in the ATP binding pocket and display similar binding modes to that observed in other Tec and Src protein kinases. The bone marrow kinase in the X chromosome structures identify conformational elements of the DFG-motif that could potentially be utilized to design potent and/or selective bone marrow kinase in the X chromosome inhibitors.« less

Identification of potential target genes and related regulatory transcription factors in spontaneous hairline fracture induced by hypervitaminosis A.

PubMed

Peng, Chuangang; Yang, Qi; Wei, Bo; Liu, Yong; Li, Yuxiang; Gu, Dawei; Yin, Guochao; Wang, Bo; Xu, Dehui; Zhang, Xuebing; Kong, Daliang

2017-07-01

The aim was to research the molecular changes of bone cells induced by excessive dose of vitamin A, and analyze molecular mechanism underlying spontaneous fracture. The gene expression profile of GSE29859, including 4 cortical bone marrow samples with excessive doses of Vitamin A and 4 control cortical bone marrow samples, was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DGEs) between cortical bone marrow samples and control samples were screened out and pathway enrichment analysis was undertaken. Based on the MSigDB database, the potential regulatory transcription factors (TFs) were identified. A total of 373 DEGs including 342 up- and 31 down-regulated genes were identified. These DEGs were significantly enriched in pathways of protein processing in endoplasmic reticulum, ubiquitin mediated proteolysis and glycerophospholipid metabolism. Finally, the most significant regulatory TFs were obtained, including E2F Transcription Factor 1 (E2F1), GA Binding Protein Transcription Factor (GABP), Nuclear Factor, Erythroid 2-Like 2 (NRF2) and ELK1, Member of ETS Oncogene Family (ELK1). Key TFs including E2F1, GABP, NRF2 and ELK1 and their targets genes such as Ube2d3, Uba1, Phb2 and Tomm22 may play potential key roles in spontaneous fracture induced by hypervitaminosis A. The pathways of protein processing in endoplasmic reticulum, ubiquitin mediated proteolysis and glycerophospholipid metabolism may be key mechanisms involved in spontaneous fracture induced by hypervitaminosis A. Our findings will provide new insights for the target selection in clinical application to prevent spontaneous fracture induced by hypervitaminosis A. Copyright © 2017 Elsevier Ltd. All rights reserved.

MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation

PubMed Central

Li, Chang-Jun; Cheng, Peng; Liang, Meng-Ke; Chen, Yu-Si; Lu, Qiong; Wang, Jin-Yu; Xia, Zhu-Ying; Zhou, Hou-De; Cao, Xu; Xie, Hui; Liao, Er-Yuan; Luo, Xiang-Hang

2015-01-01

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in osteogenesis that is accompanied by an increased propensity toward adipocyte differentiation. This switch increases adipocyte numbers and decreases the number of osteoblasts, contributing to age-related bone loss. Here, we found that the level of microRNA-188 (miR-188) is markedly higher in BMSCs from aged compared with young mice and humans. Compared with control mice, animals lacking miR-188 showed a substantial reduction of age-associated bone loss and fat accumulation in bone marrow. Conversely, mice with transgenic overexpression of miR-188 in osterix+ osteoprogenitors had greater age-associated bone loss and fat accumulation in bone marrow relative to WT mice. Moreover, using an aptamer delivery system, we found that BMSC-specific overexpression of miR-188 in mice reduced bone formation and increased bone marrow fat accumulation. We identified histone deacetylase 9 (HDAC9) and RPTOR-independent companion of MTOR complex 2 (RICTOR) as the direct targets of miR-188. Notably, BMSC-specific inhibition of miR-188 by intra–bone marrow injection of aptamer-antagomiR-188 increased bone formation and decreased bone marrow fat accumulation in aged mice. Together, our results indicate that miR-188 is a key regulator of the age-related switch between osteogenesis and adipogenesis of BMSCs and may represent a potential therapeutic target for age-related bone loss. PMID:25751060

Identification, characterization and isolation of a common progenitor for osteoclasts, macrophages and dendritic cells from murine bone marrow and periphery

PubMed Central

Jacome-Galarza, Christian E.; Lee, Sun-Kyeong; Lorenzo, Joseph A.; LeonardoAguila, Hector

2012-01-01

Osteoclasts are specialized bone resorbing cells that derive from monocyte precursors. We have identified three populations of cells with high osteoclastogenic potential in murine bone marrow, which expressed the phenotype: B220−CD3−CD11b−/low CD115+ and either CD117hi, CD117intermediate or CD117low. We have evaluated these populations for their ability to also generate macrophages and dendritic cells. At a single cell level, the population expressing higher CD117 levels was able to generate bone-resorbing osteoclasts, phagocytic macrophages and antigen-presenting dendritic cells in vitro with efficiencies of over 90 percent, indicating that there exists a common developmental pathway for these cell types. Cells with osteoclastogenic potential also exist in blood and peripheral hematopoietic organs. Their functional meaning and/or their relationship with bone marrow progenitors is not well established. Hence, we characterized murine peripheral cell populations for their ability to form osteoclasts, macrophages and dendritic cells in vitro. The spleen and peripheral blood monocyte progenitors share phenotypic markers with bone marrow progenitors, but differ in their expression of CD11b, which was low in bone marrow but high in periphery. We propose that circulating monocyte progenitors are derived from a common bone marrow osteoclasts/macrophage/dendritic cell progenitor (OcMDC), which we have now characterized at a clonal level. However, the lineage relationship between the bone marrow and peripheral monocyte progenitors has yet to be defined. PMID:23165930

Event-free survival of infants and toddlers enrolled in the HR-NBL-1/SIOPEN trial is associated with the level of neuroblastoma mRNAs at diagnosis.

PubMed

Corrias, Maria V; Parodi, Stefano; Tchirkov, Andrei; Lammens, Tim; Vicha, Ales; Pasqualini, Claudia; Träger, Catarina; Yáñez, Yania; Dallorso, Sandro; Varesio, Luigi; Luksch, Roberto; Laureys, Genevieve; Valteau-Couanet, Dominique; Canete, Adela; Pöetschger, Ulrike; Ladenstein, Ruth; Burchill, Susan A

2018-07-01

The purpose of this study was to evaluate whether levels of neuroblastoma mRNAs in bone marrow and peripheral blood from stage M infants (≤12 months of age at diagnosis, MYCN amplified) and toddlers (between 12 and 18 months, any MYCN status) predict event-free survival (EFS). Bone marrow aspirates and peripheral blood samples from 97 infants/toddlers enrolled in the European High-Risk Neuroblastoma trial were collected at diagnosis in PAXgene ™ blood RNA tubes. Samples were analyzed by reverse transcription quantitative polymerase chain reaction according to standardized procedures. Bone marrow tyrosine hydroxylase (TH) or paired-like homeobox 2b (PHOX2B) levels in the highest tertile were associated with worse EFS; hazard ratios, adjusted for age and MYCN status, were 1.5 and 1.8 respectively. Expression of both TH and PHOX2B in the highest tertile predicted worse outcome (p = 0.015), and identified 20 (23%) infants/toddlers with 5-year EFS of 20% (95%CI: 4%-44%). Prognostic significance was maintained after adjusting for over-fitting bias (p = 0.038), age and MYCN status. In peripheral blood, PHOX2B levels in the highest tertile predicted a two-fold increased risk of an event (p = 0.032), and identified 23 (34%) infants/toddlers with 5-year EFS of 29% (95%CI: 12%-48%). Time-dependent receiver operating characteristic analysis confirmed the prognostic value of combined TH and PHOX2B in bone marrow and of PHOX2B in peripheral blood during the first year of follow-up. High levels of bone marrow TH and PHOX2B and of peripheral blood PHOX2B at diagnosis allow early identification of a group of high-risk infant and toddlers with neuroblastoma who may be candidates for alternative treatments. Integration with additional biomarkers, as well as validation in additional international trials is warranted. © 2018 Wiley Periodicals, Inc.

Bone marrow monosomy 7: hematologic and clinical manifestations in childhood and adolescence.

PubMed

Hutter, J J; Hecht, F; Kaiser-McCaw, B; Hays, T; Baranko, P; Cohen, J; Durie, B

1984-01-01

The hematologic manifestations and clinical course are described for six children and adolescents with bone marrow monosomy 7. One child with secondary acute myelogenous leukemia had monosomy 7 plus a marker chromosome; the remaining patients had marrow monosomy 7 as the only karyotypic abnormality. The hematologic abnormalities were diverse, but the majority of patients had a smoldering preleukemic or myeloproliferative phase. Leukemic blasts were either undifferentiated or demonstrated evidence of myeloid differentiation. All patients responded poorly to antileukemic therapy. Bone marrow monosomy 7 was observed in one patient with severe marrow hypoplasia. Antileukemic therapy in another patient with greater than 30 per cent marrow blasts was associated with the development of a bone marrow myeloproliferative disorder with persistence of the monosomy 7 karyotype. We speculate that monosomy 7 may be a specific marker for a pluripotent hematopoietic stem cell abnormality that is associated with either blastic leukemia or a myeloproliferative disorder.

Bone marrow invasion in multiple myeloma and metastatic disease.

PubMed

Vilanova, J C; Luna, A

2016-04-01

Magnetic resonance imaging (MRI) of the spine is the imaging study of choice for the management of bone marrow disease. MRI sequences enable us to integrate structural and functional information for detecting, staging, and monitoring the response the treatment of multiple myeloma and bone metastases in the spine. Whole-body MRI has been incorporated into different guidelines as the technique of choice for managing multiple myeloma and metastatic bone disease. Normal physiological changes in the yellow and red bone marrow represent a challenge in analyses to differentiate clinically significant findings from those that are not clinically significant. This article describes the findings for normal bone marrow, variants, and invasive processes in multiple myeloma and bone metastases. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Evaluation of bone marrow aspirates in patients with acute myeloid leukemia at day 14 of induction therapy.

PubMed

Souto Filho, João Tadeu D; Loureiro, Monique M; Pulcheri, Wolmar; Morais, José Carlos; Nucci, Marcio; Portugal, Rodrigo D

2015-07-25

Early assessment of response to chemotherapy in acute myeloid leukemia may be performed by examining bone marrow aspirate (BMA) or biopsy (BMB); a hypocellular bone marrow sample indicates adequate anti-leukemic activity. We sought to evaluate the quantitative and qualitative assessment of BMA performed on day 14 (D14) of chemotherapy, to verify the inter-observer agreement, to compare the results of BMA and BMB, and to evaluate the impact of D14 blast clearance on the overall survival (OS). A total of 107 patients who received standard induction chemotherapy and had bone marrow samples were included. BMA evaluation was performed by two observers using two methods: quantitative assessment and a qualitative (Likert) scale. ROC curves were obtained correlating the BMA quantification of blasts and the qualitative scale, by both observers, with BMB result as gold-standard. There was a significant agreement between the two observers in both the qualitative and quantitative assessments (Kw = 0.737, p < 0.001, and rs = 0.798, p < 0.001; ICC = 0.836, p < 0.001, respectively). The areas under the curve (AUC) were 0.924 and 0.946 for observer 1 and 0.867 and 0.870 for observer 2 for assessments of the percentage of blasts and qualitative scale, respectively. The best cutoff for blast percentage in BMA was 6% and 7% for observers 1 and 2, respectively. A similar analysis for the qualitative scale showed the best cutoff as "probably infiltrated". Patients who attained higher grades of cytoreduction on D14 had better OS. Evaluation of D14 BMA using both methods had a significant agreement with BMB and between observers, identifying a population of patients with poor outcome.

Pressure and shear stress in trabecular bone marrow during whole bone loading.

PubMed

Metzger, Thomas A; Schwaner, Stephen A; LaNeve, Anthony J; Kreipke, Tyler C; Niebur, Glen L

2015-09-18

Skeletal adaptation to mechanical loading is controlled by mechanobiological signaling. Osteocytes are highly responsive to applied strains, and are the key mechanosensory cells in bone. However, many cells residing in the marrow also respond to mechanical cues such as hydrostatic pressure and shear stress, and hence could play a role in skeletal adaptation. Trabecular bone encapsulates marrow, forming a poroelastic solid. According to the mechanical theory, deformation of the pores induces motion in the fluid-like marrow, resulting in pressure and velocity gradients. The latter results in shear stress acting between the components of the marrow. To characterize the mechanical environment of trabecular bone marrow in situ, pore pressure within the trabecular compartment of whole porcine femurs was measured with miniature pressure transducers during stress-relaxation and cyclic loading. Pressure gradients ranging from 0.013 to 0.46 kPa/mm were measured during loading. This range was consistent with calculated pressure gradients from continuum scale poroelastic models with the same permeability. Micro-scale computational fluid dynamics models created from computed tomography images were used to calculate the micromechanical stress in the marrow using the measured pressure differentials as boundary conditions. The volume averaged shear stress in the marrow ranged from 1.67 to 24.55 Pa during cyclic loading, which exceeds the mechanostimulatory threshold for mesenchymal lineage cells. Thus, the loading of bone through activities of daily living may be an essential component of bone marrow health and mechanobiology. Additional studies of cell-level interactions during loading in healthy and disease conditions will provide further incite into marrow mechanobiology. Copyright © 2015 Elsevier Ltd. All rights reserved.

The skeletal cell-derived molecule sclerostin drives bone marrow adipogenesis.

PubMed

Fairfield, Heather; Falank, Carolyne; Harris, Elizabeth; Demambro, Victoria; McDonald, Michelle; Pettitt, Jessica A; Mohanty, Sindhu T; Croucher, Peter; Kramer, Ina; Kneissel, Michaela; Rosen, Clifford J; Reagan, Michaela R

2018-02-01

The bone marrow niche is a dynamic and complex microenvironment that can both regulate, and be regulated by the bone matrix. Within the bone marrow (BM), mesenchymal stromal cell (MSC) precursors reside in a multi-potent state and retain the capacity to differentiate down osteoblastic, adipogenic, or chondrogenic lineages in response to numerous biochemical cues. These signals can be altered in various pathological states including, but not limited to, osteoporotic-induced fracture, systemic adiposity, and the presence of bone-homing cancers. Herein we provide evidence that signals from the bone matrix (osteocytes) determine marrow adiposity by regulating adipogenesis in the bone marrow. Specifically, we found that physiologically relevant levels of Sclerostin (SOST), which is a Wnt-inhibitory molecule secreted from bone matrix-embedded osteocytes, can induce adipogenesis in 3T3-L1 cells, mouse ear- and BM-derived MSCs, and human BM-derived MSCs. We demonstrate that the mechanism of SOST induction of adipogenesis is through inhibition of Wnt signaling in pre-adipocytes. We also demonstrate that a decrease of sclerostin in vivo, via both genetic and pharmaceutical methods, significantly decreases bone marrow adipose tissue (BMAT) formation. Overall, this work demonstrates a direct role for SOST in regulating fate determination of BM-adipocyte progenitors. This provides a novel mechanism for which BMAT is governed by the local bone microenvironment, which may prove relevant in the pathogenesis of certain diseases involving marrow adipose. Importantly, with anti-sclerostin therapy at the forefront of osteoporosis treatment and a greater recognition of the role of BMAT in disease, these data are likely to have important clinical implications. © 2017 Wiley Periodicals, Inc.

SBDS Protein Expression Patterns in the Bone Marrow

PubMed Central

Wong, Trisha E.; Calicchio, Monica L.; Fleming, Mark D.; Shimamura, Akiko; Harris, Marian H.

2010-01-01

Shwachman Diamond Syndrome (SDS) is an inherited bone marrow failure syndrome caused by biallelic SBDS gene mutations. Here we examined SBDS protein levels in human bone marrow. SBDS protein expression was high in neutrophil progenitors, megakaryocytes, plasma cells and osteoblasts. In contrast, SBDS protein levels were low in all hematopoietic cell lineages from patients harboring the common SBDS mutations. We conclude that SBDS protein levels vary widely between specific marrow lineages. Uniformly low SBDS protein expression levels distinguish the majority of SDS patients from controls or other marrow failure syndromes. PMID:20658628

Amodiaquine induced agranulocytosis: inhibition of colony growth in bone marrow by antimalarial agents.

PubMed Central

Rhodes, E G; Ball, J; Franklin, I M

1986-01-01

Bone marrow was cultured in vitro for colonies of granulocytes and macrophages five months after a patient had recovered from amodiaquine induced agranulocytosis. The addition of amodiaquine, chloroquine, and sulfadoxine to the culture was followed by a dose dependent inhibition of colony growth in the patient's marrow but not in normal control bone marrow. Colony growth was, however, unaffected by proguanil, pyrimethamine, and quinine. These findings show that in vitro marrow culture may have important predictive value in some cases of drug induced agranulocytosis. PMID:3082409

TREATMENT OF STROKE WITH DETA-NONOATE AND BONE MARROW STROMAL CELLS UPREGULATES ANGIOPOIETIN-1/TIE2 AND ENHANCES NEOVASCULARIZATION

PubMed Central

CUI, X.; CHEN, J.; ZACHAREK, A.; ROBERTS, C.; SAVANT-BHONSALE, S.; CHOPP, M.

2008-01-01

Neovascularization may contribute to functional recovery after neural injury. Combination treatment of stroke with a nitric oxide donor, DETA-NONOate and bone marrow stromal cells promote functional recovery. However, the mechanisms underlying functional improvement have not been elucidated. In this study, we tested the hypothesis that combination treatment upregulates Angiopoietin1 and its receptor Tie2 in the ischemic brain and bone marrow stromal cells, thereby enhances cerebral neovascularization after stroke. Adult wild type male C57BL/6 mice were intravenously administered PBS, bone marrow stromal cells 5×105, DETA-NONOate 0.4 mg/kg or combination DETA-NONOate with bone marrow stromal cells (n=12/group) after middle cerebral artery occlusion. Combination treatment significantly upregulated Angiopoietin-1/Tie2 and tight junction protein (occludin) expression, and increased the number, diameter and perimeter of blood vessels in the ischemic brain compared with vehicle control (mean ± SE, p<0.05). In vitro, DETA-NONOate significantly increased Angiopoietin-1/Tie2 protein (n=6/group) and Tie2 mRNA (n=3/group) expression in bone marrow stromal cells. DETA-NONOate also significantly increased Angiopoietin-1 protein (n=6/group) and mRNA (n=3/group) expression in mouse brain endothelial cells (p<0.05). Angiopoietin-1 mRNA (n=3/group) was significantly increased in mouse brain endothelial cells treated with DETA-NONOate in combination with bone marrow stromal cells conditioned medium compared with cells treated with bone marrow stromal cells conditioned medium or DETA-NONOate alone. Mouse brain endothelial cell capillary tube-like formation assays (n=6/group) showed that Angiopoietin-1 peptide, the supernatant of bone marrow stromal cells and DETA-NONOate significantly increased capillary tube formation compared to vehicle control. Combination treatment significantly increased capillary tube formation compared with DETA-NONOate treatment alone. Inhibition of Angiopoietin-1 significantly attenuated combination treatment-induced tube formation. Our data indicated that combination treatment of stroke with DETA-NONOate and bone marrow stromal cells promotes neovascularization, which is at least partially mediated by upregulation of the Angiopoietin-1/Tie2 axis. PMID:18691637

Infusion of freshly isolated autologous bone marrow derived mononuclear cells prevents endotoxin-induced lung injury in an ex-vivo perfused swine model

PubMed Central

2013-01-01

Introduction The acute respiratory distress syndrome (ARDS), affects up to 150,000 patients per year in the United States. We and other groups have demonstrated that bone marrow derived mesenchymal stromal stem cells prevent ARDS induced by systemic and local administration of endotoxin (lipopolysaccharide (LPS)) in mice. Methods A study was undertaken to determine the effects of the diverse populations of bone marrow derived cells on the pathophysiology of ARDS, using a unique ex-vivo swine preparation, in which only the ventilated lung and the liver are perfused with autologous blood. Six experimental groups were designated as: 1) endotoxin alone, 2) endotoxin + total fresh whole bone marrow nuclear cells (BMC), 3) endotoxin + non-hematopoietic bone marrow cells (CD45 neg), 4) endotoxin + hematopoietic bone marrow cells (CD45 positive), 5) endotoxin + buffy coat and 6) endotoxin + in vitro expanded swine CD45 negative adherent allogeneic bone marrow cells (cultured CD45neg). We measured at different levels the biological consequences of the infusion of the different subsets of cells. The measured parameters were: pulmonary vascular resistance (PVR), gas exchange (PO2), lung edema (lung wet/dry weight), gene expression and serum concentrations of the pro-inflammatory cytokines IL-1β, TNF-α and IL-6. Results Infusion of freshly purified autologous total BMCs, as well as non-hematopoietic CD45(-) bone marrow cells significantly reduced endotoxin-induced pulmonary hypertension and hypoxemia and reduced the lung edema. Also, in the groups that received BMCs and cultured CD45neg we observed a decrease in the levels of IL-1β and TNF-α in plasma. Infusion of hematopoietic CD45(+) bone marrow cells or peripheral blood buffy coat cells did not protect against LPS-induced lung injury. Conclusions We conclude that infusion of freshly isolated autologous whole bone marrow cells and the subset of non-hematopoietic cells can suppress the acute humoral and physiologic responses induced by endotoxemia by modulating the inflammatory response, mechanisms that do not involve engraftment or trans-differentiation of the cells. These observations may have important implications for the design of future cell therapies for ARDS. PMID:23497755

DNA identification of human remains in Disaster Victim Identification (DVI): An efficient sampling method for muscle, bone, bone marrow and teeth.

PubMed

de Boer, Hans H; Maat, George J R; Kadarmo, D Aji; Widodo, Putut T; Kloosterman, Ate D; Kal, Arnoud J

2018-06-04

In disaster victim identification (DVI), DNA profiling is considered to be one of the most reliable and efficient means to identify bodies or separated body parts. This requires a post mortem DNA sample, and an ante mortem DNA sample of the presumed victim or their biological relative(s). Usually the collection of an adequate ante mortem sample is technically simple, but the acquisition of a good quality post mortem sample under unfavourable DVI circumstances is complicated due to the variable degree of preservation of the human remains and the high risk of DNA (cross) contamination. This paper provides the community with an efficient method to collect post-mortem DNA samples from muscle, bone, bone marrow and teeth, with a minimal risk of contamination. Our method has been applied in a recent, challenging DVI operation (i.e. the identification of the 298 victims of the MH17 airplane crash in 2014). 98,2% of the collected PM samples provided the DVI team with highly informative DNA genotyping results without the risk of contamination and consequent mistyping the victim's DNA. Moreover, the method is easy, cheap and quick. This paper provides the DVI community with a step-wise instructions with recommendations for the type of tissue to be sampled and the site of excision (preferably the upper leg). Although initially designed for DVI purposes, the method is also suited for the identification of individual victims. Copyright © 2018 Elsevier B.V. All rights reserved.

Splenic marginal zone lymphoma uncovered after a 10-year follow up as anemia of unknown cause.

PubMed

Koyama, Asumi; Shiotani, Chieko; Kurihara, Toshio; Mushino, Toshiki; Okamoto, Yukiharu; Tamaki, Tatsunori; Ozaki, Takashi; Ohshima, Kouichi; Tamura, Shinobu

2017-01-01

A 75-year-old man was referred to our hospital for evaluation of persistent anemia. Despite repeated diagnostic tests, including bone marrow aspiration, the cause of his anemia remained unknown. On each occasion, computed tomography had revealed neither swollen lymph nodes nor splenomegaly. After a 10-year follow-up period, he was admitted with general fatigue and had developed splenomegaly as well as the anemia. Bone marrow biopsy revealed increased abnormal lymphocytes with short villi that were positive for CD11c, CD19, CD20, and kappa chain, but not for CD5, CD10, CD23, or cyclin D1, according to flow cytometry. The bone marrow biopsy sample showed nodular proliferation of small to medium-sized abnormal lymphocytes. Based on these findings, the patient was diagnosed as having splenic marginal zone lymphoma, a rare indolent B-cell neoplasm. Although his splenomegaly diminished after eight cycles of weekly rituximab monotherapy, the anemia did not improve, and abnormal lymphocytes remained detectable in his bone marrow. The patient was then treated with bendamustine monotherapy for six cycles, after which the anemia resolved, and he has since been in good condition. Although rare, it is important to consider splenic marginal zone lymphoma during the differential diagnosis of patients with a long history of anemia of unknown cause.

Bone Marrow Is a Major Parasite Reservoir in Plasmodium vivax Infection

PubMed Central

2018-01-01

ABSTRACT Plasmodium vivax causes heavy burdens of disease across malarious regions worldwide. Mature P. vivax asexual and transmissive gametocyte stages occur in the blood circulation, and it is often assumed that accumulation/sequestration in tissues is not an important phase in their development. Here, we present a systematic study of P. vivax stage distributions in infected tissues of nonhuman primate (NHP) malaria models as well as in blood from human infections. In a comparative analysis of the transcriptomes of P. vivax and Plasmodium falciparum blood-stage parasites, we found a conserved cascade of stage-specific gene expression despite the greatly different gametocyte maturity times of these two species. Using this knowledge, we validated a set of conserved asexual- and gametocyte-stage markers both by quantitative real-time PCR and by antibody assays of peripheral blood samples from infected patients and NHP (Aotus sp.). Histological analyses of P. vivax parasites in organs of 13 infected NHP (Aotus and Saimiri species) demonstrated a major fraction of immature gametocytes in the parenchyma of the bone marrow, while asexual schizont forms were enriched to a somewhat lesser extent in this region of the bone marrow as well as in sinusoids of the liver. These findings suggest that the bone marrow is an important reservoir for gametocyte development and proliferation of malaria parasites. PMID:29739900

The protocol for the isolation and cryopreservation of osteoclast precursors from mouse bone marrow and spleen.

PubMed

Boraschi-Diaz, Iris; Komarova, Svetlana V

2016-01-01

Osteoclasts are responsible for physiological bone remodeling as well as pathological bone destruction in osteoporosis, periodontitis and rheumatoid arthritis, and thus represent a pharmacological target for drug development. We aimed to characterize and compare the cytokine-induced osteoclastogenesis of bone marrow and spleen precursors. Established protocols used to generate osteoclasts from bone marrow were modified to examine osteoclastogenesis of the spleen cells of healthy mice. Osteoclast formation was successfully induced from spleen precursors using receptor activator of nuclear factor κB ligand (50 ng/ml) and macrophage colony stimulating factor (50 ng/ml). Compared to bone marrow cultures, differentiation from spleen required a longer cultivation time (9 days for spleen, as compared to 5 days for marrow cultures) and a higher plating density of non-adherent cells (75,000/cm(2) for spleen, as compared to 50,000/cm(2) for bone marrow). Osteoclasts generated from spleen precursors expressed osteoclast marker genes calcitonin receptor, cathepsin K and matrix metalloproteinase 9 and were capable of resorbing hydroxyapatite. The differentiation capacity of spleen and bone marrow precursors was comparable for BALB/c, C57BL/6 and FVB mice. We also developed and tested a cryopreservation protocol for the osteoclast precursors. While 70-80 % of cells were lost during the first week of freezing, during the subsequent 5 weeks the losses were within 2-5 % per week. Osteoclastogenesis from the recovered bone marrow precursors was successful up to 5 weeks after freezing. Spleen precursors retained their osteoclastogenic capacity for 1 week after freezing, but not thereafter. The described protocol is useful for the studies of genetically modified animals as well as for screening new osteoclast-targeting therapeutics.

Synergy of bone marrow transplantation and curcumin ensue protective effects at early onset of diabetes in mice.

PubMed

Arivazhagan, Arivarasan; Krishna, Soni; Yadav, Shivangi; Shah, Harshit Rajesh; Kumar, Pravir; Ambasta, Rashmi Kumar

2015-07-01

The aim of this study was to investigate the early onset effects of diabetes on pro-angiogenic signaling pathway, total number of bone marrow cells, organs (pancreas and kidney) damage and the reversal effect of diabetes by combinatorial treatment of curcumin and bone marrow transplantation in streptozotocin (STZ) induced diabetic mice. In the present study, Streptozotocin induced diabetic mice were transplanted with bone marrow cells (2 × 10(6) ) followed by the administration of curcumin (80 mg/kg bodyweight). Effect of diabetes on the different organs was studied by H&E, Western blotting and immunofluorescence using vascular endothelial growth factor (VEGF), platelet/endothelial cell adhesion molecule (PECAM), insulin, Caspase-9 and Caspase-3 antibodies. The effect of diabetes results in the reduction of the total cell number and viability of the bone marrow cells, organ degeneration and lower VEGF/PECAM expression. However, transplantation with normal bone marrow cells significantly reduced the blood glucose levels (above normal range) and initiated the organ regeneration via the VEGF/PECAM mediated manner. Curcumin treatment further reduced the blood glucose level (near normal); and accelerated the organ regeneration, enhanced VEGF/PECAM expression and decreased caspase expression level in the organs. Curcumin also had a protective role against the glucotoxicity test performed on the bone marrow cells. This study suggests that bone marrow transplantation and curcumin administration is an effective treatment in reversing the early onset effects of diabetes via the VEGF/PECAM signaling pathway. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Erythropoietin induces bone marrow and plasma fibroblast growth factor 23 during acute kidney injury.

PubMed

Toro, Luis; Barrientos, Víctor; León, Pablo; Rojas, Macarena; Gonzalez, Magdalena; González-Ibáñez, Alvaro; Illanes, Sebastián; Sugikawa, Keigo; Abarzúa, Néstor; Bascuñán, César; Arcos, Katherine; Fuentealba, Carlos; Tong, Ana María; Elorza, Alvaro A; Pinto, María Eugenia; Alzamora, Rodrigo; Romero, Carlos; Michea, Luis

2018-05-01

It is accepted that osteoblasts/osteocytes are the major source for circulating fibroblast growth factor 23 (FGF23). However, erythropoietic cells of bone marrow also express FGF23. The modulation of FGF23 expression in bone marrow and potential contribution to circulating FGF23 has not been well studied. Moreover, recent studies show that plasma FGF23 may increase early during acute kidney injury (AKI). Erythropoietin, a kidney-derived hormone that targets erythropoietic cells, increases in AKI. Here we tested whether an acute increase of plasma erythropoietin induces FGF23 expression in erythropoietic cells of bone marrow thereby contributing to the increase of circulating FGF23 in AKI. We found that erythroid progenitor cells of bone marrow express FGF23. Erythropoietin increased FGF23 expression in vivo and in bone marrow cell cultures via the homodimeric erythropoietin receptor. In experimental AKI secondary to hemorrhagic shock or sepsis in rodents, there was a rapid increase of plasma erythropoietin, and an induction of bone marrow FGF23 expression together with a rapid increase of circulating FGF23. Blockade of the erythropoietin receptor fully prevented the induction of bone marrow FGF23 and partially suppressed the increase of circulating FGF23. Finally, there was an early increase of both circulating FGF23 and erythropoietin in a cohort of patients with severe sepsis who developed AKI within 48 hours of admission. Thus, increases in plasma erythropoietin and erythropoietin receptor activation are mechanisms implicated in the increase of plasma FGF23 in AKI. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Impaired Endothelial Progenitor Cell Mobilization and Dysfunctional Bone Marrow Stroma in Diabetes Mellitus

PubMed Central

Rafii, Shahin; Jaspers, Janneke E.; White, Ian A.; Hooper, Andrea T.; Doevendans, Pieter A.; Verhaar, Marianne C.

2013-01-01

Background Circulating Endothelial Progenitor Cell (EPC) levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired –at least partly– due to dysfunction of the bone marrow stromal compartment. Methods Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1+Flk-1+ EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34+ hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co-cultures. To study progenitor cell–endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. Results In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. Conclusion EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients. PMID:23555959

Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus.

PubMed

Westerweel, Peter E; Teraa, Martin; Rafii, Shahin; Jaspers, Janneke E; White, Ian A; Hooper, Andrea T; Doevendans, Pieter A; Verhaar, Marianne C

2013-01-01

Circulating Endothelial Progenitor Cell (EPC) levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment. Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+)Flk-1(+) EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+) hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

[Hematopoietic stem-cell transplantation in aplastic anemia].

PubMed

Hernández-Rivera, E Gabriela

2005-01-01

Severe aplastic anemia is a rare syndrome characterized by bone marrow failure with cytopenias and hypocellular bone marrow biopsy (usually 10-15%), without blasts or myelodysplasia. The first choice treatment for these patients is allogeneic bone marrow transplantation from a sibling matched for HLA-A, HLA-B and HLA-DR. Unfortunately only 30% of patients have an HLA-matched sibling (a 25% chance per sibling). The alternative treatment for severe aplastic anemia for the rest of the patients (70%) is immunosuppression with antithymocyte globuline and cyclosporine. The evolution of bone marrow transplantation since 1970's has been positive in terms of survival and transplant success (initial overall survival 43% vs. 90% lately, and graft rejection of 29% vs. 4%). The favorable outcome of bone marrow transplantation for severe or very severe aplastic anemia is due to: the use of conditioning with antithymocyte globuline and cyclophosphamide, the use of graft-vs.-host disease prophylaxis with short curse methotrexate and cyclosporine and the use of filtrated and irradiated blood products. For those patients without an HLA-matched related donor the first treatment to use is the immunosuppression with antithymocyte globuline and cyclosporine. Another option emerged in the late 80's is the unrelated bone marrow transplantation, with survival hardly half of the HLA-identical related bone marrow transplants. In our country, the first allogeneic bone marrow transplant was done in the Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, in a patient with aplastic anemia, making possible to perform this procedure safely in our country.

Stem cell niches and other factors that influence the sensitivity of bone marrow to radiation-induced bone cancer and leukaemia in children and adults

PubMed Central

Richardson, Richard B

2011-01-01

Purpose: This paper reviews and reassesses the internationally accepted niches or ‘targets’ in bone marrow that are sensitive to the induction of leukaemia and primary bone cancer by radiation. Conclusions: The hypoxic conditions of the 10 μm thick endosteal/osteoblastic niche where preleukemic stem cells and hematopoietic stem cells (HSC) reside provides a radioprotective microenvironment that is 2-to 3-fold less radiosensitive than vascular niches. This supports partitioning the whole marrow target between the low haematological cancer risk of irradiating HSC in the endosteum and the vascular niches within central marrow. There is a greater risk of induced bone cancer when irradiating a 50 μm thick peripheral marrow adjacent to the remodelling/reforming portion of the trabecular bone surface, rather than marrow next to the quiescent bone surface. This choice of partitioned bone cancer target is substantiated by the greater radiosensitivity of: (i) Bone with high remodelling rates, (ii) the young, (iii) individuals with hypermetabolic benign diseases of bone, and (iv) the epidemiology of alpha-emitting exposures. Evidence is given to show that the absence of excess bone-cancer in atomic-bomb survivors may be partially related to the extremely low prevalence among Japanese of Paget's disease of bone. Radiation-induced fibrosis and the wound healing response may be implicated in not only radiogenic bone cancers but also leukaemia. A novel biological mechanism for adaptive response, and possibility of dynamic targets, is advocated whereby stem cells migrate from vascular niches to stress-mitigated, hypoxic niches. PMID:21204614

Autologous bone marrow transplantation in relapsed adult acute leukemia.

PubMed

Dicke, K A; Zander, A R; Spitzer, G; Verma, D S; Peters, L J; Vellekoop, L; Thomson, S; Stewart, D; Hester, J P; McCredie, K B

1979-01-01

From March, 1976 to February, 1979, 28 cases of adult acute leukemia of which 24 were evaluable were treated in irreversible relapse with high dose chemotherapy (piperazinedione) and supra-lethal total body irradiation (TBI) in conjunction with autologous bone marrow transplantation (ABMT). The marrow cells grafted were collected and stored in liquid nitrogen at the time of remission. In 12 patients the marrow cells were fractionated using discontinuous albumin gradients in an attempt to separate normal cells from residual leukemic cells. Twelve patients achieved complete remission (CR); in 9 additional patients signs of engraftment were evident but death occurred before achievement of CR. Seven of 12 AML patients, which were treated with bone marrow transplantation as first treatment of their relapse, achieved CR. Four of 5 patients with ALL, whose bone marrows were collected during first remission, reached CR. The median CR duration was 4+ months and the median survival of the patients reaching CR was 6+ months. Autologous bone marrow transplantation offers a good chance of CR (66%), when marrow is collected during first remission and used as first treatment for AML in third relapse and ALL in second relapse.

Autologous bone marrow transplantation in relapsed adult acute leukemia.

PubMed

Dicke, K A; Zander, A R; Spitzer, G; Verma, D S; Peters, L; Vellekoop, L; Thomson, S; Stewart, D; McCredie, K B

1980-01-01

From March, 1976 to February, 1979, 28 cases of adult acute leukemia of which 24 were evaluable were treated in irreversible relapse with high dose chemotherapy (piperazinedione) and supra-lethal total body irradiation (TBI) in conjunction with autologous bone marrow transplantation (ABMT). The marrow cells grafted were collected and stored in liquid nitrogen at the time of remission. In 12 patients the marrow cells were fractionated using discontinuous albumin gradients in an attempt to separate normal cells from residual leukemic cells. Twelve patients achieved complete remission (CR); in 9 additional patients signs of engraftment were evident but death occurred before achievement of CR. Seven of 12 AML patients, which were treated with bone marrow transplantation as first treatment of their relapse, achieved CR. Four of 5 patients with ALL, whose bone marrows were collected during first remission, reached CR. The median CR duration was 4+ months and the median survival of the patients reaching CR was 6+ months. Autologous bone marrow transplantation offers a good chance of CR (66%) when marrow is collected during first remission and used as first treatment for AML in third relapse and ALL in second relapse.

[In vitro activity of human bone marrow cells after cryopreservation in liquid nitrogen for 21 - 25 years].

PubMed

Huang, You-Zhang; Shen, Jian-Liang; Gong, Li-Zhong; Zheng, Pei-Hao; Liu, Yi; Yin, Wen-Jie; Cen, Jian; Wang, Ning; Zhao, De-Feng

2010-02-01

The aim of this study was to investigate the best method to preserve human bone marrow cells and the effectiveness of long term cryopreservation at -80 degrees C. The human bone marrow cells in 20 samples were firstly frozen by a programmed freezer or -80 degrees C refrigerator, and then were preserved in liquid nitrogen with DMSO-AuP (10% dimethylsulfonamide, 10% autologous plasma) or DMSO-HES-HuA (5% dimethylsulfonamide, 6% hydroxyethyl starch, 4% human serum albumin) as cryoprotectant for 21 to 25 years. They were thawed in 38 degrees C. The cell sample frozen in -80 degrees C refrigerator was frozen at a low frozen speed of 1 degrees C/min which was the same as the programmed freezer before -30 degrees C. Before detection the bone marrow cells were taken from liquid nitrogen and were thawed in 38 degrees C, then the suspension of bone marrow cells was prepared for detection. The cell morphology and recovery rate of erythrocytes, nucleocytes and platelets; the recovery rate of hematopoietic stem progenitors cells, as well as mesenchymal stem cells were determined. The results showed that the protective effectiveness of DMSO-HES-HuA was better than DMSO-AuP. The mature erythrocytes were destroyed lightly [(3.5 +/- 1.5)% versus (12.6 +/- 4.8)%], the hemolysis rate was lower [(3.3 +/- 1.6)% versus (23.1 +/- 5.1)%]. Osmotic fragility of erythrocytes in the former was not changed, but was dropped in the latter. The recovery rates of red cell, platelet, granulocyte-macrophage colony forming units and long term culture-initiating cells were higher in the former than that in the latter [(96.1 +/- 1.8)%, (70.0 +/- 9.5)%, (49.2 +/- 10.9)%, (54.2 +/- 13.8)% versus (76.3 +/- 5.6)%, (52.7 +/- 8.1)%, (43.5 +/- 12.3)%, (47.2 +/- 13.6)% respectively]. With each kind of cryoprotectant or frozen method, the frozen MSC could keep the original growth properties. With the same cryoprotectant and different frozen method, the cryopreservative effectiveness was not different. The influence of the cryoprotectant prescriptions and the frozen methods on the cryopreservative effectiveness was little. It is concluded that the human bone marrow cells with DMSO-AuP or DMSO-HES-HuA as cryoprotectant, frozen by a programmed freezer or -80 degrees C refrigerator, could be then preserved in liquid nitrogen for long time. When the preserving time was as long as 21 to 25 years, the morphology, the recovery rate and the activity of various kinds of cells were still good. The method of freezing by -80 degrees C refrigerator with 5% DMSO-6% HES-4% HuA and preserving in liquid nitrogen would be convenient, cheap and easily-manipulated for preservation of the human bone marrow cells.

The effect of refrigeration of bone marrow and peripheral blood on cytogenetic analysis.

PubMed

Martin, P K; Rowley, J D

1986-07-01

Bone marrow samples from patients with various hematologic disorders were stored at 4 degrees C for up to 5 d before the establishment of a 24-h culture. We tested various factors, including storage time, colony stimulating factor, and methotrexate in an effort to improve metaphase and chromosome quality. Cytogenetic findings for various hematologic diseases were compared in a total of 201 cultures. Cold storage for up to 3 d did not seem to adversely affect the number of mitoses or the quality of chromosome banding when cells were cultured in a system that used both colony stimulating factor and methotrexate. In samples studied in parallel, clonal abnormalities were noted as frequently in cells stored in the cold as in those processed directly.

Dynamic T2-mapping during magnetic resonance guided high intensity focused ultrasound ablation of bone marrow

NASA Astrophysics Data System (ADS)

Waspe, Adam C.; Looi, Thomas; Mougenot, Charles; Amaral, Joao; Temple, Michael; Sivaloganathan, Siv; Drake, James M.

