Science.gov

Sample records for residual bone marrow

  1. 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; ...

  2. 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 ...

  3. Bone marrow biopsy

    MedlinePlus

    Biopsy - bone marrow ... A bone marrow biopsy may be done in the health care provider's office or in a hospital. The sample may be taken from the pelvic or breast bone. Sometimes, other areas are used. Marrow is removed ...

  4. 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 - ...

  5. Bone Marrow Diseases

    MedlinePlus

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

  6. Bone Marrow Transplantation

    MedlinePlus

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. ... platelets, which help the blood to clot. A bone marrow transplant is a procedure that replaces a person's ...

  7. Bone marrow aspiration

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003658.htm Bone marrow aspiration To use the sharing features on this page, please enable JavaScript. Bone marrow is the soft tissue inside bones that helps ...

  8. Coordinate regulation of residual bone marrow function by paracrine trafficking of AML exosomes.

    PubMed

    Huan, J; Hornick, N I; Goloviznina, N A; Kamimae-Lanning, A N; David, L L; Wilmarth, P A; Mori, T; Chevillet, J R; Narla, A; Roberts, C T; Loriaux, M M; Chang, B H; Kurre, P

    2015-12-01

    We recently demonstrated that acute myeloid leukemia (AML) cell lines and patient-derived blasts release exosomes that carry RNA and protein; following an in vitro transfer, AML exosomes produce proangiogenic changes in bystander cells. We reasoned that paracrine exosome trafficking may have a broader role in shaping the leukemic niche. In a series of in vitro studies and murine xenografts, we demonstrate that AML exosomes downregulate critical retention factors (Scf, Cxcl12) in stromal cells, leading to hematopoietic stem and progenitor cell (HSPC) mobilization from the bone marrow. Exosome trafficking also regulates HSPC directly, and we demonstrate declining clonogenicity, loss of CXCR4 and c-Kit expression, and the consistent repression of several hematopoietic transcription factors, including c-Myb, Cebp-β and Hoxa-9. Additional experiments using a model of extramedullary AML or direct intrafemoral injection of purified exosomes reveal that the erosion of HSPC function can occur independent of direct cell-cell contact with leukemia cells. Finally, using a novel multiplex proteomics technique, we identified candidate pathways involved in the direct exosome-mediated modulation of HSPC function. In aggregate, this work suggests that AML exosomes participate in the suppression of residual hematopoietic function that precedes widespread leukemic invasion of the bone marrow directly and indirectly via stromal components. PMID:26108689

  9. Bone marrow (stem cell) donation

    MedlinePlus

    Stem cell transplant; Allogeneic-donation ... There are two types of bone marrow donation: Autologous bone marrow transplant is when people donate their own bone marrow. "Auto" means self. Allogenic bone marrow transplant is when another person ...

  10. Bone marrow aspiration

    MedlinePlus

    ... creates suction. A small sample of bone marrow fluid flows into the tube. The needle is removed. Pressure and then a bandage are applied to the skin. The bone marrow fluid is sent to a laboratory and examined under ...

  11. Bone Marrow Diseases

    MedlinePlus

    ... that help with blood clotting. With bone marrow disease, there are problems with the stem cells or ... marrow makes too many white blood cells Other diseases, such as lymphoma, can spread into the bone ...

  12. Bone marrow biopsy

    MedlinePlus

    Biopsy - bone marrow ... A bone marrow biopsy may be done in the health care provider's office or in a hospital. The sample may ... This captures a tiny sample, or core, of bone marrow within the needle. The sample and needle are ...

  13. Imaging of Bone Marrow.

    PubMed

    Lin, Sopo; Ouyang, Tao; Kanekar, Sangam

    2016-08-01

    Bone marrow is the essential for function of hematopoiesis, which is vital for the normal functioning of the body. Bone marrow disorders or dysfunctions may be evaluated by blood workup, peripheral smears, marrow biopsy, plain radiographs, computed tomography (CT), MRI and nuclear medicine scan. It is important to distinguish normal spinal marrow from pathology to avoid missing a pathology or misinterpreting normal changes, either of which may result in further testing and increased health care costs. This article focuses on the diffuse bone marrow pathologies, because the majority of the bone marrow pathologies related to hematologic disorders are diffuse. PMID:27444005

  14. 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 ...

  15. Bone marrow fat.

    PubMed

    Hardouin, Pierre; Pansini, Vittorio; Cortet, Bernard

    2014-07-01

    Bone marrow fat (BMF) results from an accumulation of fat cells within the bone marrow. Fat is not a simple filling tissue but is now considered as an actor within bone microenvironment. BMF is not comparable to other fat depots, as in subcutaneous or visceral tissues. Recent studies on bone marrow adipocytes have shown that they do not appear only as storage cells, but also as cells secreting adipokines, like leptin and adiponectin. Moreover bone marrow adipocytes share the same precursor with osteoblasts, the mesenchymal stem cell. It is now well established that high BMF is associated with weak bone mass in osteoporosis, especially during aging and anorexia nervosa. But numerous questions remain discussed: what is the precise phenotype of bone marrow adipocytes? What is the real function of BMF, and how does bone marrow adipocyte act on its environment? Is the increase of BMF during osteoporosis responsible for bone loss? Is BMF involved in other diseases? How to measure BMF in humans? A better understanding of BMF could allow to obtain new diagnostic tools for osteoporosis management, and could open major therapeutic perspectives. PMID:24703396

  16. Bone marrow culture

    MedlinePlus

    ... 2015 Updated by: Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital, Boston, MA. Also reviewed ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  17. Aspiration and Biopsy: Bone Marrow

    MedlinePlus

    ... Help a Friend Who Cuts? Aspiration and Biopsy: Bone Marrow KidsHealth > For Teens > Aspiration and Biopsy: Bone Marrow Print A A A Text Size What's in ... Risks If You Have Questions What It Is Bone marrow aspirations and biopsies are performed to examine bone ...

  18. Bone marrow aspiration

    PubMed Central

    Bain, B

    2001-01-01

    Bone marrow aspiration biopsies are carried out principally to permit cytological assessment but also for immunophenotypic, cytogenetic, molecular genetic, and other specialised investigations. Often, a trephine biopsy is carried out as part of the same procedure. Bone marrow aspirations should be carried out by trained individuals who are aware of the indications, contraindications, and hazards of the procedure. They should follow a standard operating procedure. The operator should have made an adequate assessment of clinical and haematological features to ensure both that appropriate indications exist and that all relevant tests are performed. For the patient's comfort and safety, the posterior iliac crest is generally the preferred site of aspiration. Films of aspirated marrow and, when appropriate, films of crushed particles should be made and labelled. Once thoroughly dry, films should be fixed and stained. As a minimum, a Romanowsky stain and a Perls' stain are required. A cover slip should be applied. The bone marrow films should be assessed and reported in a systematic manner so that nothing of importance is overlooked, using a low power, then intermediate, then high power objective. A differential count should be performed. An interpretation of the findings, in the light of the clinical and haematological features, should be given. The report should be signed or computer authorised, using a secure password, and issued in a timely manner. Key Words: bone marrow aspirate • haematological diagnosis PMID:11533068

  19. Bone Marrow Aspiration and Biopsy

    MedlinePlus

    ... the bone marrow and capability for blood cell production, including red blood cells (RBCs), white blood cells ( ... can affect the bone marrow and blood cell production. A specialist who has expertise in the diagnosis ...

  20. Bone-marrow transplant - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100112.htm Bone-marrow transplant - series—Normal anatomy To use the sharing ... Go to slide 4 out of 4 Overview Bone-marrow is a soft, fatty tissue found inside of ...

  1. Detection of minimal residual disease by polymerase chain reaction in patients with different hematologic diseases treated by bone marrow transplantation.

    PubMed

    Stuppia, L; Calabrese, G; Guanciali Franchi, P; Di Bartolomeo, P; Antonucci, A; Peila, R; Torlontano, G; Palka, G

    1993-02-01

    Thirteen male patients affected by different hematologic diseases who underwent bone marrow transplantation (BMT) with female donors were investigated by cytogenetic analysis and polymerase chain reaction (PCR) amplification of a DNA sequence specific for the Y chromosome. In six of these patients, PCR showed the presence of the Y chromosome-related sequence; in only three of these did cytogenetic analysis confirm the presence of mixed chimerism. In the remaining three patients, the results of the PCR were confirmed by in situ hybridization on cell nuclei with a probe for the alpha-satellite of the Y chromosome. We compare results obtained with the two methods and discuss the meaning of the minimal residual disease detected by PCR in patients submitted to BMT. PMID:8453609

  2. Starvation marrow - gelatinous transformation of bone marrow.

    PubMed

    Osgood, Eric; Muddassir, Salman; Jaju, Minal; Moser, Robert; Farid, Farwa; Mewada, Nishith

    2014-01-01

    Gelatinous bone marrow transformation (GMT), also known as starvation marrow, represents a rare pathological entity of unclear etiology, in which bone marrow histopathology demonstrates hypoplasia, fat atrophy, and gelatinous infiltration. The finding of gelatinous marrow transformation lacks disease specificity; rather, it is an indicator of severe illness and a marker of poor nutritional status, found in patients with eating disorders, acute febrile illnesses, acquired immunodeficiency syndrome, alcoholism, malignancies, and congestive heart failure. We present a middle-aged woman with a history of alcoholism, depression, and anorexia nervosa who presented with failure to thrive and macrocytic anemia, with bone marrow examination demonstrative of gelatinous transformation, all of which resolved with appropriate treatment. To our knowledge, there are very few cases of GMT which have been successfully treated; thus, our case highlights the importance of proper supportive management. PMID:25317270

  3. Bone marrow trephine biopsy

    PubMed Central

    Bain, B

    2001-01-01

    Trephine biopsies of the bone marrow should be carried out, when clinically indicated, by trained individuals following a standard operating procedure. A bone marrow aspiration should be performed as part of the same procedure. For patient safety and convenience, biopsies are usually performed on the posterior iliac crest. The biopsy specimen should measure at least 1.6 cm and, if it does not, consideration should be given to repeating the procedure, possibly on the contralateral iliac crest. If bone marrow aspiration is found to be impossible, imprints from the biopsy specimen should be obtained. Otherwise, the specimen is placed immediately into fixative and after fixation is embedded in a resin or, more usually, decalcified and embedded in paraffin wax. Thin sections are cut and are stained, as a minimum, with haematoxylin and eosin and with a reticulin stain. A Giemsa stain is also desirable. A Perls' stain does not often give useful information and is not essential in every patient. The need for other histochemical or immunohistochemical stains is determined by the clinical circumstances and the preliminary findings. Trephine biopsy sections should be examined and reported in a systematic manner, assessment being made of the bones, the vessels and stroma, and the haemopoietic and any lymphoid or other tissue. Assessment should begin with a very low power objective, the entire section being examined. Further examination is then done with an intermediate and high power objective. Ideally, reporting of trephine biopsy sections should be done by an individual who is competent in both histopathology and haematology, and who is able to make an appropriate assessment of both the bone marrow aspirate and the trephine biopsy sections. When this is not possible, there should be close consultation between a haematologist and a histopathologist. The report should both describe the histological findings and give an interpretation of their importance. A signed or computer

  4. Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients

    PubMed Central

    YAMAMOTO, NOBUYUKI; KOZAKI, AIKO; HARTOMO, TRI BUDI; YANAI, TOMOKO; HASEGAWA, DAIICHIRO; KAWASAKI, KEIICHIRO; KOSAKA, YOSHIYUKI; MATSUO, MASAFUMI; HIRASE, SATOSHI; MORI, TAKESHI; HAYAKAWA, AKIRA; IIJIMA, KAZUMOTO; NISHIO, HISAHIDE; NISHIMURA, NORIYUKI

    2015-01-01

    Neuroblastoma is an aggressive solid tumor that leads to tumor relapse in more than half of high-risk patients. Minimal residual disease (MRD) is primarily responsible for tumor relapses and may be detected in peripheral blood (PB) and bone marrow (BM) samples. To evaluate the disease status and treatment response, a number of MRD detection protocols based on either common or distinct markers for PB and BM samples have been reported. However, the correlation between the expression of MRD markers in PB and BM samples remains elusive in the clinical samples. In the present study, the expression of 11 previously validated MRD markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) was determined in 23 pairs of PB and BM samples collected from seven high-risk neuroblastoma patients at the same time point, and the sample was scored as MRD-positive if one of the MRD markers exceeded the normal range. Although the number of MRD-positive samples was not significantly different between PB and BM samples, the two most sensitive markers for PB samples (CRMP1 and KIF1A) were different from those for BM samples (PHOX2B and DBH). There was no statistically significant correlation between the expression of MRD markers in the PB and BM samples. These results suggest that MRD markers were differentially expressed in PB and BM samples from high-risk neuroblastoma patients. PMID:26722317

  5. Bone Marrow Derived Eosinophil Cultures

    PubMed Central

    Lu, Thomas X.; Rothenberg, Marc E.

    2016-01-01

    Eosinophils are multifunctional effector cells implicated in the pathogenesis of a variety of diseases including asthma, eosinophil gastrointestinal disorders and helminth infection. Mouse bone marrow derived progenitor cells can be differentiated into eosinophils following IL-5 exposure. These bone marrow derived eosinophils are fully differentiated at the end of a 14 day culture based on morphology and expression of molecular markers.

  6. Aspiration and Biopsy: Bone Marrow

    MedlinePlus

    ... A Recipes En Español Teachers - Looking for Health Lessons? Visit KidsHealth in the Classroom What Other Parents ... bone marrow sample for procedures (such as a stem cell transplant ) or other testing (such as chromosomal ...

  7. Peripheral blood minimal residual disease may replace bone marrow minimal residual disease as an immunophenotypic biomarker for impending relapse in acute myeloid leukemia.

    PubMed

    Zeijlemaker, W; Kelder, A; Oussoren-Brockhoff, Y J M; Scholten, W J; Snel, A N; Veldhuizen, D; Cloos, J; Ossenkoppele, G J; Schuurhuis, G J

    2016-03-01

    As relapses are common in acute myeloid leukemia (AML), early relapse prediction is of high importance. Although conventional minimal residual disease (MRD) measurement is carried out in bone marrow (BM), peripheral blood (PB) would be an advantageous alternative source. This study aims to investigate the specificity of leukemia-associated immunophenotypes used for MRD detection in blood samples. Consistency of PB MRD as compared with BM MRD was determined in flow cytometric data of 205 paired BM and PB samples of 114 AML patients. A significant correlation was found between PB and BM MRD (r=0.67, P<0.001), while median PB MRD percentage was factor 4-5 lower compared with BM MRD. Primitive blast (CD34+/CD117+/CD133+) frequency was significantly lower in PB (median factor 23.7), indicating that PB MRD detection is more specific than BM. Cumulative incidence of relapse 1 year after induction therapy was 29% for PB MRD-negative and 89% for PB MRD-positive patients (P<0.001). Three-year OS was 52% for MRD-negative and 15% for MRD-positive patients (P=0.034). Similar differences were found after consolidation therapy. As PB MRD appeared to be an independent predictor for response duration, the highly specific PB MRD assay may have a prominent role in future MRD assessment in AML. PMID:26373238

  8. [Inherited bone marrow failure syndromes].

    PubMed

    Okuno, Yusuke

    2016-02-01

    Inherited bone marrow failure syndromes comprise a series of disorders caused by various gene mutations. Genetic tests were formerly difficult to perform because of the large size and number of causative genes. However, recent advances in next-generation sequencing has enabled simultaneous testing of all causative genes to be performed at an acceptable cost. We collaboratively conducted a series of whole-exome sequencing studies of patients with inherited bone marrow failure syndromes and discovered RPS27/RPL27 and FANCT as causative genes of Diamond-Blackfan anemia and Fanconi anemia, respectively. Furthermore, we established a target gene sequencing system to cover 189 genes associated with pediatric blood diseases to assist genetic diagnoses in clinical practice. In this review, discovery of new causative genes and possible roles of next-generation sequencing in the genetic diagnosis of inherited bone marrow failure syndromes are discussed. PMID:26935625

  9. Mechanics of intact bone marrow.

    PubMed

    Jansen, Lauren E; Birch, Nathan P; Schiffman, Jessica D; Crosby, Alfred J; Peyton, Shelly R

    2015-10-01

    The current knowledge of bone marrow mechanics is limited to its viscous properties, neglecting the elastic contribution of the extracellular matrix. To get a more complete view of the mechanics of marrow, we characterized intact yellow porcine bone marrow using three different, but complementary techniques: rheology, indentation, and cavitation. Our analysis shows that bone marrow is elastic, and has a large amount of intra- and inter-sample heterogeneity, with an effective Young׳s modulus ranging from 0.25 to 24.7 kPa at physiological temperature. Each testing method was consistent across matched tissue samples, and each provided unique benefits depending on user needs. We recommend bulk rheology to capture the effects of temperature on tissue elasticity and moduli, indentation for quantifying local tissue heterogeneity, and cavitation rheology for mitigating destructive sample preparation. We anticipate the knowledge of bone marrow elastic properties for building in vitro models will elucidate mechanisms involved in disease progression and regenerative medicine. PMID:26189198

  10. 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, ...

  11. Bone Marrow Transplants: "Another Possibility at Life"

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Bone Marrow Transplants “Another Possibility at Life” Past Issues / Summer ... year, and, for 16,000 of them, a bone marrow transplant is the best treatment option, notes Susan ...

  12. Planning for a Bone Marrow Transplant (BMT)

    MedlinePlus

    ... us Digg Facebook Google Bookmarks Planning for a Bone Marrow Transplant (BMT) If you're going to have ... to a friend or family member undergoing a bone marrow or cord blood transplant. Help Your Loved One ...

  13. Transplant Outcomes (Bone Marrow and Cord Blood)

    MedlinePlus

    ... reports show patient survival and transplant data of bone marrow and umbilical cord blood transplants in the transplant ... Data by Center Report —View the number of bone marrow and cord blood transplants performed at a specific ...

  14. Bone scan appearances following bone and bone marrow biopsy

    SciTech Connect

    McKillop, J.H.; Maharaj, D.; Boyce, B.F.; Fogelman, I.

    1984-01-01

    Bone marrow and bone biopsies are performed not infrequently in patients referred for bone scans and represent a potential cause of a ''false positive'' focal abnormality on the bone scan. The authors have therefore examined the scan appearances in a series of patients who had undergone either sternal marrow biopsy, (Salah needle, diameter 1.2 mm) trephine iliac crest marrow biopsy (Jamshidi 11 gauge needle, diameter 3.5 mm) or a transiliac bone biopsy (needle diameter 8 mm). Of 18 patients studied 1 to 45 days after sternal marrow 17 had normal scan appearances at the biopsy site and 1 had a possible abnormality. None of 9 patients studied 4 to 19 days after trephine iliac crest marrow biopsy had a hot spot at the biopsy site. A focal scan abnormality was present at the biopsy site in 9/11 patients studied 5 to 59 days after a trans iliac bone biopsy. No resultant scan abnormality was seen in 4 patients imaged within 3 days of the bone biopsy or in 3 patients imaged 79 to 138 days after the procedure. Bone marrow biopsy of the sternum or iliac crest does not usually cause bone scan abnormalities. A focal abnormality at the biopsy site is common in patients imaged 5 days to 2 months after bone biopsy. The gauge of the needle employed in the biopsy and thus the degree of bone trauma inflicted, is likely to be main factor determining the appearance of bone scan abnormalities at the biopsy site.

  15. Bone scan appearances following biopsy of bone and bone marrow

    SciTech Connect

    McKillop, J.H.; Maharaj, D.; Boyce, B.F.; Fogelman, I.

    1984-10-01

    The influence of sternal marrow aspiration, iliac crest marrow aspiration, and iliac crest bone biopsy on bone scan appearances was examined. Eighteen patients were scanned a mean of 9.9 days after sternal marrow aspiration with a Salah needle. Bone scans obtained in 9 patients a mean of 10 days aftr iliac crest trephine marrow biopsy with a Jamshidi needle showed no abnormality at the biopsy site. In 18 patients with metabolic bone disease who had undergone iliac crest bone biopsy with an 8 mm needle, a scan abnormality due to the biopsy was usually present when the interval between the biopsy and the scan was 5 days to 2 months. Patients who were scanned within 3 days of iliac crest bone biopsy or more than 2 months after biopsy had normal scan appearance at the biopsy site.

  16. Bone Marrow Matters

    ERIC Educational Resources Information Center

    Dunne, Mark; Maklad, Rania; Heaney, Emma

    2014-01-01

    As a final-year student teacher specialising in primary science, Emma Heaney faced the challenge of having to plan, organise, and conduct a small-scale, classroom-based research project. She had to teach about bones in the final block practice session and thought it would be a good idea to bring in some biological specimens obtained from the local…

  17. Gillick, bone marrow and teenagers.

    PubMed

    Cherkassky, Lisa

    2015-09-01

    The Human Tissue Authority can authorise a bone marrow harvest on a child of any age if a person with parental responsibility consents to the procedure. Older children have the legal capacity to consent to medical procedures under Gillick, but it is unclear if Gillick can be applied to non-therapeutic medical procedures. The relevant donation guidelines state that the High Court shall be consulted in the event of a disagreement, but what is in the best interests of the teenage donor under s.1 of the Children Act 1989? There are no legal authorities on child bone marrow harvests in the United Kingdom. This article considers the best interests of the older saviour sibling and questions whether, for the purposes of welfare, the speculative benefits could outweigh the physical burdens. PMID:25911618

  18. Primary bone marrow oedema syndromes.

    PubMed

    Patel, Sanjeev

    2014-05-01

    MRI scanning in patients with rheumatological conditions often shows bone marrow oedema, which can be secondary to inflammatory, degenerative, infective or malignant conditions but can also be primary. The latter condition is of uncertain aetiology and it is also uncertain whether it represents a stage in the progression to osteonecrosis in some patients. Patients with primary bone marrow oedema usually have lower limb pain, commonly the hip, knee, ankle or feet. The diagnosis is one of exclusion with the presence of typical MRI findings. Treatment is usually conservative and includes analgesics and staying off the affected limb. The natural history is that of gradual resolution of symptoms over a number of months. Evidence for medical treatment is limited, but open-label studies suggest bisphosphonates may help in the resolution of pain and improve radiological findings. Surgical decompression is usually used as a last resort. PMID:24080251

  19. Analyzing the cellular contribution of bone marrow to fracture healing using bone marrow transplantation in mice

    SciTech Connect

    Colnot, C. . E-mail: colnotc@orthosurg.ucsf.edu; Huang, S.; Helms, J.

    2006-11-24

    The bone marrow is believed to play important roles during fracture healing such as providing progenitor cells for inflammation, matrix remodeling, and cartilage and bone formation. Given the complex nature of bone repair, it remains difficult to distinguish the contributions of various cell types. Here we describe a mouse model based on bone marrow transplantation and genetic labeling to track cells originating from bone marrow during fracture healing. Following lethal irradiation and engraftment of bone marrow expressing the LacZ transgene constitutively, wild type mice underwent tibial fracture. Donor bone marrow-derived cells, which originated from the hematopoietic compartment, did not participate in the chondrogenic and osteogenic lineages during fracture healing. Instead, the donor bone marrow contributed to inflammatory and bone resorbing cells. This model can be exploited in the future to investigate the role of inflammation and matrix remodeling during bone repair, independent from osteogenesis and chondrogenesis.

  20. Starvation marrow – gelatinous transformation of bone marrow

    PubMed Central

    Osgood, Eric; Muddassir, Salman; Jaju, Minal; Moser, Robert; Farid, Farwa; Mewada, Nishith

    2014-01-01

    Gelatinous bone marrow transformation (GMT), also known as starvation marrow, represents a rare pathological entity of unclear etiology, in which bone marrow histopathology demonstrates hypoplasia, fat atrophy, and gelatinous infiltration. The finding of gelatinous marrow transformation lacks disease specificity; rather, it is an indicator of severe illness and a marker of poor nutritional status, found in patients with eating disorders, acute febrile illnesses, acquired immunodeficiency syndrome, alcoholism, malignancies, and congestive heart failure. We present a middle-aged woman with a history of alcoholism, depression, and anorexia nervosa who presented with failure to thrive and macrocytic anemia, with bone marrow examination demonstrative of gelatinous transformation, all of which resolved with appropriate treatment. To our knowledge, there are very few cases of GMT which have been successfully treated; thus, our case highlights the importance of proper supportive management. PMID:25317270

  1. Nasopharyngeal carcinoma with bone marrow metastasis.

    PubMed

    Zen, H G; Jame, J M; Chang, A Y; Li, W Y; Law, C K; Chen, K Y; Lin, C Z

    1991-02-01

    Five of 23 patients with recurrent nasopharyngeal carcinoma (NPC) were diagnosed to have bone marrow metastasis. They all had advanced local-regional disease, and were treated with neoadjuvant chemotherapy and definitive radiotherapy after the initial diagnosis. Bone marrow metastasis developed 4-24 months later. The clinical features were anemia (5 of 5), leukopenia (3 of 5), thrombocytopenia (4 of 5), sepsis (3 of 5), tenderness of the sternum (3 of 5), and fever (4 of 5). Patients frequently had elevation of serum lactic dehydrogenase (LDH), alkaline phosphatase (ALK-P), and IgG and IgA antibody titers to Epstein-Barr viral capsid antigen when bone marrow involvement was diagnosed. However, clinical manifestations and laboratory tests were not specific. It is important that three patients had normal bone scans. All five patients had a rapid downhill course; four patients died within 23 days, and the fifth 3 months after the diagnosis of bone marrow metastasis. We concluded that bone marrow was a common metastatic site in NPC patients. Bone marrow metastasis adversely affected patients' survival and required a high index of suspicion for diagnosis. We suggested that bone marrow biopsy should be considered as a routine staging procedure in NPC patients and indicated especially when patients presented with abnormal blood counts, sepsis, bone pain, or tenderness of the sternum. It may be positive in the face of a normal bone scan. PMID:1987743

  2. 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.