2012-11-01

Focal bone tumor treatments include amputation, limb-sparing surgical excision with bone reconstruction, and high-dose external-beam radiation therapy. Magnetic resonance guided high intensity focused ultrasound (MR-HIFU) is an effective non-invasive thermotherapy for palliative management of bone metastases pain. MR thermometry (MRT) measures the proton resonance frequency shift (PRFS) of water molecules and produces accurate (<1°C) and dynamic (<5s) thermal maps in soft tissues. PRFS-MRT is ineffective in fatty tissues such as yellow bone marrow and, since accurate temperature measurements are required in the bone to ensure adequate thermal dose, MR-HIFU is not indicated for primary bone tumor treatments. Magnetic relaxation times are sensitive to lipid temperature and we hypothesize that bone marrow temperature can be determined accurately by measuring changes in T2, since T2 increases linearly in fat during heating. T2-mapping using dual echo times during a dynamic turbo spin-echo pulse sequence enabled rapid measurement of T2. Calibration of T2-based thermal maps involved heating the marrow in a bovine femur and simultaneously measuring T2 and temperature with a thermocouple. A positive T2 temperature dependence in bone marrow of 20 ms/°C was observed. Dynamic T2-mapping should enable accurate temperature monitoring during MR-HIFU treatment of bone marrow and shows promise for improving the safety and reducing the invasiveness of pediatric bone tumor treatments.

Long-term cryopreservation of bone marrow for autologous transplantation.

PubMed

Attarian, H; Feng, Z; Buckner, C D; MacLeod, B; Rowley, S D

1996-03-01

Little is known about the effect of long-term cryopreservation on the viability of hematopoietic stem cells (HSC) or on the success of autologous bone marrow transplantation. Although progenitor cell assays such as culture of CFU-GM after thawing can be predictive of engraftment, the most rigorous assay for the cryosurvival of HSC is engraftment after reinfusion of stem cells. We retrospectively evaluated the engraftment data for 36 patients with hematologic malignancies or solid tumors treated at the Fred Hutchinson Cancer Research Center between 1981 and 1993 who received bone marrows stored for 2 years or more. The median duration of cryopreservation for this study group was 2.7 years (range 2.0-7.8). Ninety-seven percent of patients in the study group achieved a granulocyte count of > or = 0.5 x 1.0(9)/1 at a median of 19 days (range 10-115) vs 86% of control group (selected by diagnosis and date of storage) at a median of 20 days (P = 0.14). Seventy percent of patients in the study group achieved a platelet count > or = 20 x 10(9)/1 at a median of 27 days (range 9-69) vs 74% of control group at a median of 23 days (P = 0.47). Also, samples of 28 marrows cryopreserved for a median of 4.4 years (range 2.0-7.8) were cultured to determine if a loss of hematopoietic progenitors relative to duration of storage could be detected. The storage length was not predictive for the quantity of colonies formed (P = 0.57 for BFU-E-derived colonies; P = 0.65 for CFU-GM-derived colonies). We found no consistent detrimental effect of long-term cryopreservation on the success rate of autologous bone marrow transplantation. This report confirms previous reports that marrow cells cryopreserved for several years are capable of engrafting. Therefore, bone marrow cells may be stored at an early appropriate time before the side-effects of multiple cycles of chemotherapy and radiotherapy on hematopoietic tissues are incurred.

SU-F-J-222: Using PET Imaging to Evaluate Proliferation and Blood Flow in Irradiated and Non-Irradiated Bone Marrow 1 Year After Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGuire, S; Ponto, L; Menda, Y

Purpose: To compare proliferation and blood flow in pelvic and thoracic bone marrow 1 year after pelvic chemoradiation. Methods: Sixteen pelvic cancer patients were enrolled in an IRB-approved protocol to acquire FLT PET images during radiation therapy simulation (baseline) and 1 year after chemoradiation therapy. Three subjects also had optional O-15 water PET images acquired 1 year after chemoradiation therapy. Baseline FLT PET images were used to create IMRT plans to spare pelvic bone marrow identified as regions with FLT SUV ≥ 2 without compromising PTV coverage or OAR sparing. Marrow VOIs were defined using a 50% maximum pixel valuemore » threshold on baseline FLT PET images (VIEW, PMOD version 3.5) in the sacrum and thoracic spine representing irradiated and non-irradiated regions, respectively. FLT PET and O-15 water PET images acquired 1 year after therapy were co-registered to baseline images (FUSION PMOD) and the same VOIs were used to measure proliferation (FLT SUV) and blood flow (O-15 water uptake). Separate image-based input functions were used for blood flow quantitation in each VOI. Results: Mean 1 year FLT SUV in sacral and thoracic VOIs for were 1.1 ± 0.4 and 6.5 ± 1.7, respectively for N = 16 subjects and were 1.2 ± 0.2 and 5.6 ± 1.6, respectively for N = 3 subjects who also underwent O-15 water imaging. Blood flow measures in equivalent sacral and thoracic marrow regions (N = 3) were 21.3 ± 8.7 and 18.3 ± 4.9 mL/min/100mL respectively. Conclusion: Decreased bone marrow proliferation measured by FLT SUV does not appear to correspond to decreased blood flow as measured by O-15 water PET imaging. Based on this small sample at a single time point, reduced blood supply does not explain reductions in bone marrow proliferative activity 1 year after chemoradiation therapy.« less

Inherited Bone Marrow Failure Syndromes (IBMFS)

Cancer.gov

The NCI IBMFS Cohort Study consists of affected individuals and their immediate families in North America who have an inherited bone marrow failure syndrome (IBMFS)-either one that has been specifically identified and defined, or bone marrow failure that appears to be inherited but has not yet been clearly identified as having a genetic basis.

Fetal bovine bone marrow is a rich source of CD34+ hematopoietic progenitors with myelo-monocytic colony-forming activity.

PubMed

Pessa-Morikawa, Tiina; Niku, Mikael; Iivanainen, Antti

2012-03-01

The CD34 glycoprotein is an important marker of hematopoietic stem cells. We used a polyclonal rabbit anti-bovine CD34 antibody to stain fetal and adult bovine bone marrow cells. Flow cytometry revealed a low side scatter (SSC(low)) population of cells that were CD34(+) but negative for leukocyte lineage markers CD11b, CD14 or CD2. Hematopoietic colony assays with CD34(+) and CD34(-) bone marrow cells suggested that the colony-forming potential in SSC(low) bone marrow cells was confined to the CD34(+) fraction. In contrast, this population was not enriched for cells expressing high aldehyde dehydrogenase activity, a metabolic marker that has been used to characterize hematopoietic stem cells. Thus, the CD34 antigen can be used to identify and isolate bovine bone marrow cells exhibiting clonogenic potential in vitro. Moreover, the proportion of CD34(+) cells is very high in fetal bovine bone marrow, indicating it as a rich source of hematopoietic progenitors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of low-doses of Bacillus spp. from permafrost on differentiation of bone marrow cells.

PubMed

Kalyonova, L F; Novikova, M A; Kostolomova, E G

2015-01-01

The effects of a new microorganism species (Bacillus spp., strain M3) isolated from permafrost specimens from Central Yakutia (Mamontova Mountain) on the bone marrow hemopoiesis were studied on laboratory mice. Analysis of the count and immunophenotype of bone marrow cells indicated that even in low doses (1000-5000 microbial cells) these microorganisms modulated hemopoiesis and lymphopoiesis activity. The percentage of early hemopoietic precursors (CD117(+)CD34(-)) increased, intensity of lymphocyte precursor proliferation and differentiation (CD25(+)CD44(-)) decreased, and the percentage of lymphocytes released from the bone marrow (CD25(+)CD44(+)) increased on day 21 after injection of the bacteria. These changes in activity of hemopoiesis were associated with changes in the level of regulatory T lymphocytes (reduced expression of TCRαβ) and were most likely compensatory. The possibility of modulating hemopoiesis activity in the bone marrow by low doses of one microorganism strain isolated from the permafrost could be useful for evaluating the effects of other low dose bacteria on the bone marrow hemopoiesis.

Association of bone marrow edema with temporomandibular joint (TMJ) osteoarthritis and internal derangements.

PubMed

Wahaj, Aiyesha; Hafeez, Kashif; Zafar, Muhammad Sohail

2017-01-01

This study reviewed the dental literature in order to determine the association of bone marrow edema with osteoarthritis and temporomandibular joint (TMJ) internal derangement disorders. A literature search was performed using electronic databases PubMed/Medline (National Library of Medicine, Bethesda, Maryland) and Cochrane for articles published during the last 15 years (January 2000-December 2014). A predetermined inclusion and exclusion criteria were used for filtering the scientific papers. Research articles fulfilling the basic inclusion criteria were included in the review. The reviewed studies showed that bone marrow edema is found in painful joints with osteoarthritis in a majority of cases. A few cases with no pain or significant degenerative changes are reported to have a bone marrow edema pattern as well. Bone marrow edema, increased fluid level, and pain are associated with osteoarthritis in the majority of patients reporting TMJ arthritis. Degenerative and disc displacement conditions are multifactorial and require further investigations. Magnetic resonance imaging can be employed to detect bone marrow edema even in the absence of pain and clinical symptoms in the patients of internal derangements.

Enrichment of human bone marrow aspirates for low-density mononuclear cells using a haemonetics discontinuous blood cell separator.

PubMed

Raijmakers, R; de Witte, T; Koekman, E; Wessels, J; Haanen, C

1986-01-01

Isopycnic density floatation centrifugation has been proven to be a suitable technique to enrich bone marrow aspirates for clonogenic cells on a small scale. We have tested a Haemonetics semicontinuous blood cell separator in order to process large volumes of bone marrow with minimal bone marrow manipulation. The efficacy of isopycnic density floatation was tested in a one and a two-step procedure. Both procedures showed a recovery of about 20% of the nucleated cells and 1-2% of the erythrocytes. The enrichment of clonogenic cells in the one-step procedure appeared superior to the two-step enrichment, first separating buffy coat cells. The recovery of clonogenic cells was 70 and 50%, respectively. Repopulation capacity of the low-density cell fraction containing the clonogenic cells was excellent after autologous reinfusion (6 cases) and allogeneic bone marrow transplantation (3 cases). Fast enrichment of large volumes of bone marrow aspirates with low-density cells containing the clonogenic cells by isopycnic density floatation centrifugation can be done safely using a Haemonetics blood cell separator.

Modeling Hematopoiesis and Responses to Radiation Countermeasures in a Bone Marrow-on-a-Chip.

PubMed

Torisawa, Yu-Suke; Mammoto, Tadanori; Jiang, Elisabeth; Jiang, Amanda; Mammoto, Akiko; Watters, Alexander L; Bahinski, Anthony; Ingber, Donald E

2016-05-01

Studies on hematopoiesis currently rely on animal models because in vitro culture methods do not accurately recapitulate complex bone marrow physiology. We recently described a bone marrow-on-a-chip microfluidic device that enables the culture of living hematopoietic bone marrow and mimics radiation toxicity in vitro. In the present study, we used this microdevice to demonstrate continuous blood cell production in vitro and model bone marrow responses to potential radiation countermeasure drugs. The device maintained mouse hematopoietic stem and progenitor cells in normal proportions for at least 2 weeks in culture. Increases in the number of leukocytes and red blood cells into the microfluidic circulation also could be detected over time, and addition of erythropoietin induced a significant increase in erythrocyte production. Exposure of the bone marrow chip to gamma radiation resulted in reduction of leukocyte production, and treatment of the chips with two potential therapeutics, granulocyte-colony stimulating factor or bactericidal/permeability-increasing protein (BPI), induced significant increases in the number of hematopoietic stem cells and myeloid cells in the fluidic outflow. In contrast, BPI was not found to have any effect when analyzed using static marrow cultures, even though it has been previously shown to accelerate recovery from radiation-induced toxicity in vivo. These findings demonstrate the potential value of the bone marrow-on-a-chip for modeling blood cell production, monitoring responses to hematopoiesis-modulating drugs, and testing radiation countermeasures in vitro.

Flow cytometry in the bone marrow evaluation of follicular and diffuse large B-cell lymphomas.

PubMed

Palacio, C; Acebedo, G; Navarrete, M; Ruiz-Marcellán, C; Sanchez, C; Blanco, A; López, A

2001-09-01

Bone marrow biopsies are routinely performed in the staging of patients with lymphoma. Despite the lack of evidence for its usefulness, many institutions include flow cytometry (FC) of bone-marrow aspirates in an attempt to increase sensitivity and specificity. The aim of this study is to evaluate the usefulness of FC for the assessment of bone-marrow involvement by lymphoma in follicular (FL) and diffuse large B-cell lymphomas (DLBCL). Seventy-nine bone marrow biopsies from 65 patients diagnosed with FL or DLBCL were examined to compare histology and FC for the assessment of bone-marrow involvement by lymphoma. Bone marrow histology showed involvement (BM+) in 16 cases (20.3%), lack of infiltration (BM(-)) in 52 cases (65.8%) and undetermined or undiagnosed for involvement (BMu) in 11 cases (13.9%). FC was positive for involvement in 28 cases (35.4%) and negative in 51 cases (64.6%). 65 cases (95%) showed concordance between the results of morphology and FC (BM(+)/FC(+) or BM(-)/FC(-)). No BM(+)/FC(-) cases were observed. 3 cases showed discrepant results (BM(-)/FC(+)). In these 3 cases the molecular studies (PCR) demonstrated clonal rearrangement of the heavy immunoglobulin chain (IgH) and/or bcl2-IgH in agreement with the flow results. Among the 11 cases with BMu, all but 2 were FC(+) and concordance with the PCR results was seen in 9 cases (81.9%). We conclude that FC is just as sensitive or perhaps slightly more sensitive than histology in the detection of bone marrow involvement in FL and DLBCL. FC studies may be warranted in those cases in which the morphology is not diagnosed. The clinical relevance of the small clonal B-cell population in patients without histologic bone marrow involvement (BM(-)/FC(+) cases) remains an open question.

SU-F-R-55: Early Detection of Treatment Induced Bone Marrow Injury During Chemoradiation Therapy Using Quantitative CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, X; Song, Y; Erickson, B

Purpose: Acute hematologic toxicity associated with bone marrow injury is a common complication of chemoradiation therapy (CRT) for pelvic malignancies. In this work, we investigate the feasibility of using quantitative CT to detect bone marrow injury during CRT. Methods: Daily CTs were acquired during routine CT-guided radiation therapy using a CT-on-rails for 15 cervical cancer patients. All patients treated with a radiation dose of 45.0 to 50.4 Gy in 1.8 Gy/fraction along with chemotherapy. For each patient, the contours of bone marrow were generated in L4, L5 and sacrum on the first daily CT and then populated to other dailymore » CTs by rigid registration using MIM (MIM Software Inc., Cleveland, OH) with manual editing if possible. A series of CT texture parameters, including Hunsfield Unit (HU) histogram, mean HU, entropy, energy, in bone marrow contours were calculated using MATLAB on each daily CT and were correlated with the completed blood counts (CBC) collected weekly for each patient. The correlations were analyzed with Pearson correlation tests. Results: For all patient data analyzed, mean HU in bone marrow decreased during CRT delivery. From the first to the last fraction the average mean HU reduction is 58.1 ± 13.6 HU (P<0.01). This decrease can be observed as early as after first 5 fractions and is strongly associated with the changes of most CBC quantities, such as the reductions of white and blood cell counts (r=0.97, P=0.001). The reduction of HU is spatially varied. Conclusion: Chemoradiation induced bone marrow injury can be detected during the delivery of CRT using quantitative CT. Chemoradiation results in reductions in mean HU, which are strongly associated with the change in the pretrial blood cell counts. Early detection of bone marrow injury with commonly available CT opens a door to improve bone marrow sparing, reducing risk of hematologic toxicity.« less

Maintenance of Host Leukocytes in Peripheral Immune Compartments Following Lethal Irradiation and Bone Marrow Reconstitution: Implications for Graft Versus Host Disease

PubMed Central

Staley, Elizabeth M.; Tanner, Scott M.; Daft, Joseph G.; Stanus, Andrea L.; Martin, Steven M.; Lorenz, Robin G.

2013-01-01

Bone marrow reconstitution is utilized as a tool for disease treatment and as a research technique to elucidate the function of bone marrow derived cells. Clinically successful engraftment is indicated by the development of a functioning immune repertoire. In research, reconstitution is considered successful if >85% of splenic leukocytes are of donor origins. Previous work suggests that splenic reconstitution may not be indicative of reconstitution in the mucosa. We sought to evaluate mucosal reconstitution in animals following a standard bone marrow eradication and reconstitution technique. Bone marrow was harvested from adult B6.SJL donor mice (CD45.1) and injected via either the retro-orbital or intraperitoneal route into lethally irradiated B6 (CD45.2) adult or neonatal recipients respectively. Expression of CD45 by flow cytometry was used to calculate reconstitution with respect to immune compartment and cell type. In reconstituted adult animals 93.2±1.5% of splenic leukocytes expressed the donor CD45.1 antigen thus meeting the standard definition of reconstitution, however only 58.6±13.6% of intestinal lamina propria lymphocytes and 52.4±16.0% of intestinal intraepithelial lymphocytes were of donor origin, confirming splenic reconstitution fails to represent peripheral immune reconstitution. T-cells in the gastrointestinal tract are the most poorly reconstituted, while B-cells appear to be almost universally replaced by donor cells. The inadequate mucosal reconstitution was not corrected by evaluating later timepoints or by performing the bone marrow transfer during the neonatal period. This demonstration that substantial host T-cells remain in the intestinal mucosa after a “successful” bone marrow transplantation should cause a re-evaluation of data from research bone marrow chimera experiments, as well as the mechanisms for complications after clinical bone marrow transplantation. PMID:23334064

Maintenance of host leukocytes in peripheral immune compartments following lethal irradiation and bone marrow reconstitution: implications for graft versus host disease.

PubMed

Staley, Elizabeth M; Tanner, Scott M; Daft, Joseph G; Stanus, Andrea L; Martin, Steven M; Lorenz, Robin G

2013-03-01

Bone marrow reconstitution is utilized as a tool for disease treatment and as a research technique to elucidate the function of bone marrow derived cells. Clinically successful engraftment is indicated by the development of a functioning immune repertoire. In research, reconstitution is considered successful if >85% of splenic leukocytes are of donor origins. Previous work suggests that splenic reconstitution may not be indicative of reconstitution in the mucosa. We sought to evaluate mucosal reconstitution in animals following a standard bone marrow eradication and reconstitution technique. Bone marrow was harvested from adult B6.SJL donor mice (CD45.1) and injected via either the retro-orbital or intraperitoneal route into lethally irradiated B6 (CD45.2) adult or neonatal recipients respectively. The expression of CD45 by flow cytometry was used to calculate reconstitution with respect to immune compartment and cell type. In reconstituted adult animals 93.2±1.5% of splenic leukocytes expressed the donor CD45.1 antigen thus meeting the standard definition of reconstitution, however only 58.6±13.6% of intestinal lamina propria lymphocytes and 52.4±16.0% of intestinal intraepithelial lymphocytes were of donor origin, confirming splenic reconstitution fails to represent peripheral immune reconstitution. T-cells in the gastrointestinal tract are the most poorly reconstituted, while B-cells appear to be almost universally replaced by donor cells. The inadequate mucosal reconstitution was not corrected by evaluating later time points or by performing the bone marrow transfer during the neonatal period. This demonstration that substantial host T-cells remain in the intestinal mucosa after a "successful" bone marrow transplantation should cause a re-evaluation of data from research bone marrow chimera experiments, as well as the mechanisms for complications after clinical bone marrow transplantation. Copyright © 2013 Elsevier B.V. All rights reserved.

Busulfan Injection

MedlinePlus

... marrow and cancer cells in preparation for a bone marrow transplant. Busulfan is in a class of medications called ... days (for a total of 16 doses) before bone marrow transplant.Busulfan injection may cause seizures during therapy with ...

[Neonatal Pearson syndrome. two case studies].

PubMed

Collin-Ducasse, H; Maillotte, A-M; Monpoux, F; Boutté, P; Ferrero-Vacher, C; Paquis, V

2010-01-01

Among the etiologies of anemia in the newborn, those related to mitochondrial cytopathies are rare. Pearson syndrome is mostly diagnosed during infancy and characterized by refractory sideroblastic anemia with vacuolization of marrow progenitor cells and exocrine pancreatic dysfunction. We describe two diagnosed cases of Pearson syndrome in the early neonatal period caused by severe macrocytic aregenerative anemia. Bone marrow aspiration revealed sideroblastic anemia and vacuolization of erythroblastic precursors. The diagnosis was confirmed by genetic analysis revealing a deletion in the mitochondrial DNA. These two newborns received monthly transfusions. Five other newborns suffering from Pearson syndrome with various clinical symptoms were found in literature. Pearson syndrome, rarely diagnosed in newborns, should be suspected in the presence of macrocytic aregenerative anemia and requires a bone marrow aspirate followed by a genetic analysis from a blood sample. Copyright 2009 Elsevier Masson SAS. All rights reserved.

An Unexpected Complication of Bone Marrow Aspiration and Trephine Biopsy: Arteriovenous Fistula

PubMed Central

Berber, Ilhami; Erkurt, Mehmet Ali; Kuku, Irfan; Kaya, Emin; Kutlu, Ramazan; Koroglu, Mustafa; Yigit, Ali; Unlu, Serkan

2014-01-01

Objective To report a case of arteriovenous fistula (AVF) following bone marrow aspiration and trephine biopsy. Clinical Presentation and Intervention A 76-year-old man was diagnosed with acute myeloblastic leukemia. Pain and hematoma were detected in his left leg and hip 4 days after bone marrow aspiration and trephine biopsy. A pelvic arteriography was performed, and a diagnosis of AVF was made. Conclusion This case shows that clinicians should be aware of AVF, especially in cases with refractory bleeding after bone marrow aspiration and trephine biopsy despite normal blood coagulation parameters. PMID:24481007

Bone marrow transplant – children - discharge

MedlinePlus

Transplant - bone marrow - children - discharge; Stem cell transplant - children - discharge; Hematopoietic stem cell transplant -children - discharge; Reduced intensity, non-myeloablative transplant - children - discharge; Mini transplant - children - discharge; Allogenic bone ...

Bone morphogenetic protein 2 and decorin expression in old fracture fragments and surrounding tissues.

PubMed

Han, X G; Wang, D K; Gao, F; Liu, R H; Bi, Z G

2015-09-21

Bone morphogenetic protein 2 (BMP-2) can promote fracture healing. Although the complex role BMP-2 in bone formation is increasingly understood, the role of endogenous BMP-2 in nonunion remains unclear. Decorin (DCN) can promote the formation of bone matrix and calcium deposition to control bone morphogenesis. In this study, tissue composition and expression of BMP-2 and DCN were detected in different parts of old fracture zones to explore inherent anti-fibrotic ability and osteogenesis. Twenty-three patients were selected, including eight cases of delayed union and 15 cases of nonunion. Average duration of delayed union or nonunion was 15 months. Fracture fragments and surrounding tissues, including bone grafts, marrow cavity contents, and sticking scars, were categorically sampled during surgery. Through observation and histological testing, component comparisons were made between fracture fragments and surrounding tissue. The expression levels of DCN and BMP-2 in different tissues were detected by immunohistochemical staining and real-time polymerase chain reaction. The expression of DCN and BMP- 2 in different parts of the nonunion area showed that, compared with bone graft and marrow cavity contents, sticking scars had the highest expression of BMP-2. Compared with the marrow cavity contents and sticking scars, bone grafts had the highest expression of DCN. The low antifibrotic and osteogenic activity of the nonunion area was associated with non-co-expression of BMP-2 and DCN. Therefore, the co-injection of osteogenic factor BMP and DCN into the nonunion area can improve the induction of bone formation and enhance the conversion of the old scar, thereby achieving better nonunion treatment.

Leukemia-associated antigens in man.

PubMed

Brown, G; Capellaro, D; Greaves, M

1975-12-01

Rabbit antisera raised against acute lymphoblastic leukemia (ALL) cells were used to distinguish ALL from other leukemias, to identify rare leukemia cells in the bone marrow of patients in remission, and to define human leukemia-associated antigens. Antibody binding was studied with the use of immunofluorescence reagents and the analytic capacity of the Fluorescence Activated Cell Sorter-1 (FACS-1). The results indicated that most non-T-cell ALL have three leukemia-associated antigens on their surface which are absent from normal lymphoid cells: 1) an antigen shared with myelocytes, myeloblastic leukemia cells, and fetal liver (hematopoietic) cells; 2) an antigen shared with a subset of intermediate normoblasts in normal bone marrow and fetal liver; and 3) an antigen found thus far only on non-T-cell ALL and in some acute undifferentiated leukemias, which we therefore regard as a strong candidate for a leukemia-specific antigen. These antigens are absent from a subgroup of ALL patients in which the lymphoblasta express T-cell surface markers. Preliminary studies on the bone marrow samples of patients in remission indicated that rare leukemia cells were present in some samples. The implications of these findings with respect to the heterogeneity and cell origin(s) of ALL, its diagnosis, and its potential monitoring during treatment were discussed.

Association between Activated Partial Thromboplastin Time and the Amount of Infused Heparin at Bone Marrow Transplantation.

PubMed

Kusuda, Machiko; Kimura, Shun-Ichi; Misaki, Yukiko; Yoshimura, Kazuki; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Akahoshi, Yu; Ugai, Tomotaka; Kameda, Kazuaki; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Nakasone, Hideki; Kako, Shinichi; Tanihara, Aki; Kanda, Yoshinobu

2018-03-27

The actual heparin concentration of harvested allogeneic bone marrow varies among harvest centers. We monitor the activated partial thromboplastin time (APTT) of the patient during bone marrow infusion and administer prophylactic protamine according to the APTT. We retrospectively reviewed the charts of consecutive patients who underwent bone marrow transplantation without bone marrow processing at our center between April 2007 and March 2016 (n = 94). APTT was monitored during marrow transfusion in 52 patients. We analyzed the relationship between the APTT ratio and several parameters related to heparin administration. As a result, the weight-based heparin administration rate (U/kg/hour) seemed to be more closely related to the APTT ratio (r = .38, P = .005) than to the total amount of heparin. There was no significant correlation between the APTT ratio and renal or liver function. Bleeding complications during and early after infusion were seen in 3 of 52 patients, and included intracranial, nasal, and punctured-skin bleeding. The APTT ratio during transfusion was over 5.88 in the former 2 patients and 2.14 in the latter. All of these patients recovered without sequelae. In conclusion, slow bone marrow infusion is recommended to decrease the weight-based heparin administration rate when the heparin concentration per patient body weight is high. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Prostaglandin E2 Increased Rat Cortical Bone Mass When Administered Immediately Following Ovariectomy

NASA Technical Reports Server (NTRS)

Ke, Hua Zhu; Jee, Webster S.S.; Zeng, Qing Qiang; Li, Mei; Lin, Bai Yun

1993-01-01

To investigate the effects of ovariectomy and the simultaneous administration of prostaglandin E2 (PGE2) on rat tibial shaft cortical bone histomorphometry, thirty-five 3 month-old female Sprague-Dawley rats were either ovariectomized (OVX), or sham ovariectomy (sham-OVX). The OVX rats were divided into three groups and treated with 0, 1 and 6 mg PGE2/kg/day for 90 days. The double fluorescent labeled undecalcified tibial shaft cross sections (proximal to the tibiofibular junction) of all the subjects were used for histomorphometry analysis. No differences in cross-sectional area and cortical bone area were found between sham-OVX and OVX controls, but OVX increased marrow area, intracortical porosity area and endocortical eroded perimeter. Periosteal and endocortical bone formation rates decreased with aging yet OVX prevented these changes. These OVX-induced increases in marrow area and endocortical eroded perimeter were prevented by 1 mg PGE2/kg/day treatment and added bone to periosteal and endocortical surfaces and to the marrow cavity. At the 6 mg/kg/day dose level, PGE2-treated OVX rats increased total tissue area, cortical bone area, marrow trabmular bone area, minimal cortical width and intracortical porosity area, and decreased marrow area compared to basal, sham-OVX and OVX controls. In addition, periosteal bone formation was elevated in the 6 mg PGE2/kg/day-treated OVX rats compared to OVX controls. Endocortical eroded perimeter increased from basal and sham-OVX control levels, but decreased from OVX control levels in the 6 mg PGE2/kg/day-treated OVX rats. Our study confirmed that ovariectomy does not cause osteopenia in tibial shaft cortical bone in rats, but it does stimulate endocortical bone resorption and enlarges marrow area. The new findings from the present study demonstrate that PGE2 prevents the OVX-induced increases in endocortical bone resorption and marrow area and adds additional bone to periosteal and endocortical surfaces and to marrow cavity to increase total bone mass in the tibial shaft of OVX rats when given immediately following ovafiectomy.

Clonidine Reduces Norepinephrine and Improves Bone Marrow Function in a Rodent Model of Lung Contusion, Hemorrhagic Shock and Chronic Stress

PubMed Central

Alamo, Ines G.; Kannan, Kolenkode B.; Ramos, Harry; Loftus, Tyler J.; Efron, Philip A.; Mohr, Alicia M.

2016-01-01

Background Propranolol has been shown previously to restore bone marrow function and improve anemia after lung contusion/hemorrhagic shock. We hypothesized that daily clonidine administration would inhibit central sympathetic outflow and restore bone marrow function in our rodent model of lung contusion/hemorrhagic shock with chronic stress. Methods Male Sprague-Dawley rats underwent six days of restraint stress after lung contusion/hemorrhagic shock during which the animals received clonidine (75μg/kg) after the restraint stress. On post-injury day seven, we assessed urine norepinephrine, blood hemoglobin, plasma granulocyte colony stimulating factor (G-CSF), and peripheral blood mobilization of hematopoietic progenitor cells (HPC), as well as bone marrow cellularity and erythroid progenitor cell growth. Results The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress, significantly decreased urine norepinephrine levels, improved bone marrow cellularity, restored erythroid progenitor colony growth, and improved hemoglobin (14.1±0.6 vs. 10.8±0.6 g/dL). The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased HPC mobilization and restored G-CSF levels. Conclusions After lung contusion/hemorrhagic shock with chronic restraint stress, daily administration of clonidine restored bone marrow function and improved anemia. Alleviating chronic stress and decreasing norepinephrine is a key therapeutic target to improve bone marrow function after severe injury. PMID:27742030

Impaired glucose tolerance and dyslipidaemia as late effects after bone-marrow transplantation in childhood.

PubMed

Taskinen, M; Saarinen-Pihkala, U M; Hovi, L; Lipsanen-Nyman, M

2000-09-16

This follow-up study aimed to assess the frequency of late effects on glucose and lipid metabolism after bone-marrow transplantation in childhood. 23 long-term survivors (median age 20 years) were studied 3-18 years after bone-marrow transplantation and compared with 23 healthy controls matched for age and sex and with 13 patients in remission from leukaemia. 12 (52%) of the 23 bone-marrow transplantation patients had insulin resistance, including impaired glucose tolerance in six and type 2 diabetes in four. The core signs of the metabolic syndrome (hyperinsulinaemia and hypertriglyceridaemia combined), were found in nine (39%) of the bone-marrow transplantation patients compared with one (8%) of the 13 leukaemia patients and none of the healthy controls (p=0.0015). The frequency of insulin resistance increased with the time since bone-marrow transplantation. Abdominal obesity, but not overweight, was common among the patients with insulin resistance. Long-term survivors of bone-marrow transplantation are at substantial risk of insulin resistance, impaired glucose tolerance, and type 2 diabetes even at normal weight and young age. They also develop typical signs of the metabolic syndrome. We advocate measurement of serum lipids, fasting blood glucose, and serum insulin for the follow-up of all patients who undergo transplants in childhood, to be continued regularly and possibly life-long.

Soluble factor(s) from bone marrow cells can rescue lethally irradiated mice by protecting endogenous hematopoietic stem cells.

PubMed

Zhao, Yi; Zhan, Yuxia; Burke, Kathleen A; Anderson, W French

2005-04-01

Ionizing radiation-induced myeloablation can be rescued via bone marrow transplantation (BMT) or administration of cytokines if given within 2 hours after radiation exposure. There is no evidence for the existence of soluble factors that can rescue an animal after a lethal dose of radiation when administered several hours postradiation. We established a system that could test the possibility for the existence of soluble factors that could be used more than 2 hours postirradiation to rescue animals. Animals with an implanted TheraCyte immunoisolation device (TID) received lethal-dose radiation and then normal bone marrow Lin- cells were loaded into the device (thereby preventing direct interaction between donor and recipient cells). Animal survival was evaluated and stem cell activity was tested with secondary bone marrow transplantation and flow cytometry analysis. Donor cell gene expression of five antiapoptotic cytokines was examined. Bone marrow Lin- cells rescued lethally irradiated animals via soluble factor(s). Bone marrow cells from the rescued animals can rescue and repopulate secondary lethally irradiated animals. Within the first 6 hours post-lethal-dose radiation, there is no significant change of gene expression of the known radioprotective factors TPO, SCF, IL-3, Flt-3 ligand, and SDF-1. Hematopoietic stem cells can be protected in lethally irradiated animals by soluble factors produced by bone marrow Lin- cells.

Validation of osteogenic properties of Cytochalasin D by high-resolution RNA-sequencing in mesenchymal stem cells derived from bone marrow and adipose tissues.

PubMed

Samsonraj, Rebekah; Paradise, Christopher R; Dudakovic, Amel; Sen, Buer; Nair, Asha A; Dietz, Allan B; Deyle, David R; Cool, Simon M; Rubin, Janet; van Wijnen, Andre

2018-06-08

Differentiation of mesenchymal stromal/stem cells (MSCs) involves a series of molecular signals and gene transcription events required for attaining cell lineage commitment. Modulation of the actin cytoskeleton using cytochalasin D (CytoD) drives osteogenesis at early time points in bone marrow-derived MSCs, and also initiates a robust osteogenic differentiation program in adipose-derived MSCs. To understand the molecular basis for these pronounced effects on osteogenic differentiation, we investigated global changes in gene expression in CytoD-treated murine and human MSCs by high-resolution RNA-sequencing (RNA-seq) analysis. A three-way bioinformatic comparison between human adipose-derived, human bone marrow-derived and mouse bone marrow-derived MSCs revealed significant upregulation of genes linked to extracellular matrix organization, cell adhesion and bone metabolism. As anticipated, the activation of these differentiation related genes is accompanied by a downregulation of nuclear and cell cycle-related genes presumably reflecting cytostatic effects of CytoD. We also identified eight novel CytoD activated genes - VGLL4, ARHGAP24, KLHL24, RCBTB2, BDH2, SCARF2, ACAD10, HEPH - which are commonly upregulated across the two species and tissue sources of our MSC samples. We selected the Hippo-pathway related VGLL4 gene, which encodes the transcriptional co-factor Vestigial-like 4, for further study because this pathway is linked to osteogenesis. VGLL4 siRNA depletion reduces mineralization of adipose-derived MSCs during CytoD-induced osteogenic differentiation. Together, our RNA-seq analyses suggest that while the stimulatory effects of CytoD on osteogenesis are pleiotropic and depend on the biological state of the cell type, a small group of genes including VGLL4 may contribute to MSC commitment towards the bone lineage.

Gene expression profiling of bone marrow mesenchymal stem cells from Osteogenesis Imperfecta patients during osteoblast differentiation.

PubMed

Kaneto, Carla Martins; Pereira Lima, Patrícia S; Prata, Karen Lima; Dos Santos, Jane Lima; de Pina Neto, João Monteiro; Panepucci, Rodrigo Alexandre; Noushmehr, Houtan; Covas, Dimas Tadeu; de Paula, Francisco José Alburquerque; Silva, Wilson Araújo

2017-06-01

Mesenchymal stem cells (MSCs) are precursors present in adult bone marrow that are able to differentiate into osteoblasts, adipocytes and chondroblasts that have gained great importance as a source for cell therapy. Recently, a number of studies involving the analysis of gene expression of undifferentiated MSCs and of MSCs in the differentiation into multiple lineage processes were observed but there is no information concerning the gene expression of MSCs from Osteogenesis Imperfecta (OI) patients. Osteogenesis Imperfecta is characterized as a genetic disorder in which a generalized osteopenia leads to excessive bone fragility and severe bone deformities. The aim of this study was to analyze gene expression profile during osteogenic differentiation from BMMSCs (Bone Marrow Mesenchymal Stem Cells) obtained from patients with Osteogenesis Imperfecta and from control subjects. Bone marrow samples were collected from three normal subjects and five patients with OI. Mononuclear cells were isolated for obtaining mesenchymal cells that had been expanded until osteogenic differentiation was induced. RNA was harvested at seven time points during the osteogenic differentiation period (D0, D+1, D+2, D+7, D+12, D+17 and D+21). Gene expression analysis was performed by the microarray technique and identified several differentially expressed genes. Some important genes for osteoblast differentiation had lower expression in OI patients, suggesting a smaller commitment of these patient's MSCs with the osteogenic lineage. Other genes also had their differential expression confirmed by RT-qPCR. An increase in the expression of genes related to adipocytes was observed, suggesting an increase of adipogenic differentiation at the expense osteogenic differentiation. Copyright © 2017. Published by Elsevier Masson SAS.

β3-Adrenergic Regulation of EPC Features Through Manipulation of the Bone Marrow MSC Niche.

PubMed

Vafaei, Rana; Nassiri, Seyed Mahdi; Siavashi, Vahid

2017-12-01

Mesenchymal stem cells (MSCs) reside in a specific niche in the bone marrow, however, biological features of this niche are still not fully understood. Given the interactions of MSCs with endothelial cells in different tissues, bone marrow MSC niche may influence the biological features of endothelial progenitor cells (EPCs). To understand the role of the sympathetic nervous system in regulation of the MSC niche, we examined whether the manipulation of the MSC niche via β3-adrenergic signals will affect EPC features. A selective β3 agonist (BRL37344) or a β3 antagonist (SR59230A) was administered in mice for 2 weeks to determine the potential effects of these regimens on the population of CD133 + stem cells in the bone marrow. Then, bone marrow-derived MSCs and EPCs were harvested and expanded from the mice to examine the effect of changes in the MSC niche on EPC features. Improved MSC colony forming potency with increased bone marrow stromal cell-derived factor 1 (SDF-1) (also known as C-X-C motif chemokine 12 [CXCL12]) expression was shown as a result of intensification of the bone marrow adrenergic signals through BRL37344 injection. On the other hand, the blockage of these signals limited the expression level of SDF-1 and resulted in bone marrow enrichment of CD133 + cells. Manipulation of the MSC niche and decreased SDF-1 expression via SR59230A injection also prompted EPCs to form more colonies with augmented proliferation and differentiation capacity. Overall, our results indicate that the β3-adrenergic signals regulate the MSC niche, thereby resulting in modulation of EPC biological features. J. Cell. Biochem. 118: 4753-4761, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Restoration of prostaglandin E2-producing splenic macrophages in sup 89 Sr-treated mice with bone marrow from Corynebacterium parvum primed donors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shibata, Y.

1989-05-01

Administration of Corynebacterium parvum (CP), 56 mg/kg ip to CBA/J mice effected the induction of prostaglandin E2 (PGE2) producing macrophages (M phi) in the bone marrow and the spleen. Maximal release of PGE2 from M phi cultured in vitro with calcium ionophore A23187 for 2 h was reached by marrow M phi removed on 5 days after CP (450 ng/mg cell protein), and by splenic M phi 9 days after CP (400 ng/mg). Neither M phi population, however, yielded more than 6.0 ng/mg leukotriene C4. To assess ontogenic relationships mice were depleted of bone marrow and blood monocytes by ivmore » injection of the bone-seeking isotope, 89Sr. CP was given at several points before or after bone marrow cell depletion. PGE2 production by splenic M phi harvested on day 9 after CP was profoundly impaired when CP was administered either concurrently with or 3 days after 89Sr. When CP was administered 1, 3, 5, and 7 days before 89Sr, however, the induction of PGE2-producing M phi in the spleen was unaffected. To determine whether bone marrow cells from CP-injected donors can restore PGE2-producing splenic M phi (PGSM) in 89Sr-mice, recipient mice which had and had not received CP 3 days after 89Sr were transfused with 5 x 10(6) syngeneic bone marrow cells from donor mice prepared at varying intervals after CP administration. The results clearly indicate the capacity of bone marrow cells harvested on either day 1 or 2 following CP to restore PGSM in CP-primed, but not unprimed, recipients.« less

Understanding deregulated cellular and molecular dynamics in the haematopoietic stem cell niche to develop novel therapeutics for bone marrow fibrosis.

PubMed

Gleitz, Hélène Fe; Kramann, Rafael; Schneider, Rebekka K

2018-06-01

Bone marrow fibrosis is the continuous replacement of blood-forming cells in the bone marrow with excessive scar tissue, leading to failure of the body to produce blood cells and ultimately to death. Myofibroblasts are fibrosis-driving cells and are well characterized in solid organ fibrosis, but their role and cellular origin in bone marrow fibrosis have remained obscure. Recent work has demonstrated that Gli1 + and leptin receptor + mesenchymal stromal cells are progenitors of fibrosis-causing myofibroblasts in the bone marrow. Genetic ablation or pharmacological inhibition of Gli1 + mesenchymal stromal cells ameliorated fibrosis in mouse models of myelofibrosis. Conditional deletion of the platelet-derived growth factor (PDGF) receptor-α (PDGFRA) gene (Pdgfra) and inhibition of PDGFRA by imatinib in leptin receptor + stromal cells suppressed their expansion and ameliorated bone marrow fibrosis. Understanding the cellular and molecular mechanisms in the haematopoietic stem cell niche that govern the mesenchymal stromal cell-to-myofibroblast transition and myofibroblast expansion will be critical to understand the pathogenesis of bone marrow fibrosis in both malignant and non-malignant conditions, and will guide the development of novel therapeutics. In this review, we summarize recent discoveries of mesenchymal stromal cells as part of the haematopoietic niche and as myofibroblast precursors, and discuss potential therapeutic strategies in the specific targeting of fibrotic transformation in bone marrow fibrosis. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Clinical Utility of Dual-Energy CT Analysis of Bone Marrow Edema in Acute Wrist Fractures.

PubMed

Ali, Ismail T; Wong, William D; Liang, Teresa; Khosa, Faisal; Mian, Memoona; Jalal, Sabeena; Nicolaou, Savvas

2018-04-01

The purpose of this study is to determine the utility of dual-energy CT (DECT) for assessing carpal fractures and to obtain an attenuation value cutoff (in Hounsfield units) to identify bone marrow edema due to an acute carpal fracture. In this retrospective study, 24 patients who presented with wrist fractures from September 3, 2014, through March 9, 2015, underwent imaging with DECT (80 and 140 kVp). Using the three-material decomposition algorithm specific for virtual noncalcium to construct images, two radiologists identified carpal fractures and associated bone marrow edema. Readers noted the attenuation at areas with and without bone marrow edema. The cutoff value was obtained by ROC analysis and was internally validated on 13 separate patients with suspected wrist fractures. A p < 0.05 was considered statistically significant. CT attenuation was significantly higher in areas of bone marrow edema than in areas without it (p < 0.0001, t test). A cutoff of 5.90 HU allows detection of bone marrow edema associated with acute wrist fractures with 100% sensitivity and 99.5% specificity, compared with visual DECT interpretation. In the 13 validation cases, the cutoff of 5.90 HU identified bone marrow edema with 100% accuracy, compared with visual interpretation. Kappa values were 0.83 between the two readings by reader 1, and 0.73 and 0.96 comparing the two readings of reader 1 with the reading by reader 2. DECT is a useful tool for identifying bone marrow edema in the setting of acute wrist fractures, providing an alternative to MRI. A cutoff value of 5.90 HU can be used for accurate diagnosis and exclusion of carpal fractures.

Marrow changes in anorexia nervosa masking the presence of stress fractures on MR imaging.

PubMed

Tins, Bernhard; Cassar-Pullicino, Victor

2006-11-01

Patients with anorexia nervosa (AN) usually have abnormal bone and bone marrow metabolism resulting in osteopenia and serous bone marrow change. There is an increased risk of stress/insufficiency fractures and these can be the first presentation of AN. This case report describes a patient with previously undiagnosed AN who presented with foot pain. The serous bone marrow changes of AN were found to mask the MR imaging features of stress fractures, as both had low T1w and high T2w and STIR signal intensities. Contrast enhancement was not helpful but actually masked fractures. Scintigraphy was helpful. The radiologist might be the first clinician to raise the possibility of AN and should be aware of the difficulties in diagnosing stress fractures in bones with underlying serous bone marrow change. In this severe case of AN even the heel fat pad and the fat pad in Kager's triangle had undergone serous change.

[Search for non-relative donor by the Russian register of bone marrow donors].

PubMed

Zaretskaia, Iu M; Khamaganova, E G; Aleshchenko, S M; Murashova, L A

2002-01-01

To select maximally HLA compatible donor for hematological patients who need transplantation of bone marrow from non-relative donor. 75 patients with hematological malignancy were observed. All of them have indications to non-relative transplantation of the bone marrow. Methods of polymerase chain reaction with sequence-specific primers and classic microlymphocytotoxic test were used. Typing of HLA antigens of class I and alleles of class II loci enabled search for non-relative donor for transplantation of bone marrow in accordance with the requirements of the European Federation of Immunogenetics. Most of the patients (86.6%) had at least one potential HLA-A, -B, -DR compatible donor. Half of the patients had potential donors typed at the allele level by class II loci. This diminishes time of HLA compatible donor selection. DNA typing enables the search for the non-relative donors meeting modern requirements. This allowed 5 non-relative bone marrow transplantations.

Curative bone marrow transplantation in erythropoietic protoporphyria after reversal of severe cholestasis.

PubMed

Wahlin, Staffan; Aschan, Johan; Björnstedt, Mikael; Broomé, Ulrika; Harper, Pauline

2007-01-01

We report the case of a middle-age patient presenting with severe progressive protoporphyric cholestasis. To halt further progression of liver disease, medical treatment was given aimed at different mechanisms possibly causing cholestasis in erythropoietic protoporphyria. Within eighty days, liver biochemistry completely normalized and liver histology markedly improved. Bone marrow transplantation was performed to prevent relapse of cholestatic liver disease by correcting the main site of protoporphyrin overproduction. Thirty-three months after cholestatic presentation and ten months after bone marrow transplantation, liver and porphyrin biochemistry remains normal. The patient is in excellent condition and photosensitivity is absent. The theoretical role of each treatment used to successfully reverse cholestasis and the role of bone marrow transplantation in erythropoietic protoporphyria are discussed. Medical treatment can resolve hepatic abnormalities in protoporphyric cholestasis. Bone marrow transplantation achieves phenotypic reversal and may offer protection from future protoporphyric liver disease.

Distinct bone marrow blood vessels differentially regulate haematopoiesis.

PubMed

Itkin, Tomer; Gur-Cohen, Shiri; Spencer, Joel A; Schajnovitz, Amir; Ramasamy, Saravana K; Kusumbe, Anjali P; Ledergor, Guy; Jung, Yookyung; Milo, Idan; Poulos, Michael G; Kalinkovich, Alexander; Ludin, Aya; Kollet, Orit; Shakhar, Guy; Butler, Jason M; Rafii, Shahin; Adams, Ralf H; Scadden, David T; Lin, Charles P; Lapidot, Tsvee

2016-04-21

Bone marrow endothelial cells (BMECs) form a network of blood vessels that regulate both leukocyte trafficking and haematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs balance these dual roles, and whether these events occur at the same vascular site. We found that mammalian bone marrow stem cell maintenance and leukocyte trafficking are regulated by distinct blood vessel types with different permeability properties. Less permeable arterial blood vessels maintain haematopoietic stem cells in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the bone marrow. A functional consequence of high permeability of blood vessels is that exposure to blood plasma increases bone marrow HSPC ROS levels, augmenting their migration and differentiation, while compromising their long-term repopulation and survival. These findings may have relevance for clinical haematopoietic stem cell transplantation and mobilization protocols.

The Differentiation Balance of Bone Marrow Mesenchymal Stem Cells Is Crucial to Hematopoiesis

PubMed Central

Zhang, Weiwei; Ran, Qian; Xiang, Yang; Zhong, Jiang F.; Li, Shengwen Calvin

2018-01-01

Bone marrow mesenchymal stem cells (BMSCs), the important component and regulator of bone marrow microenvironment, give rise to hematopoietic-supporting stromal cells and form hematopoietic niches for hematopoietic stem cells (HSCs). However, how BMSC differentiation affects hematopoiesis is poorly understood. In this review, we focus on the role of BMSC differentiation in hematopoiesis. We discussed the role of BMSCs and their progeny in hematopoiesis. We also examine the mechanisms that cause differentiation bias of BMSCs in stress conditions including aging, irradiation, and chemotherapy. Moreover, the differentiation balance of BMSCs is crucial to hematopoiesis. We highlight the negative effects of differentiation bias of BMSCs on hematopoietic recovery after bone marrow transplantation. Keeping the differentiation balance of BMSCs is critical for hematopoietic recovery. This review summarises current understanding about how BMSC differentiation affects hematopoiesis and its potential application in improving hematopoietic recovery after bone marrow transplantation. PMID:29765406

Combinatorial Gata2 and Sca1 expression defines hematopoietic stem cells in the bone marrow niche

PubMed Central

Suzuki, Norio; Ohneda, Osamu; Minegishi, Naoko; Nishikawa, Mitsuo; Ohta, Takayuki; Takahashi, Satoru; Engel, James Douglas; Yamamoto, Masayuki

2006-01-01

The interaction between stem cells and their supportive microenvironment is critical for their maintenance, function, and survival. Whereas hematopoietic stem cells (HSCs) are among the best characterized of tissue stem cells, their precise site of residence (referred to as the niche) in the adult bone marrow has not been precisely defined. In this study, we found that a Gata2 promoter directs activity in all HSCs. We show that HSCs can be isolated efficiently from bone marrow cells by following Gata2-directed GFP fluorescence, and that they can also be monitored in vivo. Each individual GFP-positive cell lay in a G0/G1 cell cycle state, in intimate contact with osteoblasts beside the endosteum, at the edge of the bone marrow. We conclude that the HSC niche is composed of solitary cells and that adult bone marrow HSC are not clustered. PMID:16461905

New factors controlling the balance between osteoblastogenesis and adipogenesis.

PubMed

Abdallah, Basem M; Kassem, Moustapha

2012-02-01

The majority of conditions associated with bone loss, including aging, are accompanied by increased marrow adiposity possibly due to shifting of the balance between osteoblast and adipocyte differentiation in bone marrow stromal (skeletal) stem cells (MSC). In order to study the relationship between osteoblastogenesis and adipogenesis in bone marrow, we have characterized cellular models of multipotent MSC as well as pre-osteoblastic and pre-adipocytic cell populations. Using these models, we identified two secreted factors in the bone marrow microenviroment: secreted frizzled-related protein 1 (sFRP-1) and delta-like1 (preadipocyte factor 1) (Dlk1/Pref-1). Both exert regulatory effects on osteoblastogenesis and adipogenesis. Our studies suggest a model for lineage fate determination of MSC that is regulated through secreted factors in the bone marrow microenvironment that mediate a cross-talk between lineage committed cell populations in addition to controlling differentiation choices of multipotent MSC. Copyright © 2011 Elsevier Inc. All rights reserved.

Prominent gelatinous bone marrow transformation presenting prior to myelodysplastic syndrome: a case report with review of the literature.

PubMed

Nakanishi, Ryota; Ishida, Mitsuaki; Hodohara, Keiko; Yoshida, Takashi; Yoshii, Miyuki; Okuno, Hiroko; Horinouchi, Akiko; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Okabe, Hidetoshi

2013-01-01

Gelatinous bone marrow transformation (GMT) is a rare disorder characterized by the presence of fat cell atrophy, loss of hematopoietic cells, and deposition of extracellular gelatinous materials. GMT is not a specific disease, but is strongly associated with malnutrition and drugs. Albeit extremely rare, GMT has been reported in patients with myeloproliferative disorders. Herein, we report the second documented case of hypoplastic myelodysplastic syndrome (MDS) accompanying GMT. A 73-year-old Japanese male with excellent nutrition status and no history of alcohol or drug intake was detected with pancytopenia. The initial bone marrow aspirate specimen reveled hypocellular marrow without dysplastic signs in the myeloid cells. Bone marrow biopsy demonstrated hypocellular bone marrow with prominent GMT. He received blood transfusions, however, pancytopenia continued to progress. The second bone marrow aspirate specimen showed dysplastic changes, such as pseudo-Pelger-Huët cells, hypogranular or agranular granulocytes, and megakaryocytes with multiple small nuclei. Cytogenetic study demonstrated deletion of chromosome 7. Therefore, an ultimate diagnosis of hypoplastic MDS accompanying GMT was made. Only a limited number of cases of myeloproliferative disorders with GMT have been reported. Our analysis of these cases revealed that chromosome 7 abnormality is frequently observed in this condition. Moreover, findings from the current case suggested that myeloproliferative disorders including MDS must be included in the differential diagnostic considerations of GMT patients, who have no history of malnutrition or drugs, and careful examination of the bone marrow smear specimen and cytogenetic analysis are necessary for early detection of underlying myeloproliferative disorders.

Bone marrow induced osteogenesis in hydroxyapatite and calcium carbonate implants.

PubMed

Vuola, J; Göransson, H; Böhling, T; Asko-Seljavaara, S

1996-09-01

In this experimental study, blocks of natural coral (calcium carbonate) and its structurally similar derivate in the form of hydroxyapatite (calcium phosphate) were implanted in rat latissimus dorsi muscle with autogenous bone marrow to compare their bone-forming capability. A block without marrow placed in the opposite latissimus muscle served as a control. The animals were killed at 3, 6 and 12 weeks and, in the hydroxyapatite group, also at 24 weeks. The sections were analysed histologically and histomorphometrically. Bone was found only in implants containing bone marrow. Bone formation was significantly (p < 0.05) higher in coral than in hydroxyapatite implants at 3 weeks (10.8% versus 4.8%) and at 12 weeks (13.7% versus 6.3%, bone/total original block area). At 12 weeks all the coral implants had lost their original structure, and the cross-sectional area of the block had diminished to 40% of the original area.

Bone marrow necrosis secondary to imatinib usage, mimicking spinal metastasis on magnetic resonance imaging and FDG-PET/CT.

PubMed

Aras, Yavuz; Akcakaya, Mehmet Osman; Unal, Seher N; Bilgic, Bilge; Unal, Omer Faruk

2012-01-01

Imatinib mesylate has become the treatment of choice for gastrointestinal stromal tumors (GISTs) and has made a revolutionary impact on survival rates. Bone marrow necrosis is a very rare adverse event in malignant GIST. Bone metastases are also rarely encountered in the setting of this disease. The authors report on a patient with malignant GIST who developed a bone lesion, mimicking spinal metastasis on both MR imaging and FDG-PET/CT. Corpectomy and anterior fusion was performed, but the pathology report was consistent with bone marrow necrosis. Radiological and clinical similarities made the distinction between metastasis and bone marrow necrosis challenging for the treating physicians. Instead of radical surgical excision, more conservative methods such as percutaneous or endoscopic bone biopsies may be more useful for pathological confirmation, even though investigations such as MR imaging and FDG-PET/CT indicate metastatic disease.

A fatal case of bone marrow embolism of unknown cause masquerading clinically as dengue shock syndrome.

PubMed

Selvi, Subramanian Kalaivani; Kar, Rakhee; Vadivelan, Mehalingam; Subrahmanyam, Dharanipragada Krishna Suri

2012-01-01

Bone marrow fat embolism usually occurs following multiple bone fractures, intraosseous surgical procedures, following vigorous cardiac resuscitation, ecclampsia, sickle cell anemia, malignancies, etc. We present a case of 70-year-old male who presented with fever, cough with expectoration, respiratory distress, altered sensorium, hypotension and thrombocytopenia, and diagnosed to have dengue shock syndrome and expired within 1 day of admission. Postmortem lung biopsy revealed bone marrow fat embolism.

Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment

PubMed Central

Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Fahey, Frederic; Daley, George Q.

2009-01-01

Osteoblasts and endothelium constitute functional niches that support hematopoietic stem cells (HSC) in mammalian bone marrow (BM) 1,2,3 . Adult BM also contains adipocytes, whose numbers correlate inversely with the hematopoietic activity of the marrow. Fatty infiltration of hematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia 4. To explore whether adipocytes influence hematopoiesis or simply fill marrow space, we compared the hematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. By flow cytometry, colony forming activity, and competitive repopulation assay, HSCs and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 “fatless” mice, which are genetically incapable of forming adipocytes8, and in mice treated with the PPARγ inhibitor Bisphenol-A-DiGlycidyl-Ether (BADGE), which inhibits adipogenesis9, post-irradiation marrow engraftment is accelerated relative to wild type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone marrow microenvironment, and suggest that antagonizingmarrow adipogenesis may enhance hematopoietic recovery in clinical bone marrow transplantation. PMID:19516257

78 FR 60810 - Change to the Definition of “Human Organ” Under Section 301 of the National Organ Transplant Act...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-02

... hematopoietic stem cells (HSCs) within peripheral blood in the definition of ``bone marrow.'' This would clarify... of whether they were recovered directly from bone marrow (by aspiration) or from peripheral blood (by... consideration.'' ``Human organ'' is defined to include ``bone marrow * * * or any subpart thereof'' or any organ...

[Endogenous pyrogen formation by bone marrow cells].

PubMed

Efremov, O M; Sorokin, A V; El'kina, O A

1978-01-01

The cells of the rabbit bone marrow produced endogenous pyrogen in response to stimulation with bacterial lipopolysaccharide. Incubation of the cells in medium No 199 containing a 15% homologous serum is optimal for the release of pyrogen. It is supposed that the cells of the bone marrow take part in the formation of endgenous pyrogen and in the mechanism of pyrexia in the organism.

Long-term survival of donor bone marrow multipotent mesenchymal stromal cells implanted into the periosteum of patients with allogeneic graft failure.

PubMed

Kuzmina, L A; Petinati, N A; Sats, N V; Drize, N J; Risinskaya, N V; Sudarikov, A B; Vasilieva, V A; Drokov, M Y; Michalzova, E D; Parovichnikova, E N; Savchenko, V G

2016-09-01

The present study involved three patients with graft failure following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We obtained multipotent mesenchymal stromal cells (MSCs) from the original hematopoietic cell donors and implanted these cells in the periosteum to treat long-term bone marrow aplasia. The results showed that in all patients endogenous blood formation was recovered 2 weeks after MSC administration. Donor MSCs were found in recipient bone marrow three and 5 months following MSC implantation. Thus, our findings indicate that functional donor MSCs can persist in patient bone marrow.

Effects of Low-Dose Total-Body Irradiation on Canine Bone Marrow Function and Canine Lymphoma

DTIC Science & Technology

1981-11-01

SCIENTIFIC REPORT Effects of low-dose total-body irradiation on canine bone marrow function and canine lymphoma cc ca D. E. Cowal! 7. J. MacVittie G... CANINE BONE MARROW FUNCTION AND CANINE LYMPHOMA 6. PERFORMING O1G. REPORT NUMBER 7. AUTHO1R(s) 8. CONTRACT OR GRANT NUMBER(s) Dt E. Cowall*, T. J...ott it e r .f00 !(1414011V byt block tumbv,) canine , I’M, bone marrow, GM-CFC 20 A US TR AC y t (𔃺t 104#0 00 ,r ,. @#PS#0 It Ml 0 le~ 9 ncj0 dd0 19

[Regulatory problems regarding bone marrow transplantation from non-consanguinous donors].

PubMed

Moratti, A

1999-01-01

The paper reports the normative rules and the Italian Ministry of Health administrative instructions concerning the bone marrow unrelated donor (MUD) search in the Italian Bone Marrow Donor Registry (IBMDR) and in international registries from the preliminary activation to a MUD bone marrow transplant (BMT), when a volunteer donor, perfectly compatible with a recipient lacking a HLA identical sibling, is found. The article describes all the expenses pertinent to the different stages of search and the documents necessary to obtain the reimbursement of these expenses. A very recent Ministry Decree establishing that all the search costs will be charged to the competent local sanitary authority is added.

Molecular cloning and chromosomal mapping of bone marrow stromal cell surface gene, BST2, that may be involved in pre-B-cell growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ishikawa, Jun; Kaisho, Tsuneyasu; Tomizawa, Hitoshi

1995-04-10

Bone marrow stromal cells regulate B-cell growth and development through their surface molecules and cytokines. In this study, we generated a mAb, RS38, that recognized a novel human membrane protein, BST-2, expressed on bone marrow stromal cell lines and synovial cell lines. We cloned a cDNA encoding BST-2 from a rheumatoid arthritis-derived synovial cell line. BST-2 is a 30- to 36-kDa type II transmembrane protein, consisting of 180 amino acids. The BST-2 gene (HGMW-approved symbol BST2) is located on chromosome 19p13.2. BST-2 is expressed not only on certain bone marrow stromal cell lines but also on various normal tissues, althoughmore » its expression pattern is different from that of another bone marrow stromal cell surface molecule, BST-1. BST-2 surface expression on fibroblast cell lines facilitated the stromal cell-dependent growth of a murine bone marrow-derived pre-B-cell line, DW34. The results suggest that BST-2 may be involved in pre-B-cell growth. 45 refs., 7 figs., 2 tabs.« less

PAR1 signaling regulates the retention and recruitment of EPCR-expressing bone marrow hematopoietic stem cells

PubMed Central

Gur-Cohen, Shiri; Itkin, Tomer; Chakrabarty, Sagarika; Graf, Claudine; Kollet, Orit; Ludin, Aya; Golan, Karin; Kalinkovich, Alexander; Ledergor, Guy; Wong, Eitan; Niemeyer, Elisabeth; Porat, Ziv; Erez, Ayelet; Sagi, Irit; Esmon, Charles T; Ruf, Wolfram; Lapidot, Tsvee

2016-01-01

Retention of long-term repopulating hematopoietic stem cells (LT-HSCs) in the bone marrow is essential for hematopoiesis and for protection from myelotoxic injury. We report that signaling cascades that are traditionally viewed as coagulation-related also control retention of EPCR+ LT-HSCs in the bone marrow and their recruitment to the blood via two different protease activated receptor 1 (PAR1)-mediated pathways. Thrombin-PAR1 signaling induces nitric oxide (NO) production, leading to TACE-mediated EPCR shedding, enhanced CXCL12-CXCR4-induced motility, and rapid stem and progenitor cell mobilization. Conversely, bone marrow blood vessels provide a microenvironment enriched with protein C that retain EPCR+ LT-HSCs by limiting NO generation, reducing Cdc42 activity and enhancing VLA4 affinity and adhesion. Inhibition of NO production by activated protein C (aPC)-EPCR-PAR1 signaling reduces progenitor cell egress, increases NOlow bone marrow EPCR+ LT-HSCs retention and protects mice from chemotherapy-induced hematological failure and death. Our study reveals new roles for PAR1 and EPCR that control NO production to balance maintenance and recruitment of bone marrow EPCR+ LT-HSCs with clinical relevance. PMID:26457757

Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo.

PubMed

Massberg, Steffen; Konrad, Ildiko; Schürzinger, Katrin; Lorenz, Michael; Schneider, Simon; Zohlnhoefer, Dietlind; Hoppe, Katharina; Schiemann, Matthias; Kennerknecht, Elisabeth; Sauer, Susanne; Schulz, Christian; Kerstan, Sandra; Rudelius, Martina; Seidl, Stefan; Sorge, Falko; Langer, Harald; Peluso, Mario; Goyal, Pankaj; Vestweber, Dietmar; Emambokus, Nikla R; Busch, Dirk H; Frampton, Jon; Gawaz, Meinrad

2006-05-15

The accumulation of smooth muscle and endothelial cells is essential for remodeling and repair of injured blood vessel walls. Bone marrow-derived progenitor cells have been implicated in vascular repair and remodeling; however, the mechanisms underlying their recruitment to the site of injury remain elusive. Here, using real-time in vivo fluorescence microscopy, we show that platelets provide the critical signal that recruits CD34+ bone marrow cells and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells to sites of vascular injury. Correspondingly, specific inhibition of platelet adhesion virtually abrogated the accumulation of both CD34+ and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells at sites of endothelial disruption. Binding of bone marrow cells to platelets involves both P-selectin and GPIIb integrin on platelets. Unexpectedly, we found that activated platelets secrete the chemokine SDF-1alpha, thereby supporting further primary adhesion and migration of progenitor cells. These findings establish the platelet as a major player in the initiation of vascular remodeling, a process of fundamental importance for vascular repair and pathological remodeling after vascular injury.

Investigation into Variation of Endogenous Metabolites in Bone Marrow Cells and Plasma in C3H/He Mice Exposed to Benzene

PubMed Central

Sun, Rongli; Zhang, Juan; Yin, Lihong; Pu, Yuepu

2014-01-01

Benzene is identified as a carcinogen. Continued exposure of benzene may eventually lead to damage to the bone marrow, accompanied by pancytopenia, aplastic anemia or leukemia. This paper explores the variations of endogenous metabolites to provide possible clues for the molecular mechanism of benzene-induced hematotoxicity. Liquid chromatography coupled with time of flight-mass spectrometry (LC-TOF-MS) and principal component analysis (PCA) was applied to investigate the variation of endogenous metabolites in bone marrow cells and plasma of male C3H/He mice. The mice were injected subcutaneously with benzene (0, 300, 600 mg/day) once daily for seven days. The body weights, relative organ weights, blood parameters and bone marrow smears were also analyzed. The results indicated that benzene caused disturbances in the metabolism of oxidation of fatty acids and essential amino acids (lysine, phenylalanine and tyrosine) in bone marrow cells. Moreover, fatty acid oxidation was also disturbed in plasma and thus might be a common disturbed metabolic pathway induced by benzene in multiple organs. This study aims to investigate the underlying molecular mechanisms involved in benzene hematotoxicity, especially in bone marrow cells. PMID:24658442

CELLS INVOLVED IN THE IMMUNE RESPONSE

PubMed Central

Singhal, Sharwan K.; Richter, Maxwell

1968-01-01

Cell suspensions of immune rabbit lymph nodes and spleen were capable of undergoing blastogenesis and mitosis and of incorporating tritiated thymidine when maintained in culture with the specific antigen in vitro. They did not respond to other, non-cross-reacting antigens. The blastogenic response obtained with immune lymph node cells could be correlated with the antibody synthesizing capacity of fragment cultures prepared from the same lymph nodes. Cell suspensions of immune bone marrow responded to non-cross-reacting antigens only whereas cell suspensions of immune thymus, sacculus rotundus, and appendix did not respond when exposed to any of the antigens tested. On the other hand, neither fragments nor cell suspensions prepared from lymph nodes, spleen, and thymus of normal, unimmunized rabbits responded with antibody formation and blastogenesis when exposed to any of the antigens. However, normal bone marrow cells responded with marked blastogenesis and tritiated thymidine uptake. The specificity of this in vitro bone marrow response was demonstrated by the fact that the injection of a protein antigen in vivo resulted in the loss of reactivity by the marrow cell to that particular antigen but not to the other, non-cross-reacting antigens. Furthermore, bone marrow cells of tolerant rabbits failed to respond to the specific antigen in vitro. It was also demonstrated that normal bone marrow cells incubated with antigen are capable of forming antibody which could be detected by the fluorescent antibody technique. This response of the bone marrow cells has been localized to the lymphocyte-rich fraction of the bone marrow. It is concluded that the bone marrow lymphocyte, by virtue of its capacity to react with blastogenesis and mitosis and with antibody formation upon initial exposure to the antigen, a capacity not possessed by lymphocytes of the other lymphoid organs, has a preeminent role in the sequence of cellular events culminating in antibody formation. PMID:4176224

Treatment of stroke with (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate and bone marrow stromal cells upregulates angiopoietin-1/Tie2 and enhances neovascularization.

PubMed

Cui, X; Chen, J; Zacharek, A; Roberts, C; Savant-Bhonsale, S; Chopp, M

2008-09-22

Neovascularization may contribute to functional recovery after neural injury. Combination treatment of stroke with a nitric oxide donor, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate (DETA-NONOate) and bone marrow stromal cells promotes functional recovery. However, the mechanisms underlying functional improvement have not been elucidated. In this study, we tested the hypothesis that combination treatment upregulates angiopoietin-1 and its receptor Tie2 in the ischemic brain and bone marrow stromal cells, thereby enhancing cerebral neovascularization after stroke. Adult wild type male C57BL/6 mice were i.v. administered PBS, bone marrow stromal cells 5x10(5), DETA-NONOate 0.4 mg/kg or combination DETA-NONOate with bone marrow stromal cells (n=12/group) after middle cerebral artery occlusion. Combination treatment significantly upregulated angiopoietin-1/Tie2 and tight junction protein (occludin) expression, and increased the number, diameter and perimeter of blood vessels in the ischemic brain compared with vehicle control (mean+ or -S.E., P<0.05). In vitro, DETA-NONOate significantly increased angiopoietin-1/Tie2 protein (n=6/group) and Tie2 mRNA (n=3/group) expression in bone marrow stromal cells. DETA-NONOate also significantly increased angiopoietin-1 protein (n=6/group) and mRNA (n=3/group) expression in mouse brain endothelial cells (P<0.05). Angiopoietin-1 mRNA (n=3/group) was significantly increased in mouse brain endothelial cells treated with DETA-NONOate in combination with bone marrow stromal cell-conditioned medium compared with cells treated with bone marrow stromal cell-conditioned medium or DETA-NONOate alone. Mouse brain endothelial cell capillary tube-like formation assays (n=6/group) showed that angiopoietin-1 peptide, the supernatant of bone marrow stromal cells and DETA-NONOate significantly increased capillary tube formation compared with vehicle control. Combination treatment significantly increased capillary tube formation compared with DETA-NONOate treatment alone. Inhibition of angiopoietin-1 significantly attenuated combination treatment-induced tube formation. Our data indicated that combination treatment of stroke with DETA-NONOate and bone marrow stromal cells promotes neovascularization, which is at least partially mediated by upregulation of the angiopoietin-1/Tie2 axis.

Bone marrow biopsy

MedlinePlus

... aspiration removes a small amount of marrow in liquid form for examination. ... and a syringe is used to withdraw the liquid bone marrow. If this is done, the needle will be removed and repositioned. Or, another needle may be used for the biopsy.

Bone stress injury of the ankle in professional ballet dancers seen on MRI

PubMed Central

Elias, Ilan; Zoga, Adam C; Raikin, Steven M; Peterson, Judith R; Besser, Marcus P; Morrison, William B; Schweitzer, Mark E

2008-01-01

Background Ballet Dancers have been shown to have a relatively high incidence of stress fractures of the foot and ankle. It was our objective to examine MR imaging patterns of bone marrow edema (BME) in the ankles of high performance professional ballet dancers, to evaluate clinical relevance. Methods MR Imaging was performed on 12 ankles of 11 active professional ballet dancers (6 female, 5 male; mean age 24 years, range 19 to 32). Individuals were imaged on a 0.2 T or 1.5 T MRI units. Images were evaluated by two musculoskeletal radiologists and one orthopaedic surgeon in consensus for location and pattern of bone marrow edema. In order to control for recognized sources of bone marrow edema, images were also reviewed for presence of osseous, ligamentous, tendinous and cartilage injuries. Statistical analysis was performed to assess the strength of the correlation between bone marrow edema and ankle pain. Results Bone marrow edema was seen only in the talus, and was a common finding, observed in nine of the twelve ankles imaged (75%) and was associated with pain in all cases. On fluid-sensitive sequences, bone marrow edema was ill-defined and centered in the talar neck or body, although in three cases it extended to the talar dome. No apparent gender predilection was noted. No occult stress fracture could be diagnosed. A moderately strong correlation (phi = 0.77, p= 0.0054) was found between edema and pain in the study population. Conclusion Bone marrow edema seems to be a specific MRI finding in the talus of professional ballet dancers, likely related to biomechanical stress reactions, due to their frequently performed unique maneuvers. Clinically, this condition may indicate a sign of a bone stress injury of the ankle. PMID:18371230

Sequential growth factor application in bone marrow stromal cell ligament engineering.

PubMed

Moreau, Jodie E; Chen, Jingsong; Horan, Rebecca L; Kaplan, David L; Altman, Gregory H

2005-01-01

In vitro bone marrow stromal cell (BMSC) growth may be enhanced through culture medium supplementation, mimicking the biochemical environment in which cells optimally proliferate and differentiate. We hypothesize that the sequential administration of growth factors to first proliferate and then differentiate BMSCs cultured on silk fiber matrices will support the enhanced development of ligament tissue in vitro. Confluent second passage (P2) BMSCs obtained from purified bone marrow aspirates were seeded on RGD-modified silk matrices. Seeded matrices were divided into three groups for 5 days of static culture, with medium supplement of basic fibroblast growth factor (B) (1 ng/mL), epidermal growth factor (E; 1 ng/mL), or growth factor-free control (C). After day 5, medium supplementation was changed to transforming growth factor-beta1 (T; 5 ng/mL) or C for an additional 9 days of culture. Real-time RT-PCR, SEM, MTT, histology, and ELISA for collagen type I of all sample groups were performed. Results indicated that BT supported the greatest cell ingrowth after 14 days of culture in addition to the greatest cumulative collagen type I expression measured by ELISA. Sequential growth factor application promoted significant increases in collagen type I transcript expression from day 5 of culture to day 14, for five of six groups tested. All T-supplemented samples surpassed their respective control samples in both cell ingrowth and collagen deposition. All samples supported spindle-shaped, fibroblast cell morphology, aligning with the direction of silk fibers. These findings indicate significant in vitro ligament development after only 14 days of culture when using a sequential growth factor approach.

Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression

PubMed Central

Xu, Wen Wen; Li, Bin; Guan, Xin Yuan; Chung, Sookja K.; Wang, Yang; Yip, Yim Ling; Law, Simon Y. K.; Chan, Kin Tak; Lee, Nikki P. Y.; Chan, Kwok Wah; Xu, Li Yan; Li, En Min; Tsao, Sai Wah; He, Qing-Yu; Cheung, Annie L. M.

2017-01-01

Local interactions between cancer cells and stroma can produce systemic effects on distant organs to govern cancer progression. Here we show that IGF2 secreted by inhibitor of differentiation (Id1)-overexpressing oesophageal cancer cells instigates VEGFR1-positive bone marrow cells in the tumour macroenvironment to form pre-metastatic niches at distant sites by increasing VEGF secretion from cancer-associated fibroblasts. Cancer cells are then attracted to the metastatic site via the CXCL5/CXCR2 axis. Bone marrow cells transplanted from nude mice bearing Id1-overexpressing oesophageal tumours enhance tumour growth and metastasis in recipient mice, whereas systemic administration of VEGFR1 antibody abrogates these effects. Mechanistically, IGF2 regulates VEGF in fibroblasts via miR-29c in a p53-dependent manner. Analysis of patient serum samples showed that concurrent elevation of IGF2 and VEGF levels may serve as a prognostic biomarker for oesophageal cancer. These findings suggest that the Id1/IGF2/VEGF/VEGFR1 cascade plays a critical role in tumour-driven pathophysiological processes underlying cancer progression. PMID:28186102

Incidence of persistent viraemia and latent feline leukaemia virus infection in cats with lymphoma.

PubMed

Stützer, Bianca; Simon, Karin; Lutz, Hans; Majzoub, Monir; Hermanns, Walter; Hirschberger, Johannes; Sauter-Louis, Carola; Hartmann, Katrin

2011-02-01

In the past, feline leukaemia virus (FeLV) infection, and also latent FeLV infection, were commonly associated with lymphoma and leukaemia. In this study, the prevalence of FeLV provirus in tumour tissue and bone marrow in FeLV antigen-negative cats with these tumours was assessed. Seventy-seven diseased cats were surveyed (61 antigen-negative, 16 antigen-positive). Blood, bone marrow, and tumour samples were investigated by two polymerase chain reaction (PCR) assays detecting deoxyribonucleic acid (DNA) sequences of the long terminal repeats (LTR) and the envelope (env) region of the FeLV genome. Immunohistochemistry (IHC) was performed in bone marrow and tumour tissue. None of the antigen-negative cats with lymphoma was detectably infected with latent FeLV. The prevalence of FeLV viraemia in cats with lymphoma was 20.8%. This suggests that causes other than FeLV play a role in tumorigenesis, and that latent FeLV infection is unlikely to be responsible for most feline lymphomas and leukaemias. Copyright © 2010. Published by Elsevier Ltd.

Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression.

PubMed

Xu, Wen Wen; Li, Bin; Guan, Xin Yuan; Chung, Sookja K; Wang, Yang; Yip, Yim Ling; Law, Simon Y K; Chan, Kin Tak; Lee, Nikki P Y; Chan, Kwok Wah; Xu, Li Yan; Li, En Min; Tsao, Sai Wah; He, Qing-Yu; Cheung, Annie L M

2017-02-10

Local interactions between cancer cells and stroma can produce systemic effects on distant organs to govern cancer progression. Here we show that IGF2 secreted by inhibitor of differentiation (Id1)-overexpressing oesophageal cancer cells instigates VEGFR1-positive bone marrow cells in the tumour macroenvironment to form pre-metastatic niches at distant sites by increasing VEGF secretion from cancer-associated fibroblasts. Cancer cells are then attracted to the metastatic site via the CXCL5/CXCR2 axis. Bone marrow cells transplanted from nude mice bearing Id1-overexpressing oesophageal tumours enhance tumour growth and metastasis in recipient mice, whereas systemic administration of VEGFR1 antibody abrogates these effects. Mechanistically, IGF2 regulates VEGF in fibroblasts via miR-29c in a p53-dependent manner. Analysis of patient serum samples showed that concurrent elevation of IGF2 and VEGF levels may serve as a prognostic biomarker for oesophageal cancer. These findings suggest that the Id1/IGF2/VEGF/VEGFR1 cascade plays a critical role in tumour-driven pathophysiological processes underlying cancer progression.

Clinical, histopathologic, and genetic features of pediatric primary myelofibrosis--an entity different from adults.

PubMed

DeLario, Melissa R; Sheehan, Andrea M; Ataya, Ramona; Bertuch, Alison A; Vega, Carlos; Webb, C Renee; Lopez-Terrada, Dolores; Venkateswaran, Lakshmi

2012-05-01

Primary myelofibrosis is a chronic myeloproliferative neoplasm characterized by cytopenias, leukoerythroblastosis, extramedullary hematopoiesis, hepatosplenomegaly and bone marrow fibrosis. Primary myelofibrosis is a rare disorder in adults; children are even less commonly affected by this entity, with the largest pediatric case series reporting on three patients. Most literature suggests spontaneous resolution of myelofibrosis without long term complications in the majority of affected children. We describe the clinical, pathologic, and molecular characteristics and outcomes of nineteen children with primary myelofibrosis treated in our center from 1984 to 2011. Most patients had cytopenia significant enough to require supportive therapy. No child developed malignant transformation and only five of the 19 children (26%) had spontaneous resolution of disease. Sequence analyses for JAK2V617F and MPLW515L mutations were performed on bone marrow samples from 17 and six patients, respectively, and the results were negative. In conclusion, analysis of this large series of pediatric patients with primary myelofibrosis demonstrates distinct clinical, hematologic, bone marrow, and molecular features from adult patients. Copyright © 2012 Wiley Periodicals, Inc.

Clonidine reduces norepinephrine and improves bone marrow function in a rodent model of lung contusion, hemorrhagic shock, and chronic stress.

PubMed

Alamo, Ines G; Kannan, Kolenkode B; Ramos, Harry; Loftus, Tyler J; Efron, Philip A; Mohr, Alicia M

2017-03-01

Propranolol has been shown previously to restore bone marrow function and improve anemia after lung contusion/hemorrhagic shock. We hypothesized that daily clonidine administration would inhibit central sympathetic outflow and restore bone marrow function in our rodent model of lung contusion/hemorrhagic shock with chronic stress. Male Sprague-Dawley rats underwent 6 days of restraint stress after lung contusion/hemorrhagic shock during which the animals received clonidine (75 μg/kg) after the restraint stress. On postinjury day 7, we assessed urine norepinephrine, blood hemoglobin, plasma granulocyte colony stimulating factor, and peripheral blood mobilization of hematopoietic progenitor cells, as well as bone marrow cellularity and erythroid progenitor cell growth. The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased urine norepinephrine levels, improved bone marrow cellularity, restored erythroid progenitor colony growth, and improved hemoglobin (14.1 ± 0.6 vs 10.8 ± 0.6 g/dL). The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased hematopoietic progenitor cells mobilization and restored granulocyte colony stimulating factor levels. After lung contusion/hemorrhagic shock with chronic restraint stress, daily administration of clonidine restored bone marrow function and improved anemia. Alleviating chronic stress and decreasing norepinephrine is a key therapeutic target to improve bone marrow function after severe injury. Copyright © 2016 Elsevier Inc. All rights reserved.

ω-3 Fatty Acids Reduce Chemotherapy-Induced Hematological Toxicity by Bone Marrow Stimulation in Mice.

PubMed

Murakami, Kohei; Miyata, Hiroshi; Miyazaki, Yasuhiro; Makino, Tomoki; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Yamasaki, Makoto; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

2017-07-01

ω-3 Fatty acids exert several benefits during chemotherapy, such as preventing intestinal mucosal damage and improving response to chemotherapy. However, little is known about the effect of ω-3 fatty acids on chemotherapy-induced hematological toxicities. Mice that had consumed either an ω-3-rich or an ω-3-poor diet for 2 weeks were intraperitoneally administered cisplatin. The resultant changes in blood cell count, bone marrow cell count, and cytokine levels in bone marrow supernatant were analyzed. The effect of ω-3 fatty acids on human peripheral blood mononuclear cells (PBMCs) exposed to cisplatin was also examined. Although peripheral blood cell counts decreased after cisplatin treatment in both groups of mice, the decrease in white blood cell count was significantly lower in mice that consumed the ω-3-rich diet. The decrease in bone marrow cells after cisplatin treatment was also reduced in mice that consumed the ω-3-rich diet. Levels of stem cell factor (SCF) and fibroblast growth factor 1 (FGF-1) were significantly higher in bone marrow supernatants from mice that consumed the ω-3-rich diet. The rate of apoptosis in PBMCs (after exposure to cisplatin) cultured in medium containing ω-3 fatty acids was significantly lower than in PBMCs cultured in control medium. ω-3-Rich diets reduced chemotherapy-induced leukopenia in mice. This may be the result of increased numbers of bone marrow cells due to higher levels of SCF and FGF-1 in the bone marrow.

Long-term in vitro correction of alpha-L-iduronidase deficiency (Hurler syndrome) in human bone marrow.

PubMed Central

Fairbairn, L J; Lashford, L S; Spooncer, E; McDermott, R H; Lebens, G; Arrand, J E; Arrand, J R; Bellantuono, I; Holt, R; Hatton, C E; Cooper, A; Besley, G T; Wraith, J E; Anson, D S; Hopwood, J J; Dexter, T M

1996-01-01

Allogeneic bone marrow transplantation is the most effective treatment for Hurler syndrome but, since this therapy is not available to all patients, we have considered an alternative approach based on transfer and expression of the normal gene in autologous bone marrow. A retroviral vector carrying the full-length cDNA for alpha-L-iduronidase has been constructed and used to transduce bone marrow from patients with this disorder. Various gene-transfer protocols have been assessed including the effect of intensive schedules of exposure of bone marrow to viral supernatant and the influence of growth factors. With these protocols, we have demonstrated successful gene transfer into primitive CD34+ cells and subsequent enzyme expression in their maturing progeny. Also, by using long-term bone marrow cultures, we have demonstrated high levels of enzyme expression sustained for several months. The efficiency of gene transfer has been assessed by PCR analysis of hemopoietic colonies as 25-56%. No advantage has been demonstrated for the addition of growth factors or intensive viral exposure schedules. The enzyme is secreted into the medium and functional localization has been demonstrated by reversal of the phenotypic effects of lysosomal storage in macrophages. This work suggests that retroviral gene transfer into human bone marrow may offer the prospect for gene therapy of Hurler syndrome in young patients without a matched sibling donor. Images Fig. 2 Fig. 4 Fig. 7 Fig. 8 PMID:8700879

Effects of growth hormone administration for 6 months on bone turnover and bone marrow fat in obese premenopausal women.