  3. Bone Marrow Stress Decreases Osteogenic Progenitors.

    PubMed

    Ng, Adeline H; Baht, Gurpreet S; Alman, Benjamin A; Grynpas, Marc D

    2015-11-01

    Age-related bone loss may be a result of declining levels of stem cells in the bone marrow. Using the Col2.3Δtk (DTK) transgenic mouse, osteoblast depletion was used as a source of marrow stress in order to investigate the effects of aging on osteogenic progenitors which reside in the marrow space. Five-month-old DTK mice were treated with one or two cycles of ganciclovir to conditionally ablate differentiated osteoblasts, whereas controls were saline-treated. Treatment cycles were two weeks in length followed by four weeks of recovery. All animals were sacrificed at 8 months of age; bone marrow stromal cells (BMSCs) were harvested for cell culture and whole bones were excised for bone quality assessment. Colony-forming unit (CFU) assays were conducted to investigate the osteogenic potential of BMSC in vitro, and RNA was extracted to assess the expression of osteoblastic genes. Bone quality assessments included bone histomorphometry, TRAP staining, microcomputed tomography, and biomechanical testing. Osteoblast depletion decreased CFU-F (fibroblast), CFU-ALP (alkaline phosphatase), and CFU-VK (von Kossa) counts and BMSC osteogenic capacity in cell culture. Ex vivo, there were no differences in bone mineral density of vertebrae or femurs between treatment groups. Histology showed a decrease in bone volume and bone connectivity with repeated osteoblast depletion; however, this was accompanied by an increase in bone formation rate. There were no notable differences in osteoclast parameters or observed bone marrow adiposity. We have developed a model that uses bone marrow stress to mimic age-related decrease in osteogenic progenitors. Our data suggest that the number of healthy BMSCs and their osteogenic potential decline with repeated osteoblast depletion. However, activity of the remaining osteoblasts increases to compensate for this loss in progenitor osteogenic potential. PMID:26220824

  4. Bone Marrow Minimal Residual Disease Was an Early Response Marker and a Consistent Independent Predictor of Survival After Anti-GD2 Immunotherapy

    PubMed Central

    Cheung, Nai-Kong V.; Ostrovnaya, Irina; Kuk, Deborah; Cheung, Irene Y.

    2015-01-01

    Purpose Immunotherapy is a standard of care for children with high-risk neuroblastoma, where bone marrow (BM) is the predominant metastatic site. Early response markers of minimal residual disease (MRD) in the BM that are also predictive of survival could help individualize patient therapies. Patients and Methods After achieving first remission (n = 163), primary refractory disease (n = 102), or second remission (n = 95), children with stage 4 neuroblastoma received anti-GD2 3F8 antibody immunotherapy. BM MRD before 3F8 treatment and after cycle 2 (postMRD) was measured using a four-marker panel (B4GALNT1, PHOX2B, CCND1, and ISL1) by quantitative reverse transcription polymerase chain reaction. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Prognostic variables were tested in both univariable and multivariable analyses, and MRD markers were further assessed individually and in combination as binary composite (postMRD: 0 and 1) and as equal sum (postMRDSum: 0 to 4) using the Cox regression models, and their predictive accuracy was determined by the concordance index. Results When BM was evaluated after cycle 2, individual markers were highly predictive of PFS and OS. The prediction accuracy improved when they were combined in postMRDSum. A multivariable model taking into account all the variables significant in the univariable analyses identified postMRDSum to be independently predictive of PFS and OS. When the model for OS also included missing killer immunoglobulin-like receptor ligand, human antimouse antibody response, and the enrollment disease status, the concordance index was 0.704. Conclusion BM MRD after two cycles of immunotherapy was confirmed as an early response marker and a consistent independent predictor of survival. PMID:25559819

  5. Murine Hind Limb Long Bone Dissection and Bone Marrow Isolation.

    PubMed

    Amend, Sarah R; Valkenburg, Kenneth C; Pienta, Kenneth J

    2016-01-01

    Investigation of the bone and the bone marrow is critical in many research fields including basic bone biology, immunology, hematology, cancer metastasis, biomechanics, and stem cell biology. Despite the importance of the bone in healthy and pathologic states, however, it is a largely under-researched organ due to lack of specialized knowledge of bone dissection and bone marrow isolation. Mice are a common model organism to study effects on bone and bone marrow, necessitating a standardized and efficient method for long bone dissection and bone marrow isolation for processing of large experimental cohorts. We describe a straightforward dissection procedure for the removal of the femur and tibia that is suitable for downstream applications, including but not limited to histomorphologic analysis and strength testing. In addition, we outline a rapid procedure for isolation of bone marrow from the long bones via centrifugation with limited handling time, ideal for cell sorting, primary cell culture, or DNA, RNA, and protein extraction. The protocol is streamlined for rapid processing of samples to limit experimental error, and is standardized to minimize user-to-user variability. PMID:27168390

  6. Bone marrow lesions: A systematic diagnostic approach

    PubMed Central

    Grande, Filippo Del; Farahani, Sahar J; Carrino, John A; Chhabra, Avneesh

    2014-01-01

    Bone marrow lesions on magnetic resonance (MR) imaging are common and may be seen with various pathologies. The authors outline a systematic diagnostic approach with proposed categorization of various etiologies of bone marrow lesions. Utilization of typical imaging features on conventional MR imaging techniques and other problem-solving techniques, such as chemical shift imaging and diffusion-weighted imaging (DWI), to achieve accurate final diagnosis has been highlighted. PMID:25114392

  7. Fat embolism syndrome following bone marrow harvesting.

    PubMed

    Baselga, J; Reich, L; Doherty, M; Gulati, S

    1991-06-01

    A case of fat embolism syndrome is reported following an uncomplicated bone marrow harvest. The presenting symptoms were restlessness, shortness of breath and arterial hypoxemia. A lung perfusion scan ruled out the presence of a lung thromboembolism. The patient received supportive therapy and recovered within a few hours. We speculate that the larger gauge needle (13 vs 15) used to aspirate the bone marrow may have represented increased trauma to the iliac crest leading to fat embolism. PMID:1873595

  8. Osteosarcoma after bone marrow transplantation.

    PubMed

    Ueki, Hideaki; Maeda, Naoko; Sekimizu, Masahiro; Tsukushi, Satoshi; Nishida, Yoshihiro; Horibe, Keizo

    2013-03-01

    Three children treated with bone marrow transplantation for acute lymphoblastic leukemia, Diamond-Blackfan anemia, and congenital amegakaryocytic thrombocytopenia developed secondary osteosarcoma in the left tibia at the age of 13, 13, and 9 years, respectively, at 51, 117, and 106 months after transplantation, respectively. Through treatment with chemotherapy and surgery, all 3 patients are alive without disease. We surveyed the literature and reviewed 10 cases of osteosarcoma after hematopoietic stem cell transplantation (SCT), including our 3 cases. Eight of the patients had received myeloablative total body irradiation before SCT. The mean interval from SCT to the onset of osteosarcoma was 6 years and 4 months, and the mean age at the onset of osteosarcoma was 14 years and 5 months. The primary site of the post-SCT osteosarcoma was the tibia in 6 of 10 cases, in contrast to de novo osteosarcoma, in which the most common site is the femur. At least 7 of the 10 patients are alive without disease. Osteosarcoma should be one of the items for surveillance in the follow-up of patients who undergo SCT. PMID:22995925

  9. Bone Marrow Immunity and Myelodysplasia

    PubMed Central

    Lambert, Claude; Wu, Yuenv; Aanei, Carmen

    2016-01-01

    Myelodysplastic syndrome (MDS) is characterized by an ineffective hematopoiesis with production of aberrant clones and a high cell apoptosis rate in bone marrow (BM). Macrophages are in charge of phagocytosis. Innate Immune cells and specific T cells are in charge of immunosurveillance. Little is known on BM cell recruitment and activity as BM aspirate is frequently contaminated with peripheral blood. But evidences suggest an active role of immune cells in protection against MDS and secondary leukemia. BM CD8+ CD28− CD57+ T cells are directly cytotoxic and have a distinct cytokine signature in MDS, producing TNF-α, IL-6, CCL3, CCL4, IL-1RA, TNFα, FAS-L, TRAIL, and so on. These tools promote apoptosis of aberrant cells. On the other hand, they also increase MDS-related cytopenia and myelofibrosis together with TGFβ. IL-32 produced by stromal cells amplifies NK cytotoxicity but also the vicious circle of TNFα production. Myeloid-derived suppressing cells (MDSC) are increased in MDS and have ambiguous role in protection/progression of the diseases. CD33 is expressed on hematopoietic stem cells on MDS and might be a potential target for biotherapy. MDS also has impact on immunity and can favor chronic inflammation and emergence of autoimmune disorders. BM is the site of hematopoiesis and thus contains a complex population of cells at different stages of differentiation from stem cells and early engaged precursors up to almost mature cells of each lineage including erythrocytes, megakaryocytes, myelo-monocytic cells (monocyte/macrophage and granulocytes), NK cells, and B cells. Monocytes and B cell finalize their maturation in peripheral tissues or lymph nodes after migration through the blood. On the other hand, T cells develop in thymus and are present in BM only as mature cells, just like other well vascularized tissues. BM precursors have a strong proliferative capacity, which is usually associated with a high risk for genetic errors, cell dysfunction, and

  10. Impact of bone marrow on respiratory disease.

    PubMed

    Rankin, Sara M

    2008-06-01

    The bone marrow is not only a site of haematopoiesis but also serves as an important reservoir for mature granulocytes and stem cells, including haematopoietic stem cells, mesenchymal stem cells and fibrocytes. In respiratory diseases, such as asthma and idiopathic pulmonary fibrosis these cells are mobilised from the bone marrow in response to blood-borne mediators and subsequently recruited to the lungs. Although the granulocytes contribute to the inflammatory reaction, stem cells may promote tissue repair or remodelling. Understanding the factors and molecular mechanisms that regulate the mobilisation of granulocytes and stem cells from the bone marrow may lead to the identification of novel therapeutic targets for the treatment of a wide range of respiratory disorders. PMID:18372214

  11. Comparison of bone marrow aspiration and bone marrow biopsy in neoplastic diseases.

    PubMed

    Hamid, G A; Hanbala, N

    2009-07-01

    Naturally trephine biopsies have definitive advantages over aspirates in case of dry tap bone marrow aspirates as a result of fibrosis or densely packed bone marrow by tumour cells and may be informative independent of cytology especially in bone marrow involvement by lymphomas and carcinomas. In this prospective descriptive study we aimed to compare between the bone marrow trephine biopsy (BMTB) and bone marrow aspirates (BMAs) regarding the detection rate of solid tumours, lymphoma and myeloma involvement of the bone marrow. The study was carried out in the department of pathology and Haematology-Oncology of Al-Gamhouria Teaching Hospital/Aden during the period between Jan 2005 to Dec 2005. A total of 32 patients with suspected or confirmed malignancy undergone both BMTB and BMA from the posterior superior iliac crest and both results were compared. We divided them into three groups: those with solid tumours (21) patients, lymphoma (7) patients and with MM (4) patients. Our results showed that BMA had a 47.6% sensitivity, 100.0% specificity, with positive predictive value (100%), and negative predictive value (50.0%). In solid tumours alone it had a sensitivity of (40.0%), 100% specificity, with positive predictive value (100%), and negative predictive value (64.7%). This gives the BMA a lower sensitivity in detecting solid tumour metastasis and lymphoma involvement in comparison to BMTB. In conclusion, any patient with suspected or confirmed cancer should undergo BMTB because of its high sensitivity compared to BMA. PMID:20194084

  12. 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.

  13. MR imaging of therapy-induced changes of bone marrow

    PubMed Central

    Henning, Tobias; Link, Thomas M.

    2006-01-01

    MR imaging of bone marrow infiltration by hematologic malignancies provides non-invasive assays of bone marrow cellularity and vascularity to supplement the information provided by bone marrow biopsies. This article will review the MR imaging findings of bone marrow infiltration by hematologic malignancies with special focus on treatment effects. MR imaging findings of the bone marrow after radiation therapy and chemotherapy will be described. In addition, changes in bone marrow microcirculation and metabolism after anti-angiogenesis treatment will be reviewed. Finally, new specific imaging techniques for the depiction of regulatory events that control blood vessel growth and cell proliferation will be discussed. Future developments are directed to yield comprehensive information about bone marrow structure, function and microenvironment. PMID:17021706

  14. [Allogenic bone marrow transplantation complications. Part II].

    PubMed

    Saloua, L; Tarek, B O; Abderrahman, A; Abdeladhim, B A

    2000-03-01

    Bone marrow transplantation increase the chances of cure of many hematology and also neoplasms cancers. The procedure is however a cause of expected mortality and morbidity. The complications are represented by mucocutaneous, toxicity graft versus host disease, veno-occlusive disease and most importantly injections consequences all this complications needs to be prevented and treated considering the risk associated to the moderling immunosuppression. PMID:11026816

  15. Liver disease after bone marrow transplantation.

    PubMed Central

    Farthing, M J; Clark, M L; Sloane, J P; Powles, R L; McElwain, T J

    1982-01-01

    Liver dysfunction occurs after bone marrow transplantation but the relative importance of graft versus host disease and other factors, such as infection, radiation, and drugs, has not been clearly established. We have studied liver status before and after bone marrow transplantation in 43 consecutive patients and have related this to survival and factors that are recognised to cause liver injury. Minor abnormalities of liver tests occurred in 21% of patients before grafting but this did not influence survival or the development of liver disease after transplantation. During the first 50 days after grafting, 83% of patients had abnormal liver tests which were more severe in patients who subsequently died. Alanine transaminase was significantly higher in non-survivors and appeared to predict survival early after transplantation. Only non-survivors developed clinical signs of liver disease. Severe liver disease was always associated with graft versus host disease and atypia of the small bile ducts was the most useful histological marker of hepatic involvement with this disease. Two of the patients with hepatic graft versus host disease also has hepatic veno-occlusive disease and three fatalities had opportunistic infection of the liver, although, in the latter, death was not due primarily to liver dysfunction. Previous hepatitis and androgen therapy could not be implicated as important causes of hepatic damage but chemotherapy for acute leukaemia and conditioning regimens for bone marrow transplantation appear to be the most important factors in the development of hepatic veno-occlusive disease. Images Fig. 3 Fig. 4 PMID:7042484

  16. Bone marrow manifestations in multicentric Castleman disease.

    PubMed

    Ibrahim, Hazem A H; Balachandran, Kirsty; Bower, Mark; Naresh, Kikkeri N

    2016-03-01

    This study aimed to document the morphological and immunophenotypic features, and describe the diagnostic features of bone marrow (BM) involvement in human herpes virus 8 Multicentric Castleman disease (HHV8-MCD). BM trephine biopsy (BMTB) specimens from 28 patients were revisited. Samples were evaluated for expression of CD3, CD20, CD138, CD68R, glycophorin C, CD42b, HHV8-latency-associated nuclear antigen (LANA1), Epstein-Barr virus-encoded small RNA and light chains. Presence of significant numbers of HHV8-LANA1(+) lymphoid/plasmacytic cells, noted in 10/28 cases, was indicative of BM involvement and was associated with low CD4 and CD8 counts in peripheral blood. The characteristic morphological appearance of MCD seen in lymph nodes is a rare finding in BMTB. 4/5 cases with lymphoid aggregates were involved by MCD, whereas 6/23 cases without lymphoid aggregates were involved by MCD (P = 0·023). 9/18 cases with hypercellular marrow were involved by MCD, whilst only 1/8 cases with normo/hypocellular marrow showed involvement by MCD (P = 0·070). While 9/21 cases with increased marrow reticulin were involved by MCD, none of the cases with no increase in reticulin were involved by MCD (P = 0·080). Reactive plasmacytosis is a frequent finding. We conclude that bone marrow is involved in a significant proportion of patients with MCD (36%), and involvement can be identified by HHV8-LANA1 immunohistochemistry. PMID:26817834

  17. Bone marrow and splenic histology in hairy cell leukaemia.

    PubMed

    Wotherspoon, Andrew; Attygalle, Ayoma; Mendes, Larissa Sena Teixeira

    2015-12-01

    Hairy cell leukaemia is a rare chronic neoplastic B-cell lymphoproliferation that characteristically involves blood, bone marrow and spleen with liver, lymph node and skin less commonly involved. Histologically, the cells have a characteristic appearance with pale/clear cytoplasm and round or reniform nuclei. In the spleen, the infiltrate involves the red pulp and is frequently associated with areas of haemorrhage (blood lakes). The cells stain for B-cell related antigens as well as with antibodies against tartrate-resistant acid phosphatase, DBA44 (CD72), CD11c, CD25, CD103, CD123, cyclin D1 and annexin A1. Mutation of BRAF -V600E is present and antibody to the mutant protein can be used as a specific marker. Bone marrow biopsy is essential in the initial assessment of disease as the bone marrow may be inaspirable or unrepresentative of degree of marrow infiltration as a result of the tumour associated fibrosis preventing aspiration of the tumour cell component. Bone marrow biopsy is important in the assessment of therapy response but in this context staining for CD11c and Annexin A1 is not helpful as they are also markers of myeloid lineage and identification of low level infiltration may be obscured. In this context staining for CD20 may be used in conjunction with morphological assessment and staining of serial sections for cyclin D1 and DBA44 to identify subtle residual infiltration. Staining for CD79a and CD19 is not recommended as these antibodies will identify plasma cells and can lead to over-estimation of disease. Staining for CD20 should not be used in patients following with anti-CD20 based treatments. Down regulation of cyclin D1 and CD25 has been reported in patients following BRAF inhibitor therapy and assessment of these antigens should not be used in this context. Histologically, hairy cell leukaemia needs to be distinguished from other B-cell lymphoproliferations associated with splenomegaly including splenic marginal zone lymphoma, splenic

  18. Post-bone marrow transplant patient management.

    PubMed Central

    Poliquin, C. M.

    1990-01-01

    Increasingly, bone marrow transplant (BMT) is the treatment of choice for certain hematologic diseases. BMT is, however, a risky procedure with many potentially serious complications. Some complications are the result of the conditioning regimen, a stage of transplantation that includes large doses of chemotherapy and/or radiation therapy. Conditioning-induced neutropenia and thrombocytopenia often result in infection, bleeding, and mucositis. Veno-occlusive disease (VOD), a chemotherapy-induced hepatotoxicity, can cause a mild to severe form of liver disease. Other complications are directly attributable to the engrafted new marrow. Graft-versus-host disease, a rejection process initiated by immunocompetent donor T lymphocytes, is a complication frequently observed in allogeneic BMT. Approximately 14-28 days after the day of transplant, signs of engraftment begin to appear. When specific discharge criteria are met, the BMT patient is discharged from the hospital. Specific follow-up medical care is ongoing for about one year after BMT. PMID:2293508

  19. Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

    PubMed Central

    Zahr, Abdallah Abou; Salama, Mohamed E.; Carreau, Nicole; Tremblay, Douglas; Verstovsek, Srdan; Mesa, Ruben; Hoffman, Ronald; Mascarenhas, John

    2016-01-01

    Bone marrow fibrosis is a central pathological feature and World Health Organization major diagnostic criterion of myelofibrosis. Although bone marrow fibrosis is seen in a variety of malignant and non-malignant disease states, the deposition of reticulin and collagen fibrosis in the bone marrow of patients with myelofibrosis is believed to be mediated by the myelofibrosis hematopoietic stem/progenitor cell, contributing to an impaired microenvironment favoring malignant over normal hematopoiesis. Increased expression of inflammatory cytokines, lysyl oxidase, transforming growth factor-β, impaired megakaryocyte function, and aberrant JAK-STAT signaling have all been implicated in the pathogenesis of bone marrow fibrosis. A number of studies indicate that bone marrow fibrosis is an adverse prognostic variable in myeloproliferative neoplasms. However, modern myelofibrosis prognostication systems utilized in risk-adapted treatment approaches do not include bone marrow fibrosis as a prognostic variable. The specific effect on bone marrow fibrosis of JAK2 inhibition, and other rationally based therapies currently being evaluated in myelofibrosis, has yet to be fully elucidated. Hematopoietic stem cell transplantation remains the only curative therapeutic approach that reliably results in resolution of bone marrow fibrosis in patients with myelofibrosis. Here we review the pathogenesis, biological consequences, and prognostic impact of bone marrow fibrosis. We discuss the rationale of various anti-fibrogenic treatment strategies targeting the clonal hematopoietic stem/progenitor cell, aberrant signaling pathways, fibrogenic cytokines, and the tumor microenvironment. PMID:27252511

  20. Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies.

    PubMed

    Zahr, Abdallah Abou; Salama, Mohamed E; Carreau, Nicole; Tremblay, Douglas; Verstovsek, Srdan; Mesa, Ruben; Hoffman, Ronald; Mascarenhas, John

    2016-06-01

    Bone marrow fibrosis is a central pathological feature and World Health Organization major diagnostic criterion of myelofibrosis. Although bone marrow fibrosis is seen in a variety of malignant and non-malignant disease states, the deposition of reticulin and collagen fibrosis in the bone marrow of patients with myelofibrosis is believed to be mediated by the myelofibrosis hematopoietic stem/progenitor cell, contributing to an impaired microenvironment favoring malignant over normal hematopoiesis. Increased expression of inflammatory cytokines, lysyl oxidase, transforming growth factor-β, impaired megakaryocyte function, and aberrant JAK-STAT signaling have all been implicated in the pathogenesis of bone marrow fibrosis. A number of studies indicate that bone marrow fibrosis is an adverse prognostic variable in myeloproliferative neoplasms. However, modern myelofibrosis prognostication systems utilized in risk-adapted treatment approaches do not include bone marrow fibrosis as a prognostic variable. The specific effect on bone marrow fibrosis of JAK2 inhibition, and other rationally based therapies currently being evaluated in myelofibrosis, has yet to be fully elucidated. Hematopoietic stem cell transplantation remains the only curative therapeutic approach that reliably results in resolution of bone marrow fibrosis in patients with myelofibrosis. Here we review the pathogenesis, biological consequences, and prognostic impact of bone marrow fibrosis. We discuss the rationale of various anti-fibrogenic treatment strategies targeting the clonal hematopoietic stem/progenitor cell, aberrant signaling pathways, fibrogenic cytokines, and the tumor microenvironment. PMID:27252511

  1. Bone marrow and bone marrow derived mononuclear stem cells therapy for the chronically ischemic myocardium

    SciTech Connect

    Waksman, Ron; Baffour, Richard

    2003-09-01

    Bone marrow stem cells have been shown to differentiate into various phenotypes including cardiomyocytes, vascular endothelial cells and smooth muscle. Bone marrow stem cells are mobilized and home in to areas of injured myocardium where they are involved in tissue repair. In addition, bone marrow secretes multiple growth factors, which are essential for angiogenesis and arteriogenesis. In some patients, these processes are not enough to avert clinical symptoms of ischemic disease. Therefore, in vivo administration of an adequate number of stem cells would be a significant therapeutic advance. Unfractionated bone marrow derived mononuclear stem cells, which contain both hematopoietic and nonhematopoietic cells may be more appropriate for cell therapy. Studies in animal models suggest that implantation of different types of stem cells improve angiogenesis and arteriogenesis, tissue perfusion as well as left ventricular function. Several unanswered questions remain. For example, the optimal delivery approach, dosage and timing of the administration of cell therapy as well as durability of improvements need to be studied. Early clinical studies have demonstrated safety and feasibility of various cell therapies in ischemic disease. Randomized, double blind and placebo-controlled clinical trials need to be completed to determine the effectiveness of stem cell.

  2. Metastatic thymoma involving the bone marrow

    PubMed Central

    Wenceslao, Stella; Krause, John R.

    2016-01-01

    Although relatively rare, thymomas can be involved in a considerable variety of clinical presentations. Clinicians should be mindful of the breadth of associations with other diseases, including autoimmune disorders and many secondary nonthymic malignancies. For the pathologist, knowledge of the extremely varied histopathologic presentation of thymoma is vital to formulate a proper differential, workup, and diagnosis. The presented case illustrates the finding of very rare metastatic thymoma involvement of bone marrow, identified during evaluation for pancytopenia. The history of prior prostate cancer and an uncharacterized pancreatic lesion, as well as the familial presentation, also suggests a possible underlying hereditary syndrome. PMID:26722174

  3. The inherited bone marrow failure syndromes.

    PubMed

    Chirnomas, S Deborah; Kupfer, Gary M

    2013-12-01

    Molecular pathogenesis may be elucidated for inherited bone marrow failure syndromes (IBMFS). The study and presentation of the details of their molecular biology and biochemistry is warranted for appropriate diagnosis and management of afflicted patients and to identify the physiology of the normal hematopoiesis and mechanisms of carcinogenesis. Several themes have emerged within each subsection of IBMFS, including the ribosomopathies, which include ribosome assembly and ribosomal RNA processing. The Fanconi anemia pathway has become interdigitated with the familial breast cancer syndromes. In this article, the diseases that account for most IBMFS diagnoses are analyzed. PMID:24237972

  4. Autologous bone marrow transplantation by photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Gulliya, Kirpal S.

    1992-06-01

    Simultaneous exposure of Merocyanine 540 dye containing cultured tumor cells to 514-nm laser light (93.6 J/cm2) results in virtually complete cell destruction. Under identical conditions, 40% of the normal progenitor (CFU-GM) cells survive the treatment. Laser- photoradiation treated, cultured breast cancer cells also were killed, and living tumor cells could not be detected by clonogenic assays or by anti-cytokeratin monoclonal antibody method. Thus, laser photoradiation therapy could be useful for purging of contaminating tumor cells from autologous bone marrow.