PubMed

Bredella, Miriam A; Gerweck, Anu V; Barber, Lauren A; Breggia, Anne; Rosen, Clifford J; Torriani, Martin; Miller, Karen K

2014-05-01

Abdominal adiposity is associated with low BMD and decreased growth hormone (GH) secretion, an important regulator of bone homeostasis. The purpose of our study was to determine the effects of a short course of GH on markers of bone turnover and bone marrow fat in premenopausal women with abdominal adiposity. In a 6-month, randomized, double-blind, placebo-controlled trial we studied 79 abdominally obese premenopausal women (21-45 y) who underwent daily sc injections of GH vs. placebo. Main outcome measures were body composition by DXA and CT, bone marrow fat by proton MR spectroscopy, P1NP, CTX, 25(OH)D, hsCRP, undercarboxylated osteocalcin (ucOC), preadipocyte factor 1 (Pref 1), apolipoprotein B (ApoB), and IGF-1. GH increased IGF-1, P1NP, 25(OH)D, ucOC, bone marrow fat and lean mass, and decreased abdominal fat, hsCRP, and ApoB compared with placebo (p<0.05). There was a trend toward an increase in CTX and Pref-1. Among all participants, a 6-month increase in IGF-1 correlated with 6-month increase in P1NP (p=0.0005), suggesting that subjects with the greatest increases in IGF-1 experienced the greatest increases in bone formation. A six-month decrease in abdominal fat, hsCRP, and ApoB inversely predicted 6-month change in P1NP, and 6-month increase in lean mass and 25(OH)D positively predicted 6-month change in P1NP (p≤0.05), suggesting that subjects with greatest decreases in abdominal fat, inflammation and ApoB, and the greatest increases in lean mass and 25(OH)D experienced the greatest increases in bone formation. A six-month increase in bone marrow fat correlated with 6-month increase in P1NP (trend), suggesting that subjects with the greatest increases in bone formation experienced the greatest increases in bone marrow fat. Forward stepwise regression analysis indicated that increase in lean mass and decrease in abdominal fat were positive predictors of P1NP. When IGF-1 was added to the model, it became the only predictor of P1NP. GH replacement in abdominally obese premenopausal women for 6 months increased bone turnover and bone marrow fat. Reductions in abdominal fat, and inflammation, and increases in IGF-1, lean mass and vitamin D were associated with increased bone formation. The increase in bone marrow fat may reflect changes in energy demand from increased bone turnover. Copyright © 2014 Elsevier Inc. All rights reserved.

Short-term physical activity intervention decreases femoral bone marrow adipose tissue in young children: a pilot study

PubMed Central

Casazza, K; Hanks, LJ; Hidalgo, B; Hu, HH; Affuso, O

2011-01-01

Mechanical stimulation is necessary for maximization of geometrical properties of bone mineralization contributing to long-term strength. The amount of mineralization in bones has been reciprocally related to volume of bone marrow adipose tissue and this relationship is suggested to be an independent predictor of fracture. Physical activity represents an extrinsic factor that impacts both mineralization and marrow volume exerting permissive capacity of the growing skeleton to achieve its full genetic potential. Because geometry- and shape-determining processes primarily manifest during the linear growth period, the accelerated structural changes accompanying early childhood (ages 3 to 6 y) may have profound impact on lifelong bone health. The objective of this pilot study was to determine if a short-term physical activity intervention in young children would result in augmentation of geometric properties of bone. Three days per week the intervention group (n=10) participated in 30 minutes of moderate intensity physical activity, such as jumping, hopping and running, and stretching activities, whereas controls (n=10) underwent usual activities during the 10-week intervention period. Femoral bone marrow adipose tissue volume and total body composition were assessed by magnetic resonance imaging and dual-energy X-ray absorptiometry, respectively, at baseline and after ten weeks. Although after 10-weeks, intergroup differences were not observed, a significant decrease in femoral marrow adipose tissue volume was observed in those participating in physical activity intervention. Our findings suggest physical activity may improve bone quality via antagonistic effects on femoral bone marrow adipose tissue and possibly long-term agonistic effects on bone mineralization. PMID:21939791

Determining the best treatment for simple bone cyst: a decision analysis.

PubMed

Lee, Seung Yeol; Chung, Chin Youb; Lee, Kyoung Min; Sung, Ki Hyuk; Won, Sung Hun; Choi, In Ho; Cho, Tae-Joon; Yoo, Won Joon; Yeo, Ji Hyun; Park, Moon Seok

2014-03-01

The treatment of simple bone cysts (SBC) in children varies significantly among physicians. This study examined which procedure is better for the treatment of SBC, using a decision analysis based on current published evidence. A decision tree focused on five treatment modalities of SBC (observation, steroid injection, autologous bone marrow injection, decompression, and curettage with bone graft) were created. Each treatment modality was further branched, according to the presence and severity of complications. The probabilities of all cases were obtained by literature review. A roll back tool was utilized to determine the most preferred treatment modality. One-way sensitivity analysis was performed to determine the threshold value of the treatment modalities. Two-way sensitivity analysis was utilized to examine the joint impact of changes in probabilities of two parameters. The decision model favored autologous bone marrow injection. The expected value of autologous bone marrow injection was 0.9445, while those of observation, steroid injection, decompression, and curettage and bone graft were 0.9318, 0.9400, 0.9395, and 0.9342, respectively. One-way sensitivity analysis showed that autologous bone marrow injection was better than that of decompression for the expected value when the rate of pathologic fracture, or positive symptoms of SBC after autologous bone marrow injection, was lower than 20.4%. In our study, autologous bone marrow injection was found to be the best choice of treatment of SBC. However, the results were sensitive to the rate of pathologic fracture after treatment of SBC. Physicians should consider the possibility of pathologic fracture when they determine a treatment method for SBC.

The clinical impact of staging bone marrow examination on treatment decisions and prognostic assessment of lymphoma patients.

PubMed

Painter, Dan; Smith, Alexandra; de Tute, Ruth; Crouch, Simon; Roman, Eve; Jack, Andrew

2015-07-01

This study investigates the value of performing a staging bone marrow in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and classical hodgkin lymphoma (CHL). The results of 3112 staging bone marrow examinations were assessed for impact on prognostic assessment and critical treatment decisions. The detection of marrow involvement altered the disease-specific prognostic index for 4·3% of DLBCL, 6·2% of FL and 0·6% of CHL but marrow involvement in DLBCL was an independent prognostic factor. Knowing the marrow status potentially changed treatment in 92 patients, detection of these patients would have required 854 examinations to be performed. © 2015 John Wiley & Sons Ltd.

[Progesterone Promotes Human Bone Marrow Mesenchymal Stem Cells to Synthesize Fibronectin via ERK Pathway].

PubMed

Wu, Zhen-Yong; Chen, Jing-Li; Huang, Shu; Zhang, Hui; Wang, Fang; Wang, Yan; Bi, Xiao-Yun; Guo, Zi-Kuan

2015-12-01

To investigate whether the progesterone can promote fibronection (FN) synthesis by human bone marrow mesenchymal stem cells (MSCs) and to explore the potential underlying mechanism. The human bone marrow MSCs were cultured in a serum-free medium with progesterone for 72 hours, the MTT test was performed to observe the proliferation status and adhension ability of the treated cells. Western blot was used to detect the content of FN in MSDs with GAPDH as the internal reference, the phosphorylation of ERK1/2, as well as the FN content in MSC treated by PD98059, a specific inhibitor of ERK1/2. The progesterone at a range of certain doses not effect on the proliferation of human bone marrow MSCs. Progesterone (25 µg/L) treatment enhanced the FN expression and adherent ability of marrow MSCs. Progesterone could induce prompt phosphorylation of ERK 1/2 and its promoting effects on FN synthesis was reversed by PD98059. The progesterone can promote FN synthesis by human bone marrow MSCs via ERK 1/2 pathway, and it might be used to culture MSCs in serum-free medium.

Reproducibility of the World Health Organization 2008 criteria for myelodysplastic syndromes

PubMed Central

Senent, Leonor; Arenillas, Leonor; Luño, Elisa; Ruiz, Juan C.; Sanz, Guillermo; Florensa, Lourdes

2013-01-01

The reproducibility of the World Health Organization 2008 classification for myelodysplastic syndromes is uncertain and its assessment was the major aim of this study. The different peripheral blood and bone marrow variables required for an adequate morphological classification were blindly evaluated by four cytomorphologists in samples from 50 patients with myelodysplastic syndromes. The degree of agreement among observers was calculated using intraclass correlation coefficient and the generalized kappa statistic for multiple raters. The degree of agreement for the percentages of blasts in bone marrow and peripheral blood, ring sideroblasts in bone marrow, and erythroid, granulocytic and megakaryocytic dysplastic cells was strong (P<0.001 in all instances). After stratifying the percentages according to the categories required for the assignment of World Health Organization subtypes, the degree of agreement was not statistically significant for cases with 5-9% blasts in bone marrow (P=0.07), 0.1-1% blasts in peripheral blood (P=0.47), or percentage of erythroid dysplastic cells (P=0.49). Finally, the interobserver concordance for World Health Organization-defined subtypes showed a moderate overall agreement (P<0.001), the reproducibility being lower for cases with refractory anemia with excess of blasts type 1 (P=0.05) and refractory anemia with ring sideroblasts (P=0.09). In conclusion, the reproducibility of the World Health Organization 2008 classification for myelodysplastic syndromes is acceptable but the defining criteria for blast cells and features of erythroid dysplasia need to be refined. PMID:23065505

Reproducibility of the World Health Organization 2008 criteria for myelodysplastic syndromes.

PubMed

Senent, Leonor; Arenillas, Leonor; Luño, Elisa; Ruiz, Juan C; Sanz, Guillermo; Florensa, Lourdes

2013-04-01

The reproducibility of the World Health Organization 2008 classification for myelodysplastic syndromes is uncertain and its assessment was the major aim of this study. The different peripheral blood and bone marrow variables required for an adequate morphological classification were blindly evaluated by four cytomorphologists in samples from 50 patients with myelodysplastic syndromes. The degree of agreement among observers was calculated using intraclass correlation coefficient and the generalized kappa statistic for multiple raters. The degree of agreement for the percentages of blasts in bone marrow and peripheral blood, ring sideroblasts in bone marrow, and erythroid, granulocytic and megakaryocytic dysplastic cells was strong (P<0.001 in all instances). After stratifying the percentages according to the categories required for the assignment of World Health Organization subtypes, the degree of agreement was not statistically significant for cases with 5-9% blasts in bone marrow (P=0.07), 0.1-1% blasts in peripheral blood (P=0.47), or percentage of erythroid dysplastic cells (P=0.49). Finally, the interobserver concordance for World Health Organization-defined subtypes showed a moderate overall agreement (P<0.001), the reproducibility being lower for cases with refractory anemia with excess of blasts type 1 (P=0.05) and refractory anemia with ring sideroblasts (P=0.09). In conclusion, the reproducibility of the World Health Organization 2008 classification for myelodysplastic syndromes is acceptable but the defining criteria for blast cells and features of erythroid dysplasia need to be refined.

Mastocytosis: magnetic resonance imaging patterns of marrow disease.

PubMed

Avila, N A; Ling, A; Metcalfe, D D; Worobec, A S

1998-03-01

To report the bone marrow MRI findings of patients with mastocytosis and correlate them with clinical, pathologic, and radiographic features. Eighteen patients with mastocytosis had T1-weighted spin echo and short tau inversion recovery MRI of the pelvis at 0.5 T. In each patient the MR pattern of marrow disease was classified according to intensity and uniformity and was correlated with the clinical category of mastocytosis, bone marrow biopsy results, and radiographic findings. Two patients had normal MRI scans and normal bone marrow biopsies. One patient had a normal MRI scan and a marrow biopsy consistent with mastocytosis. Fifteen patients had abnormal MRI scans and abnormal marrow biopsies. There were several different MR patterns of marrow involvement; none was specifically associated with any given clinical category of mastocytosis. Fifteen of the 18 patients had radiographs of the pelvis; of those, 13 with abnormal MRI scans and abnormal marrow biopsies had the following radiographic findings: normal (nine); sclerosis (three); diffuse osteopenia (one). While radiographs are very insensitive for the detection of marrow abnormalities in mastocytosis, MRI is very sensitive and may display several different patterns of marrow involvement.

Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia.

PubMed

Bär, Christian; Povedano, Juan Manuel; Serrano, Rosa; Benitez-Buelga, Carlos; Popkes, Miriam; Formentini, Ivan; Bobadilla, Maria; Bosch, Fatima; Blasco, Maria A

2016-04-07

Aplastic anemia is a fatal bone marrow disorder characterized by peripheral pancytopenia and marrow hypoplasia. The disease can be hereditary or acquired and develops at any stage of life. A subgroup of the inherited form is caused by replicative impairment of hematopoietic stem and progenitor cells due to very short telomeres as a result of mutations in telomerase and other telomere components. Abnormal telomere shortening is also described in cases of acquired aplastic anemia, most likely secondary to increased turnover of bone marrow stem and progenitor cells. Here, we test the therapeutic efficacy of telomerase activation by using adeno-associated virus (AAV)9 gene therapy vectors carrying the telomerase Tert gene in 2 independent mouse models of aplastic anemia due to short telomeres (Trf1- and Tert-deficient mice). We find that a high dose of AAV9-Tert targets the bone marrow compartment, including hematopoietic stem cells. AAV9-Tert treatment after telomere attrition in bone marrow cells rescues aplastic anemia and mouse survival compared with mice treated with the empty vector. Improved survival is associated with a significant increase in telomere length in peripheral blood and bone marrow cells, as well as improved blood counts. These findings indicate that telomerase gene therapy represents a novel therapeutic strategy to treat aplastic anemia provoked or associated with short telomeres. © 2016 by The American Society of Hematology.

Alternative RNA Splicing of CSF3R in Promoting Myelodysplastic Syndromes

DTIC Science & Technology

2017-01-01

Myelodysplastic Syndromes, Bone Marrow Failure, Granulopoiesis, RNA splicing 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES...major distinguishing feature of myelodysplastic syndromes (MDS), the most common form of acquired bone marrow failure, is the presence of recurrent...model by expressing alternative splice form in the context of Csf3r-/- mice. KEYWORDS: Myelodysplastic Syndromes, Bone Marrow Failure

Small Molecule Protection of Bone Marrow Hematopoietic Stem Cells

DTIC Science & Technology

2017-12-01

using isogenic (mutant/complemented) human cell line pairs from patients with Fanconi anemia (FA), a heritable human bone marrow failure (BMF) syndrome ...small molecules could be therapeutically useful in reducing the risk of BMF in diseases such as Fanconi anemia, and perhaps after radiation exposure...damage-repair, DNA damage response, Fanconi anemia and associated bone marrow failure syndromes and environmental and molecular toxicology will all be

Bone Marrow Lipids in Rats Exposed to Total-Body Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Snyder, Fred; Cress, Edgar A.

1963-05-01

ABS>Thin-layer chromatography was used to demonstrate that bone marrow lipids of rats were primarily triglycerides; gas-liquid chromatography of the fraction revealed that palmitic and oleic acids account for more than 80% of the fatty acids. Minor lipid components present in the control and irradiated marrow are glyceryl ethers, cholesterol, fatty acids, and phospholipids. Cholesterol esters were not found. Total-body irradiation (800 r) increases the femur marrow triglyceride fraction approximately six times by 1 week after irradiation, and it remains elevated for many weeks. The relationship between dose and increase in marrow triglycerides appears to fit the equation y = bxmore » a. The water and lipid content of bone marrow bear a reciprocal relation to each other, while both water and residue are significantly reduced in the irradiated femur marrow.« less

Deficiency of bone marrow beta3-integrin enhances non-functional neovascularization.

PubMed

Watson, Alan R; Pitchford, Simon C; Reynolds, Louise E; Direkze, Natalie; Brittan, Mairi; Alison, Malcolm R; Rankin, Sara; Wright, Nicholas A; Hodivala-Dilke, Kairbaan M

2010-03-01

beta3-Integrin is a cell surface adhesion and signalling molecule important in the regulation of tumour angiogenesis. Mice with a global deficiency in beta3-integrin show increased pathological angiogenesis, most likely due to increased vascular endothelial growth factor receptor 2 expression on beta3-null endothelial cells. Here we transplanted beta3-null bone marrow (BM) into wild-type (WT) mice to dissect the role of BM beta3-integrin deficiency in pathological angiogenesis. Mice transplanted with beta3-null bone marrow show significantly enhanced angiogenesis in subcutaneous B16F0 melanoma and Lewis lung carcinoma (LLC) cell models and in B16F0 melanoma lung metastasis when compared with tumours grown in mice transplanted with WT bone marrow. The effect of bone marrow beta3-integrin deficiency was also assessed in the RIPTAg mouse model of pancreatic tumour growth. Again, angiogenesis in mice lacking BM beta3-integrin was enhanced. However, tumour weight between the groups was not significantly altered, suggesting that the enhanced blood vessel density in the mice transplanted with beta3-null bone marrow was not functional. Indeed, we demonstrate that in mice transplanted with beta3-null bone marrow a significant proportion of tumour blood vessels are non-functional when compared with tumour blood vessels in WT-transplanted controls. Furthermore, beta3-null-transplanted mice showed an increased angiogenic response to VEGF in vivo when compared with WT-transplanted animals. BM beta3-integrin deficiency affects the mobilization of progenitor cells to the peripheral circulation. We show that VEGF-induced mobilization of endothelial progenitor cells is enhanced in mice transplanted with beta3-null bone marrow when compared with WT-transplanted controls, suggesting a possible mechanism underlying the increased blood vessel density seen in beta3-null-transplanted mice. In conclusion, although BM beta3-integrin is not required for pathological angiogenesis, our studies demonstrate a role for BM beta3-integrin in VEGF-induced mobilization of bone marrow-derived cells to the peripheral circulation and for the functionality of those vessels in which BM-derived cells become incorporated.

Peripheral-blood stem cells versus bone marrow from unrelated donors.

PubMed

Anasetti, Claudio; Logan, Brent R; Lee, Stephanie J; Waller, Edmund K; Weisdorf, Daniel J; Wingard, John R; Cutler, Corey S; Westervelt, Peter; Woolfrey, Ann; Couban, Stephen; Ehninger, Gerhard; Johnston, Laura; Maziarz, Richard T; Pulsipher, Michael A; Porter, David L; Mineishi, Shin; McCarty, John M; Khan, Shakila P; Anderlini, Paolo; Bensinger, William I; Leitman, Susan F; Rowley, Scott D; Bredeson, Christopher; Carter, Shelly L; Horowitz, Mary M; Confer, Dennis L

2012-10-18

Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia. We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37). The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, -3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse. We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute-National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.).

Imaging Radiation-Induced Gastrointestinal, Bone Marrow Injury and Recovery Kinetics Using 18F-FDG PET

PubMed Central

Tang, Tien T.; Rendon, David A.; Zawaski, Janice A.; Afshar, Solmaz F.; Kaffes, Caterina K.; Sabek, Omaima M.

2017-01-01

Positron emission tomography using 18F-Fluro-deoxy-glucose (18F-FDG) is a useful tool to detect regions of inflammation in patients. We utilized this imaging technique to investigate the kinetics of gastrointestinal recovery after radiation exposure and the role of bone marrow in the recovery process. Male Sprague-Dawley rats were either sham irradiated, irradiated with their upper half body shielded (UHBS) at a dose of 7.5 Gy, or whole body irradiated (WBI) with 4 or 7.5 Gy. Animals were imaged using 18F-FDG PET/CT at 5, 10 and 35 days post-radiation exposure. The gastrointestinal tract and bone marrow were analyzed for 18F-FDG uptake. Tissue was collected at all-time points for histological analysis. Following 7.5 Gy irradiation, there was a significant increase in inflammation in the gastrointestinal tract as indicated by the significantly higher 18F-FDG uptake compared to sham. UHBS animals had a significantly higher activity compared to 7.5 Gy WBI at 5 days post-exposure. Animals that received 4 Gy WBI did not show any significant increase in uptake compared to sham. Analysis of the bone marrow showed a significant decrease of uptake in the 7.5 Gy animals 5 days post-irradiation, albeit not observed in the 4 Gy group. Interestingly, as the metabolic activity of the gastrointestinal tract returned to sham levels in UHBS animals it was accompanied by an increase in metabolic activity in the bone marrow. At 35 days post-exposure both gastrointestinal tract and bone marrow 18F-FDG uptake returned to sham levels. 18F-FDG imaging is a tool that can be used to study the inflammatory response of the gastrointestinal tract and changes in bone marrow metabolism caused by radiation exposure. The recovery of the gastrointestinal tract coincides with an increase in bone marrow metabolism in partially shielded animals. These findings further demonstrate the relationship between the gastrointestinal syndrome and bone marrow recovery, and that this interaction can be studied using non-invasive imaging modalities. PMID:28052129

Imaging Radiation-Induced Gastrointestinal, Bone Marrow Injury and Recovery Kinetics Using 18F-FDG PET.

PubMed

Tang, Tien T; Rendon, David A; Zawaski, Janice A; Afshar, Solmaz F; Kaffes, Caterina K; Sabek, Omaima M; Gaber, M Waleed

2017-01-01

Positron emission tomography using 18F-Fluro-deoxy-glucose (18F-FDG) is a useful tool to detect regions of inflammation in patients. We utilized this imaging technique to investigate the kinetics of gastrointestinal recovery after radiation exposure and the role of bone marrow in the recovery process. Male Sprague-Dawley rats were either sham irradiated, irradiated with their upper half body shielded (UHBS) at a dose of 7.5 Gy, or whole body irradiated (WBI) with 4 or 7.5 Gy. Animals were imaged using 18F-FDG PET/CT at 5, 10 and 35 days post-radiation exposure. The gastrointestinal tract and bone marrow were analyzed for 18F-FDG uptake. Tissue was collected at all-time points for histological analysis. Following 7.5 Gy irradiation, there was a significant increase in inflammation in the gastrointestinal tract as indicated by the significantly higher 18F-FDG uptake compared to sham. UHBS animals had a significantly higher activity compared to 7.5 Gy WBI at 5 days post-exposure. Animals that received 4 Gy WBI did not show any significant increase in uptake compared to sham. Analysis of the bone marrow showed a significant decrease of uptake in the 7.5 Gy animals 5 days post-irradiation, albeit not observed in the 4 Gy group. Interestingly, as the metabolic activity of the gastrointestinal tract returned to sham levels in UHBS animals it was accompanied by an increase in metabolic activity in the bone marrow. At 35 days post-exposure both gastrointestinal tract and bone marrow 18F-FDG uptake returned to sham levels. 18F-FDG imaging is a tool that can be used to study the inflammatory response of the gastrointestinal tract and changes in bone marrow metabolism caused by radiation exposure. The recovery of the gastrointestinal tract coincides with an increase in bone marrow metabolism in partially shielded animals. These findings further demonstrate the relationship between the gastrointestinal syndrome and bone marrow recovery, and that this interaction can be studied using non-invasive imaging modalities.

Long-term culture and differentiation of porcine red bone marrow hematopoietic cells co-cultured with immortalized mesenchymal cells.

PubMed

Garba, Abubakar; Acar, Delphine D; Roukaerts, Inge D M; Desmarets, Lowiese M B; Devriendt, Bert; Nauwynck, Hans J

2017-09-01

Mesenchymal cells are multipotent stromal cells with self-renewal, differentiation and immunomodulatory capabilities. We aimed to develop a co-culture model for differentiating hematopoietic cells on top of immortalized mesenchymal cells for studying interactions between hematopoietic and mesenchymal cells, useful for adequately exploring the therapeutic potential of mesenchymal cells. In this study, we investigated the survival, proliferation and differentiation of porcine red bone marrow hematopoietic cells co-cultured with immortalized porcine bone marrow mesenchymal cells for a period of five weeks. Directly after collection, primary porcine bone marrow mesenchymal cells adhered firmly to the bottom of the culture plates and showed a fibroblast-like appearance, one week after isolation. Upon immortalization, porcine bone marrow mesenchymal cells were continuously proliferating. They were positive for simian virus 40 (SV40) large T antigen and the mesenchymal cell markers CD44 and CD55. Isolated red bone marrow cells were added to these immortalized mesenchymal cells. Five weeks post-seeding, 92±6% of the red bone marrow hematopoietic cells were still alive and their number increased 3-fold during five weekly subpassages on top of the immortalized mesenchymal cells. The red bone marrow hematopoietic cells were originally small and round; later, the cells increased in size. Some of them became elongated, while others remained round. Tiny dendrites appeared attaching hematopoietic cells to the underlying immortalized mesenchymal cells. Furthermore, weekly differential-quick staining of the cells indicated the presence of monoblasts, monocytes, macrophages and lymphocytes in the co-cultures. At three weeks of co-culture, flow cytometry analysis showed an increased surface expression of CD172a, CD14, CD163, CD169, CD4 and CD8 up to 37±0.8%, 40±8%, 41±4%, 23±3% and 19±5% of the hematopoietic cells, respectively. In conclusion, continuous mesenchymal cell cultures were successfully established and characterized and they supported the proliferation of red bone marrow hematopoietic cells, which finally differentiated into monocytic cells and CD4 + and CD8 + cells. Copyright © 2017. Published by Elsevier B.V.

INF-γ encoding plasmid administration triggers bone loss and disrupts bone marrow microenvironment.

PubMed

Agas, Dimitrios; Gusmão Silva, Guilherme; Laus, Fulvio; Marchegiani, Andrea; Capitani, Melania; Vullo, Cecilia; Catone, Giuseppe; Lacava, Giovanna; Concetti, Antonio; Marchetti, Luigi; Sabbieti, Maria Giovanna

2017-02-01

IFN-γ is a pleotropic cytokine produced in the bone microenvironment. Although IFN-γ is known to play a critical role on bone remodeling, its function is not fully elucidated. Consistently, outcomes on the effects of IFN-γ recombinant protein on bone loss are contradictory among reports. In our work we explored, for the first time, the role of IFN-γ encoding plasmid (pIFN-γ) in a mouse model of osteopenia induced by ovariectomy and in the sham-operated counterpart to estimate its effects in skeletal homeostasis. Ovariectomy produced a dramatic decrease of bone mineral density (BMD). pINF-γ injected mice showed a pathologic bone and bone marrow phenotype; the disrupted cortical and trabecular bone microarchitecture was accompanied by an increased release of pro-inflammatory cytokine by bone marrow cells. Moreover, mesenchymal stem cells' (MSCs) commitment to osteoblast was found impaired, as evidenced by the decline of osterix-positive (Osx + ) cells within the mid-diaphyseal area of femurs. For instance, a reduction and redistribution of CXCL12 cells have been found, in accordance with bone marrow morphological alterations. As similar effects were observed both in sham-operated and in ovariectomized mice, our studies proved that an increased IFN-γ synthesis in bone marrow might be sufficient to induce inflammatory and catabolic responses even in the absence of pathologic predisposing substrates. In addition, the obtained data might raise questions about pIFN-γ's safety when it is used as vaccine adjuvant. © 2017 Society for Endocrinology.

Influence of bone marrow on osseointegration in long bones: an experimental study in sheep.

PubMed

Morelli, Fabrizio; Lang, Niklaus P; Bengazi, Franco; Baffone, Davide; Vila Morales, C Dadonim; Botticelli, Daniele

2015-03-01

To evaluate the influence of yellow bone marrow on osseointegration of titanium oral implants using a long bone model. The two tibiae of eight sheep were used as experimental sites. Two osteotomies for implant installation were prepared in each tibia. At the control sites, no further treatments were performed while, at the test sites, bone marrow was removed from the osteotomy site with a curette to an extent that exceeded the implant dimensions. As a result, the apical portion of the implants at the control sites was in contact with bone marrow while, at the test sites, it was in contact with the blood clot. After 2 months, the same procedures were performed in the contralateral side. After another month, the animal was sacrificed. Ground sections were obtained for histological analysis. After 1 month of healing, no differences between test and control sites were found in the apical extension of osseointegration and the percentage of new bone-to-implant contact. However, after 3 months of healing, a higher percentage of new bone-to-implant contact was found at the test compared to the control sites in the marrow compartment. The apical extension of osseointegration, however, was similar to that found at the 1-month healing period both for test and control sites. Osseointegration appeared to be favored by the presence of a blood clot when compared to the presence of yellow fatty bone marrow. Moreover, the contact with cortical bone appeared to be a prerequisite for the osseointegration process in the long bone model. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Enhanced Tendon-to-Bone Healing of Chronic Rotator Cuff Tears by Bone Marrow Aspirate Concentrate in a Rabbit Model

PubMed Central

Liu, Xiao Ning; Yang, Cheol-Jung; Kim, Ji Eui; Du, Zhen Wu; Ren, Ming; Zhang, Wei; Zhao, Hong Yu; Kim, Kyung Ok

2018-01-01

Background To evaluate the influence of bone marrow aspirate concentrate (BMAC) on tendon-to-bone healing in a rabbit rotator cuff model and to characterize the composition of growth factors in BMAC. Methods In this in vivo study, 40 rabbits were allocated into five groups: control (C), repair + saline (RS), repair + platelet-rich plasma (PRP; RP), repair + BMAC (RB) and repair + PRP + BMAC (RPB). A tear model was created by supraspinatus tendon transection at the footprint. Six weeks after transection, the torn tendon was repaired along with BMAC or PRP administration. Six weeks after repair, shoulder samples were harvested for biomechanical and histological testing. Ten rabbits were used for processing PRP and BMAC, followed by analysis of blood cell composition and the levels of growth factors in vitro. Results The ultimate load-to-failure was significantly higher in RPB group compared to RS group (p = 0.025). BMAC-treated groups showed higher values of biomechanical properties than RS group. The histology of BMAC-treated samples showed better collagen fiber continuity and orientation than RS group. BMAC contained significantly higher levels of the several growth factors than PRP. Conclusions Locally administered BMAC enhanced tendon-to-bone healing and has potential for clinical applications. PMID:29564054

Treatment of active unicameral bone cysts with percutaneous injection of demineralized bone matrix and autogenous bone marrow.

PubMed

Rougraff, Bruce T; Kling, Thomas J

2002-06-01

The treatment of unicameral bone cysts varies from open bone-grafting procedures to percutaneous injection of corticosteroids or bone marrow. The purpose of this study was to evaluate the feasibility and effectiveness of percutaneous injection of a mixture of demineralized bone matrix and autogenous bone marrow for the treatment of simple bone cysts. Twenty-three patients with an active unicameral bone cyst were treated with trephination and injection of allogeneic demineralized bone matrix and autogenous bone marrow. The patients were followed for an average of fifty months (range, thirty to eighty-one months), at which time pain, function, and radiographic signs of resolution of the cyst were assessed. The average time until the patients had pain relief was five weeks, and the average time until the patients returned to full, unrestricted activities was six weeks. Bone-healing at the site of the injection was first seen radiographically at three to six months. No patient had a pathologic fracture during this early bone-healing stage. Cortical remodeling was seen radiographically by six to nine months, and after one year the response was usually complete, changing very little from then on. Five patients required a second injection because of recurrence of the cyst, and all five had a clinically and radiographically quiescent cyst after an average of thirty-six additional months of follow-up. Seven of the twenty-three patients had incomplete healing manifested by small, persistent radiolucent areas within the original cyst. None of these cysts increased in size or resulted in pain or fracture. Percutaneous injection of allogeneic demineralized bone matrix and autogenous bone marrow is an effective treatment for unicameral bone cysts.

Characterization of a 5-fluorouracil-enriched osteoprogenitor population of the murine bone marrow.

PubMed

Falla, N; Van Vlasselaer; Bierkens, J; Borremans, B; Schoeters, G; Van Gorp, U

1993-12-15

In the presence of beta-glycerophosphate and vitamin C, cultures of normal mouse bone marrow cells form three-dimensional structures that stain positive with the Von Kossa technique and express alkaline phosphatase (ALP), collagen type I, and osteocalcin. Little is known about the characteristics and frequency of the cells that contribute to this phenomenon. Most likely, mature osteoblastic cells do not contribute to the nodule formation because no osteocalcin expressing cells are detected in the flushed marrow by in situ hybridization. Limiting dilution analysis shows that, in normal bone marrow, 1 of 2.2 x 10(5) cells has the potency to form a bone nodule and to express ALP, collagen, and osteocalcin in a temporal fashion. Upon in vivo treatment with 5-fluorouracil (5-FU), this frequency increases 12-fold, eg, 1 in 1.75 x 10(4) cells shows osteogenic activity. In comparison, fibroblast colony forming cells occur at a frequency of 1 of 2.5 x 10(4) or 1 of 5 x 10(3) plated cells in normal or 5-FU-treated marrow, respectively. Using density centrifugation, the majority of the osteoprogenitor cells in 5-FU marrow are found in the low-density (1.066 to 1.067 g/mL) fractions. In addition, these cells bind to nylon wool but not to plastic and aggregate in the presence of wheat germ agglutinin and soybean agglutinin. Scanning and transmission electron microscopy shows that the bone nodules in 5-FU marrow cultures are composed of fibroblastoid cells embedded in a mineralized collagen matrix. In conclusion, our results show that a quiescent cell population in the murine bone marrow with fibroblastoid characteristics contributes to the formation of bone-like nodules in vitro.

Diagnosis of Fanconi anemia in patients with bone marrow failure

PubMed Central

Pinto, Fernando O.; Leblanc, Thierry; Chamousset, Delphine; Le Roux, Gwenaelle; Brethon, Benoit; Cassinat, Bruno; Larghero, Jérôme; de Villartay, Jean-Pierre; Stoppa-Lyonnet, Dominique; Baruchel, André; Socié, Gérard; Gluckman, Eliane; Soulier, Jean

2009-01-01

Background Patients with bone marrow failure and undiagnosed underlying Fanconi anemia may experience major toxicity if given standard-dose conditioning regimens for hematopoietic stem cell transplant. Due to clinical variability and/or potential emergence of genetic reversion with hematopoietic somatic mosaicism, a straightforward Fanconi anemia diagnosis can be difficult to make, and diagnostic strategies combining different assays in addition to classical breakage tests in blood may be needed. Design and Methods We evaluated Fanconi anemia diagnosis on blood lymphocytes and skin fibroblasts from a cohort of 87 bone marrow failure patients (55 children and 32 adults) with no obvious full clinical picture of Fanconi anemia, by performing a combination of chromosomal breakage tests, FANCD2-monoubiquitination assays, a new flow cytometry-based mitomycin C sensitivity test in fibroblasts, and, when Fanconi anemia was diagnosed, complementation group and mutation analyses. The mitomycin C sensitivity test in fibroblasts was validated on control Fanconi anemia and non-Fanconi anemia samples, including other chromosomal instability disorders. Results When this diagnosis strategy was applied to the cohort of bone marrow failure patients, 7 Fanconi anemia patients were found (3 children and 4 adults). Classical chromosomal breakage tests in blood detected 4, but analyses on fibroblasts were necessary to diagnose 3 more patients with hematopoietic somatic mosaicism. Importantly, Fanconi anemia was excluded in all the other patients who were fully evaluated. Conclusions In this large cohort of patients with bone marrow failure our results confirmed that when any clinical/biological suspicion of Fanconi anemia remains after chromosome breakage tests in blood, based on physical examination, history or inconclusive results, then further evaluation including fibroblast analysis should be made. For that purpose, the flow-based mitomycin C sensitivity test here described proved to be a reliable alternative method to evaluate Fanconi anemia phenotype in fibroblasts. This global strategy allowed early and accurate confirmation or rejection of Fanconi anemia diagnosis with immediate clinical impact for those who underwent hematopoietic stem cell transplant. PMID:19278965

Effects of hibernation on bone marrow transcriptome in thirteen-lined ground squirrels.

PubMed

Cooper, Scott T; Sell, Shawn S; Fahrenkrog, Molly; Wilkinson, Kory; Howard, David R; Bergen, Hannah; Cruz, Estefania; Cash, Steve E; Andrews, Matthew T; Hampton, Marshall

2016-07-01

Mammalian hibernators adapt to prolonged periods of immobility, hypometabolism, hypothermia, and oxidative stress, each capable of reducing bone marrow activity. In this study bone marrow transcriptomes were compared among thirteen-lined ground squirrels collected in July, winter torpor, and winter interbout arousal (IBA). The results were consistent with a suppression of acquired immune responses, and a shift to innate immune responses during hibernation through higher complement expression. Consistent with the increase in adipocytes found in bone marrow of hibernators, expression of genes associated with white adipose tissue are higher during hibernation. Genes that should strengthen the bone by increasing extracellular matrix were higher during hibernation, especially the collagen genes. Finally, expression of heat shock proteins were lower, and cold-response genes were higher, during hibernation. No differential expression of hematopoietic genes involved in erythrocyte or megakaryocyte production was observed. This global view of the changes in the bone marrow transcriptome over both short term (torpor vs. IBA) and long term (torpor vs. July) hypothermia can explain several observations made about circulating blood cells and the structure and strength of the bone during hibernation. Copyright © 2016 the American Physiological Society.

Using [{sup 18}F]Fluorothymidine Imaged With Positron Emission Tomography to Quantify and Reduce Hematologic Toxicity Due to Chemoradiation Therapy for Pelvic Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGuire, Sarah M., E-mail: sarah-mcguire@uiowa.edu; Bhatia, Sudershan K.; Sun, Wenqing

Purpose: The purpose of the present prospective clinical trial was to determine the efficacy of [{sup 18}F]fluorothymidine (FLT)-identified active bone marrow sparing for pelvic cancer patients by correlating the FLT uptake change during and after chemoradiation therapy with hematologic toxicity. Methods and Materials: Simulation FLT positron emission tomography (PET) images were used to spare pelvic bone marrow using intensity modulated radiation therapy (IMRT BMS) for 32 patients with pelvic cancer. FLT PET scans taken during chemoradiation therapy after 1 and 2 weeks and 30 days and 1 year after completion of chemoradiation therapy were used to evaluate the acute and chronic dose responsemore » of pelvic bone marrow. Complete blood counts were recorded at each imaging point to correlate the FLT uptake change with systemic hematologic toxicity. Results: IMRT BMS plans significantly reduced the dose to the pelvic regions identified with FLT uptake compared with control IMRT plans (P<.001, paired t test). Radiation doses of 4 Gy caused an ∼50% decrease in FLT uptake in the pelvic bone marrow after either 1 or 2 weeks of chemoradiation therapy. Additionally, subjects with more FLT-identified bone marrow exposed to ≥4 Gy after 1 week developed grade 2 leukopenia sooner than subjects with less marrow exposed to ≥4 Gy (P<.05, Cox regression analysis). Apparent bone marrow recovery at 30 days after therapy was not maintained 1 year after chemotherapy. The FLT uptake in the pelvic bone marrow regions that received >35 Gy was 18.8% ± 1.8% greater at 30 days after therapy than at 1 year after therapy. The white blood cell, platelet, lymphocyte, and neutrophil counts at 1 year after therapy were all lower than the pretherapy levels (P<.05, paired t test). Conclusions: IMRT BMS plans reduced the dose to FLT-identified pelvic bone marrow for pelvic cancer patients. However, reducing hematologic toxicity is challenging owing to the acute radiation sensitivity (∼4 Gy) and chronic suppression of activity in bone marrow receiving radiation doses >35 Gy, as measured by the FLT uptake change correlated with the complete blood cell counts.« less

Reduced cellularity of bone marrow in multiple sclerosis with decreased MSC expansion potential and premature ageing in vitro.

PubMed

Redondo, Juliana; Sarkar, Pamela; Kemp, Kevin; Virgo, Paul F; Pawade, Joya; Norton, Aimie; Emery, David C; Guttridge, Martin G; Marks, David I; Wilkins, Alastair; Scolding, Neil J; Rice, Claire M

2017-05-01

Autologous bone-marrow-derived cells are currently employed in clinical studies of cell-based therapy in multiple sclerosis (MS) although the bone marrow microenvironment and marrow-derived cells isolated from patients with MS have not been extensively characterised. To examine the bone marrow microenvironment and assess the proliferative potential of multipotent mesenchymal stromal cells (MSCs) in progressive MS. Comparative phenotypic analysis of bone marrow and marrow-derived MSCs isolated from patients with progressive MS and control subjects was undertaken. In MS marrow, there was an interstitial infiltrate of inflammatory cells with lymphoid (predominantly T-cell) nodules although total cellularity was reduced. Controlling for age, MSCs isolated from patients with MS had reduced in vitro expansion potential as determined by population doubling time, colony-forming unit assay, and expression of β-galactosidase. MS MSCs expressed reduced levels of Stro-1 and displayed accelerated shortening of telomere terminal restriction fragments (TRF) in vitro. Our results are consistent with reduced proliferative capacity and ex vivo premature ageing of bone-marrow-derived cells, particularly MSCs, in MS. They have significant implication for MSC-based therapies for MS and suggest that accelerated cellular ageing and senescence may contribute to the pathophysiology of progressive MS. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Funding for this study was provided by the Medical Research Council, UK (grant no. MR/K004166/1). The ACTiMuS study is sup-ported by the Silverman Family Foundation, Multiple Sclerosis Trust, Rosetree’s Trust, Catholic Bishops of England and Wales and Friends of Frenchay and SIAMMS-II by the Sir Halley Stewart Trust. C.M.R., P.S., and K.K. received support from the Burden Neurological Institute.

77 FR 12316 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-29

..., mobilizes hematopoietic stem/progenitor cells (HSPCs) from the bone marrow into blood. These mobilized HSPCs... bone marrow. miR126 may also facilitate mobilization of bone-resident cancer cells into the circulation where they could be more easily targeted by cancer therapeutics. This discovery could replace bone...

Modular flow chamber for engineering bone marrow architecture and function.