  5. Marrow Fat and Bone: Review of Clinical Findings

    PubMed Central

    Schwartz, Ann V.

    2015-01-01

    With growing interest in the connection between fat and bone, there has been increased investigation of the relationship with marrow fat in particular. Clinical research has been facilitated by the development of non-invasive methods to measure bone marrow fat content and composition. Studies in different populations using different measurement techniques have established that higher marrow fat is associated with lower bone density and prevalent vertebral fracture. The degree of unsaturation in marrow fat may also affect bone health. Although other fat depots tend to be strongly correlated, marrow fat has a distinct pattern, suggesting separate mechanisms of control. Longitudinal studies are limited, but are crucial to understand the direct and indirect roles of marrow fat as an influence on skeletal health. With greater appreciation of the links between bone and energy metabolism, there has been growing interest in understanding the relationship between marrow fat and bone. It is well established that levels of marrow fat are higher in older adults with osteoporosis, defined by either low bone density or vertebral fracture. However, the reasons for and implications of this association are not clear. This review focuses on clinical studies of marrow fat and its relationship to bone. PMID:25870585

  6. Investigation of effect of variations in bone fraction and red marrow cellularity on bone marrow dosimetry in radio-immunotherapy

    NASA Astrophysics Data System (ADS)

    Wilderman, S. J.; Roberson, P. L.; Bolch, W. E.; Dewaraja, Y. K.

    2013-07-01

    A method is described for computing patient-specific absorbed dose rates to active marrow which accounts for spatial variation in bone volume fraction and marrow cellularity. A module has been added to the 3D Monte Carlo dosimetry program DPM to treat energy deposition in the components of bone spongiosa distinctly. Homogeneous voxels in regions containing bone spongiosa (as defined on CT images) are assumed to be comprised only of bone, active (red) marrow and inactive (yellow) marrow. Cellularities are determined from biopsy, and bone volume fractions are computed from cellularities and CT-derived voxel densities. Electrons are assumed to deposit energy locally in the three constituent components in proportions determined by electron energy absorption fractions which depend on energy, cellularity, and bone volume fraction, and which are either taken from the literature or are derived from Monte Carlo simulations using EGS5. Separate algorithms are used to model primary β particles and secondary electrons generated after photon interactions. Treating energy deposition distinctly in bone spongiosa constituents leads to marrow dosimetry results which differ from homogeneous spongiosa dosimetry by up to 20%. Dose rates in active marrow regions with cellularities of 20, 50, and 80% can vary by up to 20%, and can differ by up to 10% as a function of bone volume fraction. Dose to bone marrow exhibits a strong dependence on marrow cellularity and a potentially significant dependence on bone volume fraction.

  7. Skeletal cell fate decisions within periosteum and bone marrow during bone regeneration.

    PubMed

    Colnot, Céline

    2009-02-01

    Bone repair requires the mobilization of adult skeletal stem cells/progenitors to allow deposition of cartilage and bone at the injury site. These stem cells/progenitors are believed to come from multiple sources including the bone marrow and the periosteum. The goal of this study was to establish the cellular contributions of bone marrow and periosteum to bone healing in vivo and to assess the effect of the tissue environment on cell differentiation within bone marrow and periosteum. Results show that periosteal injuries heal by endochondral ossification, whereas bone marrow injuries heal by intramembranous ossification, indicating that distinct cellular responses occur within these tissues during repair. [corrected] Next, lineage analyses were used to track the fate of cells derived from periosteum, bone marrow, and endosteum, a subcompartment of the bone marrow. Skeletal progenitor cells were found to be recruited locally and concurrently from periosteum and/or bone marrow/endosteum during bone repair. Periosteum and bone marrow/endosteum both gave rise to osteoblasts, whereas the periosteum was the major source of chondrocytes. Finally, results show that intrinsic and environmental signals modulate cell fate decisions within these tissues. In conclusion, this study sheds light into the origins of skeletal stem cells/progenitors during bone regeneration and indicates that periosteum, endosteum, and bone marrow contain pools of stem cells/progenitors with distinct osteogenic and chondrogenic potentials that vary with the tissue environment. PMID:18847330

  8. Vertebral hyperemia associated with bone marrow insult and recovery

    SciTech Connect

    Klein, H.A.; Bolden, R.O.; Simone, F.J.

    1984-06-01

    A 15-year-old boy with rhabdoid sarcoma received chemotherapy, which was followed by bone marrow depression, massive nosebleeds and, finally, hematologic recovery. On both hepatobiliary and renal scintigraphy, prominent vertebral activity was present in early images. Correlation with his clinical course suggests that the findings reflect hyperemia due to marrow insult and recovery. Radionuclide imaging to detect hyperemia may be a useful probe for drug effects on hematopoietic bone marrow.

  9. Bone marrow lesions and subchondral bone pathology of the knee.

    PubMed

    Kon, Elizaveta; Ronga, Mario; Filardo, Giuseppe; Farr, Jack; Madry, Henning; Milano, Giuseppe; Andriolo, Luca; Shabshin, Nogah

    2016-06-01

    Bone marrow lesions (BMLs) around the knee are a common magnetic resonance imaging (MRI) finding. However, despite the growing interest on BMLs in multiple pathological conditions, they remain controversial not only for the still unknown role in the etiopathological processes, but also in terms of clinical impact and treatment. The differential diagnosis includes a wide range of conditions: traumatic contusion and fractures, cyst formation and erosions, hematopoietic and infiltrated marrow, developmental chondroses, disuse and overuse, transient bone marrow oedema syndrome and, lastly, subchondral insufficiency fractures and true osteonecrosis. Regardless the heterogeneous spectrum of these pathologies, a key factor for patient management is the distinction between reversible and irreversible conditions. To this regard, MRI plays a major role, leading to the correct diagnosis based on recognizable typical patterns that have to be considered together with coexistent abnormalities, age, and clinical history. Several treatment options have been proposed, from conservative to surgical approaches. In this manuscript the main lesion patterns and their management have been analysed to provide the most updated evidence for the differential diagnosis and the most effective treatment. PMID:27075892

  10. [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. PMID:18173180

  11. Pathophysiological role of enhanced bone marrow adipogenesis in diabetic complications

    PubMed Central

    Piccinin, Meghan A; Khan, Zia A

    2014-01-01

    Diabetes leads to complications in select organ systems primarily by disrupting the vasculature of the target organs. These complications include both micro- (cardiomyopathy, retinopathy, nephropathy, and neuropathy) and macro-(atherosclerosis) angiopathies. Bone marrow angiopathy is also evident in both experimental models of the disease as well as in human diabetes. In addition to vascular disruption, bone loss and increased marrow adiposity have become hallmarks of the diabetic bone phenotype. Emerging evidence now implicates enhanced marrow adipogenesis and changes to cellular makeup of the marrow in a novel mechanistic link between various secondary complications of diabetes. In this review, we explore the mechanisms of enhanced marrow adipogenesis in diabetes and the link between changes to marrow cellular composition, and disruption and depletion of reparative stem cells. PMID:26317050

  12. The Inherited Bone Marrow Failure Syndromes

    PubMed Central

    Chirnomas, S. Deborah; Kupfer, Gary M

    2013-01-01

    In spite of the rarity of inherited bone marrow failure syndromes (IBMFS), they represent diseases for which the molecular pathogenesis may be elucidated. Their study and presentation of the details of their molecular biology and biochemistry is warranted not only for appropriate diagnosis and management of afflicted patients but also because they lend clues to the normal physiology of the normal hematopoiesis and, in many cases, mechanisms of carcinogenesis. Several themes have emerged within each subsection of IBMFS, including the ribosomopathies that entail both ribosome assembly as well as ribosomal RNA processing. The Fanconi anemia (FA) pathway itself has become interdigitated with the familial breast cancer syndromes. The sections that follow present a more detailed analysis of the diseases that account for the majority of IBMFS diagnoses. PMID:24237972

  13. Lung function after bone marrow grafting

    SciTech Connect

    Depledge, M.H.; Barrett, A.; Powles, R.L.

    1983-02-01

    Results of a prospective lung function study are presented for 48 patients with acute myeloid leukemia (AML) treated with total body irradiation (TBI) and bone marrow transplantation (BMT) at the Royal Marsden Hospital between 1978 and 1980. Patients with active disease or who were in remission following cytoreductive chemotherapy had mildly impaired gas exchange prior to grafting. After TBI and BMT all patients studied developed progressive deterioration of lung function during the first 100 days, although these changes were subclinical. Infection and graft-versus-host disease (GvHD) were associated with further worsening of restrictive ventilatory defects and diffusing capacity (D/sub L/CO). Beyond 100 days, ventilatory ability returned to normal and gas transfer improved, although it failed to reach pre-transplant levels. There was no evidence of progressive pulmonary fibrosis during the first year after grafting.

  14. [Current problems in pediatric bone marrow transplantation].

    PubMed

    Kato, S

    1993-05-01

    Bone marrow transplantation (BMT) has been increasingly applied to a variety of potentially fatal diseases in childhood. However, trends of indication of BMT are changing because chemotherapy in leukemia and immunosuppressive therapy with/without colony stimulating factor in aplastic anemia are improving. Several progresses have been noted in matched unrelated BMT and peripheral blood stem cell transplantation as well as in sibling BMT or autologous BMT. Many efforts are being made to decrease rejection rate or leukemia relapse and to improve quality of life by new conditioning regimens. Attempts to induce GVL effects or syngeneic GVHD are currently under progress. The quality of life in long term surviving children are generally good and acceptable, although delay in growth, infertility, cataract and obstructive lung disease are seen in a few patients. PMID:8315825

  15. Bone marrow mesenchymal stem cells and TGF-β signaling in bone remodeling

    PubMed Central

    Crane, Janet L.; Cao, Xu

    2014-01-01

    During bone resorption, abundant factors previously buried in the bone matrix are released into the bone marrow microenvironment, which results in recruitment and differentiation of bone marrow mesenchymal stem cells (MSCs) for subsequent bone formation, temporally and spatially coupling bone remodeling. Parathyroid hormone (PTH) orchestrates the signaling of many pathways that direct MSC fate. The spatiotemporal release and activation of matrix TGF-β during osteoclast bone resorption recruits MSCs to bone-resorptive sites. Dysregulation of TGF-β alters MSC fate, uncoupling bone remodeling and causing skeletal disorders. Modulation of TGF-β or PTH signaling may reestablish coupled bone remodeling and be a potential therapy. PMID:24487640

  16. A Method for Generation of Bone Marrow-Derived Macrophages from Cryopreserved Mouse Bone Marrow Cells

    PubMed Central

    Lima, Djalma S.; Zamboni, Dario S.

    2010-01-01

    The broad use of transgenic and gene-targeted mice has established bone marrow-derived macrophages (BMDM) as important mammalian host cells for investigation of the macrophages biology. Over the last decade, extensive research has been done to determine how to freeze and store viable hematopoietic human cells; however, there is no information regarding generation of BMDM from frozen murine bone marrow (BM) cells. Here, we establish a highly efficient protocol to freeze murine BM cells and further generate BMDM. Cryopreserved murine BM cells maintain their potential for BMDM differentiation for more than 6 years. We compared BMDM obtained from fresh and frozen BM cells and found that both are similarly able to trigger the expression of CD80 and CD86 in response to LPS or infection with the intracellular bacteria Legionella pneumophila. Additionally, BMDM obtained from fresh or frozen BM cells equally restrict or support the intracellular multiplication of pathogens such as L. pneumophila and the protozoan parasite Leishmania (L.) amazonensis. Although further investigation are required to support the use of the method for generation of dendritic cells, preliminary experiments indicate that bone marrow-derived dendritic cells can also be generated from cryopreserved BM cells. Overall, the method described and validated herein represents a technical advance as it allows ready and easy generation of BMDM from a stock of frozen BM cells. PMID:21179419

  17. Orchiectomy increases bone marrow interleukin-6 levels in mice.

    PubMed

    Zhang, J; Pugh, T D; Stebler, B; Ershler, W B; Keller, E T

    1998-03-01

    Interleukin-6 (IL-6) appears to be an important factor in disease states associated with bone resorption. There is both in vitro and in vivo evidence supporting the fact that androgens down-regulate interleukin-6 production. These observations, in combination with the fact that osteoblasts and bone marrow stromal cells produce IL-6, led us to hypothesize that orchiectomy-induced androgen loss will result in increased IL-6 expression in the bone microenvironment. To prove our hypothesis we assessed the effect of orchiectomy on IL-6 protein and mRNA expression in bone marrow and spleen. We found that orchiectomy was associated with increased serum IL-6 levels at 3 and 28 days postsurgery. Phorbol ester-stimulated IL-6 levels were also higher in supernatants from bone marrow and spleen cell cultures from orchiectomized mice compared with unoperated or sham-operated mice. Additionally, we found that steady state IL-6 mRNA levels were increased in bone marrow but not spleen cells. Finally, we found that orchiectomized mice had splenomegaly and increased bone marrow cellularity. Histopathology of the spleen revealed lymphoid hyperplasia accompanied by a marked mononuclear cell infiltration of the red pulp. We conclude that orchiectomy induces IL-6 expression in the bone marrow. These findings suggest that endocrine and cytokine interactions contribute to bone pathophysiology. PMID:9501955

  18. A case of early gastric cancer with bone metastases: are bone marrow micrometastases significant?

    PubMed

    Soufleris, K; Pilpilidis, I; Tzilves, D; Moschos, J; Gatopoulou, A; Patakiouta, F; Tarpagos, A; Katsos, I

    2007-01-01

    Gastric adenocarcinoma is currently the 14th cause of death worldwide. Early gastric cancer, defined as cancer not penetrating deeper than the submucosa, is considered to carry an excellent prognosis with 5-year survival rates reaching more than 90%. Cases of bone metastases due to intramucosal gastric cancer are very rarely described. A case of a 70-year old male presenting with confirmed bone metastases 7 years after a curative resection for a mucosal gastric carcinoma is discussed. The patient was investigated with bone marrow biopsy and bone scan and showed no other signs of disease. The clinicopathologic features included poor differentiation, signet ring cells presence, no lymph node involvement and a negative second laparotomy two years after the initial surgery. Studies concerning the presence of residual disease in the form of bone marrow micrometastases are briefly reviewed emphasizing that intramucosal gastric cancer still carries the p sibility for metastasis, many years after a curative resection, mandating long term alertness from the attending physician. PMID:17715641

  19. Molecular relapse in chronic myelogenous leukemia patients after bone marrow transplantation detected by polymerase chain reaction

    SciTech Connect

    Sawyers, C.L.; Timson, L.; Clark, S.S.; Witte, O.N.; Champlin, R. ); Kawasaki, E.S. )

    1990-01-01

    Relapse of chronic myelogenous leukemia after bone marrow transplantation can be detected by using clinical, cytogenetic, or molecular tools. A modification of the polymerase chain reaction can be used in patients to detect low levels of the BCR-ABL-encoded mRNA transcript, a specific marker for chronic myelogenous leukemia. Early detection of relapse after bone marrow transplantation could potentially alter treatment decisions. The authors prospectively evaluated 19 patients for evidence of molecular relapse, cytogenetic relapse, and clinical relapse after bone marrow transplantation. They used the polymerase chain reaction to detect residual BCR-ABL mRNA in patients followed up to 45 months after treatment and found 4 patients with BCR-ABL mRNA expression following bone marrow transplantation. Fifteen patients did not express detectable BCR-ABL mRNA. All 19 patients remain in clinical remission. In this prospective study of chronic myelogenous leukemia patients treated with bone marrow transplantation, molecular relapse preceded cytogenetic relapse in those patients who persistently express BCR-ABL mRNA. They recommend using standard clinical and cytogenetic testing to make patient care decisions until further follow-up determines the clinical outcome of those patients with residual BCR-ABL mRNA transcripts detected by polymerase chain reaction.

  20. Bone and bone-marrow blood flow in chronic granulocytic leukemia and primary myelofibrosis

    SciTech Connect

    Lahtinen, R.; Lahtinen, T.; Romppanen, T.

    1982-03-01

    Blood flow in hematopoietic bone marrow and in nonhematopoietic bone has been measured with a Xe-133 washout method in 20 patients with chronic granulocytic leukemia (CGL) and in seven with primary myelofibrosis. Age-matched healthy persons served as controls. Bone-marrow blood flow in CGL was dependent upon the phase of the disease. In the metamorphosis phase, bone-marrow blood flow was high compared with that in the well-controlled phase. Apart from the initial phase, the mean values for bone blood flow in CGL were increased compared with the values of the healthy controls. In myelofibrosis the bone blood flow was also increased. Bone-marrow blood flow in these diseases was dependent upon the cellularity of bone marrow as measured morphometrically.

  1. Bone Marrow Adipose Tissue: A New Player in Cancer Metastasis to Bone

    PubMed Central

    Morris, Emma V.; Edwards, Claire M.

    2016-01-01

    The bone marrow is a favored site for a number of cancers, including the hematological malignancy multiple myeloma, and metastasis of breast and prostate cancer. This specialized microenvironment is highly supportive, not only for tumor growth and survival but also for the development of an associated destructive cancer-induced bone disease. The interactions between tumor cells, osteoclasts and osteoblasts are well documented. By contrast, despite occupying a significant proportion of the bone marrow, the importance of bone marrow adipose tissue is only just emerging. The ability of bone marrow adipocytes to regulate skeletal biology and hematopoiesis, combined with their metabolic activity, endocrine functions, and proximity to tumor cells means that they are ideally placed to impact both tumor growth and bone disease. This review discusses the recent advances in our understanding of how marrow adipose tissue contributes to bone metastasis and cancer-induced bone disease. PMID:27471491

  2. Endocrine complications following pediatric bone marrow transplantation.

    PubMed

    Ho, Josephine; Lewis, Victor; Guilcher, Gregory M T; Stephure, David K; Pacaud, Danièle

    2011-01-01

    Pediatric bone marrow transplantation (BMT) for various diseases can lead to endocrine system dysfunction owing to preparative regimens involving chemotherapy and radiation therapy. We assessed the prevalence of post-BMT endocrine complications in children treated at the Alberta Children's Hospital (ACH) from 1991 to 2001. Time of onset of endocrine dysfunction, underlying disease processes, chemotherapy, radiation therapy and age at BMT were characterized. Subjects of <18 years of age at the time of allogeneic or autologous BMT for whom 1-year follow-up through the ACH and a chart were available for review were included in the study. Subjects with a pre-existing endocrine condition were excluded. Of the 194 pediatric BMT procedures performed at the ACH between January 1, 1991 and December 31, 2001, 150 complete charts were available for review. Sixty five subjects received follow-up care at other centers and were excluded. Therefore, a total of 85 subjects were included in the review. The prevalence of endocrine complications identified was: primary hypothyroidism 1.2%, compensated hypothyroidism 7.0%, hyperthyroidism 2.4%, hypergonadotrophic hypogonadism 22.4%, abnormal bone density 2.4%, and secondary diabetes mellitus 1.2%. These findings emphasize the need to screen for endocrine system dysfunction, particularly hypergonadotrophic hypogonadism, in children who have undergone BMT. Children need long-term follow-up so that endocrine complications can be diagnosed and treated promptly. PMID:21823531

  3. Marrow-tumor interactions: the role of the bone marrow in controlling chemically induced tumors

    SciTech Connect

    Rosse, C

    1980-01-01

    This report summarizes work done to evaluate the role of the bone marrow in tumor growth regulation. Work done with the MCA tumor showed that several subclasses of mononuclear bone marrow cells (e.g. natural regulatory cell, NRC) play a major role in the regulation of tumor growth. Experiments with the spontaneous CE mammary carcinoma system illustrate that a rapid growth of certain neoplasms may be due to the fact that through some as yet undefined mechanism the tumor eliminates mononuclear cells in the bone marrow of the host and stops their production. (KRM)

  4. Jaw bone marrow-derived osteoclast precursors internalize more bisphosphonate than long-bone marrow precursors.

    PubMed

    Vermeer, Jenny A F; Jansen, Ineke D C; Marthi, Matangi; Coxon, Fraser P; McKenna, Charles E; Sun, Shuting; de Vries, Teun J; Everts, Vincent

    2013-11-01

    Bisphosphonates (BPs) are widely used in the treatment of several bone diseases, such as osteoporosis and cancers that have metastasized to bone, by virtue of their ability to inhibit osteoclastic bone resorption. Previously, it was shown that osteoclasts present at different bone sites have different characteristics. We hypothesized that BPs could have distinct effects on different populations of osteoclasts and their precursors, for example as a result of a different capacity to endocytose the drugs. To investigate this, bone marrow cells were isolated from jaw and long bone from mice and the cells were primed to differentiate into osteoclasts with the cytokines M-CSF and RANKL. Before fusion occurred, cells were incubated with fluorescein-risedronate (FAM-RIS) for 4 or 24h and uptake was determined by flow cytometry. We found that cultures obtained from the jaw internalized 1.7 to 2.5 times more FAM-RIS than long-bone cultures, both after 4 and 24h, and accordingly jaw osteoclasts were more susceptible to inhibition of prenylation of Rap1a after treatment with BPs for 24h. Surprisingly, differences in BP uptake did not differentially affect osteoclastogenesis. This suggests that jaw osteoclast precursors are less sensitive to bisphosphonates after internalization. This was supported by the finding that gene expression of the anti-apoptotic genes Bcl-2 and Bcl-xL was higher in jaw cells than long bone cells, suggesting that the jaw cells might be more resistant to BP-induced apoptosis. Our findings suggest that bisphosphonates have distinct effects on both populations of osteoclast precursors and support previous findings that osteoclasts and precursors are bone-site specific. This study may help to provide more insights into bone-site-specific responses to bisphosphonates. PMID:23962725

  5. 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. PMID:26767542

  6. 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. PMID:27074509

  7. [Bone marrow involvement in ovarian cancer determined by immunohistochemical methods].

    PubMed

    Gabriel, M; Obrebowska, A; Spaczyński, M

    2000-01-01

    Atypical epithelial cells in the bone marrow of patients with ovarian cancer were evaluated using immunohistochemical techniques. We investigated cytospin preparations of bone marrow taken from 9 women with benign ovarian tumors and 59 women with malignant ovarian tumors. Two monoclonal antibodies (NCL-C11 and NCL-CA 125) were used. With both antibodies we were able to detect keratin and CA 125 antigen expression in the bone marrow of 9 (18.4%) of the patients with ovarian cancer. With regard to the wide histological differentiation of ovarian carcinomas, the presence of atypical epithelial cells in the bone marrow was required as a prognostic factor for survival and relapses. This should be investigated in a larger study group. PMID:11326158

  8. Understanding Bone Marrow Transplantation as a Treatment Option

    MedlinePlus

    ... you have had, and your overall health. Transplant Process A bone marrow or cord blood transplant is ... The Transplant Process . For more about the search process, HLA matching, and steps of a transplant, such ...

  9. Technetium-99m antimony colloid for bone-marrow imaging

    SciTech Connect

    Martindale, A.A.; Papadimitriou, J.M.; Turner, J.H.

    1980-11-01

    Technetium-99m antimony colloid was prepared in our laboratory for bone-marrow imaging. Optimal production of colloid particles of size range 1 to 13 nm was achieved by the use of polyvinylpyrrolidone of mol. wt. 44,000. Electron microscopy was used to size the particles. Studies in rabbits showed exclusive concentration in the subendothelial dendritic phagocytes of the bone marrow. Pseudopods from these cells were found to traverse interendothelial junctions and concentrate colloid from the sinusoids. Imaging studies of bone marrow in rabbits showed the superiority of the Tc-99m antimony colloid over the much larger colloidal particle of Tc-99m sulfur colloid. Tissue distribution studies in the rat confirmed that bone-marrow uptake of Tc-99m antimony colloid was greater than that of Tc-99m sulfur colloid, although blood clearance was much slower.

  10. Bone Marrow Diseases - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Bone Marrow Diseases URL of this page: https://medlineplus.gov/languages/bonemarrowdiseases.html Other topics A-Z A B ...

  11. Bone Marrow Diseases - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Bone Marrow Diseases URL of this page: https://www.nlm.nih.gov/medlineplus/languages/bonemarrowdiseases.html Other topics A-Z A B ...

  12. Memory T-cell competition for bone marrow seeding.

    PubMed

    Di Rosa, Francesca; Santoni, Angela

    2003-03-01

    The presence in the bone marrow of memory CD8 T cells is well recognized. However, it is still largely unclear how T-cell migration from the lymphoid periphery to the bone marrow is regulated. In the present report, we show that antigen-specific CD4 T cells, as well as antigen-specific CD8 T cells, localize to the bone marrow of immunized mice, and are sustained there over long periods of time. To investigate the rules governing T-cell migration to the bone marrow, we generated chimeric mice in which the lymphoid periphery contained two genetically or phenotypically distinct groups of T cells, one of which was identical to the host. We then examined whether a distinct type of T cell had an advantage over the others in the colonization of bone marrow. Our results show that whereas ICAM1 and CD18 molecules are both involved in homing to lymph nodes, neither is crucial for T-cell bone marrow colonization. We also observed that memory-phenotype CD44high T cells, but not virgin-type CD44-/low T cells, preferentially home to the bone marrow upon adoptive transfer to normal young mice, but not to thymectomized old recipients where an existing memory T-cell pool precludes their free access. Thus, T-cell colonization of the bone marrow uses distinct molecules from those implicated in lymph node homing, and is regulated both by the properties of the T cell and by the competitive efficacy of other T cells inhabiting the same, saturable niche. This implies that the homing potential of an individual lymphocyte is not merely an intrinsic property of the cell, but rather a property of the lymphoid system taken as a whole. PMID:12603595

  13. A marker chromosome in post-transplant bone marrow.

    PubMed

    Morsberger, Laura; Powell, Kerry; Ning, Yi

    2016-01-01

    Detection of small supernumerary marker chromosomes in karyotype analysis represents a diagnostic challenge. While such markers are usually detected during cytogenetic studies of constitutional chromosome abnormalities, they have also been found in specimens submitted from patients with acquired malignancies. We report here the detection of a marker chromosome in a bone marrow specimen from a patient who received a bone marrow transplantation. We discuss the importance of proper characterization and interpretation of marker chromosomes in clinical practice. PMID:27252781

  14. Bone Marrow Negative Visceral Leishmaniasis in an Adolescent Male

    PubMed Central

    Jetley, S; Rana, S; Khan, S; Zeeba, JS; Hassan, MJ; Kapoor, P

    2013-01-01

    Visceral Leishmaniasis or Kala Azar is endemic in certain regions of India. In endemic areas, the constellation of fever, progressive weight loss, weakness, pronounced splenomegaly, anemia, leukopenia, and hypergammaglobulinemia is highly suggestive of visceral leishmaniasis. Demonstration of the parasite in liver, splenic or bone marrow aspirates is confirmatory. We present a case in which Leishmania donovani (LD) bodies were demonstrated on splenic aspirate. We were unable to demonstrate LD bodies on bone marrow aspiration. PMID:23682278

  15. Activation of bone marrow phagocytes following benzene treatment of mice.

    PubMed Central

    Laskin, D L; MacEachern, L; Snyder, R

    1989-01-01

    Techniques in flow cytometry/cell sorting were used to characterize the effects of benzene and its metabolites on subpopulations of bone marrow cells. Treatment of male Balb/c mice with benzene (880 mg/kg) or a combination of its metabolites, hydroquinone and phenol (50 mg/kg), resulted in a 30 to 40% decrease in bone marrow cellularity. Flow cytometric analysis revealed two subpopulations of bone marrow cells that could be distinguished by their size and density or granularity. The larger, more dense subpopulation was found to consist predominantly of macrophages and granulocytes as determined by monoclonal antibody binding and by cell sorting. Benzene treatment had no selective cytotoxic effects on subpopulations of bone marrow cells. To determine if benzene treatment activated bone marrow phagocytes, we quantified production of hydrogen peroxide by these cells using the fluorescent indicator dye, 2',7'-dichlorofluorescein diacetate. We found that macrophages and granulocytes from bone marrow of treated mice produced 50% more hydrogen peroxide in response to the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate than did cells from control animals. It is hypothesized that phagocyte activation and production of cytotoxic reactive oxygen intermediates may contribute to hematotoxicity induced by benzene. PMID:2676504

  16. Pulmonary fat and bone marrow embolism in aircraft accident victims.

    PubMed

    Bierre, A R; Koelmeyer, T D

    1983-04-01

    On 28 November 1979, an Air New Zealand DC10 aircraft crashed into Mt Erebus, Antarctica with the loss of 257 passengers and crew. Postmortem examinations were carried out on 231 victims in Auckland, 4641 kilometres north of the crash site, and lung tissue was present in 205 cases. Pulmonary fat emboli were present in 134 cases (65%), pulmonary bone marrow emboli in 60 (29%) and pulmonary edema in 76 cases (37%). Clear relationships were demonstrated, firstly between the extent of fat and bone marrow embolism, secondly between the extent of fat and bone marrow embolism and the presence of pulmonary edema, and thirdly between the extent of fat and bone marrow embolism and the extent of cardiovascular damage. It was apparent that death had occurred immediately following impact, and the extent of fat and bone marrow embolism varied inversely with the severity of the injuries found. The most severely injured victims were those seated in the rear cabin of the aircraft suggesting that this was the site of impact with the ground. Our studies show that pulmonary fat embolism occurs very rapidly after severe injury and is followed by increasing numbers of fat and bone marrow emboli depending on the nature of the mortal injuries. PMID:6888959

  17. Transplantation immunology: Solid Organ and bone marrow

    PubMed Central

    Chinen, Javier; Buckley, Rebecca H.

    2010-01-01

    Development of the field of organ and tissue transplantation has accelerated remarkably since the human major histocompatibility complex (MHC) was discovered in 1967. Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance. The roles of the different components of the immune system involved in the tolerance or rejection of grafts and in graft-versus-host disease have been clarified. These components include: antibodies, antigen presenting cells, helper and cytotoxic T cell subsets, immune cell surface molecules, signaling mechanisms and cytokines that they release. The development of pharmacologic and biological agents that interfere with the alloimmune response and graft rejection has had a crucial role in the success of organ transplantation. Combinations of these agents work synergistically, leading to lower doses of immunosuppressive drugs and reduced toxicity. Reports of significant numbers of successful solid organ transplants include those of the kidneys, liver, heart and lung. The use of bone marrow transplantation for hematological diseases, particularly hematological malignancies and primary immunodeficiencies, has become the treatment of choice in many of these conditions. Other sources of hematopoietic stem cells are also being used, and diverse immunosuppressive drug regimens of reduced intensity are being proposed to circumvent the mortality associated with the toxicity of these drugs. Gene therapy to correct inherited diseases by infusion of gene-modified autologous hematopoietic stem cells has shown efficacy in two forms of severe combined immunodeficiency, providing an alternative to allogeneic tissue transplantation. PMID:20176267

  18. Post-bone marrow transplant thrombotic microangiopathy.

    PubMed

    Obut, F; Kasinath, V; Abdi, R

    2016-07-01

    Thrombotic microangiopathy (TMA) is a systemic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and organ failure. Post-bone marrow transplant TMA (post-BMT TMA) is a life-threatening condition that has been reported to afflict between 0.5 and 63.6% of BMT patients. The incidence of post-BMT TMA is affected by evolving therapies such as conditioning regimens. The etiology of post-BMT TMA is thought to be multifactorial, including the effects of immunosuppressive agents, viral infections, TBI and GvHD. A growing body of evidence highlights the importance of complement system activation and endothelial damage in post-BMT TMA. Although plasmapheresis has commonly been used, its therapeutic rationale for the majority of post-BMT TMA cases is unclear in the absence of circulatory inhibitors. It has become possible to target complement activation with eculizumab, a drug that blocks the terminal complement pathway. Early studies have highlighted the importance of anti-complement therapies in treating post-BMT TMA. Moreover, finding complement gene mutations may identify patients at risk, but whether such patients benefit from prophylactic anti-complement therapies before BMT remains to be studied. This review focuses on diagnostic criteria, pathophysiology, treatment and renal outcomes of post-BMT TMA. PMID:26974272

  19. Bone marrow fibrosis in childhood acute lymphoblastic leukaemia.

    PubMed Central

    Wallis, J P; Reid, M M

    1989-01-01

    Bone marrow trephine biopsy specimens were obtained at diagnosis from 63 of 76 consecutively presenting children with acute lymphoblastic leukaemia (ALL). The association between marrow fibrosis and presenting features, including immunophenotype, was analysed. Reticulin was increased in 45 of 56 cases in which blasts expressed B lineage markers, but in only one of seven with T-ALL. A weak association was also found between marrow fibrosis and splenomegaly in those with common ALL. Marrow fibrosis is apparently associated with some examples of ALL of B cell lineage, but precisely which subtypes and whether the phenomenon is clinically important remain to be determined. PMID:2613918

  20. SURVIVAL EFFICACY OF THE PEGYLATED G-CSFS MAXY-G34 AND NEULASTA IN A MOUSE MODEL OF LETHAL H-ARS, AND RESIDUAL BONE MARROW DAMAGE IN TREATED SURVIVORS

    PubMed Central

    Chua, Hui Lin; Plett, P. Artur; Sampson, Carol H.; Katz, Barry P.; Carnathan, Gilbert W.; MacVittie, Thomas J.; Lenden, Keith; Orschell, Christie M.

    2013-01-01

    In an effort to expand the worldwide pool of available medical countermeasures (MCM) against radiation, the PEGylated G-CSF (PEG-G-CSF) molecules Neulasta and Maxy-G34, a novel PEG-G-CSF designed for increased half-life and enhanced activity compared to Neulasta, were examined in a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome (H-ARS), along with the lead MCM for licensure and stockpiling, G-CSF. Both PEG-G-CSFs were shown to retain significant survival efficacy when administered as a single dose 24hr post-exposure, compared to the 16 daily doses of G-CSF required for survival efficacy. Furthermore, 0.1 mg kg−1 of either PEG-G-CSF effected survival of lethally-irradiated mice that was similar to a 10-fold higher dose. The one dose/low dose administration schedules are attractive attributes of radiation MCM given the logistical challenges of medical care in a mass casualty event. Maxy-G34-treated mice that survived H-ARS were examined for residual bone marrow damage (RBMD) up to 9mo post-exposure. Despite differences in Sca-1 expression and cell cycle position in some hematopoietic progenitor phenotypes, Maxy-G34-treated mice exhibited the same degree of hematopoietic stem cell (HSC) insufficiency as vehicle treated H-ARS survivors in competitive transplantation assays of 150 purified Sca-1+cKit+lin-CD150+ cells. These data suggest that Maxy-G34, at the dose, schedule, and time frame examined, did not mitigate RBMD, but significantly increased survival from H-ARS at one-tenth the dose previously tested, providing strong support for advanced development of Maxy-G34, as well as Neulasta, as MCM against radiation. PMID:24276547

  1. Survival efficacy of the PEGylated G-CSFs Maxy-G34 and neulasta in a mouse model of lethal H-ARS, and residual bone marrow damage in treated survivors.

    PubMed

    Chua, Hui Lin; Plett, P Artur; Sampson, Carol H; Katz, Barry P; Carnathan, Gilbert W; MacVittie, Thomas J; Lenden, Keith; Orschell, Christie M

    2014-01-01

    In an effort to expand the worldwide pool of available medical countermeasures (MCM) against radiation, the PEGylated G-CSF (PEG-G-CSF) molecules Neulasta and Maxy-G34, a novel PEG-G-CSF designed for increased half-life and enhanced activity compared to Neulasta, were examined in a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome (H-ARS), along with the lead MCM for licensure and stockpiling, G-CSF. Both PEG-G-CSFs were shown to retain significant survival efficacy when administered as a single dose 24 h post-exposure, compared to the 16 daily doses of G-CSF required for survival efficacy. Furthermore, 0.1 mg kg of either PEG-G-CSF affected survival of lethally-irradiated mice that was similar to a 10-fold higher dose. The one dose/low dose administration schedules are attractive attributes of radiation MCM given the logistical challenges of medical care in a mass casualty event. Maxy-G34-treated mice that survived H-ARS were examined for residual bone marrow damage (RBMD) up to 9 mo post-exposure. Despite differences in Sca-1 expression and cell cycle position in some hematopoietic progenitor phenotypes, Maxy-G34-treated mice exhibited the same degree of hematopoietic stem cell (HSC) insufficiency as vehicle-treated H-ARS survivors in competitive transplantation assays of 150 purified Sca-1+cKit+lin-CD150+cells. These data suggest that Maxy-G34, at the dose, schedule, and time frame examined, did not mitigate RBMD but significantly increased survival from H-ARS at one-tenth the dose previously tested, providing strong support for advanced development of Maxy-G34, as well as Neulasta, as MCM against radiation. PMID:24276547

  2. Bone marrow atrophy induced by murine cytomegalovirus infection.

    PubMed Central

    Gibbons, A E; Price, P; Shellam, G R

    1994-01-01

    Acute, sublethal infection of mice with murine cytomegalovirus (MCMV) resulted in up to 80% decreases in the number of cells recoverable from the bone marrow, and a decrease in peripheral blood leucocyte counts during the first week of infection. Depopulation of the leucopoietic areas of the marrow was evident from examination of histological sections. The severity of bone marrow atrophy in MCMV-infected mice of different strains correlated with previously described genetically determined sensitivity to MCMV disease. Although the phenomenon only occurred when mice were inoculated with infectious virus preparations, fewer than one in 10(5) marrow cells were productively infected, suggesting that atrophy was not due to lytic infection of large numbers of bone marrow cells. Interestingly, increases in serum colony-stimulating activity were observed and these were proportional to the severity of bone marrow atrophy. After MCMV infection, we observed increases in the proportions of cells expressing some B-cell and myeloid cell markers and a decrease in the proportion of cells expressing an erythroid cell marker. There was no change in the frequency of marrow cells expressing mature T-cell markers. The numbers of myeloid lineage-committed progenitor cells (GM-CFU) in the marrow decreased 10- to 20-fold in BALB/c nu/+ mice, while there was a threefold decrease in their numbers in BALB/c nu/nu mice. In addition, increases in serum colony-stimulating activity were greater in BALB/c nu/+ mice than in BALB/c nu/nu mice. Our results suggest that growth factors produced after MCMV infection may accelerate the maturation and migration of cells from the marrow to sites of virus replication and inflammation, thus accounting for the depletion in numbers of marrow cells observed soon after MCMV infection. Images Figure 3 Figure 4 PMID:7959876

  3. Spinal nociceptive transmission by mechanical stimulation of bone marrow

    PubMed Central

    Tanaka, Satoshi; Sekiguchi, Takemi; Sugiyama, Daisuke; Kawamata, Mikito

    2016-01-01

    Background Since bone marrow receives innervation from A-delta and C-fibers and since an increase in intramedullary pressure in bone marrow may induce acute pain in orthopedic patients during surgery and chronic pain in patients with bone marrow edema, skeletal pain may partly originate from bone marrow. Intraosseous lesions, such as osteomyelitis and bone cancer, are also known to produce cutaneous hypersensitivity, which might be referred pain from bone. However, little is known about pain perception in bone marrow and referred pain induced by bone disease. Thus, we carried out an in vivo electrophysiological study and behavioral study to determine whether increased intraosseous pressure of the femur induces acute pain and whether increased intraosseous pressure induces referred pain in the corresponding receptive fields of the skin. Results Intraosseous balloon inflation caused spontaneous pain-related behavior and mechanical hyperalgesia and allodynia in the lumbosacral region. Single neuronal activities of spinal dorsal horn neurons were extracellularly isolated, and then evoked responses to non-noxious and noxious cutaneous stimuli and intraosseous balloon inflation were recorded. Ninety-four spinal dorsal horn neurons, which had somatic receptive fields at the lower back and thigh, were obtained. Sixty-two percent of the wide-dynamic-range neurons (24/39) and 86% of the high-threshold neurons (12/14) responded to intraosseous balloon inflation, while none of the low-threshold neurons (0/41) responded to intraosseous balloon inflation. Spinally administered morphine (1 µg) abolished balloon inflation-induced spontaneous pain-related behavior and mechanical hyperalgesia in awake rats and also suppressed evoked activities of wide-dynamic-range neurons to noxious cutaneous stimulation and intraosseous balloon inflation. Conclusions The results suggest that mechanical stimulation to bone marrow produces nociception, concomitantly producing its referred pain

  4. Urothelial Cancer With Occult Bone Marrow Metastases and Isolated Thrombocytopenia

    PubMed Central

    Alva, Ajjai; Davis, Elizabeth; Chinnaiyan, Arul M.; Dhanasekaran, Saravana; Mehra, Rohit

    2015-01-01

    Bladder cancer rarely presents clinically with a myelophthisic picture from diffuse bone marrow infiltration especially in the absence of detectable skeletal metastases. A 75-year old man presented with newly diagnosed urothelial cell carcinoma of the bladder. Pathology from transurethral resection of bladder tumor demonstrated muscle-invasive disease. Pre-therapy imaging including CT abdomen/pelvis, CXR and bone scan demonstrated liver lesions concerning for metastatic disease but no skeletal metastases. Labs were notable for isolated thrombocytopenia, hypercalcemia and acute kidney injury prompting hospitalization. Hematologic work-up including bone marrow aspiration and biopsy revealed diffuse infiltration of the bone marrow by urothelial cancer. The case illustrates the importance of fully investigating otherwise unexplained clinical findings in patients with clinically localized urothelial cancer prior to curative intent surgery. PMID:26793516

  5. Long-term survival of murine allogeneic bone marrow chimeras: effect of anti-lymphocyte serum and bone marrow dose

    SciTech Connect

    Norin, A.J.; Emeson, E.E.; Veith, F.J.

    1981-02-01

    Graft-vs-host disease (GVHD) and failure of donor stem cells to engraft permanently are two major obstacles to successful bone marrow transplantation. The effect of a single large dose of anti-lymphocyte serum (ALS) on mice receiving various numbers of H-2 incompatible bone marrow cells was evaluated. Most animals receiving lethal total body irradiation (TBI) and allogeneic marrow died within 45 days due to GVHD. Mice that were given ALS 6 to 24 h before TBI and bone marrow 24 h after irradiation survived in good health for more than 200 days. These cell preparations caused lethal GVHD in third party mice indicating that the lack of alloreactivity was specific to the strain in which the unresponsiveness was originally induced.

  6. Bone marrow cells other than stem cells seed the bone marrow after rescue transfusion of fatally irradiated mice

    SciTech Connect

    Cronkite, E.P.; Inoue, T.; Bullis, J.E.

    1987-12-01

    In a previous publication, iodinated deoxyuridine (/sup 125/IUdR) incorporation data were interpreted as indicating that spleen colony-forming units (CFU-S) in DNA synthesis preferentially seeded bone marrow. In the present studies, the CFU-S content of marrow from irradiated, bone-marrow transfused mice was directly determined. Pretreatment of the transfused cells with cytocidal tritiated thymidine resulted in an insignificant diminution in CFU-S content when compared with nontritiated thymidine pretreatment, implying that there is no preferential seeding. The /sup 125/IUdR incorporation data have been reinterpreted as being a result of the proliferation of other progenitor cells present that have seeded the bone marrow.

  7. Usefulness of bone marrow imaging in childhood malignancies

    SciTech Connect

    Oseas, R.S.; Siddiqui, A.R.; Wellman, H.N.; Baehner, R.L.

    1982-08-01

    Two hundred six /sup 99m/Tc sulfur colloid bone marrow scans in 110 pediatrics patients were reviewed. The normal distribution of sulfur colloid in the lower extremities in various age groups was established. There was progressive loss of uptake with increasing age from less than two years to greater than ten years. Tumor replacement was seen as regions of decreased radioactivity, and the extent of the scan defect paralleled the response of the disease to therapy. Both chemotherapy and irradiation resulted in an extension of the /sup 99m/Tc SC to peripheral marrow sites. In irradiated areas, marrow scan defects were demonstrated and generally recovered normal activity by six months after the completion of therapy. Marrow scan abnormalities caused by tumor replacement were present in four patients despite normal bone scans and radiographs. Ultimate confirmation of tumor involvement was by needle aspiration or biopsy. Persistent marrow defects were seen in two patients with neuroblastoma who had remission of their disease: biopsy revealed myelofibrosis. /sup 99m/Tc sulfur colloid bone marrow scanning is a sensitive monitor of altered marrow activity associated with pediatric hematologic or oncologic diseases.

  8. Cell survival kinetics in peripheral blood and bone marrow during total body irradiation for marrow transplantation

    SciTech Connect

    Shank, B.; Andreeff, M.; Li, D.

    1983-11-01

    Cell survival kinetics in both peripheral blood and in bone marrow have been studied over the time course of hyperfractionated total body irradiation (TBI) for bone marrow transplantation. Our unique TBI regimen allows the study of the in vivo radiation effect uncomplicated by prior cyclophosphamide, since this agent is given after TBI in our cytoreduction scheme. Peripheral blood cell concentrations were monitored with conventional laboratory cell counts and differentials. Absolute bone marrow cell concentrations were monitored by measuring cell concentrations in an aspirate sample and correcting for dilution with blood by a cell cycle kinetic method using cytofluorometry. For lymphocytes in peripheral blood in patients in remission, the effective D/sub 0/ ranged from 373 rad in 10 children less than or equal to 10 y old, to 536 rad in the four patients between 11 to 17 y old, while n = 1.0 in all groups. There was no trend observed according to age. Granulocytes had a much higher effective D/sub 0/, approximately 1000 rad in vivo. Absolute nucleated cell concentration in marrow dropped slowly initially, due to an increased lymphocyte concentration in marrow during a concurrent drop in lymphocyte concentration in peripheral blood, but eventually fell on the last day of TBI ranging from 7 to 44% of the initial marrow nucleated cell concentration. Marrow myeloid elements, however, dropped continuously throughout the course of TBI.

  9. The microcirculation of bone and marrow in the diaphysis of the rat hemopoietic long bones.

    PubMed

    de Saint-Georges, L; Miller, S C

    1992-06-01

    The nature of the microcirculation of the diaphyseal portion of long bones and the adjacent bone marrow is poorly understood. The purpose of this study was to describe the blood supply in the diaphyseal cortex and the relationship of the bone vascular circulation to that of the bone marrow in the growing rat. India ink-gelatin was infused in the arterial system of 3-month-old rats and the vascularization was determined from histological sections. In some studies the periosteal circulation was blocked but the nutrient and metaphyseal arteriole systems were left intact. In the growing rat, most of the vascular flow appears to be centripetally through the diaphyseal cortex and this appears to be the primary blood supply for the adjacent bone marrow. The India ink traversed the cortex and entered the marrow through osteal canals at the endocortical surface. At the marrow-endocortical bone surface interface, ink exiting from the osteal canals filled the adjacent marrow sinusoids in what appeared as "bush-like" structures. From the bone marrow the ink appeared to drain into the central vein. Some arterioles from the nutrient system were found to penetrate the inner two thirds of the cortical bone and then re-enter the bone marrow. The centripetal flow of blood and the importance of the cortical flow for perfusion of the hemopoietic tissue was further documented when periosteal flow was obstructed. In this situation, the cortical bone and adjacent bone marrow were not perfused while the nutrient system and central vein were filled with ink.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1605383

  10. Understanding donors' motivations: a study of unrelated bone marrow donors.

    PubMed

    Switzer, G E; Dew, M A; Butterworth, V A; Simmons, R G; Schimmel, M

    1997-07-01

    Medical advances in bone marrow transplantation techniques and immunosuppressive medications have dramatically increased the number of such transplants performed each year, and consequently, the demand for bone marrow from unrelated donors. Although physiological aspects of bone marrow donation have been thoroughly investigated, very few studies have examined psychosocial factors that may impact individuals' donation decisions and outcomes. To examine one particular set of donor psychosocial issues, this study investigated motives for bone marrow donation among 343 unrelated bone marrow donors who donated through the National Marrow Donor Program. Six distinct types of donor motives were identified from open-ended questionnaire responses. Donors most frequently reported motives reflecting some awareness of both the costs (to themselves) and potential benefits (to themselves and the recipient) of donation. A desire to act in accordance with social or religious precepts, expected positive feelings about donating, empathy for the recipient, and the simple desire to help another person were also commonly cited reasons for donating. Among a series of donor background characteristics, donors' gender was the variable most strongly associated with motive type; women were most likely to cite expected positive feelings, empathy, and the desire to help someone. Central study findings indicated that donor motives predicted donors reactions to donation even after the effects of donor background characteristics (including gender) were controlled. Donors who reported exchange motives (weighing costs and benefits) and donors who reported simple (or idealized) helping motives experienced the donation as less positive in terms of higher predonation ambivalence and negative postdonation psychological reactions than did remaining donors. Donors who reported positive feeling and empathy motives had the most positive donation reactions in terms of lower ambivalence, and feeling like

  11. Spine Fusion Using Cell Matrix Composites Enriched in Bone Marrow-Derived Cells

    PubMed Central

    Nitto, Hironori; Matsukura, Yoichi; Boehm, Cynthia; Valdevit, Antonio; Kambic, Helen; Davros, William; Powell, Kimerly; Easley, Kirk

    2005-01-01

    Bone marrow-derived cells including osteoblastic progenitors can be concentrated rapidly from bone marrow aspirates using the surface of selected implantable matrices for selective cell attachment. Concentration of cells in this way to produce an enriched cellular composite graft improves graft efficacy. The current study was designed to test the hypothesis that the biologic milieu of a bone marrow clot will significantly improve the efficacy of such a graft. An established posterior spinal fusion model and cancellous bone matrix was used to compare an enriched cellular composite bone graft alone, bone matrix plus bone marrow clot, and an enriched bone matrix composite graft plus bone marrow clot. Union score, quantitative computed tomography, and mechanical testing were used to define outcome. The union score for the enriched bone matrix plus bone marrow clot composite was superior to the enriched bone matrix alone and the bone matrix plus bone marrow clot. The enriched bone matrix plus bone marrow clot composite also was superior to the enriched bone matrix alone in fusion volume and in fusion area. These data confirm that the addition of a bone marrow clot to an enriched cell-matrix composite graft results in significant improvement in graft performance. Enriched composite grafts prepared using this strategy provide a rapid, simple, safe, and inexpensive method for intraoperative concentration and delivery of bone marrow-derived cells and connective tissue progenitors that may improve the outcome of bone grafting. PMID:12567137

  12. Hematopoietic bone marrow recovery after radiation therapy: MRI evaluation

    SciTech Connect

    Casamassima, F.; Ruggiero, C.; Caramella, D.; Tinacci, E.; Villari, N.; Ruggiero, M. )

    1989-05-01

    Magnetic resonance imaging (MRI) is able to detect the increase of adipocytes in the hematopoietic bone marrow that occurs as a consequence of radiotherapy and is indicative of the loss of myeloid tissue. By monitoring this process, it is also possible to determine the recovery of the bone marrow. The amount of viable hematopoietic tissue plays a fundamental role in determining whether the patient is able to undergo further antineoplastic therapy, particularly chemotherapy. We examined 35 patients who had been treated with radiotherapy for Hodgkin's lymphoma (12), uterine cervix carcinoma (nine), ovarian dysgerminoma (six), testicular seminoma (four), and non-Hodgkin's lymphoma (four). We observed that radiation-induced modifications of the MRI pattern in the bone marrow are tightly linked to two parameters; the administered radiation dose and the length of time passed after the treatment. Bone marrow recovery was observed only when patients were treated with doses lower than 50 Gy. The earlier radiation-induced modifications of the bone marrow MRI pattern occurred 6 to 12 months after irradiation, and they were most evident 5 to 6 years after the treatment. From 2 to 9 years after radiotherapy, we observed partial recovery. Complete recovery, when it occurred, was observed only 10 to 23 years after the treatment. Our results indicate that MRI studies are likely to be useful in the assessment of radiation-induced injuries.