PubMed

Di Buduo, Christian A; Soprano, Paolo M; Tozzi, Lorenzo; Marconi, Stefania; Auricchio, Ferdinando; Kaplan, David L; Balduini, Alessandra

2017-11-01

The bone marrow is a soft, spongy, gelatinous tissue found in the hollow cavities of flat and long bones that support hematopoiesis in order to maintain the physiologic turnover of all blood cells. Silk fibroin, derived from Bombyx mori silkworm cocoons, is a promising biomaterial for bone marrow engineering, because of its tunable architecture and mechanical properties, the capacity of incorporating labile compounds without loss of bioactivity and demonstrated ability to support blood cell formation. In this study, we developed a bone marrow scaffold consisting of a modular flow chamber made of polydimethylsiloxane, holding a silk sponge, prepared with salt leaching methods and functionalized with extracellular matrix components. The silk sponge was able to support efficient platelet formation when megakaryocytes were seeded in the system. Perfusion of the chamber allowed the recovery of functional platelets based on multiple activation tests. Further, inhibition of AKT signaling molecule, which has been shown to be crucial in regulating physiologic platelet formation, significantly reduced the number of collected platelets, suggesting the applicability of this tissue model for evaluation of the effects of bone marrow exposure to compounds that may affect platelet formation. In conclusion, we have bioengineered a novel modular system that, along with multi-porous silk sponges, can provide a useful technology for reproducing a simplified bone marrow scaffold for blood cell production ex vivo. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lymphatic Endothelial Cells Produce M-CSF, Causing Massive Bone Loss in Mice.

PubMed

Wang, Wensheng; Wang, Hua; Zhou, Xichao; Li, Xing; Sun, Wen; Dellinger, Michael; Boyce, Brendan F; Xing, Lianping

2017-05-01

Gorham-Stout disease (GSD) is a rare bone disorder characterized by aggressive osteolysis associated with lymphatic vessel invasion within bone marrow cavities. The etiology of GSD is not known, and there is no effective therapy or animal model for the disease. Here, we investigated if lymphatic endothelial cells (LECs) affect osteoclasts (OCs) to cause a GSD osteolytic phenotype in mice. We examined the effect of a mouse LEC line on osteoclastogenesis in co-cultures. LECs significantly increased receptor activator of NF-κB ligand (RANKL)-mediated OC formation and bone resorption. LECs expressed high levels of macrophage colony-stimulating factor (M-CSF), but not RANKL, interleukin-6 (IL-6), and tumor necrosis factor (TNF). LEC-mediated OC formation and bone resorption were blocked by an M-CSF neutralizing antibody or Ki20227, an inhibitor of the M-CSF receptor, c-Fms. We injected LECs into the tibias of wild-type (WT) mice and observed massive osteolysis on X-ray and micro-CT scans. Histology showed that LEC-injected tibias had significant trabecular and cortical bone loss and increased OC numbers. M-CSF protein levels were significantly higher in serum and bone marrow plasma of mice given intra-tibial LEC injections. Immunofluorescence staining showed extensive replacement of bone and marrow by podoplanin+ LECs. Treatment of LEC-injected mice with Ki20227 significantly decreased tibial bone destruction. In addition, lymphatic vessels in a GSD bone sample were stained positively for M-CSF. Thus, LECs cause bone destruction in vivo in mice by secreting M-CSF, which promotes OC formation and activation. Blocking M-CSF signaling may represent a new therapeutic approach for treatment of patients with GSD. Furthermore, tibial injection of LECs is a useful mouse model to study GSD. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomar, Geetanjali B.; Srivastava, Rupesh K.; Gupta, Navita

2010-03-12

Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into multiple cell lineages. Presently, bone marrow is considered as a prime source of MSCs; however, there are some drawbacks and limitations in use of these MSCs for cell therapy. In this study, we demonstrate that human gingival tissue-derived MSCs have several advantages over bone marrow-derived MSCs. Gingival MSCs are easy to isolate, homogenous and proliferate faster than bone marrow MSCs without any growth factor. Importantly, gingival MSCs display stable morphology and do not loose MSC characteristic at higher passages. In addition, gingival MSCs maintain normal karyotype and telomerase activitymore » in long-term cultures, and are not tumorigenic. Thus, we reveal that human gingiva is a better source of MSCs than bone marrow, and large number of functionally competent clinical grade MSCs can be generated in short duration for cell therapy in regenerative medicine and tissue engineering.« less

Notch-dependent T-lineage commitment occurs at extrathymic sites following bone marrow transplantation

PubMed Central

Maillard, Ivan; Schwarz, Benjamin A.; Sambandam, Arivazhagan; Fang, Terry; Shestova, Olga; Xu, Lanwei; Bhandoola, Avinash; Pear, Warren S.

2006-01-01

Early T-lineage progenitors (ETPs) arise after colonization of the thymus by multipotent bone marrow progenitors. ETPs likely serve as physiologic progenitors of T-cell development in adult mice, although alternative T-cell differentiation pathways may exist. While we were investigating mechanisms of T-cell reconstitution after bone marrow transplantation (BMT), we found that efficient donor-derived thymopoiesis occurred before the pool of ETPs had been replenished. Simultaneously, T lineage–restricted progenitors were generated at extrathymic sites, both in the spleen and in peripheral lymph nodes, but not in the bone marrow or liver. The generation of these T lineage–committed cells occurred through a Notch-dependent differentiation process. Multipotent bone marrow progenitors efficiently gave rise to extrathymic T lineage–committed cells, whereas common lymphoid progenitors did not. Our data show plasticity of T-lineage commitment sites in the post-BMT environment and indicate that Notch-driven extrathymic Tlineage commitment from multipotent progenitors may contribute to early T-lineage reconstitution after BMT. PMID:16397133

Denosumab is effective in the treatment of bone marrow oedema syndrome.

PubMed

Rolvien, Tim; Schmidt, Tobias; Butscheidt, Sebastian; Amling, Michael; Barvencik, Florian

2017-04-01

Bone marrow oedema (BMO) syndrome describes a painful condition with increase of interstitial fluid within bone and is often lately diagnosed due to unspecific symptoms. The underlying causes are diverse while it is widely assumed that in cases of BMO local bone resorption is increased. Denosumab, a human monoclonal antibody that binds to the receptor activator of nuclear factor kappa-B ligand (RANKL) inhibits osteoclastic bone resorption and is commonly administered in the treatment of osteoporosis. Besides one previous case report, its clinical effectiveness in the treatment of bone marrow oedema has not been elucidated. We treated 14 patients with primary (idiopathic) bone marrow oedema of the lower extremity with single dose denosumab application. Mean time between onset of pain and therapy was 155days. MRI scans were performed for initial diagnosis, and 6-12 weeks after denosumab injection. Vitamin D and calcium homeostasis were strived to be balanced before initiation of therapy. Furthermore bone status was analysed using Dual-energy X-ray absorptiometry (DXA) and extended bone turnover serum markers. After 6-12 weeks, BMO dissolved partly or completely in 93%, while a complete recovery was observed in 50% of the individuals. Visual analogue scale (VAS) evaluation revealed a significant decrease in pain level. Furthermore, bone turnover decreased significantly after treatment. No adverse reactions were reported. In conclusion, our retrospective analysis shows that denosumab is highly effective in the treatment of bone marrow oedema and therefore represents an alternative treatment option. Copyright © 2017 Elsevier Ltd. All rights reserved.

Innate Immunity Dysregulation in Myelodysplastic Syndromes

DTIC Science & Technology

2014-10-01

the CD34+ enriched MDS bone marrow hematopoietic stem/ progenitor cells . We also demonstrated that interference of the TLR2-JMJD3 innate immunity...able to demonstrate that TLR2 innate immune signaling is excessively activated in MDS bone marrow stem/ progenitor cells and that inhibiting this...evidence that the deregulation of innate immune and inflammatory signaling also 13 affects other cells from the immune system and the bone marrow

Effect of Zoledronate on Oral Wound Healing in Rats

PubMed Central

Yamashita, Junro; Koi, Kiyono; Yang, Dong-Ye; McCauley, Laurie K.

2010-01-01

Purpose Osteonecrosis of the jaw (ONJ) is a growing concern in patients who receive bisphosphonates which target osteoclasts. Since osteoclasts play multifunctional roles in the bone marrow, their suppression likely affects bone homeostasis and alters wound healing of the jaw. The objective was to delineate the impact of osteoclast suppression in the bone marrow and wound healing of the jaw. Experimental Design Zoledronate was administered to senile rats for 14 weeks. A portion of the gingiva was removed to denude the palatal bone. Gene expression in the bone marrow was assessed and histologic sections analyzed to determine the wound healing status. Results Angiogenesis-related genes, CD31 and VEGF-A, were not altered by zoledronate. VEGF-C, which plays a role in lymphangiogenesis, was suppressed. There was a decrease in gene expression of Tcirg1 and MMP-13. Bone denudation caused extensive osteocyte death indicative of bone necrosis. In zoledronate-treated rats, the necrotic bone was retained in the wound while, in controls, osteoclastic resorption of the necrotic bone was prominent. Even though large necrotic bone areas existed in zoledronate-treated rats, overlaying soft tissue healed clinically. Immunohistochemical staining showed rich vascularity in the overlaying soft tissue. Conclusions Zoledronate therapy impacts bone marrow by suppressing genes associated with lymphoangiogenesis and tissue remodeling, such as VEGF-C and MMP-13. Zoledronate was associated with impaired osseous wound healing but had no effect on angiogenic markers in the bone marrow or soft tissue wound healing. Zoledronate selectively blunts healing in bone but does not effect soft tissue healing in the oral cavity. PMID:21149614

Hematopoiesis in 3 dimensions: human and murine bone marrow architecture visualized by confocal microscopy.

PubMed

Takaku, Tomoiku; Malide, Daniela; Chen, Jichun; Calado, Rodrigo T; Kajigaya, Sachiko; Young, Neal S

2010-10-14

In many animals, blood cell production occurs in the bone marrow. Hematopoiesis is complex, requiring self-renewing and pluripotent stem cells, differentiated progenitor and precursor cells, and supportive stroma, adipose tissue, vascular structures, and extracellular matrix. Although imaging is a vital tool in hematology research, the 3-dimensional architecture of the bone marrow tissue in situ remains largely uncharacterized. The major hindrance to imaging the intact marrow is the surrounding bone structures are almost impossible to cut/image through. We have overcome these obstacles and describe a method whereby whole-mounts of bone marrow tissue were immunostained and imaged in 3 dimensions by confocal fluorescence and reflection microscopy. We have successfully mapped by multicolor immunofluorescence the localization pattern of as many as 4 cell features simultaneously over large tiled views and to depths of approximately 150 μm. Three-dimensional images can be assessed qualitatively and quantitatively to appreciate the distribution of cell types and their interrelationships, with minimal perturbations of the tissue. We demonstrate its application to normal mouse and human marrow, to murine models of marrow failure, and to patients with aplastic anemia, myeloid, and lymphoid cell malignancies. The technique should be generally adaptable for basic laboratory investigation and for clinical diagnosis of hematologic diseases.

The study of indicators of bone marrow and peripheral blood of rats with diabetes and transplanted liver tumor after intravenous injection of gold nanorods

NASA Astrophysics Data System (ADS)

Dikht, Nataliya I.; Bucharskaya, Alla B.; Maslyakova, Galina N.; Terentyuk, Georgy S.; Matveeva, Olga V.; Navolokin, Nikita A.; Khlebtsov, Boris N.; Khlebtsov, Nikolai G.

2015-03-01

In study the evaluation of the influence of gold nanorods on morphological indicators of red bone marrow and peripheral blood of rats with diabetes and transplanted liver tumor after intravenous administration of gold nanorods was conducted. We used gold nanorods with length 41 ± 8 nm and diameter of 10.2±2 nm, synthesized in the laboratory of nanobiotechnology IBPPM RAS (Saratov). After intravenous administration of gold nanorods the decrease of leukocytes, platelets and lymphocytes was observed in animals of control group in blood. It was marked the decrease of the number of mature cellular elements of the leukocyte germ in bone marrow - stab neutrophils and segmented leukocytes, and the increase of immature elements- metamyelocytes, indicating the activation of leukocyte germ after nanoparticle administration. The decrease of leukocyte amount was noted in blood and the increase of cellular elements of the leukocyte germ was revealed in bone marrow, indicating the activation of leukocyte germ in rats with alloxan diabetes and transplanted tumors. The changes of morphological indicators of blood and bone marrow testify about stimulation of myelocytic sprouts of hemopoiesis in bone marrow as a result of reduction of mature cells in peripheral blood after gold nanoparticle administration.

Obesity-driven disruption of haematopoiesis and the bone marrow niche.

PubMed

Adler, Benjamin J; Kaushansky, Kenneth; Rubin, Clinton T

2014-12-01

Obesity markedly increases susceptibility to a range of diseases and simultaneously undermines the viability and fate selection of haematopoietic stem cells (HSCs), and thus the kinetics of leukocyte production that is critical to innate and adaptive immunity. Considering that blood cell production and the differentiation of HSCs and their progeny is orchestrated, in part, by complex interacting signals emanating from the bone marrow microenvironment, it is not surprising that conditions that disturb bone marrow structure inevitably disrupt both the numbers and lineage-fates of these key blood cell progenitors. In addition to the increased adipose burden in visceral and subcutaneous compartments, obesity causes a marked increase in the size and number of adipocytes encroaching into the bone marrow space, almost certainly disturbing HSC interactions with neighbouring cells, which include osteoblasts, osteoclasts, mesenchymal cells and endothelial cells. As the global obesity pandemic grows, the short-term and long-term consequences of increased bone marrow adiposity on HSC lineage selection and immune function remain uncertain. This Review discusses the differentiation and function of haematopoietic cell populations, the principal physicochemical components of the bone marrow niche, and how this environment influences HSCs and haematopoiesis in general. The effect of adipocytes and adiposity on HSC and progenitor cell populations is also discussed, with the goal of understanding how obesity might compromise the core haematopoietic system.

Identification of CD22 Ligands on Bone Marrow Sinusoidal Endothelium Implicated in CD22-dependent Homing of Recirculating B Cells

PubMed Central

Nitschke, Lars; Floyd, Helen; Ferguson, David J.P.; Crocker, Paul R.

1999-01-01

CD22 is a B cell–specific transmembrane protein known to function as a negative regulator of B cell signaling. It has also been implicated in cell adhesion through recognition of α2,6-linked sialic acids on glycans of target cells. Previous studies showed that CD22-deficient mice had a strongly reduced population of mature recirculating B cells in the bone marrow despite normal B cell development. Using a soluble recombinant form of the receptor (CD22-Fc), we demonstrate here that sialylated ligands for CD22 are expressed on sinusoidal endothelial cells of murine bone marrow but not on endothelial cells in other tissues examined. Injection of CD22-Fc revealed that the CD22 ligands in the bone marrow were accessible to the circulation. Treatment of mice with either CD22-Fc or affinity-purified anti-CD22 antibody led to an ∼50% reduction in mature recirculating B cells in the bone marrow without affecting numbers in the spleen. Finally, consistent with the notion that CD22 is a homing receptor, we show that compared with wild-type mice, CD22-deficient animals have a lower number of immunoglobulin M–secreting plasma cells in the bone marrow. PMID:10224292

External bone marrow cytological examination quality assurance (EQAhem)--summary after 6 years in Poland.

PubMed

Lewandowski, Krzysztof; Kurpierz, Katarzyna; Sledzinska, Anna

2015-10-01

Bone marrow macroscopic examination remains one of the most difficult and subjective laboratory assessments in hematology. Only a few external quality assurance programs in the field are present worldwide. We have developed an external quality assurance program EQAhem that allows assessment of the whole process of bone marrow examination. The program participants assess blood and bone marrow smears from the patient, identify selected cells from photographs provided to them, and interpret the microscopic results. In this article, the results of the EQAhem program in Poland from 6 years are summarized. During this time, 62 labs were assessed in total, and positive results were achieved by 89.25 % labs, taking into account all tests. Correct responses with respect to the percentage of cell count were provided by ca. 77.5 % labs. Slightly worse results were obtained when megakaryocyte count and cell identification from photographs were tested. The worst results were obtained in case of dysplasia assessment and clinical interpretation of microscopic examination (54.1 and 58.6 % correct responses, respectively). EQAhem delivers precise information about the quality of bone marrow examinations performed in Poland and has a substantial educational value. We believe that after 6 years, EQAhem has significantly improved the quality of bone marrow microscopic examinations performed in Poland.

An Animal Model of Chronic Aplastic Bone Marrow Failure Following Pesticide Exposure in Mice

PubMed Central

Chatterjee, Sumanta; Chaklader, Malay; Basak, Pratima; Das, Prosun; Das, Madhurima; Pereira, Jacintha Archana; Dutta, Ranjan Kumar; Chaudhuri, Samaresh; Law, Sujata

2010-01-01

The wide use of pesticides for agriculture, domestic and industrial purposes and evaluation of their subsequent effect is of major concern for public health. Human exposure to these contaminants especially bone marrow with its rapidly renewing cell population is one of the most sensitive tissues to these toxic agents represents a risk for the immune system leading to the onset of different pathologies. In this experimental protocol we have developed a mouse model of pesticide(s) induced hypoplastic/aplastic marrow failure to study quantitative changes in the bone marrow hematopoietic stem cell (BMHSC) population through flowcytometric analysis, defects in the stromal microenvironment through short term adherent cell colony (STACC) forming assay and immune functional capacity of the bone marrow derived cells through cell mediated immune (CMI) parameter study. A time course dependent analysis for consecutive 90 days were performed to monitor the associated changes in the marrow’s physiology after 30th, 60th and 90th days of chronic pesticide exposure. The peripheral blood showed maximum lowering of the blood cell count after 90 days which actually reflected the bone marrow scenario. Severe depression of BMHSC population, immune profile of the bone marrow derived cells and reduction of adherent cell colonies pointed towards an essentially empty and hypoplastic marrow condition that resembled the disease aplastic anemia. The changes were accompanied by splenomegaly and splenic erythroid hyperplasia. In conclusion, this animal model allowed us a better understanding of clinico-biological findings of the disease aplastic anemia following toxic exposure to the pesticide(s) used for agricultural and industrial purposes. PMID:24855541

Distribution of Proliferating Bone Marrow in Adult Cancer Patients Determined Using FLT-PET Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hayman, James A., E-mail: hayman@umich.ed; University of Michigan Health Systems, Ann Arbor, MI; Callahan, Jason W.

2011-03-01

Purpose: Given that proliferating hematopoietic stem cells are especially radiosensitive, the bone marrow is a potential organ at risk, particularly with the use of concurrent chemotherapy and radiotherapy. Existing data on bone marrow distribution have been determined from the weight and visual appearance of the marrow in cadavers. {sup 18}F-fluoro-L-deoxythymidine concentrates in bone marrow, and we used its intensity on positron emission tomography imaging to quantify the location of the proliferating bone marrow. Methods and Materials: The {sup 18}F-fluoro-L-deoxythymidine positron emission/computed tomography scans performed at the Peter MacCallum Cancer Centre between 2006 and 2009 on adult cancer patients were analyzed.more » At a minimum, the scans included the mid-skull through the proximal femurs. A software program developed at our institution was used to calculate the percentage of administered activity in 11 separately defined bony regions. Results: The study population consisted of 13 patients, 6 of whom were men. Their median age was 61 years. Of the 13 patients, 9 had lung cancer, 2 had colon cancer, and 1 each had melanoma and leiomyosarcoma; 6 had received previous, but not recent, chemotherapy. The mean percentage of proliferating bone marrow by anatomic site was 2.9% {+-} 2.1% at the skull, 1.9% {+-} 1.2% at the proximal humeri, 2.9% {+-} 1.3% at the sternum, 8.8% {+-} 4.7% at the ribs and clavicles, 3.8% {+-} 0.9% at the scapulas, 4.3% {+-} 1.6% at the cervical spine, 19.9% {+-} 2.6% at the thoracic spine, 16.6% {+-} 2.2% at the lumbar spine, 9.2% {+-} 2.3% at the sacrum, 25.3% {+-} 4.9% at the pelvis, and 4.5% {+-} 2.5% at the proximal femurs. Conclusion: Our modern estimates of bone marrow distribution in actual cancer patients using molecular imaging of the proliferating marrow provide updated data for optimizing normal tissue sparing during external beam radiotherapy planning.« less

HISTOCOMPATIBILITY STUDIES IN A CLOSELY BRED COLONY OF DOGS

PubMed Central

Rapaport, F. T.; Watanabe, K.; Cannon, F. D.; Mollen, N.; Blumenstock, D.; Ferrebee, J. W.

1972-01-01

17 Cooperstown beagles of known DL-A genotypes were exposed to supralethal total body irradiation and received a bone marrow allograft from a DL-A-identical donor; 11 littermate and 6 nonlittermate donor-recipient pairs were studied. The recipients are surviving uneventfully for 315, 364, 424, 440, 531, 531, 584, 605, 625, 635, and 649 days in the littermate group and for 211, 279, 280, 368, 479, and 480 days in the nonlittermate group. The radiation chimeras underwent bilateral nephrectomy and received a kidney allograft obtained from their respective marrow donor within 43–120 days after bone marrow transplantation. The renal allografts are surviving for 191, 200, 221, 234, 313, 349, 361, 377, 378, 405, 441, 444, 482, 557, 580, 581, and 586 days, respectively. 12 of 13 skin allografts obtained from the marrow donor are at present surviving in the recipients for 107, 110, 110, 110, 116, 122, 128, 143, 143, 162, 178, and 199 days, respectively; one graft was rejected at 84 days. In contrast, the radiation chimeras rejected 25 skin allografts obtained from DL-A-incompatible donors within 10.5–21 days (MST = 15.2 days). Skin transplants obtained from DL-A-identical siblings of the bone marrow donors were rejected within 20–36 days (MST = 25.8 days) in recipients of bone marrow cells obtained from littermate donors. Recipients of nonlittermate bone marrow transplants accorded such allografts a prolonged survival time of 27–76 days (MST = 56.2 days). Prospective selection of genotypically DL-A-identical donor-recipient pairs results in the regularly reproducible long-term survival of bone marrow allografts. The radiation chimeras produced in this manner have developed a donor-specific state of unresponsiveness to kidney and skin allografts. The results are consistent with the existence in the canine species of at least three closely linked genetic systems relevant to transplantation, including DL-A, MLC, and a possible bone marrow transplantation locus. PMID:4404277

Effect of space flight on cytokine production and other immunologic parameters of rhesus monkeys

NASA Technical Reports Server (NTRS)

Sonnenfeld, G.; Davis, S.; Taylor, G. R.; Mandel, A. D.; Konstantinova, I. V.; Lesnyak, A.; Fuchs, B. B.; Peres, C.; Tkackzuk, J.; Schmitt, D. A.

1996-01-01

During a recent flight of a Russian satellite (Cosmos #2229), initial experiments examining the effects of space flight on immunologic responses of rhesus monkeys were performed to gain insight into the effect of space flight on resistance to infection. Experiments were performed on tissue samples taken from the monkeys before and immediately after flight. Additional samples were obtained approximately 1 month after flight for a postflight restraint study. Two types of experiments were carried out throughout this study. The first experiment determined the ability of leukocytes to produce interleukin-1 and to express interleukin-2 receptors. The second experiment examined the responsiveness of rhesus bone marrow cells to recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). Human reagents that cross-reacted with monkey tissue were utilized for the bulk of the studies. Results from both studies indicated that there were changes in immunologic function attributable to space flight. Interleukin-1 production and the expression of interleukin-2 receptors was decreased after space flight. Bone marrow cells from flight monkeys showed a significant decrease in their response to GM-CSF compared with the response of bone marrow cells from nonflight control monkeys. These results suggest that the rhesus monkey may be a useful surrogate for humans in future studies that examine the effect of space flight on immune response, particularly when conditions do not readily permit human study.

[Pathological diagnosis of pediatric Burkitt lymphoma involving bone marrow].

PubMed

Sun, Qi; Chen, Zhenping; Liu, Enbin; Li, Zhanqi; Yang, Qingying; Sun, Fujun; Ma, Yue; Zhang, Hongju; Zhang, Peihong; Ru, Kun

2015-02-01

To investigate pathologic and differential diagnostic features of pediatric Burkitt lymphoma (BL). A total of 20 cases of pediatric BL were retrospectively reviewed for their clinical and pathologic profiles. Bone marrow aspiration specimens were available in all cases and bone marrow biopsies were available for immunohistochemical study in 18 cases. Flow cytometry study was available in 16 cases. MYC translocation by FISH method was performed in 11 cases. Atypical lymphocytes with cytoplasmic vacuoles were found in bone marrow smears in all 20 cases and peripheral blood films in all 19 available cases. The bone marrow biopsies showed infiltration by uniform medium-sized atypical lymphocytes with multiple small nucleoli but without the starry-sky pattern in all 18 cases. Immunohistochemistry showed the following results in all 18 cases: positive for CD20, PAX-5, CD10, CD34 and TdT, but negative for bcl-2 and CD3 with Ki-67 > 95%.Flow cytometry showed CD19+CD20+CD10+FMC7+CD22+TdT-CD3- in 16 cases, including κ+ in 8 cases, λ+ in 7 cases, and κ-λ- in 1 case. MYC gene rearrangement by FISH was observed in 10 of the 11 cases. The histopathology of BL is distinct, including atypical lymphocytes with cytoplasmic vacuoles in bone marrow aspirate, lack of starry-sky patternin bone marrow biopsy. Generally, the diagnosis should be made with a combined immunophenotype and FISH approach. Pediatric BL must be distinguished from DLBCL and B-cell lymphoma, unclassifiable, which has intermediate features between DLBCL and Burkitt lymphoma.

Cigarette Smoke Inhibits Recruitment of Bone-Marrow-Derived Stem cells to The Uterus

PubMed Central

Zhou, Yuping; Gan, Ye; Taylor, Hugh S.

2011-01-01

Cigarette smoking leads to female infertility and a decreased incidence of endometriosis. Bone marrow derived stem cells are recruited to uterine endometrium and endometriosis. The effect of cigarette smoking on stem cell recruitment to any organ is uncharacterized. We hypothesized that bone marrow-derived mesenchymal stem cell recruitment to the uterus and differentiation would be diminished by cigarette smoke. We used human mesenchymal stem cells (hMSC) in vitro and a mouse model of cigarette smoke exposure. After myeloablation female C57BL/6J received bone marrow cells from males. Mice were exposed to room air or smoke from unfiltered cigarettes. Immunofluorescence and Y-FISH was performed on uterine sections. In vitro hMSCs were treated with 8-Br-cAMP to induce endometrial cell differentiation with or without cigarette smoke extract (CSE) and decidualization assessed morphologically and by prolactin expression. After 4 weeks the total number of Y-chromosome cells in the uterus was reduced by 68% in the smoke exposed mice. Both leukocytes and bone marrow derived endometrial cells were reduced by 60% and 73%, respectively. Differentiation of bone marrow derived cell to endometrial epithelial cells was reduced by 84%. hMSC treated with CSE failed to show cytological characteristics of decidualization. mRNA levels of the decidualization marker prolactin were decreased by 90% in CSE treated cells. Smoking inhibits both recruitment of bone marrow derived stem cells to uterus and stem cell differentiation. Inhibition of stem cells recruitment may be a general mechanism by which smoking leads to long term organ damage through inability to repair or regenerate multiple tissues. PMID:20955787

Oestrogen receptor specificity in oestradiol-mediated effects on B lymphopoiesis and immunoglobulin production in male mice

PubMed Central

Erlandsson, M C; Jonsson, C A; Islander, U; Ohlsson, C; Carlsten, H

2003-01-01

Oestrogen treatment down-regulates B lymphopoiesis in the bone marrow of mice. Meanwhile it up-regulates immunoglobulin production. To understand better the oestrogen action on bone marrow male mice lacking oestrogen receptor α (ERα; ERKO mice), lacking ERβ (BERKO mice), lacking both receptors (DERKO mice) or wild-type (wt) littermates were castrated and treated for 2·5 weeks with 30 μg/kg 17β-oestradiol (E2) or vehicle oil as controls. The B lymphopoiesis in the bone marrow was examined by flow cytometry and mature B-cell function was studied using an ELISPOT assay enumerating the B cells in bone marrow and spleen that were actively producing immunoglobulins. In wt mice the frequency of B-lymphopoietic (B220+) cells in the bone marrow decreased from 15% to 5% upon E2 treatment. In ERKO and BERKO mice significant reduction was seen but not of the same magnitude. In DERKO mice no reduction of B lymphopoiesis was seen. In addition, our results show that E2 mediated reduction of different steps in B lymphopoiesis require only ERα or both receptors. In wt and BERKO mice E2 treatment resulted in significantly increased levels of B cells actively producing immunoglobulin, while in ERKO and DERKO mice no such change was seen. Similar results were found in both bone marrow and spleen. In conclusion our results clearly show that both ERα and ERβ are required for complete down-regulation of B lymphopoiesis while only ERα is needed to up-regulate immunoglobulin production in both bone marrow and spleen. PMID:12603601

Moxibustion relieves visceral hyperalgesia via inhibition of transient receptor potential vanilloid 1 (TRPV1) and heat shock protein (HSP) 70 expression in rat bone marrow cells.

PubMed

Zou, Weiying; Lin, Hua; Liu, Wenwen; Yang, Bei; Wu, Lei; Duan, Limin; Ling, Ping; Zhu, Lingyan; Dai, Qun; Zhao, Lintong; Zou, Ting; Zhang, Dalei

2016-04-01

To investigate the effects of moxibustion on visceral hyperalgesia (VH) and bone marrow cell transient receptor potential vanilloid type 1 (TRPV1) and heat shock protein (HSP) 70 expression in a rat model of VH. Mechanical colorectal distension was performed to induce VH in neonatal Sprague-Dawley rats. Eight-week-old VH rats were treated with moxibustion at acupuncture point BL25 or an ipsilateral non-acupuncture point. Abdominal withdrawal reflex (AWR) scoring and pain threshold pressure assessment were performed before and after moxibustion treatment for 7 consecutive days. The expression of TRPV1 and HSP70 in bone marrow cells was quantified by real-time quantitative PCR. The expression of TRPV1 and HSP70 in bone marrow cells was increased in rats with VH. Moxibustion at BL25 significantly decreased AWR scores and increased pain threshold pressure in rats with VH. Furthermore, moxibustion at BL25 significantly inhibited the VH-induced increase in the expression of TRPV1 and HSP70 in bone marrow cells. The up-regulation of TRPV1 and HSP70 expression in bone marrow cells may be involved in visceral pain development and the analgesic effect of moxibustion on VH may be mediated through down-regulation of TRPV1 and HSP70 expression in bone marrow cells. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Frequency and natural history of inherited bone marrow failure syndromes: the Israeli Inherited Bone Marrow Failure Registry.

PubMed

Tamary, Hannah; Nishri, Daniella; Yacobovich, Joanne; Zilber, Rama; Dgany, Orly; Krasnov, Tanya; Aviner, Shraga; Stepensky, Polina; Ravel-Vilk, Shoshana; Bitan, Menachem; Kaplinsky, Chaim; Ben Barak, Ayelet; Elhasid, Ronit; Kapelusnik, Joseph; Koren, Ariel; Levin, Carina; Attias, Dina; Laor, Ruth; Yaniv, Isaac; Rosenberg, Philip S; Alter, Blanche P

2010-08-01

Inherited bone marrow failure syndromes are rare genetic disorders characterized by bone marrow failure, congenital anomalies, and cancer predisposition. Available single disease registries provide reliable information regarding natural history, efficacy and side effects of treatments, and contribute to the discovery of the causative genes. However, these registries could not shed light on the true incidence of the various syndromes. We, therefore, established an Israeli national registry in order to investigate the relative frequency of each of these syndromes and their complications. Patients were registered by their hematologists in all 16 medical centers in Israel. We included patients with Fanconi anemia, severe congenital neutropenia, Diamond-Blackfan anemia, congenital amegakaryocytic thrombocytopenia, dyskeratosis congenita, Shwachman-Diamond syndrome, and thrombocytopenia with absent radii. One hundred and twenty-seven patients diagnosed between 1966 and 2007 were registered. Fifty-two percent were found to have Fanconi anemia, 17% severe congenital neutropenia, 14% Diamond-Blackfan anemia, 6% congenital amegakaryocytic thrombocytopenia, 5% dyskeratosis congenita, 2% Shwachman-Diamond syndrome, and 2% thrombocytopenia with absent radii. No specific diagnosis was made in only 2 patients. Of the thirty patients (24%) developing severe bone marrow failure, 80% had Fanconi anemia. Seven of 9 patients with leukemia had Fanconi anemia, as did all 6 with solid tumors. Thirty-four patients died from their disease; 25 (74%) had Fanconi anemia and 6 (17%) had severe congenital neutropenia. This is the first comprehensive population-based study evaluating the incidence and complications of the different inherited bone marrow failure syndromes. By far the most common disease was Fanconi anemia, followed by severe congenital neutropenia and Diamond-Blackfan anemia. Fanconi anemia carried the worst prognosis, with severe bone marrow failure and cancer susceptibility. Diamond-Blackfan anemia had the best prognosis. The data presented provide a rational basis for prevention programs and longitudinal surveillance of the complications of inherited bone marrow failure syndromes.

Adeno Associated Viral-mediated intraosseus labeling of bone marrow derived cells for CNS tracking

PubMed Central

Selenica, Maj-Linda B.; Reid, Patrick; Pena, Gabriela; Alvarez, Jennifer; Hunt, Jerry B.; Nash, Kevin R.; Morgan, Dave; Gordon, Marcia N.; Lee, Daniel C.

2016-01-01

Inflammation, including microglial activation in the CNS, is an important hallmark in many neurodegenerative diseases. Microglial stimuli not only impact the brain microenvironment by production and release of cytokines and chemokines, but also influence the activity of bone marrow derived cells and blood born macrophage populations. In many diseases including brain disorders and spinal cord injury, researchers have tried to harbor the neuroprotective and repair properties of these subpopulations. Hematopoietic bone marrow derived cells (BMDCs) are of great interest, especially during gene therapy because certain hematopoietic cell subpopulations traffic to the sites of injury and inflammation. The aim of this study was to develop a method of labeling endogenous bone marrow derived cells through intraosseus impregnation of recombinant adeno-associated virus (rAAV) or lentivirus. We utilized rAAV serotype 9 (rAAV-9) or lentivirus for gene delivery of green florescence protein (GFP) to the mouse bone marrow cells. Flow cytometry showed that both viruses were able to efficiently transduce mouse bone marrow cells in vivo. However, the rAAV9–GFP viral construct transduced BMDCs more efficiently than the lentivirus (11.2% vs. 6.8%), as indicated by cellular GFP expression. We also demonstrate that GFP labeled cells correspond to bone marrow cells of myeloid origin using CD11b as a marker. Additionally, we characterized the ability of bone marrow derived, GFP labeled cells to extravasate into the brain parenchyma upon acute and subchronic neuroinflammatory stimuli in the mouse CNS. Viral mediated over expression of chemokine (C-C motif) ligand 2 (CCL2) or intracranial injection of lipopolysaccharide (LPS) recruited GFP labeled BMDCs from the periphery into the brain parenchyma compared to vehicle treated mice. Altogether our findings demonstrate a useful method of labeling endogenous BMDCs via viral transduction and the ability to track subpopulations throughout the body following insult or injury. Alternatively, this method might find utility in delivering therapeutic genes for neuroinflammatory conditions. PMID:26784524

Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone.

PubMed

Prisby, Rhonda D

2014-07-01

Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4-6 month; n=8) and old (22-24 month; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner's Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via μCT to quantify microvascular ossification. Bone marrow blood vessels from the rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and "normal" vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (p<0.05) in the old vs. young rats. Calcified and ossified vessel volumes per tissue volume and calcified vessel volume per patent vessel volume were augmented (p<0.05) 262%, 375% and 263%, respectively, in the old vs. young rats. Ossified and patent vessel number was higher (171%) and lower (40%), respectively, in the old vs. young rats. Finally, adipocyte volume per patent vessel volume was higher (86%) with age. This study is the first to report ossification of bone marrow blood vessels in rats and humans. Ossification presumably results in "microvascular dead space" in regard to loss of patency and vasomotor function as opposed to necrosis. Progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly. Copyright © 2014 Elsevier Inc. All rights reserved.

Bone Marrow Blood Vessel Ossification and “Microvascular Dead Space” in Rat and Human Long Bone

PubMed Central

Prisby, Rhonda D.

2014-01-01

Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4–6 mon; n=8) and old (22–24 mon; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner’s Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via µCT to quantify microvascular ossification. Bone marrow blood vessels from rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and “normal” vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (p <0.05) in old vs. young rats. Calcified and ossified vessel volumes per tissue volume and calcified vessel volume per patent vessel volume were augmented (p <0.05) 262%, 375% and 263%, respectively, in old vs. young rats. Ossified and patent vessel number was higher (171%) and lower (40%), respectively, in old vs. young rats. Finally, adipocyte volume per patent vessel volume was higher (86%) with age. This study is the first to report ossification of bone marrow blood vessels in rats and humans. Ossification presumably results in “microvascular dead space” in regards to loss of patency and vasomotor function as opposed to necrosis. The progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly. PMID:24680721

Assessment of alveolar bone marrow fat content using 15 T MRI.

PubMed

Cortes, Arthur Rodriguez Gonzalez; Cohen, Ouri; Zhao, Ming; Aoki, Eduardo Massaharu; Ribeiro, Rodrigo Alves; Abu Nada, Lina; Costa, Claudio; Arita, Emiko Saito; Tamimi, Faleh; Ackerman, Jerome L

2018-03-01

Bone marrow fat is inversely correlated with bone mineral density. The aim of this study is to present a method to quantify alveolar bone marrow fat content using a 15 T magnetic resonance imaging (MRI) scanner. A 15 T MRI scanner with a 13-mm inner diameter loop-gap radiofrequency coil was used to scan seven 3-mm diameter alveolar bone biopsy specimens. A 3-D gradient-echo relaxation time (T1)-weighted pulse sequence was chosen to obtain images. All images were obtained with a voxel size (58 µm 3 ) sufficient to resolve trabecular spaces. Automated volume of the bone marrow fat content and derived bone volume fraction (BV/TV) were calculated. Results were compared with actual BV/TV obtained from micro-computed tomography (CT) scans. Mean fat tissue volume was 20.1 ± 11%. There was a significantly strong inverse correlation between fat tissue volume and BV/TV (r = -0.68; P = .045). Furthermore, there was a strong agreement between BV/TV derived from MRI and obtained with micro-CT (interclass correlation coefficient = 0.92; P = .001). Bone marrow fat of small alveolar bone biopsy specimens can be quantified with sufficient spatial resolution using an ultra-high-field MRI scanner and a T1-weighted pulse sequence. Copyright © 2017 Elsevier Inc. All rights reserved.

Hematologic Toxicity in RTOG 0418: A Phase 2 Study of Postoperative IMRT for Gynecologic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klopp, Ann H., E-mail: aklopp@mdanderson.org; Moughan, Jennifer; Portelance, Lorraine

2013-05-01

Purpose: Intensity modulated radiation therapy (IMRT), compared with conventional 4-field treatment, can reduce the volume of bone marrow irradiated. Pelvic bone marrow sparing has produced a clinically significant reduction in hematologic toxicity (HT). This analysis investigated HT in Radiation Therapy Oncology Group (RTOG) 0418, a prospective study to test the feasibility of delivering postoperative IMRT for cervical and endometrial cancer in a multiinstitutional setting. Methods and Materials: Patients in the RTOG 0418 study were treated with postoperative IMRT to 50.4 Gy to the pelvic lymphatics and vagina. Endometrial cancer patients received IMRT alone, whereas patients with cervical cancer received IMRTmore » and weekly cisplatin (40 mg/m{sup 2}). Pelvic bone marrow was defined within the treatment field by using a computed tomography density-based autocontouring algorithm. The volume of bone marrow receiving 10, 20, 30, and 40 Gy and the median dose to bone marrow were correlated with HT, graded by Common Terminology Criteria for Adverse Events, version 3.0, criteria. Results: Eighty-three patients were eligible for analysis (43 with endometrial cancer and 40 with cervical cancer). Patients with cervical cancer treated with weekly cisplatin and pelvic IMRT had grades 1-5 HT (23%, 33%, 25%, 0%, and 0% of patients, respectively). Among patients with cervical cancer, 83% received 5 or more cycles of cisplatin, and 90% received at least 4 cycles of cisplatin. The median percentage volume of bone marrow receiving 10, 20, 30, and 40 Gy in all 83 patients, respectively, was 96%, 84%, 61%, and 37%. Among cervical cancer patients with a V40 >37%, 75% had grade 2 or higher HT compared with 40% of patients with a V40 less than or equal to 37% (P =.025). Cervical cancer patients with a median bone marrow dose of >34.2 Gy also had higher rates of grade ≥2 HT than did those with a dose of ≤34.2 Gy (74% vs 43%, P=.049). Conclusions: Pelvic IMRT with weekly cisplatin is associated with low rates of HT and high rates of weekly cisplatin use. The volume of bone marrow receiving 40 Gy and the median dose to bone marrow correlated with higher rates of grade ≥2 toxicity among patients receiving weekly cisplatin (cervical cancer patients). Evaluation and limitation of the volume of bone marrow treated with pelvic IMRT is warranted in patients receiving concurrent chemotherapy.« less

Essential requirement of I-A region-identical host bone marrow or bone marrow-derived cells for tumor neutralization by primed L3T4+ T cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ozawa, H.; Iwaguchi, T.; Kataoka, T.