  13. Lasting engraftment of histoincompatible bone marrow cells in dogs

    SciTech Connect

    Vriesendorp, H.M.; Klapwijk, W.M.; van Kessel, A.M.C.; Zurcher, C.; van Bekkum, D.W.

    1981-05-01

    Conditioning protocols were tested for their efficacy in increasng the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradiation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-h interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplotype-mismatched donor. Possibilities for further improvement of this protocol are discussed.

  14. Lasting engraftment of histoincompatible bone marrow cells in dogs

    SciTech Connect

    Vriesendorp, H.M.; Klapwijk, W.M.; van Kessel, A.M.; Zurcher, C.; van Bekkum, D.W.

    1981-05-01

    Conditioning protocols were tested for their efficacy in increasing the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-hr interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplo-type-mismatched donor. Possibilities for further improvement of this protocol are discussed.

  15. Targeting bone marrow lymphoid niches in acute lymphoblastic leukemia.

    PubMed

    Uy, Geoffrey L; Hsu, Yen-Michael S; Schmidt, Amy P; Stock, Wendy; Fletcher, Theresa R; Trinkaus, Kathryn M; Westervelt, Peter; DiPersio, John F; Link, Daniel C

    2015-12-01

    In acute lymphoblastic leukemia (ALL) the bone marrow microenvironment provides growth and survival signals that may confer resistance to chemotherapy. Granulocyte colony-stimulating factor (G-CSF) potently inhibits lymphopoiesis by targeting stromal cells that comprise the lymphoid niche in the bone marrow. To determine whether lymphoid niche disruption by G-CSF sensitizes ALL cells to chemotherapy, we conducted a pilot study of G-CSF in combination with chemotherapy in patients with relapsed or refractory ALL. Thirteen patients were treated on study; three patients achieved a complete remission (CR/CRi) for an overall response rate of 23%. In the healthy volunteers, G-CSF treatment disrupted the lymphoid niche, as evidenced by reduced expression of CXCL12, interleukin-7, and osteocalcin. However, in most patients with relapsed/refractory ALL expression of these genes was markedly suppressed at baseline. Thus, although G-CSF treatment was associated with ALL cell mobilization into the blood, and increased apoptosis of bone marrow resident ALL cells, alterations in the bone marrow microenvironment were modest and highly variable. These data suggest that disruption of lymphoid niches by G-CSF to sensitize ALL cells to chemotherapy may be best accomplished in the consolidation where the bone marrow microenvironment is more likely to be normal. PMID:26467815

  16. Mechanical stimulation of bone marrow in situ induces bone formation in trabecular explants.

    PubMed

    Birmingham, E; Kreipke, T C; Dolan, E B; Coughlin, T R; Owens, P; McNamara, L M; Niebur, G L; McHugh, P E

    2015-04-01

    Low magnitude high frequency (LMHF) loading has been shown to have an anabolic effect on trabecular bone in vivo. However, the precise mechanical signal imposed on the bone marrow cells by LMHF loading, which induces a cellular response, remains unclear. This study investigates the influence of LMHF loading, applied using a custom designed bioreactor, on bone adaptation in an explanted trabecular bone model, which isolated the bone and marrow. Bone adaptation was investigated by performing micro CT scans pre and post experimental LMHF loading, using image registration techniques. Computational fluids dynamic models were generated using the pre-experiment scans to characterise the mechanical stimuli imposed by the loading regime prior to adaptation. Results here demonstrate a significant increase in bone formation in the LMHF loaded group compared to static controls and media flow groups. The calculated shear stress in the marrow was between 0.575 and 0.7 Pa, which is within the range of stimuli known to induce osteogenesis by bone marrow mesenchymal stem cells in vitro. Interestingly, a correlation was found between the bone formation balance (bone formation/resorption), trabecular number, trabecular spacing, mineral resorption rate, bone resorption rate and mean shear stresses. The results of this study suggest that the magnitude of the shear stresses generated due to LMHF loading in the explanted bone cores has a contributory role in the formation of trabecular bone and improvement in bone architecture parameters. PMID:25281407

  17. 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

  18. Cell Fate and Differentiation of Bone Marrow Mesenchymal Stem Cells

    PubMed Central

    Jimi, Eijiro

    2016-01-01

    Osteoblasts and bone marrow adipocytes originate from bone marrow mesenchymal stem cells (BMMSCs) and there appears to be a reciprocal relationship between adipogenesis and osteoblastogenesis. Alterations in the balance between adipogenesis and osteoblastogenesis in BMMSCs wherein adipogenesis is increased relative to osteoblastogenesis are associated with decreased bone quality and quantity. Several proteins have been reported to regulate this reciprocal relationship but the exact nature of the signals regulating the balance between osteoblast and adipocyte formation within the bone marrow space remains to be determined. In this review, we focus on the role of Transducin-Like Enhancer of Split 3 (TLE3), which was recently reported to regulate the balance between osteoblast and adipocyte formation from BMMSCs. We also discuss evidence implicating canonical Wnt signalling, which plays important roles in both adipogenesis and osteoblastogenesis, in regulating TLE3 expression. Currently, there is demand for new effective therapies that target the stimulation of osteoblast differentiation to enhance bone formation. We speculate that reducing TLE3 expression or activity in BMMSCs could be a useful approach towards increasing osteoblast numbers and reducing adipogenesis in the bone marrow environment. PMID:27298623

  19. Whole bone marrow irradiation for the treatment of multiple myeloma

    SciTech Connect

    Coleman, M.; Saletan, S.; Wolf, D.; Nisce, L.; Wasser, J.; McIntyre, O.R.; Tulloh, M.

    1982-04-01

    Nine patients with multiple myeloma were treated with whole bone marrow irradiation. Six had heavily pretreated disease refractory to chemotherapy. Three had stable disease lightly pretreated by chemotherapy. A modification of the ''three and two'' total nodal radiation technique was employed. Although varying and often severe treatment related cytopenia occurred, infectious complications, clinical bleeding, and nonhematalogic complications were minimal. Five of nine patients showed a decrease in monoclonal protein components, and one showed an increase during treatment. These preliminary results indicate that a reduction of tumor cell burden may occur in patients following whole bone marrow irradiation and that the technique is feasible. Whole bone marrow irradiation combined with chemotherapy represents a new conceptual therapeutic approach for multiple myeloma.

  20. Modeling Selective Elimination of Quiescent Cancer Cells from Bone Marrow

    PubMed Central

    Cavnar, Stephen P.; Rickelmann, Andrew D.; Meguiar, Kaille F.; Xiao, Annie; Dosch, Joseph; Leung, Brendan M.; Cai Lesher-Perez, Sasha; Chitta, Shashank; Luker, Kathryn E.; Takayama, Shuichi; Luker, Gary D.

    2015-01-01

    Patients with many types of malignancy commonly harbor quiescent disseminated tumor cells in bone marrow. These cells frequently resist chemotherapy and may persist for years before proliferating as recurrent metastases. To test for compounds that eliminate quiescent cancer cells, we established a new 384-well 3D spheroid model in which small numbers of cancer cells reversibly arrest in G1/G0 phase of the cell cycle when cultured with bone marrow stromal cells. Using dual-color bioluminescence imaging to selectively quantify viability of cancer and stromal cells in the same spheroid, we identified single compounds and combination treatments that preferentially eliminated quiescent breast cancer cells but not stromal cells. A treatment combination effective against malignant cells in spheroids also eliminated breast cancer cells from bone marrow in a mouse xenograft model. This research establishes a novel screening platform for therapies that selectively target quiescent tumor cells, facilitating identification of new drugs to prevent recurrent cancer. PMID:26408255

  1. P-glycoprotein expression in normal and reactive bone marrows.

    PubMed Central

    Hegewisch-Becker, S.; Fliegner, M.; Tsuruo, T.; Zander, A.; Zeller, W.; Hossfeld, D. K.

    1993-01-01

    The expression of mdr1 gene product P-glycoprotein (P-gp) was investigated in 53 normal and reactive bone marrows by means of immunocytochemistry, using the monoclonal antibody (mAb) C219 and the alkaline phosphatase anti-alkaline phosphatase method. In a limited number of patients, data were confirmed by using the mAb MRK16 or a polymerase chain reaction assay for mdr1 gene expression. There was no history of prior chemotherapy or any malignancy in this group. Bone marrow aspirates were obtained as part of a routine diagnostic programme in bone marrow donors or in patients presenting with a variety of diagnoses such as unexplained gammopathy, fever, anaemia, other changes in peripheral blood smear, rheumatoid arthritis, vasculitis, or urticaria pigmentosa. Morphologically the bone marrow was normal in 23 patients, a megaloblastic erythropoiesis was seen in two patients and unspecific changes were seen in 28 patients. Twenty-seven of 53 samples were found to be positive for P-gp expression with the percentage of positive cells ranging from 2%-80% (mean = 24%). With a cutoff point of 10%, five of 23 normal (22%) and 13 of 28 reactive bone marrows (46%) were considered positive for P-gp expression. There was no obvious correlation between diagnosis or age and P-gp expression. Additional staining for the early surface marker CD-34 was performed in 12 samples, with none of them revealing more than 1% positivity. Since P-gp expression has so far been described only in CD-34 positive bone marrow cells, data suggest that P-gp expression may be reinduced in CD-34 negative cells under conditions which remain to be determined. Images Figure 1 Figure 2 PMID:8094974

  2. Hematogones: a multiparameter analysis of bone marrow precursor cells.

    PubMed

    Longacre, T A; Foucar, K; Crago, S; Chen, I M; Griffith, B; Dressler, L; McConnell, T S; Duncan, M; Gribble, J

    1989-02-01

    Morphologically distinct lymphoid cells with homogeneous, condensed chromatin and scant cytoplasm can be observed in large numbers in the bone marrow of children with a variety of hematologic and nonhematologic disorders. In some patients, these cells may account for greater than 50% of the bone marrow cells, creating a picture that can be confused with acute lymphoblastic leukemia (ALL) or metastatic tumor. Although originally called hematogones (HGs), a variety of other names have been proposed for these unique cells. The clinical significance of expanded HGs has not been resolved, and the biologic features of these cells are incompletely described. In this study, we correlate the clinical, morphologic, cytochemical, flow cytometric, molecular, and cytogenetic properties of bone marrow samples from 12 children with substantial numbers of HGs (range 8% to 55% of bone marrow cells). Diagnoses in these patients included anemia, four; neutropenia, one; anemia and neutropenia, one; idiopathic thrombocytopenic purpura, two; retinoblastoma, two; Ewing's sarcoma, one; and germ cell tumor, one. Flow cytometric analyses of bone marrow cells demonstrated a spectrum extending from early B-cell precursors (CD10+, CD19+, TdT+, HLA-Dr+) to mature surface immunoglobulin-bearing B cells in these patients, corroborating our morphologic impression of HGs, intermediate forms, and mature lymphocytes. DNA content was normal, and no clonal abnormality was identified by either cytogenetic or immunoglobulin and T-cell receptor (TCR) gene rearrangement studies. Follow-up ranged from 3 months to 3 years. None of the patients has developed acute leukemia or bone marrow involvement by solid tumor. The possible role of HGs in immune recovery and hematopoiesis is presented. PMID:2917189

  3. Enhancement of bone marrow allografts from nude mice into mismatched recipients by T cells void of graft-versus-host activity

    SciTech Connect

    Lapidot, T.; Lubin, I.; Terenzi, A.; Faktorowich, Y.; Erlich, P.; Reisner, Y. )

    1990-06-01

    Transplantation of 8 x 10(6) C57BL/6-Nu+/Nu+ (nude) bone marrow cells into C3H/HeJ recipients after conditioning with 8 Gy of total body irradiation has resulted in a markedly higher rate of graft rejection or graft failure compared to that found in recipients of normal C57BL/6 or C57BL/6-Bg+/Bg+ (beige) T-cell-depleted bone marrow. Mixing experiments using different numbers of nude bone marrow cells with or without mature thymocytes (unagglutinated by peanut agglutinin) revealed that engraftment of allogeneic T-cell-depleted bone marrow is T-cell dependent. To ensure engraftment, a large inoculum of nude bone marrow must be supplemented with a trace number of donor T cells, whereas a small bone marrow dose from nude donors requires a much larger number of T cells for engraftment. Marked enhancement of donor type chimerism was also found when F1 thymocytes were added to nude bone marrow cells, indicating that the enhancement of bone marrow engraftment by T cells is not only mediated by alloreactivity against residual host cells but may rather be generated by growth factors, the release of which may require specific interactions between T cells and stem cells or between T cells and bone marrow stroma cells.

  4. 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

  5. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC).

    PubMed

    Huh, Sung Woo; Shetty, Asode Ananthram; Ahmed, Saif; Lee, Dong Hwan; Kim, Seok Jung

    2016-01-01

    Degenerative and traumatic articular cartilage defects are common, difficult to treat, and progressive lesions that cause significant morbidity in the general population. There have been multiple approaches to treat such lesions, including arthroscopic debridement, microfracture, multiple drilling, osteochondral transplantation and autologous chondrocyte implantation (ACI) that are currently being used in clinical practice. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC) is a single-staged arthroscopic procedure. This method combines a modified microfracture technique with the application of a bone marrow aspirate concentrate (BMAC), hyaluronic acid and fibrin gel to treat articular cartilage defects. We reviewed the current literatures and surgical techniques for mesenchymal cell induced chondrogenesis. PMID:27489409

  6. Inherited bone marrow failure syndromes in adolescents and young adults.

    PubMed

    Wilson, David B; Link, Daniel C; Mason, Philip J; Bessler, Monica

    2014-09-01

    The inherited bone marrow failure syndromes are a diverse group of genetic diseases associated with inadequate production of one or more blood cell lineages. Examples include Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, thrombocytopenia absent radii syndrome, severe congenital neutropenia, and Shwachman-Diamond syndrome. The management of these disorders was once the exclusive domain of pediatric subspecialists, but increasingly physicians who care for adults are being called upon to diagnose or treat these conditions. Through a series of patient vignettes, we highlight the clinical manifestations of inherited bone marrow failure syndromes in adolescents and young adults. The diagnostic and therapeutic challenges posed by these diseases are discussed. PMID:24888387

  7. Immune Cell Isolation from Mouse Femur Bone Marrow

    PubMed Central

    Liu, Xiaoyu; Quan, Ning

    2016-01-01

    The bone marrow is the site of hematopoesis and contains mixed population of blood cells including erythrocytes, granulocytes, monocytes, dendritic cells, lymphocytes and hematopoietic stem cells. The following protocol provides a simple and fast method for isolation of bone marrow immune cells (no erythrocytes) from mouse femurs with a yield of approximate 8 × 107 cells in 5 ml culture media (1.6 × 104 cells/μl). Further isolation or flow cytometric analysis might be required for study of specific immune cell types.

  8. Inherited bone marrow failure syndromes in adolescents and young adults

    PubMed Central

    Wilson, David B.; Link, Daniel C.; Mason, Philip J.; Bessler, Monica

    2015-01-01

    The inherited bone marrow failure syndromes are a diverse group of genetic diseases associated with inadequate production of one or more blood cell lineages. Examples include Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, thrombocytopenia absent radii syndrome, severe congenital neutropenia, and Shwachman-Diamond syndrome. The management of these disorders was once the exclusive domain of pediatric subspecialists, but increasingly physicians who care for adults are being called upon to diagnose or treat these conditions. Through a series of patient vignettes, we highlight the clinical manifestations of inherited bone marrow failure syndromes in adolescents and young adults. The diagnostic and therapeutic challenges posed by these diseases are discussed. PMID:24888387

  9. Growth Hormone Regulates the Balance Between Bone Formation and Bone Marrow Adiposity

    PubMed Central

    Menagh, Philip J; Turner, Russell T; Jump, Donald B; Wong, Carmen P; Lowry, Malcolm B; Yakar, Shoshana; Rosen, Clifford J; Iwaniec, Urszula T

    2010-01-01

    Cancellous bone decreases and bone marrow fat content increases with age. Osteoblasts and adipocytes are derived from a common precursor, and growth hormone (GH), a key hormone in integration of energy metabolism, regulates the differentiation and function of both cell lineages. Since an age-related decline in GH is associated with bone loss, we investigated the relationship between GH and bone marrow adiposity in hypophysectomized (HYPOX) rats and in mice with defects in GH signaling. HYPOX dramatically reduced body weight gain, bone growth and mineralizing perimeter, serum insulin-like growth factor 1 (IGF-1) levels, and mRNA levels for IGF-1 in liver and bone. Despite reduced body mass and adipocyte precursor pool size, HYPOX resulted in a dramatic increase in bone lipid levels, as reflected by increased bone marrow adiposity and bone triglyceride and cholesterol content. GH replacement normalized bone marrow adiposity and precursor pool size, as well as mineralizing perimeter in HYPOX rats. In contrast, 17β -estradiol, IGF-1, thyroxine, and cortisone were ineffective. Parathyroid hormone (PTH) reversed the inhibitory effects of HYPOX on mineralizing perimeter but had no effect on adiposity. Finally, bone marrow adiposity was increased in mice deficient in GH and IGF-1 but not in mice deficient in serum IGF-1. Taken together, our findings indicate that the reciprocal changes in bone and fat mass in GH signaling-deficient rodents are not directly coupled with one another. Rather, GH enhances adipocyte as well as osteoblast precursor pool size. However, GH increases osteoblast differentiation while suppressing bone marrow lipid accumulation. © 2010 American Society for Bone and Mineral Research PMID:19821771

  10. Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

    PubMed

    Krug, L M; Grant, S C; Miller, V A; Ng, K K; Kris, M G

    1999-10-01

    In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three potential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination. PMID:10566613

  11. Significance of bone marrow edema in pathogenesis of rheumatoid arthritis

    PubMed Central

    Sudoł-Szopińska, Iwona; Kontny, Ewa; Maśliński, Włodzimierz; Prochorec-Sobieszek, Monika; Warczyńska, Agnieszka; Kwiatkowska, Brygida

    2013-01-01

    Summary Assessing the pathology of the synovium, its thickening and increased vascularity through ultrasound and magnetic resonance examinations (more often an ultrasound study alone) is still considered a sensitive parameter in the diagnosis of rheumatoid arthritis and in monitoring of treatment efficacy. Magnetic resonance studies showed that, aside from the joint pannus, the subchondral bone tissue constitutes an essential element in the development of rheumatoid arthritis. Bone marrow edema correlates with inflammation severity, joint destruction, clinical signs and symptoms of rheumatoid arthritis, and thus is considered a predictor of rapid radiological progression of the disease. The newest studies reveal that bone marrow edema may be a more sensitive indicator of the response to therapy than appearance of the synovium. Bone marrow edema presents with increased signal in T2-weighted images, being most visible in fat saturation or IR sequences (STIR, TIRM). On the other hand, it is hypointense and less evident in T1-weighted images. It becomes enhanced (hyperintense) after contrast administration. Histopathological studies confirmed that it is a result of bone inflammation (osteitis/osteomyelitis), i.e. replacememt of bone marrow fat by inflammatory infiltrates containing macrophages, T lymphocytes, B lymphocytes, plasma cells and osteoclasts. Bone marrow edema appears after a few weeks from occurrence of symptoms and therefore is considered an early marker of inflammation. It correlates with clinical assessment of disease activity and elevated markers of acute inflammatory phase, i.e. ESR and CRP. It is a reversible phenomenon and may become attenuated due to biological treatment. It is considered a “herald” of erosions, as the risk of their formation is 6-fold higher in sites where BME was previously noted PMID:23493495

  12. The survival of cryopreserved human bone marrow stem cells.

    PubMed

    Hill, R S; Mackinder, C A; Postlewaight, B F; Blacklock, H A

    1979-07-01

    Two methods for cryopreservation of bone marrow stem cells were compared using bone marrow obtained from 36 patients. Included in this group were 21 persons with the diagnosis of leukaemia including 14 either with acute myeloid or lymphoblastic leukaemia in remission following intensive remission induction chemotherapy. After freeze-preservation and reconstitution, all marrow samples were tested for nucleated cell (NC) recovery and grown on agar to assess colony forming units (CFUC) and cluster forming units in culture (CluFUc). A slow dilution reconstitution method using freezing media containing AB negative plasma resulted in recovery of 85% of the CFUc activity of fresh marrow. This result was significantly better than the 47% CFUc recovery obtained when freezing media without plasma and a rapid dilution reconstitution technique were used. NC recoveries following slow dilution (51%) and rapid dilution (44%) were not significantly different. CluFUc were disproportionately reduced compared with CFUc although yielding similar results with both methods (26% and 32%). No correlation was found for either method between CFUc and NC recovery or between CFUc and CluFUc recovery in cryopreserved bone marrow. PMID:392422

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  14. Total body irradiation in bone marrow transplantation: the influence of fractionation and delay of marrow infusion

    SciTech Connect

    Lichter, A.S.; Tracy, D.; Lam, W.C.; Order, S.E.

    1980-03-01

    Bone marrow transplantation (BMT) after total body irradiation (TBI) and cyclophosphamide is being employed increasingly in the therapy of end stage leukemia. Interstitial pneumonitis (IP) represents a major acute toxicity after allogeneic transplantation. A more rapid reconstitution of lymphoid organs and bone marrow post transplant may result in increased immune competence and hence fewer opportunistic pulmonary infections and IP. By delaying the infusion of marrow to 72 hr after TBI (1250 rad at 7.5 rad/min) instead of the customary 24 hr, we can demonstrate an increase in initial repopulation of thymus, spleen and bone marrow, with syngeneic transplants in Lewis rats. Interstitial pneumonitis may also be caused, in part, by the pulmonary toxicity of large single exposures of TBI. Clinical and laboratory data suggest that fractionated TBI may be less toxic to the lung. When fractionated TBI (625 rad x 2, 7.5 rad/min) is compared to single dose TBI (1250 rad, 7.5 rad/min), and increased initial repopulation of lymphoid organs is observed when fractionated therapy is employed. Delay in marrow infusion and fractionation of TBI exposure may have clinical advantages in patients who receive BMT.

  15. Therapy Effects of Bone Marrow Stromal Cells on Ischemic Stroke

    PubMed Central

    Ye, Xinchun; Hu, Jinxia; Cui, Guiyun

    2016-01-01

    Stroke is the second most common cause of death and major cause of disability worldwide. Recently, bone marrow stromal cells (BMSCs) have been shown to improve functional outcome after stroke. In this review, we will focus on the protective effects of BMSCs on ischemic brain and the relative molecular mechanisms underlying the protective effects of BMSCs on stroke. PMID:27069533

  16. Treating Families of Bone Marrow Recipients and Donors

    ERIC Educational Resources Information Center

    Cohen, Marie; And Others

    1977-01-01

    Luekemia and aplastic anemia are beginning to be treated by bone marrow transplants, involving donors and recipients from the same family. Such intimate involvement in the patient's life and death struggles typically produces a family crisis and frequent maladaptive responses by various family members. (Author)

  17. [Bone marrow biopsy: processing and use of molecular techniques].

    PubMed

    Quintanilla-Martinez, L; Tinguely, M; Bonzheim, I; Fend, F

    2012-11-01

    The rapid technological development in diagnostic pathology, especially of immunohistochemical and molecular techniques, also has a significant impact on diagnostic procedures for the evaluation of bone marrow trephine biopsies. The necessity for optimal morphology, combined with preservation of tissue antigens and nucleic acids on one hand and the wish for short turnaround times on the other hand require careful planning of the workflow for fixation, decalcification and embedding of trephines. Although any kind of bone marrow processing has its advantages and disadvantages, formalin fixation followed by EDTA decalcification can be considered a good compromise, which does not restrict the use of molecular techniques. Although the majority of molecular studies in haematological neoplasms are routinely performed on bone marrow aspirates or peripheral blood cells, there are certain indications, in which molecular studies such as clonality determination or detection of specific mutations need to be performed on the trephine biopsy. Especially, the determination of B- or T-cell clonality for the diagnosis of lymphoid malignancies requires stringent quality controls and knowledge of technical pitfalls. In this review, we discuss technical aspects of bone marrow biopsy processing and the application of diagnostic molecular techniques. PMID:23085692

  18. Effect of Rosiglitazone on Radiation Damage in Bone Marrow Hemopoiesis

    SciTech Connect

    Benko', Klara; Pintye, Eva; Szabo, Boglarka; Geresi, Krisztina; Megyeri, Attila; Benko, Ilona

    2008-12-08

    To study radiobiological effects and drugs, which can modify radiation injury, has an importance if we would like to avoid harmful effects of radiation due to emergency situations or treat patients with malignant diseases by radiotherapy. During the long treatment schedules patients may be treated by not only anticancer but many other drugs because of accompanying diseases. These drugs may also modify radiobiological effects. Rosiglitazone pre-treatment proved to be myeloprotective and accelerated recovery of 5-fluorouracil-damaged bone marrow in our previous experiments. Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects in radiation-damaged hemopoiesis. Bone marrow damage was precipitated by total body irradiation (TBI) using single increasing doses (2-10 Gy) of {gamma}--irradiation in groups of mice. Lethality was well correlated with damage in hemopoiesis measured by cellularity of bone marrow (LD{sub 50} values were 4.8 and 5.3 gray respectively). Rosiglitazone, an insulin-sensitizing drug, had no significant effect on bone marrow cellularity. Insulin resistance associated with obesity or diabetes mellitus type 2 is intensively growing among cancer patients requiring some kind of radiotherapy. Therefore it is important to know whether drugs used for their therapy can modify radiation effects.

  19. Effect of Rosiglitazone on Radiation Damage in Bone Marrow Hemopoiesis

    NASA Astrophysics Data System (ADS)

    Benkő, Klára; Pintye, Éva; Szabó, Boglárka; Géresi, Krisztina; Megyeri, Attila; Benkő, Ilona

    2008-12-01

    To study radiobiological effects and drugs, which can modify radiation injury, has an importance if we would like to avoid harmful effects of radiation due to emergency situations or treat patients with malignant diseases by radiotherapy. During the long treatment schedules patients may be treated by not only anticancer but many other drugs because of accompanying diseases. These drugs may also modify radiobiological effects. Rosiglitazone pre-treatment proved to be myeloprotective and accelerated recovery of 5-fluorouracil-damaged bone marrow in our previous experiments. Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects in radiation-damaged hemopoiesis. Bone marrow damage was precipitated by total body irradiation (TBI) using single increasing doses (2-10 Gy) of γ—irradiation in groups of mice. Lethality was well correlated with damage in hemopoiesis measured by cellularity of bone marrow (LD50 values were 4.8 and 5.3 gray respectively). Rosiglitazone, an insulin-sensitizing drug, had no significant effect on bone marrow cellularity. Insulin resistance associated with obesity or diabetes mellitus type 2 is intensively growing among cancer patients requiring some kind of radiotherapy. Therefore it is important to know whether drugs used for their therapy can modify radiation effects.

  20. Body/bone-marrow differential-temperature sensor

    NASA Technical Reports Server (NTRS)

    Anselmo, V. J.; Berdahl, C. M.

    1978-01-01

    Differential-temperature sensor developed to compare bone-marrow and body temperature in leukemia patients uses single stable amplifier to monitor temperature difference recorded by thermocouples. Errors are reduced by referencing temperatures to each other, not to separate calibration points.

  1. Agent-Based Deterministic Modeling of the Bone Marrow Homeostasis

    PubMed Central

    2016-01-01

    Modeling of stem cells not only describes but also predicts how a stem cell's environment can control its fate. The first stem cell populations discovered were hematopoietic stem cells (HSCs). In this paper, we present a deterministic model of bone marrow (that hosts HSCs) that is consistent with several of the qualitative biological observations. This model incorporates stem cell death (apoptosis) after a certain number of cell divisions and also demonstrates that a single HSC can potentially populate the entire bone marrow. It also demonstrates that there is a production of sufficient number of differentiated cells (RBCs, WBCs, etc.). We prove that our model of bone marrow is biologically consistent and it overcomes the biological feasibility limitations of previously reported models. The major contribution of our model is the flexibility it allows in choosing model parameters which permits several different simulations to be carried out in silico without affecting the homeostatic properties of the model. We have also performed agent-based simulation of the model of bone marrow system proposed in this paper. We have also included parameter details and the results obtained from the simulation. The program of the agent-based simulation of the proposed model is made available on a publicly accessible website. PMID:27340402

  2. Agent-Based Deterministic Modeling of the Bone Marrow Homeostasis.

    PubMed

    Kurhekar, Manish; Deshpande, Umesh

    2016-01-01

    Modeling of stem cells not only describes but also predicts how a stem cell's environment can control its fate. The first stem cell populations discovered were hematopoietic stem cells (HSCs). In this paper, we present a deterministic model of bone marrow (that hosts HSCs) that is consistent with several of the qualitative biological observations. This model incorporates stem cell death (apoptosis) after a certain number of cell divisions and also demonstrates that a single HSC can potentially populate the entire bone marrow. It also demonstrates that there is a production of sufficient number of differentiated cells (RBCs, WBCs, etc.). We prove that our model of bone marrow is biologically consistent and it overcomes the biological feasibility limitations of previously reported models. The major contribution of our model is the flexibility it allows in choosing model parameters which permits several different simulations to be carried out in silico without affecting the homeostatic properties of the model. We have also performed agent-based simulation of the model of bone marrow system proposed in this paper. We have also included parameter details and the results obtained from the simulation. The program of the agent-based simulation of the proposed model is made available on a publicly accessible website. PMID:27340402

  3. A Dosimetric Study of Radionuclide Therapy for Bone Marrow Ablation.

    NASA Astrophysics Data System (ADS)

    Bayouth, John Ellis

    In a phase I clinical trial, six multiple myeloma patients, who were non-responsive to conventional therapy and were scheduled for bone marrow transplantation, received Holmium-166 (166Ho) labeled to a bone seeking agent, DOTMP (1,4,7,10-tetraazacyclododecane -1,4,7,10-tetramethylene-phosphonic acid), for the purpose of bone marrow ablation. The specific aims of my research within this protocol were to evaluate the toxicity and efficacy of 166Ho DOTMP by quantifying the in vivo pharmacokinetics and radiation dosimetry, and by correlating these results to the biologic response observed. The reproducibility of pharmacokinetics from multiple injections of 166 Ho DOTMP administered to these myeloma patients was demonstrated from both blood and whole body retention. The skeletal concentration of 166 Ho DOTMP was heterogenous in all six patients: high in the ribs, pelvis, and lumbar vertebrae regions, and relatively low in the femurs, arms, and head. A novel technique was developed to calculate the radiation dose to the bone marrow in each skeletal ROI, and was applied to all six 166 Ho DOTMP patients. Radiation dose estimates for the bone marrow calculated using the standard MIRD "S" factors were compared with the average values derived from the heterogenous distribution of activity in the skeleton (i.e., the regional technique). The results from the two techniques were significantly different; the average of the dose estimates from the regional technique were typically 30% greater. Furthermore, the regional technique provided a range of radiation doses for the entire marrow volume, while the MIRD "S" factors only provided a single value. Dose volume histogram analysis of data from the regional technique indicated a range of dose estimates that varied by a factor of 10 between the high dose and low dose regions. Finally, the observed clinical response of cells and abnormal proteins measured in bone marrow aspirates and peripheral blood samples were compared with

  4. Stimulation of bone marrow cells and bone formation by nacre: in vivo and in vitro studies.

    PubMed

    Lamghari, M; Almeida, M J; Berland, S; Huet, H; Laurent, A; Milet, C; Lopez, E

    1999-08-01

    There is frequently a loss of vertebral bone due to disease or aging. Nacre (mother of pearl from the oyster Pinctada maxima) stimulates bone cell differentiation and bone formation in vitro and in vivo. Experimental bone defects were prepared in the vertebrae of sheep and used to test the suitability of nacre as an injectable osteogenic biomaterial for treating vertebral bone loss. Twenty-one cavities were prepared in the first four upper lumbar vertebrae of 11 sheep and filled with nacre powder. The lumbar vertebrae were removed after 1 to 12 weeks, embedded undecalcified in methacrylate, and processed for histological studies. The nacre slowly dissolved and the experimental cavities contained a large active cell population. By 12 weeks, the experimental cavity was occupied by newly matured bone trabeculae in contact with or adjacent to the dissolving nacre. The functional new bone trabeculae were covered with osteoid lined with osteoblasts, indicating continuing bone formation. The in vitro study on rat bone marrow explants cultured with a water-soluble extract of the nacre organic matrix also resulted in the stimulation of osteogenic bone marrow cells with enhanced alkaline phosphatase activity. Thus, both the in vivo and in vitro findings suggest that nacre contains one or more signal molecules capable of activating osteogenic bone marrow cells. PMID:10458284

  5. 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. PMID:26283413

  6. Bone marrow-derived stem cells and radiation response.

    PubMed

    Greenberger, Joel S; Epperly, Michael

    2009-04-01

    The recovery of tissues and organs from ionizing irradiation is critically dependent on the repopulation of resident stem cells, defined as the subset of cells with capacity for both self-renewal and differentiation. Stem cells of both hematopoietic and epithelial origin reside in defined areas of the cellular microenvironment (recently defined as the stem cell "niche"). Experiments using serial repopulation assays in serial generations of total body irradiated mice receiving transplanted marrow and in continuous bone marrow cultures both identified specific microanatomic sites that comprise the bone marrow stem cell niche. Supportive cells of the hematopoietic microenvironment not only contribute to stem cell repopulation capacity but also to the maintenance of their quiescent or nonproliferative state, which allows the most primitive hematopoietic stem cells to stay in a noncycling state protected from both direct ionizing radiation-induced cell-cycle phase-specific killing and indirect cytokine and free radical mediated killing. Recent evidence has defined both cell contact and humoral mechanisms of protection of hematopoietic stem cells by stromal cells. There is also recent evidence for multilineage differentiation capacity of cells of the hematopoietic microenvironment termed bone marrow stromal cells (mesenchymal stem cells). Both hematopoietic stem cells and mesenchymal stem cell populations have been shown to be involved in the repair of ionizing irradiation damage of distant epithelial as well as other hematopoietic sites through their capacity to migrate through the circulation. The radiobiology of these 2 bone marrow stem cell populations is the subject of intense investigation. This review defines the status of research in the areas of stem cell quiescence, niche contact, and migratory responses to ionizing irradiation. PMID:19249651

  7. Probabilistic Prediction of the Outcome of Bone-Marrow Transplantation

    PubMed Central

    Suermondt, H. Jacques; Amylon, Michael D.

    1989-01-01

    Bone-marrow transplantation is considered the treatment of choice for pediatric patients with recurring acute lymphoblastic leukemia, provided that a suitable donor is available. Many prognostic factors are known that help to predict the likely outcome of transplantation. We have implemented a system that applies probabilistic reasoning to the available data about individual patients to help determine the risk of recurrence and morbidity after transplantation, and to predict life expectancy. The resulting predictions can be used to decide whether marrow transplantation is the most desirable treatment modality for the patient.

  8. Bone marrow ablation followed by allogeneic marrow grafting during first complete remission of acute nonlymphocytic leukemia

    SciTech Connect

    Forman, S.J.; Spruce, W.E.; Farbstein, M.J.

    1983-03-01

    Of 33 patients who had undergone allogeneic bone marrow transplantation during first complete remission of acute nonlymphocytic leukemia, 21 patients have now been followed in continued complete remission for 6-64 mo (median greater than 18 mo) without maintenance chemotherapy. The median age of the surviving patients is 27 yr. Transplant-related complications occurring throughout the first year after marrow grafting were fatal in 7 patients, and leukemic recurrence led to the death of 5 patients. The actuarial long-term disease-free survival is 60% and the actuarial remission rate is 79%.

  9. 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. PMID:24240026

  10. Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow

    PubMed Central

    Yu, Vionnie W.C.; Saez, Borja; Cook, Colleen; Lotinun, Sutada; Pardo-Saganta, Ana; Wang, Ying-Hua; Lymperi, Stefania; Ferraro, Francesca; Raaijmakers, Marc H.G.P.; Wu, Joy Y.; Zhou, Lan; Rajagopal, Jayaraj; Kronenberg, Henry M.; Baron, Roland

    2015-01-01

    Production of the cells that ultimately populate the thymus to generate α/β T cells has been controversial, and their molecular drivers remain undefined. Here, we report that specific deletion of bone-producing osteocalcin (Ocn)-expressing cells in vivo markedly reduces T-competent progenitors and thymus-homing receptor expression among bone marrow hematopoietic cells. Decreased intrathymic T cell precursors and decreased generation of mature T cells occurred despite normal thymic function. The Notch ligand DLL4 is abundantly expressed on bone marrow Ocn+ cells, and selective depletion of DLL4 from these cells recapitulated the thymopoietic abnormality. These data indicate that specific mesenchymal cells in bone marrow provide key molecular drivers enforcing thymus-seeding progenitor generation and thereby directly link skeletal biology to the production of T cell–based adaptive immunity. PMID:25918341

  11. Homing of chloromethylbenzoyl ammonia-labeled bone marrow mesenchymal stem cells in an immune-mediated bone marrow failure mouse model in vivo.

    PubMed

    Xiao, Y; Wang, Y; Li, L; Li, Y H; Pang, Y; Song, J Y; Jiang, Z J

    2014-01-01

    Aplastic anemia is an abnormal immune reaction disease in which T lymphocytes destroy hematopoietic stem and progenitor cells because of immune hyperactivity. Bone marrow mesenchymal stem cells (BMSCs) have hematopoietic supporting and immune regulation functions. This study investigated BMSCs homing in mice transplantation models after bone marrow failure. BALB/c mice were randomly divided into three groups: normal control, bone marrow failure model, and BMSC transplantation group. Chloromethyl benzamido-labeled BMSCs of BALB/c mice were transplanted through tail vein injection in mouse models with bone marrow failure. Flow cytometry and histological fluorescence microscopy were used to observe the dynamic distribution of labeled cells in different tissues. Average survival time, peripheral blood, and bone marrow morphological features were observed in mice from each group. Twenty-four hours after tail vein infusion of BMSCs, positively labeled cells were observed in the bone marrows of recipient mice, and the number of positive cells increased significantly at 72 h (P < 0.05). In dead or dying mice, white blood cells, hemoglobin, platelets, and bone marrow mononuclear cells were all significantly higher in the BMSC transplantation group than in the BMSCs of the model group (P < 0.01). Mean survival time was significantly shorter in the bone marrow failure model group than in the transplantation group (P < 0.05). These results confirmed that the major of BMSCs injected via tail vein could migrate to injured bone marrow tissues within 24-72 h in a mouse model of bone marrow failure. Furthermore, BMSCs can promote hematopoietic recovery, reduce the degree of bone marrow failure, and significantly prolong survival time. PMID:24421151

  12. Effects of prostaglandin on experimental bone malignancy and on scintigrams of bone and marrow. [Rabbits

    SciTech Connect

    Otsuka, N.; Ito, Y.; Nagai, K.; Terashima, H.; Yanagimoto, S.; Muranaka, A.

    1981-05-01

    The correlation between prostaglandin E (PgE) and scintigrams of bone (Tc-99m MDP) and bone marrow (Tc-99m SC) was investigated in normal and VX-2-bearing rabbits. PgE in plasma of normal rabbits was 486.2. In rabbits with VX-2 transplanted into femoral muscles, PgE was in the normal range unless the tumor invaded bone. PgE was not increase significantly in rabbits when the tumor was transplanted into the marrow cavity. When tumor invaded bone, PgE increassed markedly (to 1335). Elevation of PgE did not necessarily coincide with the appearance of positive bone scans. PgE in an indomethacin-treated group did not necessarily coincide with the appearance of positive bone scans. PgE in an indomethacin-treated group did not higher than in the untreated group. Indomethacin may suppress the local acceleration of calcium metabolism.

  13. A stochastic model of radiation-induced bone marrow damage

    SciTech Connect

    Cotlet, G.; Blue, T.E.

    2000-03-01

    A stochastic model, based on consensus principles from radiation biology, is used to estimate bone-marrow stem cell pool survival (CFU-S and stroma cells) after irradiation. The dose response model consists of three coupled first order linear differential equations which quantitatively describe time dependent cellular damage, repair, and killing of red bone marrow cells. This system of differential equations is solved analytically through the use of a matrix approach for continuous and fractionated irradiations. The analytic solutions are confirmed through the dynamical solution of the model equations using SIMULINK. Rate coefficients describing the cellular processes of radiation damage and repair, extrapolated to humans from animal data sets and adjusted for neutron-gamma mixed fields, are employed in a SIMULINK analysis of criticality accidents. The results show that, for the time structures which may occur in criticality accidents, cell survival is established mainly by the average dose and dose rate.

  14. Bone marrow examination before steroids in thrombocytopenic purpura or arthritis.

    PubMed

    Reid, M M

    1992-12-01

    Corticosteroids were used to treat two children with presumed idiopathic thrombocytopenic purpura and one with juvenile rheumatoid arthritis without examination of the bone marrow. Of the two with presumed idiopathic thrombocytopenic purpura, one had Fanconi's anaemia and the other may have had aplastic anaemia. The third child had acute lymphoblastic leukaemia. The diagnosis of Fanconi's anaemia was delayed. A diagnostic and therapeutic dilemma was caused in the second case. In the third, delayed diagnosis and, perhaps, compromised outlook resulted. These three cases re-emphasize the well aired caveats about the diagnosis of idiopathic thrombocytopenic purpura and juvenile rheumatoid arthritis and provide further support for the arguments of those who believe that if corticosteroids are to be used to treat such children, their bone marrow should be examined first. PMID:1290852

  15. Ethical issues in bone marrow transplantation in children.

    PubMed

    Bendorf, Aric; Kerridge, Ian H

    2011-09-01

    In the 50 years since the first successful human bone marrow transplant (BMT) was performed in 1959, BMT has become the optimal therapy for a wide variety of life-threatening paediatric haematological, immunological and genetic disorders. Unfortunately, while BMT generally provides the only possibility of cure for such afflicted children, few (25%) have a matched sibling available, and suitably matched unrelated donors are often not identified for many children in need of BMT. And even where BMT is possible, treatment is complex and arduous and associated with significant mortality and morbidity. The issues raised when either or both the donor and recipient are children and lack the capacity to make informed and rational decisions relating to BMT pose great challenges for all involved. This paper examines some of the ethical dilemmas that confront patients, families and medical practitioners when considering bone marrow transplantation in a child. PMID:21951444

  16. Total lymphatic irradiation and bone marrow in human heart transplantation

    SciTech Connect

    Kahn, D.R.; Hong, R.; Greenberg, A.J.; Gilbert, E.F.; Dacumos, G.C.; Dufek, J.H.

    1984-08-01

    Six patients, aged 36 to 59 years, had heart transplants for terminal myocardial disease using total lymphatic irradiation (TLI) and donor bone marrow in addition to conventional therapy. All patients were poor candidates for transplantation because of marked pulmonary hypertension, unacceptable tissue matching, or age. Two patients are living and well more than four years after the transplants. Two patients died of infection at six and seven weeks with normal hearts. One patient, whose preoperative pulmonary hypertension was too great for an orthotopic heart transplant, died at 10 days after such a procedure. The other patient died of chronic rejection seven months postoperatively. Donor-specific tolerance developed in 2 patients. TLI and donor bone marrow can produce specific tolerance to donor antigens and allow easy control of rejection, but infection is still a major problem. We describe a new technique of administering TLI with early reduction of prednisone that may help this problem.

  17. 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. PMID:15131104

  18. [Diagnosis and management of inherited bone marrow failure syndrome].

    PubMed

    Yabe, Miharu; Yabe, Hiromasa

    2015-10-01

    The inherited bone marrow failure syndromes (IBMFS) are rare disorders in which there is usually some form of bone marrow failure and typical changes in physical appearance, associated with a family history of the same disorder. Patients with IBMFS have a very high risk of developing myelodysplastic syndrome, acute myeloid leukemia, and solid tumors. The latest technology applied to the molecular pathogenesis of these disorders has led to identification of specific genetic mutations and now facilitates determining the appropriate diagnosis and management of afflicted patients. In this section, we describe physical and laboratory findings and management of the major IBMFS: Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, and Diamond Blackfan anemia. We also discuss their possible implications in the clinical features of Japanese patients. PMID:26458429

  19. Bone marrow stem cell as a potential treatment for diabetes.

    PubMed

    Li, Ming; Ikehara, Susumu

    2013-01-01

    Diabetes mellitus (DM) is a group of metabolic diseases in which a person has high blood glucose levels resulting from defects in insulin secretion and insulin action. The chronic hyperglycemia damages the eyes, kidneys, nerves, heart, and blood vessels. Curative therapies mainly include diet, insulin, and oral hypoglycemic agents. However, these therapies fail to maintain blood glucose levels in the normal range all the time. Although pancreas or islet-cell transplantation achieves better glucose control, a major obstacle is the shortage of donor organs. Recently, research has focused on stem cells which can be classified into embryonic stem cells (ESCs) and tissue stem cells (TSCs) to generate functional β cells. TSCs include the bone-marrow-, liver-, and pancreas-derived stem cells. In this review, we focus on treatment using bone marrow stem cells for type 1 and 2 DM. PMID:23671865

  20. Bone marrow-derived stem cells and respiratory disease.

    PubMed

    Jones, Carla P; Rankin, Sara M

    2011-07-01

    Adult bone marrow contains a number of discrete populations of progenitor cells, including endothelial, mesenchymal, and epithelial progenitor cells and fibrocytes. In the context of a range of diseases, endothelial progenitor cells have been reported to promote angiogenesis, mesenchymal stem cells are potent immunosuppressors but can also contribute directly to tissue regeneration, and fibrocytes have been shown to induce tissue fibrosis. This article provides an overview of the basic biology of these different subsets of progenitor cells, reporting their distinct phenotypes and functional activities. The differences in their secretomes are highlighted, and the relative role of cellular differentiation vs paracrine effects of progenitor cells is considered. The article reviews the literature examining the contribution of progenitor cells to the pathogenesis of respiratory disease, and discusses recent studies using bone marrow progenitor cells as stem cell therapies in the context of pulmonary hypertension, COPD, and asthma. PMID:21729891

  1. Late renal dysfunction in adult survivors of bone marrow transplantation

    SciTech Connect

    Lawton, C.A.; Cohen, E.P.; Barber-Derus, S.W.; Murray, K.J.; Ash, R.C.; Casper, J.T.; Moulder, J.E. )

    1991-06-01

    Until recently long-term renal toxicity has not been considered a major late complication of bone marrow transplantation (BMT). Late renal dysfunction has been described in a pediatric population status post-BMT which was attributable to the radiation in the preparatory regimen. A thorough review of adults with this type of late renal dysfunction has not previously been described. Fourteen of 103 evaluable adult patients undergoing allogeneic (96) or autologous (7) bone marrow transplantation, predominantly for leukemia and lymphomas, at the Medical College of Wisconsin (Milwaukee, WI) have had a syndrome of renal insufficiency characterized by increased serum creatinine, decreased glomerular filtration rate, anemia, and hypertension. This syndrome developed at a median of 9 months (range, 4.5 to 26 months) posttransplantation in the absence of specific identifiable causes. The cumulative probability of having this renal dysfunction is 20% at 1 year. Renal biopsies performed on seven of these cases showed the endothelium widely separated from the basement membrane, extreme thickening of the glomerular basement membrane, and microthrombi. Previous chemotherapy, antibiotics, and antifungals as well as cyclosporin may add to and possibly potentiate a primary chemoradiation marrow transplant renal injury, but this clinical syndrome is most analogous to clinical and experimental models of radiation nephritis. This late marrow transplant-associated nephritis should be recognized as a potentially limiting factor in the use of some intensive chemoradiation conditioning regimens used for BMT. Some selective attenuation of the radiation to the kidneys may decrease the incidence of this renal dysfunction.

  2. 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

  3. Primary cutaneous aspergillosis and idiopathic bone marrow aplasia.

    PubMed

    Furlan, Karina Colossi; Pires, Mario Cezar; Kakizaki, Priscila; Chartuni, Juliana Cabral Nunes; Valente, Neusa Yuriko Sakai

    2016-01-01

    We describe the case of a 9-year-old boy with idiopathic bone marrow aplasia and severe neutropenia, who developed skin ulcers under cardiac monitoring electrodes. The diagnosis of primary cutaneous aspergillosis was made after the second biopsy and culture. Imaging investigation did not reveal internal fungal infection. The child was treated, but did not improve and died 3 months after admission. The report highlights and discusses the preventable risk of aspergillus skin infection in immunocompromised patients. PMID:27438213

  4. Shifts in bone marrow cell phenotypes caused by spaceflight.

    PubMed

    Ortega, M Teresa; Pecaut, Michael J; Gridley, Daila S; Stodieck, Louis S; Ferguson, Virginia; Chapes, Stephen K

    2009-02-01

    Bone marrow cells were isolated from the humeri of C57BL/6 mice after a 13-day flight on the space shuttle Space Transportation System (STS)-118 to determine how spaceflight affects differentiation of cells in the granulocytic lineage. We used flow cytometry to assess the expression of molecules that define the maturation/activation state of cells in the granulocytic lineage on three bone marrow cell subpopulations. These molecules included Ly6C, CD11b, CD31 (platelet endothelial cell adhesion molecule-1), Ly6G (Gr-1), F4/80, CD44, and c-Fos. The three subpopulations were small agranular cells [region (R)1], larger granular cells (R2), which were mostly neutrophils, and very large, very granular cells (R3), which had properties of macrophages. Although there were no composite phenotypic differences between total bone marrow cells isolated from spaceflight and ground-control mice, there were subpopulation differences in Ly6C (R1 and R3), CD11b (R2), CD31 (R1, R2, and R3), Ly6G (R3), F4/80 (R3), CD44(high) (R3), and c-Fos (R1, R2, and R3). In particular, the elevation of CD11b in the R2 subpopulation suggests neutrophil activation in response to landing. In addition, decreases in Ly6C, c-Fos, CD44(high), and Ly6G and an increase in F4/80 suggest that the cells in the bone marrow R3 subpopulation of spaceflight mice were more differentiated compared with ground-control mice. The presence of more differentiated cells may not pose an immediate risk to immune resistance. However, the reduction in less differentiated cells may forebode future consequences for macrophage production and host defenses. This is of particular importance to considerations of future long-term spaceflights. PMID:19056998

  5. Primary cutaneous aspergillosis and idiopathic bone marrow aplasia*

    PubMed Central

    Furlan, Karina Colossi; Pires, Mario Cezar; Kakizaki, Priscila; Chartuni, Juliana Cabral Nunes; Valente, Neusa Yuriko Sakai

    2016-01-01

    We describe the case of a 9-year-old boy with idiopathic bone marrow aplasia and severe neutropenia, who developed skin ulcers under cardiac monitoring electrodes. The diagnosis of primary cutaneous aspergillosis was made after the second biopsy and culture. Imaging investigation did not reveal internal fungal infection. The child was treated, but did not improve and died 3 months after admission. The report highlights and discusses the preventable risk of aspergillus skin infection in immunocompromised patients. PMID:27438213

  6. Pancytopenia after allogeneic bone marrow transplant due to copper deficiency.

    PubMed

    Hudspeth, Michelle; Turner, Amy; Miller, Nicole; Lazarchick, John

    2014-05-01

    Pancytopenia occurring 1 year or later after allogeneic bone marrow transplantation typically prompts a primary consideration for relapse. We present the case of a 15-year old-girl who underwent transplantation for therapy-related myelodysplasia secondary to Ewing sarcoma treatment who developed pancytopenia with myelodysplasia 1 year after transplant due to copper deficiency. Copper deficiency is an important consideration in the evaluation of pancytopenia and myelodysplasia in pediatric patients. PMID:23652881

  7. Thymopoietic and Bone Marrow Response to Murine Pneumocystis Pneumonia▿

    PubMed Central

    Shi, Xin; Zhang, Ping; Sempowski, Gregory D.; Shellito, Judd E.