1987-12-01

The antitumor activity of Meth A-hyperimmunized BALB/c mouse spleen cells (Meth A-Im-SPL) was assayed by the Winn test in H-2 incompatible bone marrow chimeras in closed colony CD-1 (nu/nu), inbred DDD/1(nu/nu) (H-2s), or inbred BALB/c(nu/nu) (H-2d) mice as recipients. We found that Meth A-Im-SPL suppressed Meth A growth in the chimera nude mice which were reconstituted with bone marrow cells of the H-2d haplotype (i.e., BALB/c, DBA/2 and B10.D2), but not in the chimeras which were reconstituted with bone marrow cells of the H-2a, H-2b, or H-2k haplotype (i.e., B10.A, B10, and B10.BR). These results suggested that H-2 restriction occurredmore » between Meth A-Im-SPL and bone marrow or bone marrow-derived cells in tumor neutralization. Furthermore, Meth A-Im-SPL did not suppress Meth 1 tumors (antigenically distinct from Meth A tumors) in the presence or absence of mitomycin C-treated Meth A in a Winn assay. These results suggested that there is tumor specificity in the effector phase as well as in the induction phase. The phenotype of the effectors in the Meth A-Im-SPL was Thy-1.2+ and L3T4+, because Meth A-Im-SPL lost their antitumor activity with pretreatment with anti-Thy-1.2 monoclonal antibody (mAb) and complement or anti-L3T4 mAb and complement, but not with anti-Lyt-2.2 mAb and complement or complement alone. Positively purified L3T4+ T cells from Meth A-Im-SPL (Meth A-Im-L3T4), obtained by the panning method, suppressed the tumor growth in the chimera nude mice which were reconstituted with bone marrow cells of B10.KEA2 mice (that were I-A region-identical with Meth A-Im-L3T4 cells but not others in H-2) as well as B10.D2 cells (that were fully identical with Meth A-Im-L3T4 cells in H-2). We conclude that Meth A-Im-SPL (L3T4+) neutralized the tumors in collaboration with I-A region-identical host bone marrow or bone marrow-derived cells, and the neutralization was not accompanied by the bystander effect.« less

Bone Shaft Revascularization After Marrow Ablation Is Dramatically Accelerated in BSP-/- Mice, Along With Faster Hematopoietic Recolonization.

PubMed

Bouleftour, Wafa; Granito, Renata Neves; Vanden-Bossche, Arnaud; Sabido, Odile; Roche, Bernard; Thomas, Mireille; Linossier, Marie Thérèse; Aubin, Jane E; Lafage-Proust, Marie-Hélène; Vico, Laurence; Malaval, Luc

2017-09-01

The bone organ integrates the activity of bone tissue, bone marrow, and blood vessels and the factors ensuring this coordination remain ill defined. Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis. In rodents, bone marrow ablation induces a rapid formation of medullary bone which peaks by ∼8 days (d8) and is blunted in BSP-/- mice. We investigated the coordinate hematopoietic and vascular recolonization of the bone shaft after marrow ablation of 2 month old BSP+/+ and BSP-/- mice. At d3, the ablated area in BSP-/- femurs showed higher vessel density (×4) and vascular volume (×7) than BSP+/+. Vessel numbers in the shaft of ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants. At d6, a much higher number of Lin - (×3) as well as LSK (Lin - IL-7Rα - Sca-1 hi c-Kit hi , ×2) and hematopoietic stem cells (HSC: Flt3 - LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization. However, the proportion of LSK and HSC within the Lin - was lower in BSP-/- and more differentiated stages were more abundant, as also observed in unablated bone, suggesting that hematopoietic differentiation is favored in the absence of BSP. Interestingly, unablated BSP-/- femur marrow also contains more blood vessels than BSP+/+, and in both intact and ablated shafts expression of VEGF and OPN are higher, and DMP1 lower in the mutants. In conclusion, bone marrow ablation in BSP-/- mice is followed by a faster vascular and hematopoietic recolonization, along with lower medullary bone formation. Thus, lack of BSP affects the interplay between hematopoiesis, angiogenesis, and osteogenesis, maybe in part through higher expression of VEGF and the angiogenic SIBLING, OPN. J. Cell. Physiol. 232: 2528-2537, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effects of Spaceflight on Cells of Bone Marrow Origin

PubMed Central

Özçivici, Engin

2013-01-01

Once only a subject for science fiction novels, plans for establishing habitation on space stations, the Moon, and distant planets now appear among the short-term goals of space agencies. This article reviews studies that present biomedical issues that appear to challenge humankind for long-term spaceflights. With particularly focus on cells of bone marrow origin, studies involving changes in bone, immune, and red blood cell populations and their functions due to extended weightlessness were reviewed. Furthermore, effects of mechanical disuse on primitive stem cells that reside in the bone marrow were also included in this review. Novel biomedical solutions using space biotechnology will be required in order to achieve the goal of space exploration without compromising the functions of bone marrow, as spaceflight appears to disrupt homeostasis for all given cell types. Conflict of interest:None declared. PMID:24385745

Cancer treatment - preventing infection

MedlinePlus

... preventing infection; Bone marrow transplant - preventing infection; Cancer treatment - immunosuppression ... types of cancer, such as leukemia, and some treatments including bone marrow transplant and chemotherapy affect your ...

TU-F-12A-02: Quantitative Characterization of Normal Bone Marrow Proliferative Activity with FLT PET/CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weisse, N; Jeraj, R

Purpose: [F-18]FLT PET is a tool for assessing health of bone marrow by evaluating its proliferative activity. This study establishes a baseline quantitative characterization of healthy marrow proliferation to aid in diagnosis of hematological disease. Methods: 31 patients (20 male, 11 female, 41–76 years) being treated for solid cancers with no history of hematological disease, osseous metastatic disease, or radiation therapy received pre-treatment FLT PET/CT scans. Total bone marrow was isolated from whole body FLT PET images by manually removing organs and applying a standardize uptake value (SUV) threshold of 1.0. Because adult marrow is concentrated in the axial skeleton,more » quantitative total bone marrow analysis (QTBMA) was used to isolate marrow in the lumbar spine, thoracic spine, sacrum, and pelvis for analysis. SUV mean, SUV max, and SUV CV were used to quantify bone marrow proliferation. Correlations were explored between SUV and patient characteristics including age, weight, height, and BMI using the Spearman coefficient (ρ). Results: The population-averaged whole-skeleton SUV mean, SUV max, and SUV CV were 3.0±0.6, 18.4±5.7, and 0.6±0.1, respectively. Uptake values in the axial skeleton were similar to the whole-skeleton demonstrated by SUV mean in the thoracic spine (3.6±0.6), lumbar spine (3.3±0.5), sacrum (3.0±0.6), and pelvis regions (2.8±0.5). Whole-skeleton SUV max correlated with patient weight (ρ=0.47, p<0.01) and BMI (ρ=0.60, p<0.01), suggesting marrow activity is related to the body's burden. SUV measures in the thoracic spine, lumbar spine, sacrum, and pelvis were negatively correlated with age (ρ:−0.41 to −0.46, p≤0.02). These negative correlations reflect the fact that active marrow in the adult skeleton is localized in the axial skeleton and decreases with age. Conclusions: Normal bone marrow characterizations were determined using FLT PET. These results provide a baseline characterization against which proliferative activity of abnormal marrow can be compared.« less

First report of Leishmania infantum infection in the endangered orangutan (Pongo pygmaeus pygmaeus) in Madrid, Spain.

PubMed

Miró, Guadalupe; Troyano, Amelia; Montoya, Ana; Fariñas, Fernando; Fermín, Ma Luisa; Flores, Luís; Rojo, Carlos; Checa, Rocío; Gálvez, Rosa; Marino, Valentina; Fragío, Cristina; Martínez-Nevado, Eva

2018-03-20

Some wild animals have been recognized as potential reservoirs of Leishmania infantum infection (e.g. carnivores, lagomorphs, rodents, etc.). Leishmania infantum was also identified infecting humans and lagomorphs (i.e. hares and rabbits) over the period of 2009-2016, with the latter acting as the main reservoirs involved in the human leishmaniosis outbreak in Madrid. Two cases of clinical leishmaniosis are reported in orangutans (Pongo pygmaeus pygmaeus) housed at two different centres in Madrid. The first is the case of a 36-year-old male orangutan with severe weight loss and apathy. A complete blood count and biochemical profile revealed anaemia, neutropenia, hypoalbuminaemia and elevated transaminases. Hepato-splenomegaly was also observed. Four months later, due to worsening of clinical signs (mainly bilateral epistaxis), blood and bone marrow samples were collected. Amastigotes of L. infantum were detected in macrophages from a bone marrow aspirate and by specific polymerase chain reaction. The second case was a 34-year-old female orangutan with severe weight loss and apathy and no other apparent clinical signs. A complete blood count and biochemical profile revealed anaemia, pancytopenia and hypoalbuminaemia. Splenomegaly and pericardial effusion were also observed. As leishmaniosis was included in the differential diagnosis, both blood and bone marrow samples were collected. Leishmania infantum infection was confirmed by microscopy, molecular diagnosis and serology (immunofluorescence antibody test). Both animals were treated daily with oral miltefosine for 28 days; allopurinol was also given uninterruptedly in Case 2 for at least 6 months. During follow-up, though good clinical recovery was clear, a lack of parasitological cure was confirmed molecularly in both blood and bone marrow samples from the two orangutans. In both habitats, the presence of the sand fly vector identified as Phlebotomus perniciosus was confirmed. To our knowledge, this is the first report of L. infantum infection in great apes and in the endangered species P. p. pygmaeus. We are presently looking for L. infantum in other non-human primates living in the same peri-urban areas. If detected, we will examine the impacts of this serious disease on these critically endangered species.

Increased expression of metalloproteinase-2 and -9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase-1 and -2 (TIMP-1, TIMP-2), and EMMPRIN (CD147) in multiple myeloma.

PubMed

Urbaniak-Kujda, Donata; Kapelko-Slowik, Katarzyna; Prajs, Iwona; Dybko, Jarosław; Wolowiec, Dariusz; Biernat, Monika; Slowik, Miroslaw; Kuliczkowski, Kazimierz

2016-01-01

Activity of metalloproteinases (MMP) is controlled both by specific tissue inhibitors (TIMP) and activators (extracellular matrix metalloproteinase inducer, EMMPRIN). There are few data available concerning concentration the bone marrow of MMP-2, MMP-9, TIMP-1, and TIMP-2, or EMMPRIM expression by bone marrow mesenchymal stromal cells (BMSCs) in patients with multiple myeloma (MM). We studied 40 newly diagnosed, untreated patients: 18 males and 22 females with de novo MM and 11 healthy controls. Bone marrow was collected prior to therapy. BMSCs were derived by culturing bone marrow cells on MesenCult. Protein concentrations were determined in bone marrow plasma and culture supernatants by ELISA. EMMPRIN expression by BMSCs was assessed by flow cytometry. The median concentrations of MMP-9, TIMP-1, and TIMP-2 in both marrow plasma and culture supernatants were significantly higher in MM patients than controls. EMMPRIN expression and ratios MMP-9/TIMP-1 and MMP-2/TIMP-2 were higher in MM patients, our results demonstrate that in MM patients MMP-2 and MMP-9 are secreted in higher amounts and are not balanced by inhibitors.

Postmortem bone marrow analysis in forensic science: study of 73 cases and review of the literature.

PubMed

Tattoli, Lucia; Tsokos, Michael; Sautter, Julia; Anagnostopoulos, Joannis; Maselli, Eloisa; Ingravallo, Giuseppe; Delia, Mario; Solarino, Biagio

2014-01-01

In forensic sciences, bone marrow (BM) is an alternative matrix in postmortem toxicology because of its good resistance to autolysis and contaminations. Nevertheless, few studies have been focused on postmortem BM morphological changes after pathological stimuli. We examined 73 BM samples from forensic autopsies; causes of death were both natural and traumatic. BM samples were collected from the sternum by needle aspiration and biopsy; in selected cases, immunohistochemistry was performed. Few autolytic changes were found; BM cellularity decreased with increasing age and postmortem interval. Notable cell changes were detected in 45 cases (61.64%): neoplastic (n=4), and non-neoplastic BM findings (n=41), including multiorgan failure/sepsis (n=26), myelodisplastic-like conditions (n=11), and anaphylactic reactions (n=4). The results showed that BM cellularity supported circumstantial and autopsy findings, suggesting that BM samples could be a useful tool in forensic science applications. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

2010 report from the Center for International Blood and Marrow Transplant Research (CIBMTR): current uses and outcomes of hematopoietic cell transplants for blood and bone marrow disorders.

PubMed

Pasquini, Marcelo C; Wang, Zhiwei; Horowitz, Mary M; Gale, Robert Peter

2010-01-01

These data indicate increasing use of HCT for persons with blood and bone marrow disorders. Recent trends include increasing use of alternative donors including HLA-matched unrelated persons and of HLA-matched umbilical cord blood cells, increasing use of blood cell rather than bone marrow grafts and increasing use of reduced-intensity pretransplant conditioning regimens. Many of these shifts are driven by logistical considerations like the need for donors in persons without an HLA-identical sibling or expanding access to allotransplants to older patients. In other instances, like the shift from bone marrow to blood cell grafts or from conventional to reduced-intensity pretransplant conditioning regimens few randomized clinical trials have been reported to justify these shifts. More data are needed to critically-assess the impact of these changes.

Use of G-CSF-stimulated marrow in allogeneic hematopoietic stem cell transplantation settings: a comprehensive review.

PubMed

Chang, Ying-Jun; Huang, Xiao-Jun

2011-01-01

In recent years, several researchers have unraveled the previously unrecognized effects of granulocyte colony-stimulating factor (G-CSF) on hematopoiesis and the immune cell functions of bone marrow in healthy donors. In human leukocyte antigen-matched or haploidentical transplant settings, available data have established the safety of using G-CSF-stimulated bone marrow grafts, as well as the ability of this source to produce rapid and sustained engraftment. Interestingly, G-CSF-primed bone marrow transplants could capture the advantages of blood stem cell transplants, without the increased risk of chronic graft-versus-host disease that is associated with blood stem cell transplants. This review summarizes the growing body of evidence that supports the use of G-CSF-stimulated bone marrow grafts as an alternative stem cell source in allogeneic hematopoietic stem cell transplantation. © 2010 John Wiley & Sons A/S.

Epigenetic and microenvironmental alterations in bone marrow associated with ROS in experimental aplastic anemia.

PubMed

Chatterjee, Ritam; Law, Sujata

2018-01-01

Aplastic anemia or bone marrow failure often develops as an effect of chemotherapeutic drug application for the treatment of various pathophysiological conditions including cancer. The long-term bone marrow injury affects the basic hematopoietic population including hematopoietic stem/progenitor cells (HSPCs). The present study aimed in unearthing the underlying mechanisms of chemotherapeutics mediated bone marrow aplasia with special focus on altered redox status and associated effects on hematopoietic microenvironment and epigenetic status of hematopoietic cells. The study involves the development of busulfan and cyclophosphamide mediated mouse model for aplastic anemia, characterization of the disease with blood and marrow analysis, cytochemical examinations of bone marrow, flowcytometric analysis of hematopoietic population and microenvironmental components, determination of ROS generation, apoptosis profiling, expressional studies of Notch-1 signaling cascade molecules, investigation of epigenetic modifications including global CpG methylation of DNA, phosphorylation of histone-3 with their effects on bone marrow kinetics and expressional analysis of the anti-oxidative molecules viz; SOD-2 and Sdf-1. Severe hematopoietic catastrophic condition was observed during aplastic anemia which involved peripheral blood pancytopenia, marrow hypocellularity and decreased hematopoietic stem/progenitor population. Generation of ROS was found to play a central role in the cellular devastation in aplastic marrow which on one hand can be correlated with the destruction of hematopoiesis supportive niche components and alteration of vital Notch-1 signaling and on other hand was found to be associated with the epigenetic chromatin modifications viz; global DNA CpG hypo-methylation, histone-3 phosphorylation promoting cellular apoptosis. Decline of anti-oxidant components viz; Sdf-1 and SOD-2 hinted towards the irreversible nature of the oxidative damage during marrow aplasia. Collectively, the findings hinted towards the mechanistic correlation among ROS generation, microenvironmental impairment and epigenetic alterations that led to hematopoietic catastrophe under aplastic stress. The findings may potentiate successful therapeutic strategy development for the dreadful condition concerned. Copyright © 2017 Elsevier GmbH. All rights reserved.

Bone marrow transplantation in a patient with drug-induced aplastic anemia.

PubMed

Banerjee, T K; Band, P R; Pabst, H; Goldsand, G; Armstrong, W D; Brown, J; Hill, J R; Dossetor, J B

1972-09-09

A 23-year-old woman gravely ill with Pseudomonas septicemia secondary to presumed drug-induced bone marrow aplasia received marrow transplantation from two male HL-A identical sibling donors. She had a successful engraftment with excellent but temporary clinical improvement. Subsequently she succumbed to graft-versus-host disease manifested by Pseudomonas and Candida albicans septicemia, cytomegalovirus pneumonitis, three phases of dermatitis, nausea, vomiting, dysphagia, diarrhea, fever, edema and bone pain, with gradual but complete graft suppression by the 74th day after the transplantation. A second marrow transplant on the 70th day was unsuccessful.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knospe, W.H.; Husseini, S.G.

Cellulose ester membranes (CEM) were coated with stromal cells from murine bone or bone marrow irradiated in vitro with 1000, 2000, or 4000 rad and then implanted i.p. in CAF1 mice for periods of six and 12 months. CEM coated with stromal cells from bone showed excellent regeneration of bone and hematopoiesis after 1000 rad in vitro irradiation. After 2000 rad, hematopoietic and bone regeneration was reduced by about 50%, and after 4000 rad it was completely absent in CEM coated with stromal cells from bone. CEM coated with stromal cells from bone marrow showed no regeneration of hematopoiesis ormore » bone after 1000, 2000, and 4000 rad in vitro irradiation and residence i.p. for six and 12 months. These results indicate that regeneration of the hematopoietic microenvironment is dependent upon living stromal cells. A difference in radiation sensitivity is demonstrated between stromal cells from bone and from bone marrow.« less

Drug diffusion, integration, and stability of nanoengineered drug-releasing implants in bone ex-vivo.

PubMed

Rahman, Shafiur; Gulati, Karan; Kogawa, Masakazu; Atkins, Gerald J; Pivonka, Peter; Findlay, David M; Losic, Dusan

2016-03-01

To treat skeletal conditions such as bone infections, osteoporotic fractures, and osteosarcoma, it would be ideal to introduce drugs directly to the affected site. Localized drug delivery from the bone implants is a promising alternative to systemic drug administration. In this study we investigated electrochemically nanoengineered Ti wire implants with titania nanotubes (TNTs), as minimally invasive drug-releasing implants for the delivery of drugs directly into the bone tissue. Since trabecular bone in vivo contains a highly interconnected bone marrow, we sought to determine the influence of marrow on drug release and diffusion. Electrochemical anodization of Ti wires (length 10 mm) was performed to create an oxide layer with TNTs on the surface, followed by loading with a fluorescent model drug, Rhodamine B (RhB). Cores of bovine trabecular bone were generated from the sternum of a young steer, and were processed to have an intact bone marrow, or the marrow was removed. RhB-loaded TNTs/Ti wires were inserted into the bone cores, which were then cultured ex vivo using the ZetOS™ bioreactor system to maintain bone viability. Release and diffusion of RhB inside the bone was monitored using fluorescence imaging and different patterns of drug transport in the presence or absence of marrow were observed. Scanning electron microscopy of the implants after retrieval from bone cores confirmed survival of the TNTs structures. Histological investigation showed the presence of bone cells adherent on the implants. This study shows a potential of Ti drug-releasing implants based on TNTs technology towards localized bone therapy. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 714-725, 2016. © 2015 Wiley Periodicals, Inc.

Whole-body MR imaging, bone diffusion imaging: how and why?

PubMed

Jaramillo, Diego

2010-06-01

Whole-body MRI (W-B MRI) and diffusion-weighted imaging (DWI) are two novel techniques that greatly facilitate the evaluation of many disorders of childhood. In the musculoskeletal system, these techniques primarily aid in the evaluation of the marrow, although there is increasing interest in the study of soft-tissue abnormalities with W-B MRI and of cartilage with DWI.The normal pattern of marrow transformation affects both modalities throughout childhood. Haematopoietic marrow has a much higher signal intensity than fatty marrow on W-B MRI short tau inversion recovery (STIR) images (Darge et al. Eur J Radiol 68:289-298, 2008). Diffusion is greater in haematopoietic marrow than in fatty marrow and decreases in the skeleton with age (Jaramillo et al. Pediatr Radiol 34:S48, 2004). It is important therefore to remember that the entire skeleton is haematopoietic at birth and that there is a process of marrow transformation to fatty marrow. Marrow conversion proceeds from the fingers to the shoulders and from the toes to the hips. Within each bone, fatty marrow transformation begins in the epiphyses, and within the shaft of the long bones fatty marrow transformation begins at the diaphysis and proceeds towards the metaphyses.

THE PROTECTIVE EFFECT OF LOCAL BONE MARROW ASPHYXIA IN ACUTE RADIATION SICKNESS IN ANIMALS (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zherebchenko, P.G.; Krasnykh, I.G.; Lebkova, N.P.

1960-10-01

In experiments on mice, rats, and dogs, a study was made of the effect of local bone marrow asphyxia on the course and outcome of radiation sickness. Asphyxia was induced by applying a hemostatic tourniquet on the extremity of animals during irradiation. It was established that local asphyxia of the bone marrow alleviates the severity of acute radiation sickness and increases the survival of animals. It is shown that at the basis of the radioprotective action lies the reduced degeneration of the bone marrow, subsequently facilitating the regeneration of hematopeiesis. Data are obtained relative to the intensification of the effectmore » of local asphyxia with the aid of prophylactic (mercamine) and curative (streptomycin) agents. (auth)« less

Prevalence and Implications of Bone Marrow Involvement in Patients with Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

PubMed Central

Choi, Sang Il; Kook, Myeong-Cherl; Hwang, Sanghyun; Kim, Young-Il; Lee, Jong Yeul; Kim, Chan Gyoo; Choi, Il Ju; Lee, Hyewon; Eom, Hyeon Seok

2018-01-01

Background/Aims Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach is an uncommon disease. Bone marrow involvement is reported even in patients with only a mucosal lesion. We evaluated the prevalence and risk factors of marrow involvement and its implications for diagnosis and treatment. Methods In total, 132 patients who were diagnosed with gastric MALT lymphoma at the National Cancer Center in Korea between January 2001 and December 2016 were enrolled in the study. The patient data were collected and analyzed retrospectively. Results Of the 132 patients, 47 (35.6%) were male, with a median age of 52 years (range, 17 to 81 years). The median follow-up duration was 48.8 months (range, 0.5 to 169.9 months). Helicobacter pylori infection was detected in 82 patients (62.1%). Most patients (80.3%) had stage IE1 according to the modified Ann Arbor staging system. Ninety-two patients underwent bone marrow evaluation, and four patients (4.3%) had marrow involvement. Of these patients, one presented with abdominal lymph node involvement, while the other three had stage IE1 disease if marrow involvement was disregarded. All three patients had no significant symptoms and were monitored after local treatment without evidence of disease aggravation. Conclusions Bone marrow involvement was found in 4.3% of the patients with gastric MALT lymphoma. Bone marrow examination may be deferred because marrow involvement does not change the treatment options or outcome in gastric MALT lymphoma confined to the stomach wall. PMID:29409307

Archeological Investigations in Cochiti Reservoir, New Mexico. Volume 3. 1976-1977 Field Seasons.

DTIC Science & Technology

1979-01-01

or methods are in a constant state of flux, and will undoubtedly continue so. The present In 1959, Baumhoff and Heizer suggested that the sys- paper...marrow extraction and when as estimates rather than counts were insect bodies and rendering bone grease. parts (10-25%), cocoons/larvae/eggs (1-10%), and...A yielded rendering bone grease or making soup. The association of 40 burned bone fragments. A 500 ml sample from grid the unidentified fragments and

Management of unicameral bone cyst by using freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow.

PubMed

Datta, N K; Das, K P; Alam, M S; Kaiser, M S

2014-07-01

Unicameral bone cyst is a common benign bone tumor and most frequent cause of the pathological fracture in children. We have started a prospective study for that treatment of unicameral bone cyst by using freeze dried radiation sterilized bone allograft impregnated with autogenous bone marrow in the department of Orthopaedics, Bangabandhu Sheikh Mujib Medical University (BSMMU) during May 1999 to April 2012. Aim of this study was to see Freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow a satisfactory graft material in the treatment of unicameral bone cyst as well as factors such as patients age, sex, cyst size and site of lesion influence on cyst healing. A total 35 patients of unicameral bone cyst were operated. In this study out of 35 patients, male were 22(62.86%) and female were 13(37.14). Male Female ratio 22:13(1.70:1) Age of the patients ranging from 2 years 6 month to 20 years, mean age 12.18 years more common 11 years to 20 years 29(82.86%) patients. Common bones sites involvements are proximal end of Humerus 20(57.14%), proximal end of Femur 7(20 %), proximal end of Tibia 3(8.57%), Calcanium 2(5.71%), proximal end of Ulna 1(2.86%), shaft of Radius 1(2.86%) and Phalanx 1(2.86%). Final clinical outcome of unicameral bone cyst treated by thorough curettage of cavity and tightly filled with freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow in which healed (success rate) 88.57% (31) and recurrence rate is 11.43% (4). P value is <0.001. Follow up period was 6 month to 11 years. From our study it was realized that freeze dried radiation sterilized bone allograft impregnated with autogenous bone marrow is useful graft material for healing of the lesional area as well as restoring structural integrity for the treatment of unicameral bone cyst.

Bone Marrow Diseases - Multiple Languages

MedlinePlus

... Marrow Biopsy - العربية (Arabic) Bilingual PDF Health Information Translations Chinese, Simplified (Mandarin dialect) (简体中文) Expand Section Bone ... Chinese, Simplified (Mandarin dialect)) Bilingual PDF Health Information Translations Chinese, Traditional (Cantonese dialect) (繁體中文) Expand Section Bone ...

Diagnosis of central nervous system relapse of pediatric acute lymphoblastic leukemia: Impact of routine cytological CSF analysis at the time of intrathecal chemotherapy.

PubMed

Gassas, Adam; Krueger, Joerg; Alvi, Saima; Sung, Lillian; Hitzler, Johanne; Lieberman, Lani

2014-12-01

Despite the success of central nervous system (CNS) directed therapy in pediatric acute lymphoblastic leukemia (ALL), relapse involving the CNS continues to be observed in 5-10% of children when utilizing standard intrathecal prophylactic chemotherapy. While most pediatric ALL treatment protocols mandate regular lumbar punctures (LP) for the intrathecal injection of chemotherapy, the value of routine cytological analysis of cerebrospinal fluid (CSF) during therapy is unknown. Our objective was to assess the diagnostic value of routine CSF analysis during ALL therapy. To allow for at least 10 years of follow up from ALL diagnosis, children (0-18 years) with ALL diagnosed and treated at SickKids, Toronto, Canada between 1994-2004 were studied. Medical records of patients with CNS relapse were examined to determine whether CNS relapse was diagnosed based on cytology of a routinely obtained CSF sample, a CSF sample obtained because of signs and symptoms or a CSF sample obtained after the diagnosis of a bone marrow relapse. Of 494 children treated for ALL, 31 (6.6%) developed a relapse of ALL involving the CNS. Twenty-two had an isolated CNS relapse and nine had a combined bone marrow and CNS relapse. Among patients with isolated CNS relapse, 73% (16/22) were diagnosed based on routine CSF samples obtained from asymptomatic children. Conversely, 89% (8/9) of children with combined bone marrow and CNS relapse presented with symptoms and signs that prompted CSF examination. Routine CSF examination at the time of LP for intrathecal chemotherapy is useful in detecting CNS relapse. © 2014 Wiley Periodicals, Inc.

Massive periosteal reaction a presenting feature of acute megakaryocytic leukemia.

PubMed

Ueda, Takahiro; Ito, Yasuhiko; Maeda, Miho; Fukunaga, Yoshitaka

2007-12-01

Acute megakaryoblastic leukemia (AML M7) is a biologically heterogeneous form of acute myeloid leukemia accounting for 14.6% of cases. In many instances in the past, AML M7 has been classified as undifferentiated leukemia, myelodysplasia, myelofibrosis or some other disease because of its complex clinical presentation or the difficulty of obtaining and interpreting bone marrow samples. However, with currently available morphological, cytochemical, cytogenetic and immunophenotypic methods, AML M7 can now be reliably diagnosed. Although the radiographic spectrum of bony changes in leukemia have been well characterized, skeletal X-ray abnormalities in the setting of AML M7 in pediatric patients have been described in few reports that were associated with bone marrow fibrosis. Here we report on a 14-month-old girl who presented with a massive periosteal reaction of the extremities and clavicles associated with myelofibrosis, a presenting feature of AML M7. The bone changes were very unusual in this case.

SU-E-J-125: A Novel IMRT Planning Technique to Spare Sacral Bone Marrow in Pelvic Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGuire, S; Bhatia, S; Sun, W

Purpose: Develop an IMRT planning technique that can preferentially spare sacral bone marrow for pelvic cancer patients. Methods: Six pelvic cancer patients (two each with anal, cervical, and rectal cancer) were enrolled in an IRB approved protocol to obtain FLT PET images at simulation, during, and post chemoradiation therapy. Initially, conventional IMRT plans were created to maintain target coverage and reduce dose to OARs such as bladder, bowel, rectum, and femoral heads. Simulation FLT PET images were used to create IMRT plans to spare bone marrow identified as regions with SUV of 2 or greater (IMRT-BMS) within the pelvic bonesmore » from top of L3 to 5mm below the greater trochanter without compromising PTV coverage or OAR sparing when compared to the initial IMRT plan. IMRT-BMS plans used 8–10 beam angles that surrounded the subject. These plans were used for treatment. Retrospectively, the same simulation FLT PET images were used to create IMRT plans that spared bone marrow located in the sacral pelvic bone region (IMRT-FAN) also without compromising PTV coverage or OAR sparing. IMRT-FAN plans used 16 beam angles every 12° anteriorly from 90° – 270°. Optimization objectives for the sacral bone marrow avoidance region were weighted to reduce ≥V10. Results: IMRT-FAN reduced dose to the sacral bone marrow for all six subjects. The average V5, V10, V20, and V30 differences from the IMRT-BMS plan were −2.2 ± 1.7%, −11.4 ± 3.6%, −17.6 ± 5.1%, and −19.1 ± 8.1% respectively. Average PTV coverage change was 0.5% ± 0.8% from the conventional IMRT plan. Conclusion: An IMRT planning technique that uses beams from the anterior and lateral directions reduced the volume of sacral bone marrow that receives ≤10Gy while maintaining PTV coverage and OAR sparing. Additionally, the volume of sacral bone marrow that received 20 or 30 Gy was also reduced.« less

Silk fibroin/chitosan thin film promotes osteogenic and adipogenic differentiation of rat bone marrow-derived mesenchymal stem cells.

PubMed

Li, Da-Wei; He, Jin; He, Feng-Li; Liu, Ya-Li; Liu, Yang-Yang; Ye, Ya-Jing; Deng, Xudong; Yin, Da-Chuan

2018-04-01

As a biodegradable polymer thin film, silk fibroin/chitosan composite film overcomes the defects of pure silk fibroin and chitosan films, respectively, and shows remarkable biocompatibility, appropriate hydrophilicity and mechanical properties. Silk fibroin/chitosan thin film can be used not only as metal implant coating for bone injury repair, but also as tissue engineering scaffold for skin, cornea, adipose, and other soft tissue injury repair. However, the biocompatibility of silk fibroin/chitosan thin film for mesenchymal stem cells, a kind of important seed cell of tissue engineering and regenerative medicine, is rarely reported. In this study, silk fibroin/chitosan film was prepared by solvent casting method, and the rat bone marrow-derived mesenchymal stem cells were cultured on the silk fibroin/chitosan thin film. Osteogenic and adipogenic differentiation of rat bone marrow-derived mesenchymal stem cells were induced, respectively. The proliferation ability, osteogenic and adipogenic differentiation abilities of rat bone marrow-derived mesenchymal stem cells were systematically compared between silk fibroin/chitosan thin film and polystyrene tissue culture plates. The results showed that silk fibroin/chitosan thin film not only provided a comparable environment for the growth and proliferation of rat bone marrow-derived mesenchymal stem cells but also promoted their osteogenic and adipogenic differentiation. This work provided information of rat bone marrow-derived mesenchymal stem cells behavior on silk fibroin/chitosan thin film and extended the application of silk fibroin/chitosan thin film. Based on the results, we suggested that the silk fibroin/chitosan thin film could be a promising material for tissue engineering of bone, cartilage, adipose, and skin.

Foot bone marrow edema after a 10-wk transition to minimalist running shoes.

PubMed

Ridge, Sarah T; Johnson, A Wayne; Mitchell, Ulrike H; Hunter, Iain; Robinson, Eric; Rich, Brent S E; Brown, Stephen Douglas

2013-07-01

Minimalist running shoes are becoming a more popular choice for runners in the past few years. However, there is little conclusive evidence about the advantages or disadvantages of running in these shoes. Although performance benefits may exist, injury may also occur from the added stress of running without the benefit of cushioning under the foot. Bone marrow edema can be a manifestation of added stress on the foot. This study measured bone marrow edema in runners' feet before and after a 10-wk period of transitioning from traditional to minimalist running shoes. Thirty-six experienced recreational runners underwent magnetic resonance imaging (MRI) before and after a 10-wk period. Seventeen subjects were in the control group (ran in their traditional shoes only for 10 wk), whereas the other 19 were in the experimental group (gradually transitioned to Vibram FiveFinger running shoes for 10 wk). The severity of the bone marrow edema was scored on a range of 0-4 (0 = no bone marrow edema, 4 = edema in more than 50% of the length of the bone). A score of 4 represented a stress fracture. Pretraining MRI scores were not statistically different between the groups. The posttraining MRI scores showed that more subjects in the Vibram group (10 of 19) showed increases in bone marrow edema in at least one bone after 10 wk of running than that in the control group (P = 0.009). Runners interested in transitioning to minimalist running shoes, such as Vibram FiveFingers, should transition very slowly and gradually to avoid potential stress injury in the foot.

Correlation between p65 and TNF-α in patients with acute myelocytic leukemia.

PubMed

Dong, Qiao-Mei; Ling, Chun; Zhu, Jun-Fang; Chen, Xuan; Tang, Yan; Zhao, L I

2015-11-01

The correlation between the expression levels of p65 and TNF-α in patients with acute myelocytic leukemia (AML) and AML cell lines were investigated. The bone marrow samples of 30 AML patients and 10 non-leukemia controls were studied. The mRNA expression levels of p65 and TNF-α were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Pearson's Correlation test was used to demonstrate the correlation between TNF-α and p65 expression levels in AML specimens. Receiver operating characteristic (ROC) curves were plotted to determine whether TNF-α and p65 expression levels could be used to differentiate AML samples from non-leukemia samples. MG132 and anti-TNF-α antibody were used to inhibit the expression of p65 and TNF-α in the AML cell line, HL-60. The expression of p65 and TNF-α were detected by RT-qPCR and western blot analysis. The mRNA expression levels of p65 and TNF-α were significantly increased in AML patients compared with non-leukemia control bone marrow samples by RT-qPCR, and the two molecules expression pattern's exhibited sufficient predictive power to distinguish AML patients from non-leukemia control samples. Pearson's correlation analysis demonstrated that TNF-α expression was strongly correlated with p65 expression in AML bone marrow samples. In HL-60 cells, inhibition of TNF-α reduced the expression of p65; in addition, inhibition of p65 reduced the expression of TNF-α as assessed by RT-qPCR and western blot analysis. p65 and TNF-α were highly expressed in AML patients, and these 2 molecules were strongly correlated. The present study indicates that p65 and TNF-α have potential as molecular markers to distinguish AML patients from non-leukemia control samples, and that these 2 molecules may be useful prognostic factor for patients with AML.

Pore cross-section area on predicting elastic properties of trabecular bovine bone for human implants.

PubMed

Maciel, Alfredo; Presbítero, Gerardo; Piña, Cristina; del Pilar Gutiérrez, María; Guzmán, José; Munguía, Nadia

2015-01-01

A clear understanding of the dependence of mechanical properties of bone remains a task not fully achieved. In order to estimate the mechanical properties in bones for implants, pore cross-section area, calcium content, and apparent density were measured in trabecular bone samples for human implants. Samples of fresh and defatted bone tissue, extracted from one year old bovines, were cut in longitudinal and transversal orientation of the trabeculae. Pore cross-section area was measured with an image analyzer. Compression tests were conducted into rectangular prisms. Elastic modulus presents a linear tendency as a function of pore cross-section area, calcium content and apparent density regardless of the trabecular orientation. The best variable to estimate elastic modulus of trabecular bone for implants was pore cross-section area, and affirmations to consider Nukbone process appropriated for marrow extraction in trabecular bone for implantation purposes are proposed, according to bone mechanical properties. Considering stress-strain curves, defatted bone is stiffer than fresh bone. Number of pores against pore cross-section area present an exponential decay, consistent for all the samples. These graphs also are useful to predict elastic properties of trabecular samples of young bovines for implants.

A case of rectal carcinoma with skin and bone marrow metastasis with concurrent extensive visceral involvement; unusual and dismal co-incidence.

PubMed

Arslan, Cagatay; Sen, Cenk Ahmet; Ortac, Ragip

2015-06-01

Novel systemic therapies and modern surgical and ablative approaches have improved the survival rates for the patients with metastatic colorectal cancer. However, there are still patients with poor prognosis and underlying mechanisms that could not be defined clearly. Metastatic colorectal cancer patients with skin metastasis have a poor prognosis. A 45-year-old man, who presented with large bowel obstruction, was diagnosed with metastatic rectal adenocarcinoma. Unresectable liver metastases were found at diagnosis. FOLFOX plus bevacizumab treatment was started, but the patient developed bowel obstruction after the third cycle. Therefore, ileostomy was performed. Multiple skin, lung, liver and bone metastases appeared during that time. Bone marrow biopsy demonstrated diffuse infiltration by adenocarcinoma cells. Even though partial remission was achieved after 4 cycles of FOLFIRI-cetuximab, the disease progressed after the 8th cycle. The patient lost his life due to disease progression 8 months after the diagnosis. Bone marrow and skin are unusual sites of metastasis for colorectal carcinoma. Metastases in bone marrow and skin develop at later stages of metastatic disease. This patient lived only 4 months after the development of skin and bone marrow metastases. Skin and bone marrow metastases may be the harbingers of short survival. Biopsy of metastatic sites is crucial for diagnosis and detailed molecular analysis. Molecular pathway alterations underlying worse disease course may be found, and hence probable targets for drug improvement may be indicated.

Comparison of direct and indirect radiation effects on osteoclast formation from progenitor cells derived from different hemopoietic sources.

PubMed

Scheven, B A; Wassenaar, A M; Kawilarang-de Haas, E W; Nijweide, P J

1987-07-01

Hemopoietic stem and progenitor cells from different sources differ in radiosensitivity. Recently, we have demonstrated that the multinucleated cell responsible for bone resorption and marrow cavity formation, the osteoclast, is in fact of hemopoietic lineage. In this investigation we have studied the radiosensitivity of osteoclast formation from two different hemopoietic tissues: fetal liver and adult bone marrow. Development of osteoclasts from hemopoietic progenitors was induced by coculture of hemopoietic cell populations with fetal mouse long bones depleted of their own osteoclast precursor pool. During culture, osteoclasts developed from the exogenous cell population and invaded the calcified hypertrophic cartilage of the long bone model, thereby giving rise to the formation of a primitive marrow cavity. To analyze the radiosensitivity of osteoclast formation, either the hemopoietic cells or the bone rudiments were irradiated before coculture. Fetal liver cells were found to be less radiosensitive than bone marrow cells. The D0, Dq values and extrapolation numbers were 1.69 Gy, 5.30 Gy, and 24.40 for fetal liver cells and 1.01 Gy, 1.85 Gy, and 6.02 for bone marrow cells. Irradiation of the (pre)osteoclast-free long bone rudiments instead of the hemopoietic sources resulted in a significant inhibition of osteoclast formation at doses of 4 Gy or more. This indirect effect appeared to be more prominent in the cocultures with fetal than with adult hemopoietic cells. Furthermore, radiation doses of 8.0-10.0 Gy indirectly affected the appearance of other cell types (e.g., granulocytes) in the newly formed but underdeveloped marrow cavity. The results indicate that osteoclast progenitors from different hemopoietic sources exhibit a distinct sensitivity to ionizing irradiation. Radiation injury to long bone rudiments disturbs the osteoclast-forming capacity as well as the hemopoietic microenvironment.

Quality of life and its socio-demographic and psychological determinants after bone marrow transplantation.

PubMed

Janicsák, Henriett; Masszi, Tamás; Reményi, Péter; Ungvari, Gabor S; Gazdag, Gábor

2013-08-01

A host of medical, socio-demographic, and psychological factors that affect bone marrow transplantation (BMT) patients' quality of life (QOL) have been identified, but due to the methodological diversity of the studies, the findings have been contradictory. The aim of this study was to examine the influence of somatic status, social characteristics, and psychological symptoms on QOL in BMT patients. The study had a cross-sectional design. QOL was evaluated using the Hungarian version of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale. Anxiety and depression were assessed using Spielberger's State and Trait Anxiety Inventory (SSTAI) and the Beck Depression Inventory (BDI). A questionnaire designed for the study was used to record socio-demographic variables. One hundred and twenty-one patients formed the study sample. Patients' QOL was better in our sample than in another study with similar mean time after BMT. BDI scores indicated mild depression; SSTAI scores corresponded with healthy population levels. QOL was strongly influenced by psychological symptoms (depression P < 0.001; anxiety P = 0.001; psychiatric comorbidity P = 0.001), employment status (P = 0.042), and gender (P = 0.05). The somatic factors influenced only separate aspects of QOL; somatic comorbidity only affected cancer-associated QOL (P = 0.004). This is the first study on a Hungarian BMT sample that included economic factors in the assessment of QOL. Psychological variables were the strongest determinants of QOL in this study. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Elemental Analysis of Bone, Teeth, Horn and Antler in Different Animal Species Using Non-Invasive Handheld X-Ray Fluorescence.

PubMed

Buddhachat, Kittisak; Klinhom, Sarisa; Siengdee, Puntita; Brown, Janine L; Nomsiri, Raksiri; Kaewmong, Patcharaporn; Thitaram, Chatchote; Mahakkanukrauh, Pasuk; Nganvongpanit, Korakot

2016-01-01

Mineralized tissues accumulate elements that play crucial roles in animal health. Although elemental content of bone, blood and teeth of human and some animal species have been characterized, data for many others are lacking, as well as species comparisons. Here we describe the distribution of elements in horn (Bovidae), antler (Cervidae), teeth and bone (humerus) across a number of species determined by handheld X-ray fluorescence (XRF) to better understand differences and potential biological relevance. A difference in elemental profiles between horns and antlers was observed, possibly due to the outer layer of horns being comprised of keratin, whereas antlers are true bone. Species differences in tissue elemental content may be intrinsic, but also related to feeding habits that contribute to mineral accumulation, particularly for toxic heavy metals. One significant finding was a higher level of iron (Fe) in the humerus bone of elephants compared to other species. This may be an adaptation of the hematopoietic system by distributing Fe throughout the bone rather than the marrow, as elephant humerus lacks a marrow cavity. We also conducted discriminant analysis and found XRF was capable of distinguishing samples from different species, with humerus bone being the best source for species discrimination. For example, we found a 79.2% correct prediction and success rate of 80% for classification between human and non-human humerus bone. These findings show that handheld XRF can serve as an effective tool for the biological study of elemental composition in mineralized tissue samples and may have a forensic application.

Elemental Analysis of Bone, Teeth, Horn and Antler in Different Animal Species Using Non-Invasive Handheld X-Ray Fluorescence

PubMed Central

Buddhachat, Kittisak; Klinhom, Sarisa; Siengdee, Puntita; Brown, Janine L.; Nomsiri, Raksiri; Kaewmong, Patcharaporn; Thitaram, Chatchote; Mahakkanukrauh, Pasuk; Nganvongpanit, Korakot

2016-01-01

Mineralized tissues accumulate elements that play crucial roles in animal health. Although elemental content of bone, blood and teeth of human and some animal species have been characterized, data for many others are lacking, as well as species comparisons. Here we describe the distribution of elements in horn (Bovidae), antler (Cervidae), teeth and bone (humerus) across a number of species determined by handheld X-ray fluorescence (XRF) to better understand differences and potential biological relevance. A difference in elemental profiles between horns and antlers was observed, possibly due to the outer layer of horns being comprised of keratin, whereas antlers are true bone. Species differences in tissue elemental content may be intrinsic, but also related to feeding habits that contribute to mineral accumulation, particularly for toxic heavy metals. One significant finding was a higher level of iron (Fe) in the humerus bone of elephants compared to other species. This may be an adaptation of the hematopoietic system by distributing Fe throughout the bone rather than the marrow, as elephant humerus lacks a marrow cavity. We also conducted discriminant analysis and found XRF was capable of distinguishing samples from different species, with humerus bone being the best source for species discrimination. For example, we found a 79.2% correct prediction and success rate of 80% for classification between human and non-human humerus bone. These findings show that handheld XRF can serve as an effective tool for the biological study of elemental composition in mineralized tissue samples and may have a forensic application. PMID:27196603

Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors

PubMed Central

Anasetti, Claudio; Logan, Brent R.; Lee, Stephanie J.; Waller, Edmund K.; Weisdorf, Daniel J.; Wingard, John R.; Cutler, Corey S.; Westervelt, Peter; Woolfrey, Ann; Couban, Stephen; Ehninger, Gerhard; Johnston, Laura; Maziarz, Richard T.; Pulsipher, Michael A.; Porter, David L.; Mineishi, Shin; McCarty, John M.; Khan, Shakila P.; Anderlini, Paolo; Bensinger, William I.; Leitman, Susan F.; Rowley, Scott D.; Bredeson, Christopher; Carter, Shelly L.; Horowitz, Mary M.; Confer, Dennis L.

2012-01-01

BACKGROUND Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia. METHODS We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37). RESULTS The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P = 0.29), with an absolute difference of 5 percentage points (95% CI, −3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P = 0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P = 0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse. CONCLUSIONS We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute–National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.) PMID:23075175

Treatment for unicameral bone cysts in long bones: an evidence based review.

PubMed

Donaldson, Sandra; Chundamala, Josie; Yandow, Suzanne; Wright, James G

2010-03-20

The purpose of this paper is to perform an evidence based review for treatment of unicameral bone cysts. A search of MEDLINE (1966 to 2009) was conducted and the studies were classified according to levels of evidence. This review includes only comparative Level I-III studies. The systematic review identified 16 studies. There is one level I study, one level II study and the remaining 14 studies are level III. Seven of the sixteen studies had statistically different results: three studies indicated that steroid injection was superior to bone marrow injection or curettage and bone grafting; one study indicated that cannulated screws were superior to steroid injections; one study indicated resection and myoplasty was superior to steroid injection; one study indicated a combination of steroid, demineralized bone matrix and bone marrow aspirate, and curettage and bone grafting were superior to steroid injection; and one study indicated that curettage and bone grafting was superior to non-operative immobilization. Based on one Level I study, including a limited number of individuals, steroid injection seems to be superior to bone marrow injection. As steroid injections have already demonstrated superiority over bone marrow injections in a randomized clinical trial, the next step would be a prospective trial comparing steroid injections with other treatments.

Treatment for unicameral bone cysts in long bones: an evidence based review

PubMed Central

Donaldson, Sandra; Chundamala, Josie; Yandow, Suzanne; Wright, James G.

2010-01-01

The purpose of this paper is to perform an evidence based review for treatment of unicameral bone cysts. A search of MEDLINE (1966 to 2009) was conducted and the studies were classified according to levels of evidence. This review includes only comparative Level I-III studies. The systematic review identified 16 studies. There is one level I study, one level II study and the remaining 14 studies are level III. Seven of the sixteen studies had statistically different results: three studies indicated that steroid injection was superior to bone marrow injection or curettage and bone grafting; one study indicated that cannulated screws were superior to steroid injections; one study indicated resection and myoplasty was superior to steroid injection; one study indicated a combination of steroid, demineralized bone matrix and bone marrow aspirate, and curettage and bone grafting were superior to steroid injection; and one study indicated that curettage and bone grafting was superior to non-operative immobilization. Based on one Level I study, including a limited number of individuals, steroid injection seems to be superior to bone marrow injection. As steroid injections have already demonstrated superiority over bone marrow injections in a randomized clinical trial, the next step would be a prospective trial comparing steroid injections with other treatments. PMID:21808696

Organ-on-a-chip: development and clinical prospects toward toxicity assessment with an emphasis on bone marrow.

PubMed

Kim, Jeehye; Lee, Hanna; Selimović, Šeila; Gauvin, Robert; Bae, Hojae

2015-05-01

Conventional approaches for toxicity evaluation of drugs and chemicals, such as animal tests, can be impractical due to the large experimental scale and the immunological differences between species. Organ-on-a-chip models have recently been recognized as a prominent alternative to conventional toxicity tests aiming to simulate the human in vivo physiology. This review focuses on the organ-on-a-chip applications for high-throughput screening of candidate drugs against toxicity, with a particular emphasis on bone-marrow-on-a-chip. Studies in which organ-on-a-chip models have been developed and utilized to maximize the efficiency and predictability in toxicity assessment are introduced. The potential of these devices to replace tests of acute systemic toxicity in animals, and the challenges that are inherent in simulating the human immune system are also discussed. As a promising approach to overcome the limitations, we further focus on an in-depth analysis of the development of bone-marrow-on-a-chip that is capable of simulating human immune responses against external stimuli due to the key roles of marrow in immune systems with hematopoietic activities. Owing to the complex interactions between hematopoietic stem cells and marrow microenvironments, precise control of both biochemical and physical niches that are critical in maintenance of hematopoiesis remains a key challenge. Thus, recently developed bone-marrow-on-a-chip models support immunogenicity and immunotoxicity testing in long-term cultivation with repeated antigen stimulation. In this review, we provide an overview of clinical studies that have been carried out on bone marrow transplants in patients with immune-related diseases and future aspects of clinical and pharmaceutical application of bone-marrow-on-a-chip.

Gene expression profile in mesenchymal stem cells derived from dental tissues and bone marrow

PubMed Central

Kim, Su-Hwan; Kim, Young-Sung; Lee, Su-Yeon; Kim, Kyoung-Hwa; Lee, Yong-Moo; Kim, Won-Kyung

2011-01-01

Purpose The aim of this study is to compare the gene expression profile in mesenchymal stem cells derived from dental tissues and bone marrow for characterization of dental stem cells. Methods We employed GeneChip analysis to the expression levels of approximately 32,321 kinds of transcripts in 5 samples of bone-marrow-derived mesenchymal stem cells (BMSCs) (n=1), periodontal ligament stem cells (PDLSCs) (n=2), and dental pulp stem cells (DPSCs) (n=2). Each cell was sorted by a FACS Vantage Sorter using immunocytochemical staining of the early mesenchymal stem cell surface marker STRO-1 before the microarray analysis. Results We identified 379 up-regulated and 133 down-regulated transcripts in BMSCs, 68 up-regulated and 64 down-regulated transcripts in PDLSCs, and 218 up-regulated and 231 down-regulated transcripts in DPSCs. In addition, anatomical structure development and anatomical structure morphogenesis gene ontology (GO) terms were over-represented in all three different mesenchymal stem cells and GO terms related to blood vessels, and neurons were over-represented only in DPSCs. Conclusions This study demonstrated the genome-wide gene expression patterns of STRO-1+ mesenchymal stem cells derived from dental tissues and bone marrow. The differences among the expression profiles of BMSCs, PDLSCs, and DPSCs were shown, and 999 candidate genes were found to be definitely up- or down-regulated. In addition, GOstat analyses of regulated gene products provided over-represented GO classes. These data provide a first step for discovering molecules key to the characteristics of dental stem cells. PMID:21954424

8p11 myeloproliferative syndrome: diagnostic challenges and pitfalls.

PubMed

Antic, Darko A; Vukovic, Vojin M; Milosevic Feenstra, Jelena D; Kralovics, Robert; Bogdanovic, Andrija D; Dencic Fekete, Marija S; Mihaljevic, Biljana S

2016-01-01

8p11 myeloproliferative syndrome (EMS) is a very rare clinicopathological entity which is characterized by the appearance of a myeloproliferative neoplasm in the bone marrow, peripheral lymphadenopathy, usually caused by T or B lymphoblastic lymphoma/leukemia, and a reciprocal translocation involving chromosome 8p11. Herein we describe a 22-year-old male patient with unusual clinical presentation of EMS. Namely, he initially presented with prolonged epistaxis. Complete blood count showed elevated hemoglobin (17.7g/dl), thrombocytopenia (98x109/l) and leukocytosis (57x109/l). Bone marrow aspirate and biopsy findings corresponded with the presence of a myeloproliferative neoplasm while cytogenetic analysis revealed t(8;13)(p11q12). After that ZMYM2-FGFR1 in-frame fusion was confirmed at the molecular level. Immediately after establishing the diagnosis of a myeloproliferative neoplasm (MPN) generalized lymphadenopathy was developed. Histopathologic examination of lymph node sample confirmed the diagnosis of a T cell lymphoblastic lymphoma without bone marrow involvement. Four cycles of Hyper CVAD chemotherapy were administered with complete morphological and cytogenetic remission. Four weeks after evaluation, patient developed peripheral blood monocytosis and eosinophilia without bone marrow criteria for acute leukemia. Cytogenetic analysis showed t(8;13) accompanied by complex numerical and structural aberrations. The patient underwent allogeneic stem cell transplantation (allo-SCT) from HLA matched sister and he subsequently achieved complete remission. In conclusion, patients with MPN and translocations involving chromosome 8 need to be carefully evaluated for EMS. However, having in mind the very aggressive clinical course of EMS allo-SCT is the only potential curative option.

Human Leukocyte Antigen-A, B, C, DRB1, and DQB1 Allele and Haplotype Frequencies in a Subset of 237 Donors in the South African Bone Marrow Registry

PubMed Central

Ingram, Charlotte; Schlaphoff, Terry; Borrill, Veronica; Christoffels, Alan

2018-01-01

Human leukocyte antigen- (HLA-) A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele and haplotype frequencies were studied in a subset of 237 volunteer bone marrow donors registered at the South African Bone Marrow Registry (SABMR). Hapl-o-Mat software was used to compute allele and haplotype frequencies from individuals typed at various resolutions, with some alleles in multiple allele code (MAC) format. Four hundred and thirty-eight HLA-A, 235 HLA-B, 234 HLA-DRB1, 41 HLA-DQB1, and 29 HLA-C alleles are reported. The most frequent alleles were A∗02:02g (0.096), B∗07:02g (0.082), C∗07:02g (0.180), DQB1∗06:02 (0.157), and DRB1∗15:01 (0.072). The most common haplotype was A∗03:01g~B∗07:02g~C∗07:02g~DQB1∗06:02~DRB1∗15:01 (0.067), which has also been reported in other populations. Deviations from Hardy-Weinberg equilibrium were observed in A, B, and DRB1 loci, with C~DQB1 being the only locus pair in linkage disequilibrium. This study describes allele and haplotype frequencies from a subset of donors registered at SABMR, the only active bone marrow donor registry in Africa. Although the sample size was small, our results form a key resource for future population studies, disease association studies, and donor recruitment strategies. PMID:29850621

Isolation and purification of rabbit mesenchymal stem cells using an optimized protocol.

PubMed

Lin, Chunbo; Shen, Maorong; Chen, Weiping; Li, Xiaofeng; Luo, Daoming; Cai, Jinhong; Yang, Yuan

2015-11-01

Mesenchymal stem cells were first isolated and grown in vitro by Friedenstein over 40 yr ago; however, their isolation remains challenging as they lack unique markers for identification and are present in very small quantities in mesenchymal tissues and bone marrow. Using whole marrow samples, common methods for mesenchymal stem cell isolation are the adhesion method and density gradient fractionation. The whole marrow sample adhesion method still results in the nonspecific isolation of mononuclear cells, and activation and/or potential loss of target cells. Density gradient fractionation methods are complicated, and may result in contamination with toxic substances that affect cell viability. In the present study, we developed an optimized protocol for the isolation and purification of mesenchymal stem cells based on the principles of hypotonic lysis and natural sedimentation.

Hematopoietic progenitors express neural genes

PubMed Central

Goolsby, James; Marty, Marie C.; Heletz, Dafna; Chiappelli, Joshua; Tashko, Gerti; Yarnell, Deborah; Fishman, Paul S.; Dhib-Jalbut, Suhayl; Bever, Christopher T.; Pessac, Bernard; Trisler, David

2003-01-01

Bone marrow, or cells selected from bone marrow, were reported recently to give rise to cells with a neural phenotype after in vitro treatment with neural-inducing factors or after delivery into the brain. However, we showed previously that untreated bone marrow cells express products of the neural myelin basic protein gene, and we demonstrate here that a subset of ex vivo bone marrow cells expresses the neurogenic transcription factor Pax-6 as well as neuronal genes encoding neurofilament H, NeuN (neuronal nuclear protein), HuC/HuD (Hu-antigen C/Hu-antigen D), and GAD65 (glutamic acid decarboxylase 65), as well as the oligodendroglial gene encoding CNPase (2′,3′ cyclic nucleotide 3′-phosphohydrolase). In contrast, astroglial glial fibrillary acidic protein (GFAP) was not detected. These cells also were CD34+, a marker of hematopoietic stem cells. Cultures of these highly proliferative CD34+ cells, derived from adult mouse bone marrow, uniformly displayed a phenotype comparable with that of hematopoietic progenitor cells (CD45+, CD34+, Sca-1+, AA4.1+, cKit+, GATA-2+, and LMO-2+). The neuronal and oligodendroglial genes expressed in ex vivo bone marrow also were expressed in all cultured CD34+ cells, and GFAP was not observed. After CD34+ cell transplantation into adult brain, neuronal or oligodendroglial markers segregated into distinct nonoverlapping cell populations, whereas astroglial GFAP appeared, in the absence of other neural markers, in a separate set of implanted cells. Thus, neuronal and oligodendroglial gene products are present in a subset of bone marrow cells, and the expression of these genes can be regulated in brain. The fact that these CD34+ cells also express transcription factors (Rex-1 and Oct-4) that are found in early development elicits the hypothesis that they may be pluripotent embryonic-like stem cells. PMID:14634211

Bone marrow fat content is correlated with hepatic fat content in paediatric non-alcoholic fatty liver disease.

PubMed

Yu, N Y; Wolfson, T; Middleton, M S; Hamilton, G; Gamst, A; Angeles, J E; Schwimmer, J B; Sirlin, C B

2017-05-01

To investigate the relationship between bone marrow fat content and hepatic fat content in children with known or suspected non-alcoholic fatty liver disease (NAFLD). This was an institutional review board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant, cross-sectional, prospective analysis of data collected between October 2010 to March 2013 in 125 children with known or suspected NAFLD. Written informed consent was obtained for same-day research magnetic resonance imaging (MRI) of the lumbar spine, liver, and abdominal adiposity. Lumbar spine bone marrow proton density fat fraction (PDFF) and hepatic PDFF were estimated using complex-based MRI (C-MRI) techniques and magnitude-based MRI (M-MRI), respectively. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SCAT) were quantified using high-resolution MRI. All images were acquired by two MRI technologists. Hepatic M-MRI images were analysed by an image analyst; all other images were analysed by a single investigator. The relationship between lumbar spine bone marrow PDFF and hepatic PDFF was assessed with and without adjusting for the presence of covariates using correlation and regression analysis. Lumbar spine bone marrow PDFF was positively associated with hepatic PDFF in children with known or suspected NAFLD prior to adjusting for covariates (r=0.33, p=0.0002). Lumbar spine bone marrow PDFF was positively associated with hepatic PDFF in children with known or suspected NAFLD (r=0.24, p=0.0079) after adjusting for age, sex, body mass index z-score, VAT, and SCAT in a multivariable regression analysis. Bone marrow fat content is positively associated with hepatic fat content in children with known or suspected NAFLD. Further research is needed to confirm these results and understand their clinical and biological implications. Copyright © 2016 The Royal College of Radiologists. All rights reserved.

Transcoronary sinus delivery of autologous bone marrow and angiogenesis in pig models with myocardial injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vicario, J.; Piva, J.; Pierini, A.

2002-06-01

Purpose: The aim of the investigation is to study myocardial injury on pig model with two objectives: (1) feasibility of stimulating angiogenesis with fresh autologous bone marrow; (2) administration of the same fresh autologous bone marrow via coronary sinus with transitory occlusion. Methods: A controlled study was done in animal model with three phases, in a study group of 12 pigs (bone marrow administration) as well as in control group of 4 pigs (saline administration). Phase 1--production of coronary stenosis and myocardial injury; Phase 2--two weeks later, administration of bone marrow through coronary sinus with 10 min occlusion in themore » study group and saline solution in the control group. Phase 3--two weeks later, histological staining with hematoxylin-eosin and inmunohistochemical staining with monoclonal antibody for smooth muscle {alpha}-actin were conducted on both study and control groups. Results: The percentage of angionenesis observed in the study group was 91% and 0% in control group. Counting of positive actin in affected and control areas showed statistically significant differences in relation to both groups: study group (1.37 vs. 0.79) and control group (0.47 vs. 0.51). The percentage of mononuclear immature cells observed in the myocardium in the study group was 25% and in the control group was 0%. There was no increment in the coronary collateral circulation when comparing coronary angiography. Conclusions: Autologous bone marrow in animal model with experimental myocardial injury enhances angiogenesis, as well as vessels with smooth muscles. The transitory occlusion of the coronary sinus might be an effective way to administer cells as those from the bone marrow.« less

Advances in Bone Marrow Stem Cell Therapy for Retinal Dysfunction

PubMed Central

Park, Susanna S.; Moisseiev, Elad; Bauer, Gerhard; Anderson, Johnathon D.; Grant, Maria B.; Zam, Azhar; Zawadzki, Robert J.; Werner, John S.; Nolta, Jan A.

2016-01-01

The most common cause of untreatable vision loss is dysfunction of the retina. Conditions, such as age-related macular degeneration, diabetic retinopathy and glaucoma remain leading causes of untreatable blindness worldwide. Various stem cell approaches are being explored for treatment of retinal regeneration. The rationale for using bone marrow stem cells to treat retinal dysfunction is based on preclinical evidence showing that bone marrow stem cells can rescue degenerating and ischemic retina. These stem cells have primarily paracrine trophic effects although some cells can directly incorporate into damaged tissue. Since the paracrine trophic effects can have regenerative effects on multiple cells in the retina, the use of this cell therapy is not limited to a particular retinal condition. Autologous bone marrow-derived stem cells are being explored in early clinical trials as therapy for various retinal conditions. These bone marrow stem cells include mesenchymal stem cells, mononuclear cells and CD34+ cells. Autologous therapy requires no systemic immunosuppression or donor matching. Intravitreal delivery of CD34+ cells and mononuclear cells appears to be tolerated and is being explored since some of these cells can home into the damaged retina after intravitreal administration. The safety of intravitreal delivery of mesenchymal stem cells has not been well established. This review provides an update of the current evidence in support of the use of bone marrow stem cells as treatment for retinal dysfunction. The potential limitations and complications of using certain forms of bone marrow stem cells as therapy are discussed. Future directions of research include methods to optimize the therapeutic potential of these stem cells, non-cellular alternatives using extracellular vesicles, and in vivo high-resolution retinal imaging to detect cellular changes in the retina following cell therapy. PMID:27784628

Ginsenoside Rg1 improves bone marrow haematopoietic activity via extramedullary haematopoiesis of the spleen

PubMed Central

Liu, Hua-Hsing; Chen, Fei-Peng; Liu, Rong-Kai; Lin, Chun-Lin; Chang, Ko-Tung

2015-01-01

Cyclophosphamide (CY) is a chemotherapeutic agent used for cancer and immunological diseases. It induces cytotoxicity of bone marrow and causes myelosuppression and extramedullary haematopoiesis (EMH) in treated patients. EMH is characterized with the emergence of multipotent haematopoietic progenitors most likely in the spleen and liver. Previous studies indicated that a Chinese medicine, ginsenoside Rg1, confers a significant effect to elevate the number of lineage (Lin−) Sca-1+ c-Kit+ haematopoietic stem and progenitor cells (HSPCs) and restore the function of bone marrow in CY-treated myelosuppressed mice. However, whether the amelioration of bone marrow by Rg1 accompanies an alleviation of EMH in the spleen was still unknown. In our study, the cellularity and weight of the spleen were significantly reduced after Rg1 treatment in CY-treated mice. Moreover, the number of c-Kit+ HSPCs was significantly decreased but not as a result of apoptosis, indicating that Rg1 alleviated EMH of the spleen induced by CY. Unexpectedly, the proliferation activity of c-Kit+ HSPCs was only up-regulated in the spleen, but not in the bone marrow, after Rg1 treatment in CY-treated mice. We also found that a fraction of c-Kit+/CD45+ HSPCs was simultaneously increased in the circulation after Rg1 treatment. Interestingly, the effects of Rg1 on the elevation of HSPCs in bone marrow and in the peripheral blood were suppressed in CY-treated splenectomized mice. These results demonstrated that Rg1 improves myelosuppression induced by CY through its action on the proliferation of HSPCs in EMH of the spleen and migration of HSPCs from the spleen to the bone marrow. PMID:26153045

Ginsenoside Rg1 improves bone marrow haematopoietic activity via extramedullary haematopoiesis of the spleen.

PubMed

Liu, Hua-Hsing; Chen, Fei-Peng; Liu, Rong-Kai; Lin, Chun-Lin; Chang, Ko-Tung

2015-11-01

Cyclophosphamide (CY) is a chemotherapeutic agent used for cancer and immunological diseases. It induces cytotoxicity of bone marrow and causes myelosuppression and extramedullary haematopoiesis (EMH) in treated patients. EMH is characterized with the emergence of multipotent haematopoietic progenitors most likely in the spleen and liver. Previous studies indicated that a Chinese medicine, ginsenoside Rg1, confers a significant effect to elevate the number of lineage (Lin(-) ) Sca-1(+) c-Kit(+) haematopoietic stem and progenitor cells (HSPCs) and restore the function of bone marrow in CY-treated myelosuppressed mice. However, whether the amelioration of bone marrow by Rg1 accompanies an alleviation of EMH in the spleen was still unknown. In our study, the cellularity and weight of the spleen were significantly reduced after Rg1 treatment in CY-treated mice. Moreover, the number of c-Kit(+) HSPCs was significantly decreased but not as a result of apoptosis, indicating that Rg1 alleviated EMH of the spleen induced by CY. Unexpectedly, the proliferation activity of c-Kit(+) HSPCs was only up-regulated in the spleen, but not in the bone marrow, after Rg1 treatment in CY-treated mice. We also found that a fraction of c-Kit(+) /CD45(+) HSPCs was simultaneously increased in the circulation after Rg1 treatment. Interestingly, the effects of Rg1 on the elevation of HSPCs in bone marrow and in the peripheral blood were suppressed in CY-treated splenectomized mice. These results demonstrated that Rg1 improves myelosuppression induced by CY through its action on the proliferation of HSPCs in EMH of the spleen and migration of HSPCs from the spleen to the bone marrow. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Human regulatory T cells do not suppress the antitumor immunity in the bone marrow: a role for bone marrow stromal cells in neutralizing regulatory T cells.

PubMed

Guichelaar, Teun; Emmelot, Maarten E; Rozemuller, Henk; Martini, Bianka; Groen, Richard W J; Storm, Gert; Lokhorst, Henk M; Martens, Anton C; Mutis, Tuna

2013-03-15

Regulatory T cells (Tregs) are potent tools to prevent graft-versus-host disease (GVHD) induced after allogeneic stem cell transplantation or donor lymphocyte infusions. Toward clinical application of Tregs for GVHD treatment, we investigated the impact of Tregs on the therapeutic graft-versus-tumor (GVT) effect against human multiple myeloma tumors with various immunogenicities, progression rates, and localizations in a humanized murine model. Immunodeficient Rag2(-/-)γc(-/-) mice, bearing various human multiple myeloma tumors, were treated with human peripheral blood mononuclear cell (PBMC) alone or together with autologous ex vivo cultured Tregs. Mice were analyzed for the in vivo engraftment, homing of T-cell subsets, development of GVHD and GVT. In additional in vitro assays, Tregs that were cultured together with bone marrow stromal cells were analyzed for phenotype and functions. Treatment with PBMC alone induced variable degrees of antitumor response, depending on the immunogenicity and the growth rate of the tumor. Coinfusion of Tregs did not impair the antitumor response against tumors residing within the bone marrow, irrespective of their immunogenicity or growth rates. In contrast, Tregs readily inhibited the antitumor effect against tumors growing outside the bone marrow. Exploring this remarkable phenomenon, we discovered that bone marrow stroma neutralizes the suppressive activity of Tregs in part via production of interleukin (IL)-1β/IL-6. We furthermore found in vitro and in vivo evidence of conversion of Tregs into IL-17-producing T cells in the bone marrow environment. These results provide new insights into the Treg immunobiology and indicate the conditional benefits of future Treg-based therapies.

Femoroacetabular impingement: bone marrow oedema associated with fibrocystic change of the femoral head and neck junction.

PubMed

James, S L J; Connell, D A; O'Donnell, P; Saifuddin, A

2007-05-01

To describe the association of bone marrow oedema adjacent to areas of fibrocystic change at the femoral head and neck junction in patients with femoroacetabular impingement. The clinical and imaging findings in six patients with bone marrow oedema adjacent to an area of fibrocystic change at the femoral head and neck junction are presented. There were five males and one female (age range 19-42 years, mean age 34.5 years). Three patients were referred with a clinical suspicion of femoroacetabular impingement, two with suspected osteoid osteoma and one with a clinical diagnosis of sciatica. The volume of bone marrow oedema (grade 1: 0-25%, grade 2: 26-50%, grade 3: 51-75% and grade 4: 76-100% of the femoral neck width), presence of labral and articular cartilage abnormality, joint effusion, and femoral head and neck morphology were recorded. Magnetic resonance imaging (MRI) identified fibrocystic change in the anterolateral aspect of the femoral head and neck junction in all cases (mean size 9 mm, range 5-14 mm, three multilocular and three unilocular cysts). The volume of oedema was variable (one grade 1, two grade 2, one grade 3 and two grade 4). All patients had abnormality of the anterosuperior labrum with five patients demonstrating chondral loss. An abnormal femoral head and neck junction was identified in five patients. The radiological finding of fibrocystic change at the anterosuperior femoral neck with or without bone marrow oedema should prompt the search for femoroacetabular impingement. Bone marrow oedema may rarely be identified adjacent to these areas of cystic change and should be considered in the differential diagnosis of bone marrow oedema in the femoral neck.

High Mobility Group Box 1 Promotes Angiogenesis from Bone Marrow-derived Endothelial Progenitor Cells after Myocardial Infarction.

PubMed

Nakamura, Yuichi; Suzuki, Satoshi; Shimizu, Takeshi; Miyata, Makiko; Shishido, Tetsuro; Ikeda, Kazuhiko; Saitoh, Shu-Ichi; Kubota, Isao; Takeishi, Yasuchika

2015-01-01

High mobility group box 1 (HMGB1) is a DNA-binding protein secreted into the extracellular space from necrotic cells that acts as a cytokine. We examined the role of HMGB1 in angiogenesis from bone marrow-derived cells in the heart using transgenic mice exhibiting the cardiac-specific overexpression of HMGB1 (HMGB1-TG). HMGB1-TG mice and wild-type littermate (WT) mice were lethally irradiated and injected with bone marrow cells from green fluorescent protein mice through the tail vein. After bone marrow transplantation, the left anterior descending artery was ligated to induce myocardial infarction (MI). Flow cytometry revealed that the levels of circulating endothelial progenitor cells (EPCs) mobilized from the bone marrow increased after MI in the HMGB-TG mice versus the WT mice. In addition, the size of MI was smaller in the HMGB1-TG mice than in the WT mice, and immunofluorescence staining demonstrated that the number of engrafted vascular endothelial cells derived from bone marrow in the border zones of the MI areas was increased in the HMGB1-TG mice compared to that observed in the WT mice. Moreover, the levels of cardiac vascular endothelial growth factor after MI were higher in the HMGB1-TG mice than in the WT mice. The present study demonstrated that HMGB1 promotes angiogenesis and reduces the MI size by enhancing the mobilization and differentiation of bone marrow cells to EPCs as well as their migration to the border zones of the MI areas and engraftment as vascular endothelial cells in new capillaries or arterioles in the infarcted heart.

Bone marrow fibrosis in myelodysplastic syndromes: a prospective evaluation including mutational analysis

PubMed Central

Ramos, Fernando; Robledo, Cristina; Izquierdo-García, Francisco Miguel; Suárez-Vilela, Dimas; Benito, Rocío; Fuertes, Marta; Insunza, Andrés; Barragán, Eva; del Rey, Mónica; de Morales, José María García-Ruiz; Tormo, Mar; Salido, Eduardo; Zamora, Lurdes; Pedro, Carmen; Sánchez-del-Real, Javier; Díez-Campelo, María; del Cañizo, Consuelo; Sanz, Guillermo F.; Hernández-Rivas, Jesús María

2016-01-01

The biological and molecular events that underlie bone marrow fibrosis in patients with myelodysplastic syndromes are poorly understood, and its prognostic role in the era of the Revised International Prognostic Scoring System (IPSS-R) is not yet fully determined. We have evaluated the clinical and biological events that underlie bone marrow fibrotic changes, as well as its prognostic role, in a well-characterized prospective patient cohort (n=77) of primary MDS patients. The degree of marrow fibrosis was linked to parameters of erythropoietic failure, marrow cellularity, p53 protein accumulation, WT1 gene expression, and serum levels of CXCL9 and CXCL10, but not to other covariates including the IPSS-R score. The presence of bone marrow fibrosis grade 2 or higher was associated with the presence of mutations in cohesin complex genes (31.5% vs. 5.4%, p=0.006). By contrast, mutations in CALR, JAK2, PDGFRA, PDGFRB, and TP53 were very rare. Survival analysis showed that marrow fibrosis grade 2 or higher was a relevant significant predictor for of overall survival, and independent of age, performance status, and IPSS-R score in multivariate analysis. PMID:27127180

Automated processing of human bone marrow can result in a population of mononuclear cells capable of achieving engraftment following transplantation.

PubMed

Areman, E M; Cullis, H; Spitzer, T; Sacher, R A

1991-10-01

A concentrate of mononuclear bone marrow cells is often desired for ex vivo treatment with pharmacologic agents, monoclonal antibodies, cytokines, and other agents prior to transplantation. A method has been developed for automated separation of mononuclear cells from large volumes of harvested bone marrow. A programmable instrument originally designed for clinical ex vivo cell separation and the plasma-pheresis of patients and blood donors was adapted to permit rapid preparation, in a closed sterile system, of a bone marrow product enriched with mononuclear cells. A mean (+/- SEM) of 53 +/- 30 percent of the original mononuclear cells was recovered in a volume of 125 +/- 42 mL containing 82 +/- 12 percent mononuclear cells. This technique removed 95 +/- 9 percent of the red cells in the original marrow. No density gradient materials or sedimenting agents were employed in this process. Of 36 marrows processed by this technique, 19 autologous (6 of which were purged with 4-hydroperoxycyclophosphamide) and 7 allogeneic marrows have been transplanted, with all evaluable patients achieving a neutrophil count of 0.5 x 10(9) per L in a mean (+/- SEM) of 21 +/- 6 days.

Unicameral bone cysts: a comparison of injection of steroid and grafting with autologous bone marrow.

PubMed

Cho, H S; Oh, J H; Kim, H-S; Kang, H G; Lee, S H

2007-02-01

Open surgery is rarely justified for the initial treatment of a unicameral bone cyst, but there is some debate concerning the relative effectiveness of closed methods. This study compared the results of steroid injection with those of autologous bone marrow grafting for the treatment of unicameral bone cysts. Between 1990 and 2001, 30 patients were treated by steroid injection and 28 by grafting with autologous bone marrow. The overall success rates were 86.7% and 92.0%, respectively (p>0.05). The success rate after the initial procedure was 23.3% in the steroid group and 52.0% in those receiving autologous bone marrow (p<0.05), and the respective cumulative success rates after second injections were 63.3% and 80.0% (p>0.05). The mean number of procedures required was 2.19 (1 to 5) and 1.57 (1 to 3) (p<0.05), the mean interval to healing was 12.5 months (4 to 32) and 14.3 months (7 to 36) (p>0.05), and the rate of recurrence after the initial procedure was 41.7% and 13.3% in the steroid and in the autologous bone marrow groups, respectively (p<0.05). Although the overall rates of success of both methods were similar, the steroid group had higher recurrence after a single procedure and required more injections to achieve healing.

The Effects of Rm-CSF and Ril-6 Therapy on Immunosuppressed Antiorthostatically Suspended Mice

NASA Technical Reports Server (NTRS)

Armstong, Jason W.; Kirby-Dobbels, Kathy; Chapes, Steven K.

1995-01-01

Antiorthostatically suspended mice had suppressed macrophage development in both unloaded and loaded bones, indicating a systemic effect. Bone marrow cells from those mice secreted less macrophage colony-stimulating factor (M-CSF) and interleukin-6 (IL-6) than did control mice. Because M-CSF and IL-6 are important to bone marrow macrophage maturation, we formulated the hypothesis that suppressed macrophage development occurred as a result of the depressed levels of either M-CSF or IL-6. To test the hypothesis, mice were administered recombinant M-CSF or IL-6 intraperitoneally. We showed that recombinant M-CSF therapy, but not recombinant IL-6 therapy, reversed the suppressive effects of orthostatic suspension on macrophage development. These data suggest that bone marrow cells that produce M-CSF are affected by antiorthostatic suspension and may contribute to the inhibited maturation of bone marrow macrophage progenitors.

High-dose etoposide (VP-16)-containing preparatory regimens in allogeneic and autologous bone marrow transplantation for hematologic malignancies.

PubMed

Blume, K G; Forman, S J

1992-12-01

High-dose etoposide has been added to total body irradiation, cyclophosphamide, carmustine, or busulfan in preparatory regimens for allogeneic or autologous bone marrow transplantation for patients with leukemia, Hodgkin's disease, lymphoma, or multiple myeloma. The treatment results are encouraging, indicating that etoposide may be a valuable addition to the previously established regimens. Etoposide should be incorporated into collaborative, prospective trials to define its ultimate role in bone marrow transplantation.

The Role of Histone Demethylase Jmjd3 in Immune-Mediated Aplastic Anemia

DTIC Science & Technology

2017-03-01

anemia (AA) is a condition of bone marrow failure (BMF) characterized by blood pancytopenia and BM hypoplasia. In most cases, AA is an immune-mediated...is a condition of bone marrow failure (BMF) characterized by blood pancytopenia and BM hypoplasia. In most cases, AA is an immune-mediated disorder...GVHD) 2.11. Bone marrow transplantation 2.12. NSG mice 2.13. xGVHD 2.14. Hematopoietic stem cells (HSCs) 3. ACCOMPLISHMENTS: The PI is

Redox Regulation in Bone Marrow Failure

DTIC Science & Technology

2012-06-01

Fanconi anemia mutation for hematopoietic senescence. J Cell Sci, 2007. 120(Pt 9): p. 1572-83. 2. Aylon, Y. and M. Oren, Living with p53, dying of p53...aplastic anemia patients with a p38 MAPK inhibitor can restore defective hematopoietic activity, suggesting the critical role of p38 in bone marrow...hematopoietic stem cells, and eventually leading to bone marrow failure [7, 8] [9] [10]. On the other hand, treating aplastic anemia patients with a p38

Erythroblast apoptosis and microenvironmental iron restriction trigger anemia in the VK*MYC model of multiple myeloma

PubMed Central

Bordini, Jessica; Bertilaccio, Maria Teresa Sabrina; Ponzoni, Maurilio; Fermo, Isabella; Chesi, Marta; Bergsagel, P. Leif; Camaschella, Clara; Campanella, Alessandro

2015-01-01

Multiple myeloma is a malignant disorder characterized by bone marrow proliferation of plasma cells and by overproduction of monoclonal immunoglobulin detectable in the sera (M-spike). Anemia is a common complication of multiple myeloma, but the underlying pathophysiological mechanisms have not been completely elucidated. We aimed to identify the different determinants of anemia using the Vk*MYC mouse, which spontaneously develops an indolent bone marrow localized disease with aging. Affected Vk*MYC mice develop a mild normochromic normocytic anemia. We excluded the possibility that anemia results from defective erythropoietin production, inflammation or increased hepcidin expression. Mature erythroid precursors are reduced in Vk*MYC bone marrow compared with wild-type. Malignant plasma cells express the apoptogenic receptor Fas ligand and, accordingly, active caspase 8 is detected in maturing erythroblasts. Systemic iron homeostasis is not compromised in Vk*MYC animals, but high expression of the iron importer CD71 by bone marrow plasma cells and iron accumulation in bone marrow macrophages suggest that iron competition takes place in the local multiple myeloma microenvironment, which might contribute to anemia. In conclusion, the mild anemia of the Vk*MYC model is mainly related to the local effect of the bone marrow malignant clone in the absence of an overt inflammatory status. We suggest that this reproduces the initial events triggering anemia in patients. PMID:25715406

Erythroblast apoptosis and microenvironmental iron restriction trigger anemia in the VK*MYC model of multiple myeloma.

PubMed

Bordini, Jessica; Bertilaccio, Maria Teresa Sabrina; Ponzoni, Maurilio; Fermo, Isabella; Chesi, Marta; Bergsagel, P Leif; Camaschella, Clara; Campanella, Alessandro

2015-06-01

Multiple myeloma is a malignant disorder characterized by bone marrow proliferation of plasma cells and by overproduction of monoclonal immunoglobulin detectable in the sera (M-spike). Anemia is a common complication of multiple myeloma, but the underlying pathophysiological mechanisms have not been completely elucidated. We aimed to identify the different determinants of anemia using the Vk*MYC mouse, which spontaneously develops an indolent bone marrow localized disease with aging. Affected Vk*MYC mice develop a mild normochromic normocytic anemia. We excluded the possibility that anemia results from defective erythropoietin production, inflammation or increased hepcidin expression. Mature erythroid precursors are reduced in Vk*MYC bone marrow compared with wild-type. Malignant plasma cells express the apoptogenic receptor Fas ligand and, accordingly, active caspase 8 is detected in maturing erythroblasts. Systemic iron homeostasis is not compromised in Vk*MYC animals, but high expression of the iron importer CD71 by bone marrow plasma cells and iron accumulation in bone marrow macrophages suggest that iron competition takes place in the local multiple myeloma microenvironment, which might contribute to anemia. In conclusion, the mild anemia of the Vk*MYC model is mainly related to the local effect of the bone marrow malignant clone in the absence of an overt inflammatory status. We suggest that this reproduces the initial events triggering anemia in patients. Copyright© Ferrata Storti Foundation.

ANTIBODY FORMATION BY TRANSPLANTED BONE MARROW, SPLEEN, LYMPH NODE AND THYMUS CELLS IN IRRADIATED RECIPIENTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoner, R.D.; Bond, V.P.