    2011-01-01

    CD4+ T cells play a key role in host defense against Pneumocystis infection. To define the role of naïve CD4+ T cell production through the thymopoietic response in host defense against Pneumocystis infection, Pneumocystis murina infection in the lung was induced in adult male C57BL/6 mice with and without prior thymectomy. Pneumocystis infection caused a significant increase in the number of CCR9+ multipotent progenitor (MPP) cells in the bone marrow and peripheral circulation, an increase in populations of earliest thymic progenitors (ETPs) and double negative (DN) thymocytes in the thymus, and recruitment of naïve and total CD4+ T cells into the alveolar space. The level of murine signal joint T cell receptor excision circles (msjTRECs) in spleen CD4+ cells was increased at 5 weeks post-Pneumocystis infection. In thymectomized mice, the numbers of naïve, central memory, and total CD4+ T cells in all tissues examined were markedly reduced following Pneumocystis infection. This deficiency of naïve and central memory CD4+ T cells was associated with delayed pulmonary clearance of Pneumocystis. Extracts of Pneumocystis resulted in an increase in the number of CCR9+ MPPs in the cultured bone marrow cells. Stimulation of cultured bone marrow cells with ligands to Toll-like receptor 2 ([TLR-2] zymosan) and TLR-9 (ODN M362) each caused a similar increase in CCR9+ MPP cells via activation of the Jun N-terminal protein kinase (JNK) pathway. These results demonstrate that enhanced production of naïve CD4+ T lymphocytes through the thymopoietic response and enhanced delivery of lymphopoietic precursors from the bone marrow play an important role in host defense against Pneumocystis infection. PMID:21343353

  8. The bone marrow niche for haematopoietic stem cells

    PubMed Central

    Morrison, Sean J.; Scadden, David T.

    2015-01-01

    Preface Niches are local tissue microenvironments that maintain and regulate stem cells. Haematopoiesis provides a paradigm for understanding mammalian stem cells and their niches, yet the haematopoietic stem cell (HSC) niche remains incompletely defined and beset by competing models. Here we review progress in elucidating the location and cellular components of the HSC niche in the bone marrow. The niche is perivascular, created partly by mesenchymal stromal cells and endothelial cells and often, but not always, located near trabecular bone. Outstanding questions concern the cellular complexity of the niche, the role of the endosteum, and functional heterogeneity among perivascular microenvironments. PMID:24429631

  9. The in situ mechanics of trabecular bone marrow: the potential for mechanobiological response.

    PubMed

    Metzger, Thomas A; Kreipke, Tyler C; Vaughan, Ted J; McNamara, Laoise M; Niebur, Glen L

    2015-01-01

    Bone adapts to habitual loading through mechanobiological signaling. Osteocytes are the primary mechanical sensors in bone, upregulating osteogenic factors and downregulating osteoinhibitors, and recruiting osteoclasts to resorb bone in response to microdamage accumulation. However, most of the cell populations of the bone marrow niche,which are intimately involved with bone remodeling as the source of bone osteoblast and osteoclast progenitors, are also mechanosensitive. We hypothesized that the deformation of trabecular bone would impart mechanical stress within the entrapped bone marrow consistent with mechanostimulation of the constituent cells. Detailed fluid-structure interaction models of porcine femoral trabecular bone and bone marrow were created using tetrahedral finite element meshes. The marrow was allowed to flow freely within the bone pores, while the bone was compressed to 2000 or 3000 microstrain at the apparent level.Marrow properties were parametrically varied from a constant 400 mPas to a power law rule exceeding 85 Pas. Deformation generated almost no shear stress or pressure in the marrow for the low viscosity fluid, but exceeded 5 Pa when the higher viscosity models were used. The shear stress was higher when the strain rate increased and in higher volume fraction bone. The results demonstrate that cells within the trabecular bone marrow could be mechanically stimulated by bone deformation, depending on deformation rate, bone porosity, and bone marrow properties. Since the marrow contains many mechanosensitive cells, changes in the stimulatory levels may explain the alterations in bone marrow morphology with aging and disease, which may in turn affect the trabecular bone mechanobiology and adaptation. PMID:25363343

  10. High Incidence of Xenogenic Bone Marrow Engraftment in Pig-to-Baboon Intra-Bone Bone Marrow Transplantation

    PubMed Central

    Tasaki, M.; Wamala, I.; Tena, A.; Villani, V.; Sekijima, M.; Pathiraja, V.; Wilkinson, R. A.; Pratts, S.; Cormack, T.; Clayman, E.; Arn, J. S.; Shimizu, A.; Fishman, J. A.; Sachs, D. H.; Yamada, K.

    2015-01-01

    Previous attempts of α-1,3-galactocyltransferase knockout (GalTKO) pig bone marrow (BM) transplantation (Tx) into baboons have demonstrated a loss of macro-chimerism within 24 h in most cases. In order to achieve improved engraftment with persistence of peripheral chimerism, we have developed a new strategy of intra-bone BM (IBBM) Tx. Six baboons received GalTKO BM cells, with one-half of the cells transplanted into the bilateral tibiae directly and the remaining cells injected intravenously (IBBM/BM-Tx) with a conditioning immunosuppressive regimen. In order to assess immune responses induced by the combined IBBM/BM-Tx, three recipients received donor SLA-matched GalTKO kidneys in the peri-operative period of IBBM/BM-Tx (Group 1), and the others received kidneys 2 months after IBBM/BM-Tx (Group 2). Peripheral macro-chimerism was continuously detectable for up to 13 days (mean 7.7 days; range 3–13) post-IBBM/BM-Tx and in three animals, macro-chimerism reappeared at days 10, 14 and 21. Pig CFUs, indicating porcine progenitor cell engraftment, were detected in the host BM in four of six recipients on days 14, 15, 19 and 28. In addition, anti-pig unresponsiveness was observed by in vitro assays. GalTKO/pCMV-kidneys survived for extended periods (47 and 60 days). This strategy may provide a potent adjunct for inducing xenogeneic tolerance through BM-Tx. PMID:25676635

  11. Bone marrow stem cells: current and emerging concepts.

    PubMed

    Méndez-Ferrer, Simón; Scadden, David T; Sánchez-Aguilera, Abel

    2015-01-01

    The interactions of stromal cells with hematopoietic cells in the bone marrow have long been a subject of research, but only recently have technologies allowed us to dissect them at the stem cell level. On the other hand, limitations of these technical tools might explain numerous discrepancies in this field. It is becoming increasingly clear that mesenchymal stem cells (MSCs) represent an important component of the hematopoietic stem cell (HSC) niche in the bone marrow. However, there is heterogeneity among HSCs, and many putatively different mesenchymal progenitors identified in the bone marrow using Cre recombinase-driven mouse lines seem to exhibit HSC niche properties. Development of better reporter lines has demonstrated that some of these Cre lines do not always specifically mark the expected cells. Also, characterization of different cell populations has often been partial, and issues of redundancy and compensation might explain apparently contradictory results. Recognizing and overcoming these limitations, while also clearly defining the distinctions between subgroups of mesenchymal cells, will be essential to advance the field. PMID:25573321

  12. Effect of cyclophosphamide and electromagnetic fields on mouse bone marrow

    SciTech Connect

    Cadossi, R.; Zucchini, P.; Emilia, G.; Torelli, G. )

    1990-02-26

    The authors have previously shown that the exposure to low frequency pulsing electromagnetic fields (PEMF) of mice X-ray irradiated resulted in an increased damage to the bone marrow. The series of experiments here reported were designed to investigate the effect of PEMF exposure after intraperitoneum injection of 200mg/kg of cyclophosphamide (CY). Control mice were CY injected only; experimental mice were CY injected and then exposed to PEMF. Exposure to PEMF (24 hours/day) increased the rate of decline of white blood cells in peripheral blood. Spleen weight was statistically higher among control mice than among mice exposed to PEMF at day 6, 8 and 10 after CY injection. Spleen autoradiography proved to be higher among PEMF exposed mice than among controls at day 8 and 9 after CY injection. The grafting efficiency of the bone marrow obtained from control mice was higher than the grafting efficiency of the bone marrow recovered from mice exposed to PEMF. All these data indicate that the exposure to PEMF increases the cytotoxic effect of CY.

  13. Isolation of Mouse Bone Marrow Mesenchymal Stem Cells.

    PubMed

    Boregowda, Siddaraju V; Krishnappa, Veena; Phinney, Donald G

    2016-01-01

    Mesenchymal stem cells (MSCs) were initially characterized as connective tissue progenitors resident in bone marrow, but have now been isolated from a variety of tissues and organs and shown to also exhibit potent tissue regenerative properties mediated largely via paracrine actions. These findings have spurred the development of MSC-based therapies for treating a diverse array of nonskeletal diseases. Although genetic and experimental rodent models of disease represent important tools for developing efficacious MSC-based therapies, development of reliable methods to isolate MSCs from mouse bone marrow has been hampered by the unique biological properties of these cells. Indeed, few isolation schemes afford high yields and purity while maintaining the genomic integrity of cells. We recently demonstrated that mouse MSCs are highly sensitive to oxidative stress, and long-term expansion of these cells in atmospheric oxygen selects for immortalized clones that lack a functional p53 protein. Herein, we describe a protocol for the isolation of primary MSCs from mouse bone marrow that couples immunodepletion with culture in a low-oxygen environment and affords high purity and yield while preserving p53 function. PMID:27236673

  14. Bone Marrow Stem Cell Contribution to Pulmonary Homeostasis and Disease

    PubMed Central

    McDonald, Lindsay T; LaRue, Amanda C

    2015-01-01

    The understanding of bone marrow stem cell plasticity and contribution of bone marrow stem cells to pathophysiology is evolving with the advent of innovative technologies. Recent data has led to new mechanistic insights in the field of mesenchymal stem cell (MSC) research, and an increased appreciation for the plasticity of the hematopoietic stem cell (HSC). In this review, we discuss current research examining the origin of pulmonary cell types from endogenous lung stem and progenitor cells as well as bone marrow-derived stem cells (MSCs and HSCs) and their contributions to lung homeostasis and pathology. We specifically highlight recent findings from our laboratory that demonstrate an HSC origin for pulmonary fibroblasts based on transplantation of a clonal population of cells derived from a single HSC. These findings demonstrate the importance of developing an understanding of the sources of effector cells in disease state. Finally, a perspective is given on the potential clinical implications of these studies and others addressing stem cell contributions to lung tissue homeostasis and pathology. PMID:26798846

  15. Bone marrow leishmaniasis: a review of situation in Thailand.

    PubMed

    Wiwanitkit, Viroj

    2011-10-01

    Leishmaniasis is an important tropical vector-borne disease. This infection can be seen in tropical area and it is considered to be one of the most important vector-borne infections at present. The general situation of the leishmaniasis in Thailand is hereby reviewed. Although Thailand is a tropical country, the leishmaniasis is not endemic but sporadic. The imported cases are documented in some literatures. The serious form of leishmaniasis, the visceral leishmaniasis is also detectable in Thailand. Also, the author performed an in depth literature review of the reports of bone marrow leishmaniasis, a specific kind of visceral leishmaniasis, in Thailand in order to summarize the characteristics of this infection among Thai patients. According to this review, there have been at least 5 reports in the literature of 6 cases of bone marrow leishmaniasis in the Thai population, of which no case was lethal. Concerning the clinical manifestations, all except had prolonged fever with unknown origin. From physical examination, all had hepatosplenomegaly. The striking findings were active hemophagocytosis with increased proliferation of lymphoidplasma cell line in the bone marrow and amastigotes of Leishmania donovani was demonstrated. Considering the treatment, pantavalent antimony compound was used and the excellent improvement and complete recovery. Finally, the author also discussed on the importance of leishmaniasis in Thailand relating to the present globalization and good traveling system. PMID:22014727

  16. T2 vertebral bone marrow changes after space flight

    NASA Technical Reports Server (NTRS)

    LeBlanc, A.; Lin, C.; Evans, H.; Shackelford, L.; Martin, C.; Hedrick, T.

    1999-01-01

    Bone biopsies indicate that during immobilization bone marrow adipose tissue increases while the functional cellular fraction decreases. One objective of our Spacelab flight experiment was to determine, using in vivo volume-localized magnetic resonance spectroscopy (VLMRS), whether bone marrow composition was altered by space flight. Four crew members of a 17 day Spacelab mission participated in the experiment. The apparent cellular fraction and transverse relaxation time (T2) were determined twice before launch and at several times after flight. Immediately after flight, no significant change in the cellular fraction was found. However, the T2 of the cellular, but not the fat component increased following flight, although to a variable extent, in all crew members with a time course for return to baseline lasting several months. The T2 of seven control subjects showed no significant change. Although these observations may have several explanations, it is speculated that the observed T2 changes might reflect increased marrow osteoblastic activity during recovery from space flight.

  17. Bone marrow purging by a xanthine oxidase-antibody conjugate.

    PubMed

    Dinota, A; Tazzari, P L; Abbondanza, A; Battelli, M G; Gobbi, M; Stirpe, F

    1990-07-01

    The selective cytotoxicity of the xanthine oxidase conjugated to an 8A monoclonal antibody recognizing a human plasma cell-associated antigen has been described. The selectivity and the toxicity of the hypoxanthine/conjugated xanthine oxidase system was increased by removing the excess of conjugate and by adding chelated iron. Under these experimental conditions the cytotoxicity of the conjugate exceeded that of free xanthine oxidase by one order of magnitude. The conjugate effectively purged bone marrow from infiltrating neoplastic plasma cells and added target Raji cells, provided blood was removed and bone marrow peroxidases were exhausted. In conditions of purging effectiveness the conjugate had no toxicity to CFU-GM. No toxicity to mice was observed after i.v. injection of xanthine oxidase-antibody conjugate up to 2.9 U/kg body weight. Thus the hypoxanthine/conjugated xanthine oxidase system could be an effective and nontoxic tool for the ex vivo bone marrow purging in multiple myeloma patients for autologous transplantation. PMID:2390631

  18. [The role of blood banks in bone marrow transplantation].

    PubMed

    Höcker, P; Wagner, A; Sklenar, G

    1991-01-01

    The transfusion service (TS) plays an important role in bone marrow transplantation (BMT). Many of the techniques and methods employed are also used in the daily work of a TS like tissue typing, apheresis techniques, handling of blood and its components under sterile conditions. In the pretransplantation phase the TS is responsible for the typing of recipient and presumptive donors, harvesting of autologous blood and selection of appropriate blood components. During BMT the TS can perform bone marrow harvesting, depletion of red cells in case of ABO-incompatibility and bone marrow manipulation when T-cell depletion or purging procedures are considered. Peripheral stem cell harvest by apheresis is also best performed by the TS experienced in such techniques. Storage of hematopoietic cells in liquid nitrogen and thawing are also techniques already used in most of the transfusion services. Post BMT, the support with blood components, irradiated and almost free of white cells to avoid TA-GVH and CMV-infection, is a major job of the TS. These facts demonstrate that a well organized transfusion service is a 'conditio sine qua non' for successful BMT. PMID:1725636

  19. The effect of autologous bone marrow stromal cells differentiated on scaffolds for canine tibial bone reconstruction.

    PubMed

    Özdal-Kurt, F; Tuğlu, I; Vatansever, H S; Tong, S; Deliloğlu-Gürhan, S I

    2015-01-01

    Bone marrow contains mesenchymal stem cells that form many tissues. Various scaffolds are available for bone reconstruction by tissue engineering. Osteoblastic differentiated bone marrow stromal cells (BMSC) promote osteogenesis on scaffolds and stimulate bone regeneration. We investigated the use of cultured autologous BMSC on different scaffolds for healing defects in tibias of adult male canines. BMSC were isolated from canine humerus bone marrow, differentiated into osteoblasts in culture and loaded onto porous ceramic scaffolds including hydroxyapatite 1, hydroxyapatite gel and calcium phosphate. Osteoblast differentiation was verified by osteonectine and osteocalcine immunocytochemistry. The scaffolds with stromal cells were implanted in the tibial defect. Scaffolds without stromal cells were used as controls. Sections from the defects were processed for histological, ultrastructural, immunohistochemical and histomorphometric analyses to analyze the healing of the defects. BMSC were spread, allowed to proliferate and differentiate to osteoblasts as shown by alizarin red histochemistry, and osteocalcine and osteonectine immunostaining. Scanning electron microscopy showed that BMSC on the scaffolds were more active and adhesive to the calcium phosphate scaffold compared to the others. Macroscopic bone formation was observed in all groups, but scaffolds with stromal cells produced significantly better results. Bone healing occurred earlier and faster with stromal cells on the calcium phosphate scaffold and produced more callus compared to other scaffolds. Tissue healing and osteoblastic marker expression also were better with stromal cells on the scaffolds. Increased trabecula formation, cell density and decreased fibrosis were observed in the calcium phosphate scaffold with stromal cells. Autologous cultured stromal cells on the scaffolds were useful for healing of canine tibial bone defects. The calcium phosphate scaffold was the best for both cell

  20. Generation of clinical grade human bone marrow stromal cells for use in bone regeneration.

    PubMed

    Robey, Pamela G; Kuznetsov, Sergei A; Ren, Jiaqiang; Klein, Harvey G; Sabatino, Marianna; Stroncek, David F

    2015-01-01

    In current orthopaedic practice, there is a need to increase the ability to reconstruct large segments of bone lost due to trauma, resection of tumors and skeletal deformities, or when normal regenerative processes have failed such as in non-unions and avascular necrosis. Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells), when used in conjunction with appropriate carriers, represent a means by which to achieve bone regeneration in such cases. While much has been done at the bench and in pre-clinical studies, moving towards clinical application requires the generation of clinical grade cells. What is described herein is an FDA-approved cell manufacturing procedure for the ex vivo expansion of high quality, biologically active human BMSCs. This article is part of a Special Issue entitled Stem Cells and Bone. PMID:25064527

  1. Thy-1+ dendritic cells in murine epidermis are bone marrow-derived

    SciTech Connect

    Breathnach, S.M.; Katz, S.I.

    1984-07-01

    Thy-1+, Ly-5+ dendritic cells have recently been described as a resident cell population in murine epidermis, but their ontogeny and function are unknown. The origin and turnover of epidermal Thy-1+ cells utilizing chimeric mice were investigated. Lethally x-irradiated AKR/J (Thy-1.1+) and AKR/Cum (Thy-1.2+) mice were reconstituted with allogeneic bone marrow cells with or without thymocytes from congenic AKR/Cum or AKR/J mice, respectively. The density of residual indigenous Thy-1.1+ cells in AKR/J chimeras and Thy-1.2+ cells in AKR/Cum chimeras was substantially reduced following x-irradiation, as determined by immunofluorescence staining of epidermal sheets. Epidermal repopulation by allogeneic Thy-1+ dendritic epidermal cells was first observed at 5 weeks in AKR/J chimeras and at 7 weeks in AKR/Cum chimeras and progressed slowly. Repopulation was not enhanced by increasing the number of allogeneic bone marrow cells injected from 2 X 10(7) to 10(8) cells or by the addition of 8 X 10(7) allogeneic thymocytes to the donor inoculate. Epidermal repopulation by allogeneic Thy-1.2+ cells was not seen in AKR/J mice reconstituted with syngeneic bone marrow cells and allogeneic Thy-1.2+ AKR/Cum thymocytes. Taken together, these results indicate that Thy-1+ dendritic epidermal cells are derived from the bone marrow and suggest that they are not related to conventional peripheral T-lymphocytes.

  2. A comparison of flow cytometry, bone marrow biopsy, and bone marrow aspirates in the detection of lymphoid infiltration in B cell disorders

    PubMed Central

    Sah, S P; Matutes, E; Wotherspoon, A C; Morilla, R; Catovsky, D

    2003-01-01

    Aims: To evaluate the diagnostic value of bone marrow aspirates, trephine biopsies (BMB), and flow cytometry (FC) in the assessment of bone marrow infiltration in chronic lymphoid disorders. Methods: Investigations were carried out in 110 diagnostic and follow up specimens from B cell disorders, namely: chronic lymphocytic leukaemia (CLL; 65), non-Hodgkin’s lymphoma (NHL; 39), and hairy cell leukaemia (HCL; 6). A selected panel of monoclonal antibodies was used both for FC and immunohistochemistry. Results: In CLL there was agreement between the three investigations in 71% of samples and in 88% when only FC and BMB were compared. In nine of 65 samples, FC and BMB were positive, although the aspirate was reported as negative. Four BMB negative samples had minimal residual disease (MRD) detected by FC, whereas two samples were positive both on BMB and aspirate but showed no evidence of disease on FC. In NHL, there was agreement between the three investigations in 22 of 39 cases, and in 27 of 39 cases there was agreement between FC and BMB. In eight of 39 NHL cases, FC was negative but the BMB was either positive (five) or uncertain (three), whereas in three of 39, FC was positive but BMB was either negative (one) or uncertain (two). In three of five uncertain BMB, no clonal population was detected by the polymerase chain reaction, whereas in the remaining two cases the nodular aggregates disappeared on further sectioning. Conclusions: Both BMB and FC are better than bone marrow aspirates for the detection of infiltration in B cell disorders. FC might be slightly more sensitive than BMB to detect MRD in CLL, whereas BMB may be slightly better than FC in NHL. PMID:12560392

  3. Changes in vertebral bone marrow fat and bone mass after gastric bypass surgery: A pilot study.

    PubMed

    Schafer, A L; Li, X; Schwartz, A V; Tufts, L S; Wheeler, A L; Grunfeld, C; Stewart, L; Rogers, S J; Carter, J T; Posselt, A M; Black, D M; Shoback, D M

    2015-05-01

    Bone marrow fat may serve a metabolic role distinct from other fat depots, and it may be altered by metabolic conditions including diabetes. Caloric restriction paradoxically increases marrow fat in mice, and women with anorexia nervosa have high marrow fat. The longitudinal effect of weight loss on marrow fat in humans is unknown. We hypothesized that marrow fat increases after Roux-en-Y gastric bypass (RYGB) surgery, as total body fat decreases. In a pilot study of 11 morbidly obese women (6 diabetic, 5 nondiabetic), we measured vertebral marrow fat content (percentage fat fraction) before and 6 months after RYGB using magnetic resonance spectroscopy. Total body fat mass declined in all participants (mean ± SD decline 19.1 ± 6.1 kg or 36.5% ± 10.9%, p<0.001). Areal bone mineral density (BMD) decreased by 5.2% ± 3.5% and 4.1% ± 2.6% at the femoral neck and total hip, respectively, and volumetric BMD decreased at the spine by 7.4% ± 2.8% (p<0.001 for all). Effects of RYGB on marrow fat differed by diabetes status (adjusted p=0.04). There was little mean change in marrow fat in nondiabetic women (mean +0.9%, 95% CI -10.0 to +11.7%, p=0.84). In contrast, marrow fat decreased in diabetic women (-7.5%, 95% CI -15.2 to +0.1%, p=0.05). Changes in total body fat mass and marrow fat were inversely correlated among nondiabetic (r=-0.96, p=0.01) but not diabetic (r=0.52, p=0.29) participants. In conclusion, among those without diabetes, marrow fat is maintained on average after RYGB, despite dramatic declines in overall fat mass. Among those with diabetes, RYGB may reduce marrow fat. Thus, future studies of marrow fat should take diabetes status into account. Marrow fat may have unique metabolic behavior compared with other fat depots. PMID:25603463

  4. Changes in Vertebral Bone Marrow Fat and Bone Mass After Gastric Bypass Surgery: A Pilot Study

    PubMed Central

    Schafer, AL; Li, X; Schwartz, AV; Tufts, LS; Wheeler, AL; Grunfeld, C; Stewart, L; Rogers, SJ; Carter, JT; Posselt, AM; Black, DM; Shoback, DM

    2015-01-01

    Bone marrow fat may serve a metabolic role distinct from other fat depots, and it may be altered by metabolic conditions including diabetes. Caloric restriction paradoxically increases marrow fat in mice, and women with anorexia nervosa have high marrow fat. The longitudinal effect of weight loss on marrow fat in humans is unknown. We hypothesized that marrow fat increases after Roux-en-Y gastric bypass (RYGB) surgery, as total body fat decreases. In a pilot study of 11 morbidly obese women (6 diabetic, 5 nondiabetic), we measured vertebral marrow fat content (percentage fat fraction) before and 6 months after RYGB using magnetic resonance spectroscopy. Total body fat mass declined in all participants (mean ±SD decline 19.1 ±6.1 kg or 36.5 ±10.9%, p<0.001). Areal bone mineral density (BMD) decreased by 5.2 ±3.5% and 4.1 ±2.6% at the femoral neck and total hip, respectively, and volumetric BMD decreased at the spine by 7.4 ±2.8% (p<0.001 for all). Effects of RYGB on marrow fat differed by diabetes status (adjusted p=0.04). There was little mean change in marrow fat in nondiabetic women (mean +0.9%, 95% CI -10.0 to +11.7%, p=0.84). In contrast, marrow fat decreased in diabetic women (−7.5%, 95% CI -15.2 to +0.1%, p=0.05). Changes in total body fat mass and marrow fat were inversely correlated among nondiabetic (r=−0.96, p=0.01) but not diabetic (r=0.52, p=0.29) participants. In conclusion, among those without diabetes, marrow fat is maintained on average after RYGB, despite dramatic declines in overall fat mass. Among those with diabetes, RYGB may reduce marrow fat. Thus, future studies of marrow fat should take diabetes status into account. Marrow fat may have unique metabolic behavior compared with other fat depots. PMID:25603463

  5. Failure to Generate Bone Marrow Adipocytes Does Not Protect Mice from Ovariectomy-Induced Osteopenia

    PubMed Central

    Iwaniec, Urszula T.; Turner, Russell T.