1963-01-14

Immunological competence of immunized mouse bone marrow, spleen, lymph node, and thymus cells was demonstrated when specific recall tetanus antitoxin responses were elicited after transfer of these cells to isologous irradiated mice or rats. Lesser amounts of antibody were obtained as the genetic strain distance was increased between the relation of donor and host in the parental to F/sub 1/ and in the homologous combination within the same species. It was not possible in the heterologous situation to elicit significant amounts of antibody from rat bone marrow and other lymphoid cells following their transplantation into irradiated mice. Minimal but notmore » significant antibody responses were elicited from cells obtained from immunized rat spleen and thymus tissue. In a few experiments, it was possible to elicit antibody formation from a buffy coat suspension of circulating white cells following their transfer to irradiated recipients. Isologous nonimmunized bone marrow did not stimulate or hasten recovery of the ability to eiicit secondary antibody responses in previously immunized irradiated mice. The capacity to elicit primary antibody responses to tetanus toxoid was depressed in parental-bone-marrow-protected F/sub 1/ mice when these chimeras exhibited varying degrees of secondary disease. The depression of primary antibody responses in irradiated F/sub 1/ mice given parental bone marrow provides evidence for a donor mediated immunological depression of antibody synthesis by host-lymphoid tissues. (auth)« less

Survival of irradiated recipient mice after transplantation of bone marrow from young, old and "early aging" mice.

PubMed

Guest, Ian; Ilic, Zoran; Scrable, Heidi; Sell, Stewart

2015-12-01

Bone marrow transplantation is used to examine survival, hematopoietic stem cell function and pathology in recipients of young and old wild type bone marrow derived stem cells (BMDSCs) as well as cells from p53-based models of premature aging. There is no difference in the long term survival of recipients of 8 week-old p53+/m donor cells compared to recipients of 8 week-old wild-type (WT) donor cells (70 weeks) or of recipients of 16-18 weeks-old donor cells from either p53+/m or WT mice. There is shorter survival in recipients of older versus younger WT donor bone marrow, but the difference is only significant when comparing 8 and 18 week-old donors. In the p44-based model, short term survival/engraftment is significantly reduced in recipients of 11 month-old p44 donor cells compared to 4 week-old p44 or wild type donor cells of either age; mid-life survival at 40 weeks is also significantly less in recipients of p44 cells. BMDSCs are readily detectable within recipient bone marrow, lymph node, intestinal villi and liver sinusoids, but not in epithelial derived cells. These results indicate that recipients of young BMDSCs may survive longer than recipients of old bone marrow, but the difference is marginal at best.

Survival of irradiated recipient mice after transplantation of bone marrow from young, old and “early aging” mice

PubMed Central

Guest, Ian; Ilic, Zoran; Sell, Stewart

2015-01-01

Bone marrow transplantation is used to examine survival, hematopoietic stem cell function and pathology in recipients of young and old wild type bone marrow derived stem cells (BMDSCs) as well as cells from p53-based models of premature aging. There is no difference in the long term survival of recipients of 8 week-old p53+/m donor cells compared to recipients of 8 week-old wild-type (WT) donor cells (70 weeks) or of recipients of 16–18 weeks-old donor cells from either p53+/m or WT mice. There is shorter survival in recipients of older versus younger WT donor bone marrow, but the difference is only significant when comparing 8 and 18 week-old donors. In the p44-based model, short term survival/engraftment is significantly reduced in recipients of 11 month-old p44 donor cells compared to 4 week-old p44 or wild type donor cells of either age; mid-life survival at 40 weeks is also significantly less in recipients of p44 cells. BMDSCs are readily detectable within recipient bone marrow, lymph node, intestinal villi and liver sinusoids, but not in epithelial derived cells. These results indicate that recipients of young BMDSCs may survive longer than recipients of old bone marrow, but the difference is marginal at best. PMID:26796640

Getting to the Heart of Being the Match: A Qualitative Analysis of Bone Marrow Donor Recruitment and Retention Among College Students

PubMed Central

Rogers, Charles R.; Jeon, Kwon Chan; Rosen, Brittany

2014-01-01

Introduction For those with certain blood or bone cancers, bone marrow donation can mean the difference between life and death. The National Marrow Donor Program® (NMDP) operates the largest bone marrow registry of potential donors; however, at times when potential matches are identified, many donors opt not to donate. The purpose of this study was to describe perspectives from college-aged students on recruitment to a bone marrow donation registry and retention to the registry/follow-through with the donation process. Methods Researchers employed a one-time qualitative study using 7 focus groups comprised of 10 – 11 college students each (n = 76). Results Results yielded three overarching themes: donor recruitment, donor retention, and factors contributing to the overall donation process. More specifically, this study identified key factors affecting bone marrow donation in an essential population: facilitators, barriers, knowledge, and ‘goodness’. Additionally, marketing and communication were found to be major determinants of potential donors staying with the NMDP. Conclusion Better explanations and awareness/promotion campaigns are necessary for recruiting potential donors to the NMDP and to increase the likelihood that the donor will follow through with the donation should a potential match be identified. Recommendations from this study may improve recruitment and retention rates among the NMDP campaigns targeting college students. PMID:25632376

[Tolerance in transplantation: potential contribution of haematopoietic transplantation and cell therapy].

PubMed

Kleinclauss, François; Bittard, Hugues; Perruche, Sylvain; de Carvalho-Bittencourt, Marcello; Chalopin, Jean-Marc; Hervé, Patrick; Tiberghien, Pierre; Saas, Philippe

2003-12-01

The ultimate objective of organ transplantation is to obtain a state of tolerance, i.e. long-term acceptance of the graft without immunosuppressive therapy in order to limit the complications of these treatments (viral infections, tumours, etc.). The various immunological mechanisms allowing a state of tolerance will be described in this review. Among these various experimental strategies, combined bone marrow (or haematopoietic stem cell) transplantation and organ transplantation, made possible by the development of non-myeloablative or less intensive conditioning, appears to be one of the most promising lines of research. This approach leads to colonization of the recipient by donor cells. This state is described as "macro-chimerism" and achieves a real state of central tolerance in relation to an organ derived from the bone marrow donor. We have shown recently that intravenous injection of apoptotic cells in combination with allogeneic bone marrow cells increases the success rate of bone marrow transplantation. In a model of combined bone marrow/solid organ transplantation, these apoptotic cells induce tolerance limited to the donor's bone marrow cell antigens without inducing auto-immunization. We therefore propose a new approach to cell-based therapy (using the immunomodulating properties of apoptotic cells) to promote the success of haematopoietic stem cell transplantation. This approach can be particularly useful in combined haematopoietic stem cell and organ transplantation in order to induce a state of macro-chimerism.

Columnar metaplasia in a surgical mouse model of gastro-esophageal reflux disease is not derived from bone marrow-derived cell.

PubMed

Aikou, Susumu; Aida, Junko; Takubo, Kaiyo; Yamagata, Yukinori; Seto, Yasuyuki; Kaminishi, Michio; Nomura, Sachiyo

2013-09-01

The incidence of esophageal adenocarcinoma has increased in the last 25 years. Columnar metaplasia in Barrett's mucosa is assumed to be a precancerous lesion for esophageal adenocarcinoma. However, the induction process of Barrett's mucosa is still unknown. To analyze the induction of esophageal columnar metaplasia, we established a mouse gastro-esophageal reflux disease (GERD) model with associated development of columnar metaplasia in the esophagus. C57BL/6 mice received side-to-side anastomosis of the esophagogastric junction with the jejunum, and mice were killed 10, 20, and 40 weeks after operation. To analyze the contribution of bone marrow-derived cells to columnar metaplasia in this surgical GERD model, some mice were transplanted with GFP-marked bone marrow after the operation. Seventy-three percent of the mice (16/22) showed thickened mucosa in esophagus and 41% of mice (9/22) developed columnar metaplasia 40 weeks after the operation with a mortality rate of 4%. Bone marrow-derived cells were not detected in columnar metaplastic epithelia. However, scattered epithelial cells in the thickened squamous epithelia in regions of esophagitis did show bone marrow derivation. The results demonstrate that reflux induced by esophago-jejunostomy in mice leads to the development of columnar metaplasia in the esophagus. However, bone marrow-derived cells do not contribute directly to columnar metaplasia in this mouse model. © 2013 Japanese Cancer Association.

A clinical and molecular study of a Bedouin family with dysmegakaryopoiesis, mild anemia, and neutropenia cured by bone marrow transplantation.

PubMed

Tamary, H; Yaniv, I; Stein, J; Dgany, O; Shalev, Z; Shechter, T; Resnitzky, P; Shaft, D; Zoldan, M; Kornreich, L; Levy, R; Cohen, A; Moser, R A; Kapelushnik, J; Shalev, H

2003-09-01

Familial thrombocytopenia is a relatively rare and heterogeneous group of clinical and genetic syndromes of unknown etiology. Recently, mutations in a few hematopoietic transcription factors were implicated in dysmegakaryopoiesis with and without dyserythropoietic anemia. The aim of the present study was to describe the clinical and hematologic picture of members of a Bedouin family with severe congenital thrombocytopenia associated with neutropenia and anemia and to determine the possible involvement of hematopoietic transcription factor genes in their disease. Four members of a Bedouin family presented with severe bleeding tendency, including intracranial hemorrhage in three. Three of the four were successfully treated with allogenic human leukocyte antigen (HLA)-matched bone marrow transplants. Measurements of serum erythropoietin and thrombopoietin levels, bone marrow electron microscopy, and megakaryocytic colony were grown for each patient in addition to DNA amplification and single-strand conformation polymorphism of each exon of the NF-E2, Fli-1, FOG-1, and Gfi-1b in genes. Bone marrow studies revealed dysmegakaryopoiesis and mild dyserythropoiesis. A low number of bone marrow megakaryocyte colony-forming units was found, as well as a slightly elevated serum thrombopoietin level. No mutation was identified in any of the transcription factor genes examined. A unique autosomal recessive bone marrow disorder with prominent involvement of megakaryocytes is described. Defects were not identified in transcription factors affecting the common myeloid progenitor.

A prospective study on MRI findings and prognostic factors in athletes with MTSS.

PubMed

Moen, M H; Schmikli, S L; Weir, A; Steeneken, V; Stapper, G; de Slegte, R; Tol, J L; Backx, F J G

2014-02-01

In medial tibial stress syndrome (MTSS) bone marrow and periosteal edema of the tibia on the magnetic resonance imaging (MRI) is frequently reported. The relationship between these MRI findings and recovery has not been previously studied. This prospective study describes MRI findings of 52 athletes with MTSS. Baseline characteristics were recorded and recovery was related to these parameters and MRI findings to examine for prognostic factors. Results showed that 43.5% of the symptomatic legs showed bone marrow or periosteal edema. Absence of periosteal and bone marrow edema on MRI was associated with longer recovery (P = 0.033 and P = 0.013). A clinical scoring system for sports activity (SARS score) was significantly higher in the presence of bone marrow edema (P = 0.027). When clinical scoring systems (SARS score and the Lower Extremity Functional Scale) were combined in a model, time to recovery could be predicted substantially (explaining 54% of variance, P = 0.006). In conclusion, in athletes with MTSS, bone marrow or periosteal edema is seen on MRI in 43,5% of the symptomatic legs. Furthermore, periosteal and bone marrow edema on MRI and clinical scoring systems are prognostic factors. Future studies should focus on MRI findings in symptomatic MTSS and compare these with a matched control group. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[MRI characteristic of proximal femur bone marrow edema syndrome].

PubMed

Wu, Xi-Yuan

2014-07-01

To study the MRI features of proximal femur bone marrow edema syndrome for further improve the understanding of the disease. MRI imaging of 10 patients with proximal femur bone marrow edema syndrome was retrospectively reviewed,including 6 males and 4 females with an average age of 41.5 years old ranging from 36 to 57. The courses of diseases ranged from 1 week to 3 months. Among them, 9 cases had clinical manifestations of sudden hip pain, 7 cases had limited ability of walking and hip movement;all patients had no obvious injury history, non of the female patients was pregnant. All patients were followed up from 3 to 12 months, the following-up were topped after MRI when the symptoms disappeared for 3 months. The MRI demonstrated diffuse bone marrow edema involving the femoral head, neck and the inter-trochanteric region, 13 hips of 10 patients with bone marrow edema included 6 cases in grade 1, 5 cases in grade 2,2 cases in grade 3; 9 hips with hip hydrarthrosis included 6 hips in grade I ,1 hip in grade II, 2 hips in grade III. After treatment for 3 to 12 months the hip symptoms of the patients disappeared and MRI images were normal. MRI is useful in defining the location and extent of proximal femur bone marrow edema syndrome.

Leukemia

MedlinePlus

Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

USP10 Is an Essential Deubiquitinase for Hematopoiesis and Inhibits Apoptosis of Long-Term Hematopoietic Stem Cells.

PubMed

Higuchi, Masaya; Kawamura, Hiroki; Matsuki, Hideaki; Hara, Toshifumi; Takahashi, Masahiko; Saito, Suguru; Saito, Kousuke; Jiang, Shuying; Naito, Makoto; Kiyonari, Hiroshi; Fujii, Masahiro

2016-12-13

Self-renewal, replication, and differentiation of hematopoietic stem cells (HSCs) are regulated by cytokines produced by niche cells in fetal liver and bone marrow. HSCs must overcome stresses induced by cytokine deprivation during normal development. In this study, we found that ubiquitin-specific peptidase 10 (USP10) is a crucial deubiquitinase for mouse hematopoiesis. All USP10 knockout (KO) mice died within 1 year because of bone marrow failure with pancytopenia. Bone marrow failure in these USP10-KO mice was associated with remarkable reductions of long-term HSCs (LT-HSCs) in bone marrow and fetal liver. Such USP10-KO fetal liver exhibited enhanced apoptosis of hematopoietic stem/progenitor cells (HSPCs) including LT-HSCs but not of lineage-committed progenitor cells. Transplantation of USP10-competent bone marrow cells into USP10-KO mice reconstituted multilineage hematopoiesis. These results suggest that USP10 is an essential deubiquitinase in hematopoiesis and functions by inhibiting apoptosis of HSPCs including LT-HSCs. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Probable essential thrombocythemia in a dog

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hopper, P.E.; Mandell, C.P.; Turrel, J.M.

1989-04-01

Essential thrombocythemia (ET), in an 11-year-old dog was characterized by persistently high platelet counts range, 4.19 X 10(6)/microliters to 4.95 X 10(6)/microliters, abnormal platelet morphology, marked megakaryocytic hyperplasia in the bone marrow, absence of circulating megakaryoblasts, and history of splenomegaly and gastrointestinal bleeding. Increased numbers of megakaryocytes and megakaryoblasts (15% to 20%) in the bone marrow were confirmed by a positive acetylcholinesterase reaction. Another significant finding was the presence of a basophilia in blood (4,836/microliters) and bone marrow. The marked persistent thrombocytosis, absence of reactive (secondary) thrombocytosis, abnormal platelet morphology, and quantitative and qualitative changes in the megakaryocytic series inmore » the bone marrow suggested the presence of a myeloproliferative disease. Cytochemical and ultrastructural findings aided in the diagnosis of ET. The dog was treated with radiophosphorus. The results was a rapid decline in the numbers of megakaryoblasts and megakaryocytes in the bone marrow and platelets and basophils in the peripheral blood. The dog died unexpectedly of acute necrotizing pancreatitis and diabetes mellitus before a complete remission was achieved.« less

Reliability analysis of instrument design of noninvasive bone marrow disease detector

NASA Astrophysics Data System (ADS)

Su, Yu; Li, Ting; Sun, Yunlong

2016-02-01

Bone marrow is an important hematopoietic organ, and bone marrow lesions (BMLs) may cause a variety of complications with high death rate and short survival time. Early detection and follow up care are particularly important. But the current diagnosis methods rely on bone marrow biopsy/puncture, with significant limitations such as invasion, complex operation, high risk, and discontinuous. It is highly in need of a non-invasive, safe, easily operated, and continuous monitoring technology. So we proposed to design a device aimed for detecting bone marrow lesions, which was based on near infrared spectrum technology. Then we fully tested its reliabilities, including the sensitivity, specificity, signal-to-noise ratio (SNR), stability, and etc. Here, we reported this sequence of reliability test experiments, the experimental results, and the following data analysis. This instrument was shown to be very sensitive, with distinguishable concentration less than 0.002 and with good linearity, stability and high SNR. Finally, these reliability-test data supported the promising clinical diagnosis and surgery guidance of our novel instrument in detection of BMLs.

Raman Spectroscopy: A New Proposal for the Detection of Leukemia Using Blood Samples

NASA Astrophysics Data System (ADS)

Martínez-Espinosa, J. C.; González-Solís, J. L.; Frausto-Reyes, C.; Miranda-Beltrán, M. L.; Soria-Fregoso, C.; Medina-Valtierra, J.; Sánchez-Gómez, R.

2008-08-01

The use of Raman spectroscopy to analyze blood biochemistry and hence distinguish between normal and abnormal blood was investigated. The blood samples were obtained from 6 patients who were clinically diagnosed with leukemia and 6 healthy volunteer. The imprint was put under the microscope and several points were chosen for Raman measurement. All spectra were collected at confocal Raman micro-spectroscopy (Renishaw) with NIR 830 nm laser. It is shown that the serum samples from patients with leukemia and from the control group can be discriminated when the multivariate statistical methods of principal component analysis (PCA) and linear discriminated analysis (LDA) is applied to their Raman spectra. The ratios of some band intensities were analyzed and some band ratios were significant and corresponded to proteins, phospholipids, and polysaccharides. In addition, currently the degree of damage to the bone marrow is estimated through biopsies and therefore it is a very procedure painful. The preliminary results suggest that Raman spectroscopy could be a new technique to study the bone marrow using just blood samples.

State-of-the-art of bone marrow analysis in forensic toxicology: a review.

PubMed

Cartiser, Nathalie; Bévalot, Fabien; Fanton, Laurent; Gaillard, Yvan; Guitton, Jérôme

2011-03-01

Although blood is the reference medium in the field of forensic toxicology, alternative matrices are required in case of limited, unavailable or unusable blood samples. The present review investigated the suitability of bone marrow (BM) as an alternative matrix to characterize xenobiotic consumption and its influence on the occurrence of death. Basic data on BM physiology are reported in order to highlight the specificities of this matrix and their analytical and toxicokinetic consequences. A review of case reports, animal and human studies involving BM sample analysis focuses on the various parameters of interpretation of toxicological results: analytic limits, sampling location, pharmacokinetics, blood/BM concentration correlation, stability and postmortem redistribution. Tables summarizing the analytical conditions and quantification of 45 compounds from BM samples provide a useful tool for toxicologists. A specific section devoted to ethanol shows that, despite successful quantification, interpretation is highly dependent on postmortem interval. In conclusion, BM is an interesting alternative matrix, and further experimental data and validated assays are required to confirm its great potential relevance in forensic toxicology.

mRNA of cytokines in bone marrow and bone biomarkers in response to propranolol in a nutritional growth retardation model.

PubMed

Tasat, Deborah R; Lezón, Christian E; Astort, Francisco; Pintos, Patricia M; Macri, Elisa V; Friedman, Silvia M; Boyer, Patricia M

2014-10-01

The aim of this study was to assess mRNA of IL-6, TNFα and IL-10 cytokines in bone marrow, possible mediators involved in altered bone remodeling with detrimental consequences on bone quality in NGR (Nutritional growth retardation) rats. Weanling male Wistar rats were assigned either to control (C) or experimental group (NGR) (n=20 each). C and NGR groups were assigned to 2 groups according to receiving saline solution (SS) or propranolol hydrochloride (P): C, C+P (CP), NGR or NGR+P (NGRP). For 4 weeks, NGR and NGRP rats received 80% of the amount of food consumed by C and CP, respectively, the previous day, corrected by body weight. P (7 mg/kg/day) was injected ip 5 days/week, for 4 weeks in CP and NGRP rats. Body weight and length were recorded. After 4 weeks, blood was drawn. Femurs were dissected for RNA isolation from bone marrow and mRNA of cytokines assays. Food restriction induced a significant negative effect on body growth in NGR and NGRP rats (p<0.001). P had no effects on zoometric parameters (p>0.05). CTX-I increased in NGR rats vs. C (p<0.001), but diminished in NGRP (p<0.01). Serum osteocalcin, PTH, calcium and phosphate levels remained unchanged between groups (p>0.05). In NGR, bone marrow IL-6 mRNA and IL-10 mRNA levels were low as compared to other groups (p<0.05). In contrast, bone marrow TNF-α mRNA levels were significantly high (p<0.05). This study provides evidences that NGR outcomes in a bone marrow proinflammatory microenvironment leading to unbalanced bone remodeling by enhancement of bone resorption reverted by propranolol. Copyright © 2014. Published by Elsevier Urban & Partner Sp. z o.o.

Histomorphometric analysis following augmentation of the posterior mandible using cancellous bone-block allograft.

PubMed

Nissan, Joseph; Marilena, Vered; Gross, Ora; Mardinger, Ofer; Chaushu, Gavriel

2011-06-15

The present study was conducted to histologically and histomorphometrically evaluate the application of cancellous bone-block allografts for the augmentation of the posterior atrophic mandible. Twenty-four consecutive patients underwent augmentation with cancellous bone-block allografts in the posterior mandible. A bony deficiency of at least 3 mm horizontally and/or vertically according to CT para-axial reconstruction served as inclusion criteria. Following 6 months, 85 implants were placed and a cylindrical sample core was collected. All specimens were prepared for histological and histomorphometrical examination. Implant survival rate was 95.3%. Follow-up ranged 12-66 months (mean 43 ± 19 months). The mean newly formed bone was 44 ± 28%, that of the residual cancellous bone-block allograft 29 ± 24%, and of the marrow and connective tissue 27 ± 21%. Statistically significant histomorphometric differences regarding newly formed bone (69% vs. 31%, p = 0.05) were found between younger (< 45 years) and older (> 45 years) patients, respectively. Histomorphometric differences regarding residual cancellous bone-block allograft (17% vs. 35%) and of the marrow and connective tissue (14% vs. 34%) were not statistically significant. Cancellous bone-block allograft is biocompatible and osteoconductive, permitting new bone formation following augmentation of extremely atrophic posterior mandible with a two-stage implant placement procedure. New bone formation was age-dependent. Copyright © 2011 Wiley Periodicals, Inc.

Reciprocal regulation of adipocyte and osteoblast differentiation of mesenchymal stem cells by Eupatorium japonicum prevents bone loss and adiposity increase in osteoporotic rats.

PubMed

Kim, Min-Ji; Jang, Woo-Seok; Lee, In-Kyoung; Kim, Jong-Keun; Seong, Ki-Seung; Seo, Cho-Rong; Song, No-Joon; Bang, Min-Hyuk; Lee, Young Min; Kim, Haeng Ran; Park, Ki-Moon; Park, Kye Won

2014-07-01

Pathological increases in adipogenic potential with decreases in osteogenic differentiation occur in osteoporotic bone marrow cells. Previous studies have shown that bioactive materials isolated from natural products can reciprocally regulate adipogenic and osteogenic fates of bone marrow cells. In this study, we showed that Eupatorium japonicum stem extracts (EJE) suppressed lipid accumulation and inhibited the expression of adipocyte markers in multipotent C3H10T1/2 and primary bone marrow cells. Conversely, EJE stimulated alkaline phosphatase activity and induced the expression of osteoblast markers in C3H10T1/2 and primary bone marrow cells. Daily oral administration of 50 mg/kg of EJE for 6 weeks to ovariectomized rats prevented body weight increase and bone mineral density decrease. Finally, activity-guided fractionation led to the identification of coumaric acid and coumaric acid methyl ester as bioactive anti-adipogenic and pro-osteogenic components in EJE. Taken together, our data indicate a promising possibility of E. japonicum as a functional food and as a therapeutic intervention for preventing osteoporosis and bone fractures.

Essential thrombocythemia

MedlinePlus

... leukemia (cancer that starts in the bone marrow) Polycythemia vera (bone marrow disease that leads to an ... PA: Elsevier Saunders; 2013:chap 68. Tefferi A. Polycythemia vera, essential thrombocythemia, and primary myelofibrosis. In: Goldman ...

Mechanisms of apoptosis induction by simultaneous inhibition of PI3K and FLT3-ITD in AML cells in the hypoxic bone marrow microenvironment

PubMed Central

Jin, Linhua; Tabe, Yoko; Lu, Hongbo; Borthakur, Gautam; Miida, Takashi; Kantarjian, Hagop; Andreeff, Michael; Konopleva, Marina

2013-01-01

We investigated the antileukemia effects and molecular mechanisms of apoptosis induction by simultaneous blockade of PI3K and mutant FLT3 in AML cells grown under hypoxia in co-cultures with bone marrow stromal cells. Combined treatment with selective class I PI3K inhibitor GDC-0941 and sorafenib reversed the protective effects of bone marrow stromal cells on FLT3-mutant AML cells in hypoxia, which was associated with downregulation of Pim-1 and Mcl-1 expression levels. These findings suggest that combined inhibition of PI3K and FLT3-ITD may constitute a targeted approach to eradicating chemoresistant AML cells sequestered in hypoxic bone marrow niches. PMID:23036488

Mechanisms of apoptosis induction by simultaneous inhibition of PI3K and FLT3-ITD in AML cells in the hypoxic bone marrow microenvironment.

PubMed

Jin, Linhua; Tabe, Yoko; Lu, Hongbo; Borthakur, Gautam; Miida, Takashi; Kantarjian, Hagop; Andreeff, Michael; Konopleva, Marina

2013-02-01

We investigated the antileukemia effects and molecular mechanisms of apoptosis induction by simultaneous blockade of PI3K and mutant FLT3 in AML cells grown under hypoxia in co-cultures with bone marrow stromal cells. Combined treatment with selective class I PI3K inhibitor GDC-0941 and sorafenib reversed the protective effects of bone marrow stromal cells on FLT3-mutant AML cells in hypoxia, which was associated with downregulation of Pim-1 and Mcl-1 expression levels. These findings suggest that combined inhibition of PI3K and FLT3-ITD may constitute a targeted approach to eradicating chemoresistant AML cells sequestered in hypoxic bone marrow niches. Copyright © 2012 Elsevier Ltd. All rights reserved.

Noradrenergic and cholinergic innervation of the bone marrow.

PubMed

Artico, Marco; Bosco, Sandro; Cavallotti, Carlo; Agostinelli, Enzo; Giuliani-Piccari, Gabriella; Sciorio, Salvatore; Cocco, Lucio; Vitale, Marco

2002-07-01

Bone marrow is supplied by sensory and autonomic innervation. Although it is well established that hematopoiesis is regulated by cytokines and cell-to-cell contacts, the role played by neuromediators on the proliferation, differentiation and release of hematopoietic cells is still controversial. We studied the innervation of rat femur bone marrow by means of fluorescence histochemistry and immunohistochemistry. Glyoxylic acid-induced fluorescence was used to demonstrate catecholaminergic nerve fibers. The immunoperoxidase method with nickel amplification was applied to detect the distribution of nerve fibers using antibodies against the general neuronal marker PGP 9.5 (neuron-specific cytoplasmic protein), while the cholinacetyltransferase immunoreactivity was studied by immunohistochemistry. Our results show the presence of an extensive network of innervation in the rat bone marrow, providing a morphological basis for the neural modulation of hemopoiesis.

[Recent research advance on bone marrow microenvironment-mediated leukemia drug resistant mechanism].

PubMed

Fu, Bing; Ling, Yan-Juan

2011-06-01

The bone marrow microenvironment consists of bone marrow stromal cells, osteoblasts and osteoclasts which facilities the survival, differentiation and proliferation of hematopoietic cells through secreting soluble factors and extracellular matrix proteins that mediate these functions. This environment not only supports the growth of normal and malignant hematopoietic cells, but also protects them against the damage from chemotherapeutic agents through the secretion of soluble cytokines, cell adhesion, up-regulation of resistant genes and changes of cell cycle. In this review, the research advances on drug-resistance mechanisms mediated by bone marrow microenvironment are summarized briefly, including soluble factors mediating drug resistance, intercellular adhesion inducing drug resistance, up-regulation of some drug resistance genes, regulation in metabolism of leukemic cells, changes in cell cycles of tumor cells and so on.

Stem Cell Mobilizers: Novel Therapeutics for Acute Kidney Injury.

PubMed

Xu, Yue; Zeng, Song; Zhang, Qiang; Zhang, Zijian; Hu, Xiaopeng

2017-01-01

In the past decade, rapid developments in stem cell studies have occurred. Researchers have confirmed the plasticity of bone marrow stem cells and the repair and regeneration effects of bone marrow hematopoietic stem cells on solid organs. These findings have suggested the possibility of using bone marrow stem cell mobilizers to repair and regenerate injured organs. Recent studies on the effects of granulocyte colony-stimulating factor (G-CSF) and Plerixafor (AMD3100) on mouse acute kidney injury models have confirmed that the use of bone marrow stem cell mobilizers may be an effective therapeutic measure. This paper summarizes studies describing the effects of G-CSF and AMD3100 on various acute kidney injury models over the past 10 years. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Long-term accumulation and microdistribution of uranium in the bone and marrow of beagle dog.

PubMed

Arruda-Neto, J D T; Manso Guevara, M V; Nogueira, G P; Taricano, I D; Saiki, M; Zamboni, C B; Bonamin, L V; Camargo, S P; Cestari, A C; Deppman, A; Garcia, F; Gouveia, A N; Guzman, F; Helene, O A M; Jorge, S A C; Likhachev, V P; Martins, M N; Mesa, J; Rodriguez, O; Vanin, V R

2004-08-01

The accumulation and microdistribution of uranium in the bone and marrow of Beagle dogs were determined by both neutron activation and neutron-fission analysis. The experiment started immediately after the weaning period, lasting till maturity. Two animal groups were fed daily with uranyl nitrate at concentrations of 20 and 100 microg g(-1) food. Of the two measuring techniques, uranium accumulated along the marrow as much as in the bone, contrary to the results obtained with single, acute doses. The role played by this finding for the evaluation of radiobiological long-term risks is discussed. It was demonstrated, by means of a biokinetical approach, that the long-term accumulation of uranium in bone and marrow could be described by a piling up of single dose daily incorporation.

Acute Myeloid Leukemia

MedlinePlus

Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

Chronic Myeloid Leukemia

MedlinePlus

Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

Chronic Lymphocytic Leukemia

MedlinePlus

Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

Acute Lymphocytic Leukemia

MedlinePlus

Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment.

PubMed

Snyder, Robert

2014-03-01

Detection, treatment, and prevention of bone marrow diseases have long been the aims of experimental and clinical hematologists and mechanistically oriented toxicologists. Among these diseases is aplastic anemia, which manifests as the cessation of normal blood cell production; the leukemias, in contrast, feature the production of excessive hematologic cancer cells. Both diseases are associated with exposure to either industrial chemicals or cancer chemotherapeutic agents. Studies of hematopoietic bone marrow cells in culture have shown that the generation of circulating blood cells requires the interaction of hematopoietic stem cells (HSCs) with supporting marrow stromal cells; yet, isolation of HSCs from bone destroys the unique morphology of the marrow stroma in which the HSCs reside. Imaging techniques and related studies have made it possible to examine specific niches where HSCs may either initiate differentiation toward mature blood cells or reside in a dormant state awaiting a signal to begin differentiation. HSCs and related cells may be highly vulnerable to the mutagenic or toxic effects of drugs or other chemicals early in these processes. Additional studies are required to determine the mechanisms by which drug or chemical exposure may affect these cells and lead to either depression of bone marrow function or to leukemia. © 2014 New York Academy of Sciences.

Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve Repair and Functional Outcomes

DTIC Science & Technology

2016-07-01

AWARD NUMBER: W81XWH-15-2-0026 TITLE: Clinical Evaluation of Decellularized Nerve Allograft With Autologous Bone Marrow Stem Cells To Improve...5b. GRANT NUMBER W81XWH-15-2-0026 CClinical Evaluation of Decellularized Nerve Allograft With Autologous Bone Marrow Stem Cells To Improve...co- treatments of a commercially available decellularized processed peripheral nerve allograft scaffold (Avance® Nerve Graft, AxoGen, Alachua FL) with

Intramuscular Transplantation and Survival of Freshly Isolated Bone Marrow Cells following Skeletal Muscle Ischemia-reperfusion Injury

DTIC Science & Technology

2013-01-01

2) in a rat I/R model, consis- tent with this time course of functional recovery, evidence of muscle fiber damage and regeneration was still present...Contractile function of the anterior crural muscles was assessed by measuring maximal isometric torque as a function of stimulation frequency (20Y200 Hz...from the direct conver- sion of bone marrowYderived cells to muscle fibers , the paracrine secretory effects of stem cells resident in bone marrow

Osteogenically differentiated mesenchymal stem cells and ceramics for bone tissue engineering.

PubMed

Ohgushi, Hajime

2014-02-01

In the human body, cells having self-renewal and multi-differentiation capabilities reside in many tissues and are called adult stem cells. In bone marrow tissue, two types of stem cells are well known: hematopoietic stem cells and mesenchymal stem cells (MSCs). Though the number of MSCs in bone marrow tissue is very low, it can be increased by in vitro culture of the marrow, and culture-expanded MSCs are available for various tissue regeneration. The culture-expanded MSCs can further differentiate into osteogenic cells such as bone forming osteoblasts by culturing the MSCs in an osteogenic medium. This paper discusses osteogenically differentiated MSCs derived from the bone marrow of patients. Importantly, the differentiation can be achieved on ceramic surfaces which demonstrate mineralized bone matrix formation as well as appearance of osteogenic cells. The cell/matrix/ceramic constructs could show immediate in vivo bone formation and are available for bone reconstruction surgery. Currently, MSCs are clinically available for the regeneration of various tissues due to their high proliferation/differentiation capabilities. However, the capabilities are still limited and thus technologies to improve or recover the inherent capabilities of MSCs are needed.

Transient engraftment of syngeneic bone marrow after conditioning with high-dose cyclophosphamide and thoracoabdominal irradiation in a patient with aplastic anemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsue, K.; Niki, T.; Shiobara, S.

1990-01-01

We describe the clinical course of a 16 year old girl with aplastic anemia who was treated by syngeneic bone marrow transplantation. Engraftment was not obtained by simple infusion of bone marrow without immunosuppression. The patient received a high-dose cyclophosphamide and thoracoabdominal irradiation, followed by second marrow transplantation from the same donor. Incomplete but significant hematologic recovery was observed; however, marrow failure recurred 5 months after transplantation. Since donor and recipient pairs were genotypically identical, graft failure could not be attributed to immunological reactivity of recipient cells to donor non-HLA antigens. This case report implies that graft failure in somemore » cases of aplastic anemia might be mediated by inhibitory cells resistant to cyclophosphamide and irradiation.« less

Juridical and liability reflexes of bone marrow processing.

PubMed

Flores, A

1991-03-01

Author analyzes bone marrow processing procedures and points out juridical and forensic-medicine reflexes of this therapeutical act. The aspects of informed consent and professional liability of hematologist are clarified.

Selection, proliferation and differentiation of bone marrow-derived liver stem cells with a culture system containing cholestatic serum in vitro.

PubMed

Cai, Yun-Feng; Zhen, Zuo-Jun; Min, Jun; Fang, Tian-Ling; Chu, Zhong-Hua; Chen, Ji-Sheng

2004-11-15

To explore the feasibility of direct separation, selective proliferation and differentiation of the bone marrow-derived liver stem cells (BDLSC) from bone marrow cells with a culture system containing cholestatic serum in vitro. Whole bone marrow cells of rats cultured in routine medium were replaced with conditioning selection media containing 20 mL/L, 50 mL/L, 70 mL/L, and 100 mL/L cholestatic sera, respectively, after they attached to the plates. The optimal concentration of cholestatic serum was determined according to the outcome of the selected cultures. Then the selected BDLSC were induced to proliferate and differentiate with the addition of hepatocyte growth factor (HGF). The morphology and phenotypic markers of BDLSC were characterized using immunohistochemistry, RT-PCR and electron microscopy. The metabolic functions of differentiated cells were also determined by glycogen staining and urea assay. Bone marrow cells formed fibroblast-like but not hepatocyte-like colonies in the presence of 20 mL/L cholestatic serum. In 70 mL/L cholestatic serum, BDLSC colonies could be selected but could not maintain good growth status. In 100 mL/L cholestatic serum, all of the bone marrow cells were unable to survive. A 50 mL/L cholestatic serum was the optimal concentration for the selection of BDLSC at which BDLSC could survive while the other populations of the bone marrow cells could not. The selected BDLSC proliferated and differentiated after HGF was added. Hepatocyte-like colony-forming units (H-CFU) then were formed. H-CFU expressed markers of embryonic hepatocytes (AFP, albumin and cytokeratin 8/18), biliary cells (cytokeratin 19), hepatocyte functional proteins (transthyretin and cytochrome P450-2b1), and hepatocyte nuclear factors (HNF-1alpha and HNF-3beta). They also had glycogen storage and urea synthesis functions, two of the critical features of hepatocytes. The selected medium containing cholestatic serum can select BDLSC from whole bone marrow cells. It will be a new way to provide a readily available alternate source of cells for clinical hepatocyte therapy.

A novel model for ectopic, chronic, intravital multiphoton imaging of bone marrow vasculature and architecture in split femurs

PubMed Central

Bălan, Mirela; Kiefer, Friedemann

2015-01-01

Creating a model for intravital visualization of femoral bone marrow, a major site of hematopoiesis in adult mammalian organisms, poses a serious challenge, in that it needs to overcome bone opacity and the inaccessibility of marrow. Furthermore, meaningful analysis of bone marrow developmental and differentiation processes requires the repetitive observation of the same site over long periods of time, which we refer to as chronic imaging. To surmount these issues, we developed a chronic intravital imaging model that allows the observation of split femurs, ectopically transplanted into a dorsal skinfold chamber of a host mouse. Repeated, long term observations are facilitated by multiphoton microscopy, an imaging technique that combines superior imaging capacity at greater tissue depth with low phototoxicity. The transplanted, ectopic femur was stabilized by its sterile environment and rapidly connected to the host vasculature, allowing further development and observation of extended processes. After optimizing transplant age and grafting procedure, we observed the development of new woven bone and maturation of secondary ossification centers in the transplanted femurs, preceded by the sprouting of a sinusoidal-like vascular network, which was almost entirely composed of femoral endothelial cells. After two weeks, the transplant was still populated with stromal and haematopoietic cells belonging both to donor and host. Over this time frame, the transplant partially retained myeloid progenitor cells with single and multi-lineage differentiation capacity. In summary, our model allowed repeated intravital imaging of bone marrow angiogenesis and hematopoiesis. It represents a promising starting point for the development of improved chronic optical imaging models for femoral bone marrow. PMID:28243515

Bone Marrow Regeneration Promoted by Biophysically Sorted Osteoprogenitors From Mesenchymal Stromal Cells

PubMed Central

Poon, Zhiyong; Lee, Wong Cheng; Guan, Guofeng; Nyan, Lin Myint; Lim, Chwee Teck; Han, Jongyoon

2015-01-01

Human tissue repair deficiencies can be supplemented through strategies to isolate, expand in vitro, and reimplant regenerative cells that supplant damaged cells or stimulate endogenous repair mechanisms. Bone marrow-derived mesenchymal stromal cells (MSCs), a subset of which is described as mesenchymal stem cells, are leading candidates for cell-mediated bone repair and wound healing, with hundreds of ongoing clinical trials worldwide. An outstanding key challenge for successful clinical translation of MSCs is the capacity to produce large quantities of cells in vitro with uniform and relevant therapeutic properties. By leveraging biophysical traits of MSC subpopulations and label-free microfluidic cell sorting, we hypothesized and experimentally verified that MSCs of large diameter within expanded MSC cultures were osteoprogenitors that exhibited significantly greater efficacy over other MSC subpopulations in bone marrow repair. Systemic administration of osteoprogenitor MSCs significantly improved survival rates (>80%) as compared with other MSC subpopulations (0%) for preclinical murine bone marrow injury models. Osteoprogenitor MSCs also exerted potent therapeutic effects as “cell factories” that secreted high levels of regenerative factors such as interleukin-6 (IL-6), interleukin-8 (IL-8), vascular endothelial growth factor A, bone morphogenetic protein 2, epidermal growth factor, fibroblast growth factor 1, and angiopoietin-1; this resulted in increased cell proliferation, vessel formation, and reduced apoptosis in bone marrow. This MSC subpopulation mediated rescue of damaged marrow tissue via restoration of the hematopoiesis-supporting stroma, as well as subsequent hematopoiesis. Together, the capabilities described herein for label-freeisolation of regenerative osteoprogenitor MSCs can markedly improve the efficacy of MSC-based therapies. PMID:25411477

Direct comparison of progenitor cells derived from adipose, muscle, and bone marrow from wild-type or craniosynostotic rabbits

PubMed Central

GM, Cooper; EL, Lensie; JJ, Cray; MR, Bykowski; GE, DeCesare; MA, Smalley; MP, Mooney; PG, Campbell; JE, Losee

2010-01-01

Background Reports have identified cells capable of osteogenic differentiation in bone marrow, muscle, and adipose tissues, but there are few direct comparisons of these different cell-types. Also, few have investigated the potential connection between a tissue-specific pathology and cells derived from seemingly unrelated tissues. Here, we compare cells isolated from wild-type rabbits or rabbits with nonsyndromic craniosynostosis, defined as the premature fusion of one or more of the cranial sutures. Methods Cells were derived from bone marrow, adipose, and muscle of 10 day-old wild-type rabbits (WT; n=17) or from age-matched rabbits with familial nonsyndromic craniosynostosis (CS; n=18). Cells were stimulated with bone morphogenetic protein 4 (BMP4) and alkaline phosphatase expression and cell proliferation were assessed. Results In WT rabbits, cells derived from muscle had more alkaline phosphatase activity than cells derived from either adipose or bone marrow. The cells derived from CS rabbit bone marrow and muscle were significantly more osteogenic than WT. Adipose-derived cells demonstrated no significant differences. While muscle-derived cells were most osteogenic in WT rabbits, bone marrow-derived cells were most osteogenic in CS rabbits. Conclusions Results suggest that cells from different tissues have different potentials for differentiation. Furthermore, cells derived from rabbits with craniosynostosis were different from wild-type derived cells. Interestingly, cells derived from the craniosynostotic rabbits were not uniformly more responsive compared with wild-type cells, suggesting that specific tissue-derived cells may react differently in individuals with craniosynostosis. PMID:20871482