    2012-01-01

    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 (kitW/W-v) have no bone marrow adipocytes in tibia or lumbar vertebra. We therefore tested the hypothesis that marrow fat contributes to development of osteopenia by comparing the skeletal response to ovariectomy (ovx) in growing wild type (WT) and bone marrow adipocyte-deficient kitW/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 kitW/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 kitW/W-v mice. However, ovx in WT and kitW/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. PMID:23246792

  6. Bone marrow transplantation after the Chernobyl nuclear accident

    SciTech Connect

    Baranov, A.; Gale, R.P.; Guskova, A.; Piatkin, E.; Selidovkin, G.; Muravyova, L.; Champlin, R.E.; Danilova, N.; Yevseeva, L.; Petrosyan, L. )

    1989-07-27

    On April 26, 1986, an accident at the Chernobyl nuclear power station in the Soviet Union exposed about 200 people to large doses of total-body radiation. Thirteen persons exposed to estimated total-body doses of 5.6 to 13.4 Gy received bone marrow transplants. Two transplant recipients, who received estimated doses of radiation of 5.6 and 8.7 Gy, are alive more than three years after the accident. The others died of various causes, including burns (the cause of death in five), interstitial pneumonitis (three), graft-versus-host disease (two), and acute renal failure and adult respiratory distress syndrome (one). There was hematopoietic (granulocytic) recovery in nine transplant recipients who could be evaluated, six of whom had transient partial engraftment before the recovery of their own marrow. Graft-versus-host disease was diagnosed clinically in four persons and suspected in two others. Although the recovery of endogenous hematopoiesis may occur after exposure to radiation doses of 5.6 to 13.4 Gy, we do not know whether it is more likely after the transient engraftment of transplanted stem cells. Because large doses of radiation affect multiple systems, bone marrow recovery does not necessarily ensure survival. Furthermore, the risk of graft-versus-host disease must be considered when the benefits of this treatment are being weighed.

  7. Role of immobilization of irradiated rats in the protective effect of bone marrow shielding

    NASA Technical Reports Server (NTRS)

    Gronskaya, N. F.; Strelin, G. S.

    1982-01-01

    Rats were exposed to X-radiation to study the influence of immobilization and shielding of part of bone marrow during exposure on survival. It is concluded that (1) the beneficial effect of the stress factor (created by the immobilization of rats during exposure) can aggregate with the effect of bone marrow shielding and, under certain conditions, imitate the latter; and (2) the probability of the protective effect of immobilization should be taken into account when assessing the influence of bone marrow shielding.

  8. Different expression of chemokines in rheumatoid arthritis and osteoarthritis bone marrow

    PubMed Central

    Kurowska, Weronika J.; Radzikowska, Anna; Massalska, Magdalena A.; Burakowski, Tomasz; Kontny, Ewa; Słowińska, Iwona; Gasik, Robert; Maśliński, Włodzimierz

    2016-01-01

    Objectives Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction. In addition to involvement of the joints, there is growing evidence that inflammatory/autoimmune processes take place in bone marrow, beginning the disease onset. Activated T and B cells accumulate in bone marrow, where also effective antigen presentation takes place. An increased number of activated T cells was observed in RA in comparison to osteoarthritis (OA) bone marrow. In the present study we analyzed the levels of chemokines that may be responsible for accumulation/retention of T-cells in the bone marrow of RA and OA patients. Material and methods Bone marrow samples were obtained from RA and OA patients during total hip replacement surgery, and bone marrow plasma was obtained by gradient centrifugation. Levels of the chemokines CX3CL1, CCL5, CCL2, CXCL12 and CXCL1 were measured in bone marrow plasma by specific ELISAs. Comparison between the groups of patients and statistical significance were analyzed by the two-tailed Mann-Whitney U test. Results Increased levels of CX3CL1 (818 ±431 pg/ml vs. 502 ±131 pg/ml, p < 0.0007) and CCL5 (5967 ±1680 pg/ml vs. 4878 ±2360 pg/ml, p < 0.05) respectively in bone marrow plasma from RA in comparison with OA patients were observed. In contrast, similar levels of CCL2, CXCL12 and CXCL1 in RA and OA bone marrow suggest that these cytokines do not play a significant role in the observed T cell accumulation in RA bone marrow. Conclusions CX3CL1 and CCL5 overproduced in RA bone marrow may contribute to the accumulation of T cells observed in RA bone marrow. PMID:27407279

  9. Bone Marrow Dosimetry Using 124I-PET

    PubMed Central

    Schwartz, Jazmin; Humm, John L.; Divgi, Chaitanya R.; Larson, Steven M.; O'Donoghue, Joseph A.

    2012-01-01

    Bone marrow is usually dose-limiting for radioimmunotherapy. In this study, we directly estimated red marrow activity concentration and the self-dose component of absorbed radiation dose to red marrow based on PET/CT of 2 different 124I-labeled antibodies (cG250 and huA33) and compared the results with plasma activity concentration and plasma-based dose estimates. Methods Two groups of patients injected with 124I-labeled monoclonal antibodies (11 patients with renal cancer receiving 124I-cG250 and 5 patients with colorectal cancer receiving 124I- huA33) were imaged by PET or PET/CT on 2 or 3 occasions after infusion. Regions of interest were drawn over several lumbar vertebrae, and red marrow activity concentration was quantified. Plasma activity concentration was also quantified using multiple patient blood samples. The red marrow–to–plasma activity concentration ratio (RMPR) was calculated at the times of imaging. The self-dose component of the absorbed radiation dose to the red marrow was estimated from the images, from the plasma measurements, and using a combination of both sets of measurements. Results RMPR was observed to increase with time for both groups of patients. Mean (±SD) time-dependent RMPR (RMPR(t)) for the cG250 group increased from 0.13 ± 0.06 immediately after infusion to 0.23 ± 0.09 at approximately 6 d after infusion. For the huA33 group, mean RMPR(t) was 0.10 ± 0.04 immediately after infusion, 0.13 ± 0.05 approximately 2 d after infusion, and 0.20 ± 0.09 approximately 7 d after infusion. Plasma-based estimates of red marrow self-dose tended to be greater than image-based values by, on average, 11% and 47% for cG250 and huA33, respectively, but by as much as −73% to 62% for individual patients. The hybrid method combining RMPR(t) and plasma activity concentration provided a closer match to the image-based dose estimates (average discrepancies, −2% and 18% for cG250 and huA33, respectively). Conclusion These results suggest that

  10. Male genital lichen sclerosus in recipients of bone marrow transplants.

    PubMed

    Thomas, L J; Shim, T N; Borysiewicz, C; Dinneen, M; Fawcett, H; Roy, A; Francis, N; Bunker, C B

    2016-07-01

    We describe two patients who received haematopoietic stem cell marrow transplantation, and developed male genital lichen sclerosus (MGLSc), one of whom also had squamous carcinoma in situ (Bowen disease). MGLSc has previously been associated with graft-versus-host disease. Various aetiological factors for LSc have been proposed, including a role for chronic occluded epithelial exposure to urine. A number of factors imply that the risk of malignant transformation in this bone marrow transplant group is likely to be higher than the overall figure of 2-9% cited for MGLSc. It is vital, therefore, that clinicians involved in the care of those with haematological malignancies are adequately prepared to examine the genitals of their patients, and to recognize and refer any suspect penile lesions. PMID:26936088

  11. Lamellar Spacing in Cuboid Hydroxyapatite Scaffolds Regulates Bone Formation by Human Bone Marrow Stromal Cells

    PubMed Central

    Afghani, Shahrzad; Franco, Jaime; Launey, Max; Marshall, Sally; Marshall, Grayson W.; Nissenson, Robert; Lee, Janice; Tomsia, Antoni P.; Saiz, Eduardo

    2011-01-01

    Background A major goal in bone engineering is the creation of large volume constructs (scaffolds and stem cells) that bear load. The scaffolds must satisfy two competing requirements—they need be sufficiently porous to allow nutrient flow to maintain cell viability, yet sufficiently dense to bear load. We studied the effect of scaffold macroporosity on bone formation and scaffold strength, for bone formed by human bone marrow stromal cells. Methods Rigid cubical hydroxyapatite/tricalcium phosphate scaffolds were produced by robo-casting. The ceramic line thickness was held constant, but the distance between adjacent lines was either 50, 100, 200, 500, or 1000 μm. Cultured human bone marrow stromal cells were combined with the scaffolds in vitro; transplants were placed into the subcutis of immunodeficient mice. Transplants were harvested 9, 18, 23, 38, or 50 weeks later. Bone formation and scaffold strength were analyzed using histology and compression testing. Results Sixty transplants were evaluated. Cortical bone increased with transplant age, and was greatest among 500 μm transplants. In contrast, maximum transplant strength was greatest among 200 μm transplants. Conclusions Lamellar spacing within scaffolds regulates the extent of bone formation; 500 μm yields the most new bone, whereas 200 μm yields the strongest transplants. PMID:21294634

  12. Dissecting the Role of Bone Marrow Stromal Cells on Bone Metastases

    PubMed Central

    Buenrostro, Denise; Park, Serk In; Sterling, Julie A.

    2014-01-01

    Tumor-induced bone disease is a dynamic process that involves interactions with many cell types. Once metastatic cancer cells reach the bone, they are in contact with many different cell types that are present in the cell-rich bone marrow. These cells include the immune cells, myeloid cells, fibroblasts, osteoblasts, osteoclasts, and mesenchymal stem cells. Each of these cell populations can influence the behavior or gene expression of both the tumor cells and the bone microenvironment. Additionally, the tumor itself can alter the behavior of these bone marrow cells which further alters both the microenvironment and the tumor cells. While many groups focus on studying these interactions, much remains unknown. A better understanding of the interactions between the tumor cells and the bone microenvironment will improve our knowledge on how tumors establish in bone and may lead to improvements in diagnosing and treating bone metastases. This review details our current knowledge on the interactions between tumor cells that reside in bone and their microenvironment. PMID:25054153

  13. Effect of nephrotoxic drugs on the development of radiation nephropathy after bone marrow transplantation

    SciTech Connect

    Lawton, C.A.; Fish, B.L.; Moulder, J.E. )

    1994-03-01

    Chronic renal failure is a significant cause of late morbidity in bone marrow transplant patients whose conditioning regimen includes total body irradiation (TBI). Radiation is a major cause of this syndrome (bone marrow transplant nephropathy), but it may not be the only cause. These studies use a rat syngeneic bone marrow transplant model to determine whether nephrotoxic agents used in conjunction with bone marrow transplantation (BMT) could be enhancing or accelerating the development of radiation nephropathy. Rats received 11-17 Gy TBI in six fractions over 3 days followed by syngeneic bone marrow transplant. In conjunction with the bone marrow transplants, animals received either no drugs, cyclosporine, amphotericin, gentamicin, or busulfan. Drugs were given in schedules analogous to their use in clinical bone marrow transplantation. Drug doses were chosen so that the drug regimen alone caused detectable acute nephrotoxicity. Animals were followed for 6 months with periodic renal function tests. Gentamicin had no apparent interactions with TBI. Amphotericin increased the incidence of engraftment failure, but did not enhance radiation nephropathy. Cyclosporin with TBI caused late morbidity that appeared to be due to neurological problems, but did not enhance radiation nephropathy. Busulfan resulted in a significant enhancement of radiation nephropathy. Of the nephrotoxins used in conjunction with bone marrow transplantation only radiation and busulfan were found to be risk factors for bone marrow transplant nephropathy. 34 refs., 4 figs., 2 tabs.

  14. Use of impedance plethysmography to continually monitor bone marrow blood flow

    NASA Technical Reports Server (NTRS)

    Montgomery, L. D.; Mcewen, G. N., Jr.; Gerber, R. L.; Cann, C. E.; Morey, E. R.

    1984-01-01

    An impedance-plethysmographic technique is described which can be used to quantify temporal bone-marrow blood-flow changes. Results obtained with the impedance technique compare favorably with the data from simultaneously administered microspheres. Injection of sympathomimetic drugs produced measurable responses: isoproterenol caused a significant increase in bone-marrow blood flow within 1 min, and levarterenol decreased bone-marrow blood flow. Data obtained with impedance plethysmography suggest that the technique is feasible for multiple measurements on the same animal and that the technique can be used to study acute or chronic changes in bone-marrow blood flow following various experimental treatments.

  15. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies

    PubMed Central

    Li, Guihong; Yu, Fengbo; Lei, Ting; Gao, Haijun; Li, Peiwen; Sun, Yuxue; Huang, Haiyan; Mu, Qingchun

    2016-01-01

    Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research. PMID:27482235

  16. Characterization of functions of neutrophils from bone marrow of cattle with leukocyte adhesion deficiency.

    PubMed

    Nagahata, H; Nochi, H; Tamoto, K; Yamashita, K; Noda, H; Kociba, G J

    1995-02-01

    Marked differences in bone marrow cellularity were observed between cattle affected with leukocyte adhesion deficiency (LAD) and control cattle. The number of nucleated cells in bone marrow was 2.9 to 8.8 times higher in cattle affected with LAD, compared with controls. The myeloid-to-erythroid ratio of bone marrow from 3 cattle affected with LAD ranged from 2.4 to 12. Deficient CD18 expression on neutrophils isolated from bone marrow of cattle with LAD was clearly detected by flow cytometric analysis. Neutrophils from bone marrow of cattle affected with LAD appeared round and not flat, after adherence to plastic wells under agarose, whereas neutrophils from bone marrow of clinically normal cattle were firmly spread on the surface of plastic wells. In the chemotaxis under-agarose assay, many pseudopodia were detected on bone marrow neutrophils from clinically normal cattle, but were not detected on bone marrow neutrophils from cattle with LAD. Activities of chemotactic movements and phagocytosis of neutrophils isolated from bone marrow of cattle affected with LAD were documented to be severely impaired. PMID:7717579

  17. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies.

    PubMed

    Li, Guihong; Yu, Fengbo; Lei, Ting; Gao, Haijun; Li, Peiwen; Sun, Yuxue; Huang, Haiyan; Mu, Qingchun

    2016-06-01

    Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research. PMID:27482235

  18. Myeloid regeneration after whole body irradiation, autologous bone marrow transplantation, and treatment with an anabolic steroid.

    PubMed

    Ambrus, C M; Ambrus, J L

    1975-01-01

    Stumptail monkeys (Macaca speciosa) received lethal whole body radiation. Autologous bone marrow injection resulted in survival of the majority of the animals. Treatment with Deca-Durabolin, an anabolic steroid, caused more rapid recovery of colony-forming cell numbers in the bone marrow than in control animals. Both the Deca-Durabolin-treated and control groups were given autologous bone marrow transplantation. Anabolic steroid effect on transplanted bone marrow colonyforming cells may explain the increased rate of leukopoietic regeneration in anabolic steroid-treated animals as compared to controls. PMID:124758

  19. 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

  20. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury

    PubMed Central

    Anbari, Fatemeh; Khalili, Mohammad Ali; Bahrami, Ahmad Reza; Khoradmehr, Arezoo; Sadeghian, Fatemeh; Fesahat, Farzaneh; Nabi, Ali

    2014-01-01

    To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intravenous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and administered 3 × 106 rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat cerebral cortex and rat neurological function was improved significantly. These findings suggest that intravenously administered bone marrow mesenchymal stem cells can promote nerve cell regeneration in injured cerebral cortex, which supplement the lost nerve cells. PMID:25206912

  1. Avascular necrosis of bone after allogeneic bone marrow transplantation: clinical findings, incidence and risk factors.

    PubMed

    Socié, G; Sélimi, F; Sedel, L; Frija, J; Devergie, A; Esperou Bourdeau, H; Ribaud, P; Gluckman, E

    1994-03-01

    In the present study we describe the incidence, clinical course, and management of avascular necrosis of bone following allogeneic bone marrow transplantation, and identify risk factors related to its development. All patients developing avascular necrosis of bone after allogeneic bone marrow transplantation between January 1974 and September 1992 were included in the analysis and were studied using the Hôpital Saint Louis Bone Marrow Transplant Database and hospital records. 27/727 allogeneic transplant recipients developed avascular necrosis leading to an 8.1% incidence at 5 years, by product limit estimate, ranging from 5% to 11.2%. Symptoms developed 119-1747 d (median 398 d) after transplantation. In these 27 patients a total of 52 joints were affected (mean 1.92 per patient, range 1-7). The hip joint was most often affected (69% of patients). All patients had joint pain that led to diagnosis by means of standard radiographs with or without the help of technetium-99 scans and/or magnetic resonance imaging. All but three patients received steroid therapy for acute graft-versus-host disease. Among 10 factors tested, three were shown to be significantly linked to an increased risk for developing avascular necrosis by multivariate analysis: male gender (relative risk (RR) 4.72, P = 0.002), age older than 16 (RR = 3.87, P = 0.004), and acute graft-versus-host disease requiring steroid therapy (RR = 6.30, P = 0.0002). 10 patients (37%) required joint replacement within 19 months (range 2-42) following diagnosis of avascular necrosis. In conclusion, avascular necrosis of bone is a frequent late complication of allogeneic bone marrow transplantation causing significant morbidity and requiring replacement surgery in one-third of affected patients. In this 18-year single-centre survey, older age, male gender and steroid therapy given for acute graft-versus-host disease were shown to independently increase the risk of avascular necrosis of bone. PMID:8043445

  2. Combination chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil causes trabecular bone loss, bone marrow cell depletion and marrow adiposity in female rats.

    PubMed

    Fan, Chiaming; Georgiou, Kristen R; McKinnon, Ross A; Keefe, Dorothy M K; Howe, Peter R C; Xian, Cory J

    2016-05-01

    The introduction of anthracyclines to adjuvant chemotherapy has increased survival rates among breast cancer patients. Cyclophosphamide, epirubicin and 5-fluorouracil (CEF) combination therapy is now one of the preferred regimens for treating node-positive breast cancer due to better survival with less toxicity involved. Despite the increasing use of CEF, its potential in causing adverse skeletal effects remains unclear. Using a mature female rat model mimicking the clinical setting, this study examined the effects of CEF treatment on bone and bone marrow in long bones. Following six cycles of CEF treatment (weekly intravenous injections of cyclophosphamide at 10 mg/kg, epirubicin at 2.5 mg/kg and 5-flurouracil at 10 mg/kg), a significant reduction in trabecular bone volume was observed at the metaphysis, which was associated with a reduced serum level of bone formation marker alkaline phosphatase (ALP), increased trends of osteoclast density and osteoclast area at the metaphysis, as well as an increased size of osteoclasts being formed from the bone marrow cells ex vivo. Moreover, a severe reduction of bone marrow cellularity was observed following CEF treatment, which was accompanied by an increase in marrow adipose tissue volume. This increase in marrow adiposity was associated with an expansion in adipocyte size but not in marrow adipocyte density. Overall, this study indicates that six cycles of CEF chemotherapy may induce some bone loss and severe bone marrow damage. Mechanisms for CEF-induced bone/bone marrow pathologies and potential preventive strategies warrant further investigation. PMID:26056019

  3. Hyaluronan scaffold supports osteogenic differentiation of bone marrow concentrate cells.

    PubMed

    Cavallo, C; Desando, G; Ferrari, A; Zini, N; Mariani, E; Grigolo, B

    2016-01-01

    Osteochondral lesions are considered a challenge for orthopedic surgeons. Currently, the treatments available are often unsatisfactory and unable to stimulate tissue regeneration. Tissue engineering offers a new therapeutic strategy, taking into account the role exerted by cells, biomaterial and growth factors in restoring tissue damage. In this light, Mesenchymal Stem Cells (MSCs) have been indicated as a fascinating tool for regenerative medicine thanks to their ability to differentiate into bone, cartilage and adipose tissue. However, in vitro-cultivation of MSCs could be associated with some risks such as de-differentiation/reprogramming, infection and contaminations of the cells. To overcome these shortcomings, a new approach is represented by the use of Bone Marrow Concentrate (BMC), that could allow the delivery of cells surrounded by their microenvironment in injured tissue. For this purpose, cells require a tridimensional scaffold that can support their adhesion, proliferation and differentiation. This study is focused on the potentiality of BMC seeded onto a hyaluronan-based scaffold (Hyaff-11) to differentiate into osteogenic lineage. This process depends on the specific interaction between cells derived from bone marrow (surrounded by their niche) and scaffold, that create an environment able to support the regeneration of damaged tissue. The data obtained from the present study demonstrate that BMC grown onto Hyaff-11 are able to differentiate toward osteogenic sense, producing specific osteogenic genes and matrix proteins. PMID:27358127

  4. Targeted Pathologic Evaluation of Bone Marrow Donors Identifies Previously Undiagnosed Marrow Abnormalities

    PubMed Central

    Tilson, MP; Jones, RJ; Sexauer, A; Griffin, CA; Morsberger, LA; Batista, DAS; Small, D; Burns, KH; Gocke, CD; Vuica-Ross, M; Borowitz, MJ; Duffield, AS

    2013-01-01

    Potential bone marrow donors are screened to ensure the safety of both the donor and recipient. At our institution, potential donors with abnormal peripheral blood cell counts, a personal history of malignancy, or age >60 years are evaluated to ensure that they are viable candidates for donation. Evaluation of the marrow includes morphologic, flow cytometric and cytogenetic studies. 122 potential donors were screened between the years of 2001–2011, encompassing approximately 10% of all donors. The median age of the screened potential donors was 59 years, and included 59 men and 63 women. The donors were screened because of age >60 years old (33), anemia (22), cytopenias other than anemia (27), elevated peripheral blood counts without a concurrent cytopenia (20), elevated peripheral blood counts with a concurrent cytopenia (10), history of malignancy (4), abnormal peripheral blood differential (3), prior graft failure (1), history of treatment with chemotherapy (1), and body habitus (1). Marrow abnormalities were detected in 9% (11/122) of donors. These donors were screened because of anemia (5/22; 23%), age >60 years (2/33; 6%), history of malignancy (2/4; 50%), elevated peripheral blood counts (1/20; 5%), and body habitus (1/1; 100%). Abnormalities included plasma cell dyscrasia (3), abnormal marrow cellularity (3), clonal cytogenetic abnormalities (2), low-grade myelodysplastic syndrome (1), a mutated JAK2 V617F allele (1), and monoclonal B-cell lymphocytosis (1). Our experience indicates that extended screening of potential donors identifies a significant number of donors with previously undiagnosed marrow abnormalities. PMID:23769818

  5. Rosiglitazone Promotes Bone Marrow Adipogenesis to Impair Myelopoiesis under Stress

    PubMed Central

    Lu, Wenyi; Wang, Weimin; Wang, Shujuan; Feng, Yonghuai; Liu, Kaiyan

    2016-01-01

    Objective The therapeutic use of thiazolidinediones (TZDs) causes unwanted hematological side effects, although the underlying mechanisms of these effects are poorly understood. This study tests the hypothesis that rosiglitazone impairs the maintenance and differentiation of hematopoietic stem/progenitor cells, which ultimately leads to hematological abnormalities. Methods Mice were fed a rosiglitazone-supplemented diet or a normal diet for 6 weeks. To induce hematopoietic stress, all mice were injected once with 250 mg/kg 5-fluorouracil (5-Fu) intraperitoneally. Next, hematopoietic recovery, hematopoietic stem/progenitor cells (HSPCs) subsets, and myeloid differentiation after 5-Fu treatment were evaluated. The adipogenesis induced by rosiglitazone was assessed by histopathology and oil red O staining. The effect of adipocytes on HSPCs was studied with an in vitro co-culture system. Results Rosiglitazone significantly enhanced bone marrow adipogenesis and delayed hematopoietic recovery after 5-Fu treatment. Moreover, rosiglitazone inhibited proliferation of a granulocyte/monocyte progenitor (GMP) cell population and granulocyte/macrophage colony-stimulating factor (GM-CSF) colonies, although the proliferation and mobilization of Lin-c-kit+Sca-1+ cells (LSK) was maintained following hematopoietic stress. These effects could be partially reversed by the selective PPARγ antagonist BADGE. Finally, we demonstrated in a co-culture system that differentiated adipocytes actively suppressed the myeloid differentiation of HSPCs. Conclusion Taken together, our results demonstrate that rosiglitazone inhibits myeloid differentiation of HSPCs after stress partially by inducing bone marrow adipogenesis. Targeting the bone marrow microenvironment might be one mechanism by which rosiglitazone impairs stress-induced hematopoiesis. PMID:26895498

  6. Effects of Mössbauer radiation on bone marrow cultures

    NASA Astrophysics Data System (ADS)

    Ortalli, I.; Pedrazzi, G.; Jiang, K.; Zhang, X.; Carlo-Stella, C.; Mangoni, L.; Rizzoli, V.

    1992-04-01

    A low radiation dose approach to cell eradication would be highly desirable in cancer treatments in order to reduce the side ellects of conventional radiotherapy. In the present work we present a preliminary study on coltures of bone marrow mononuclear cells collected from normal subjects and patients with chronic myelogenous leukaemia (CML). Hematin (104, 10-3, 10°M) has been added to mattow culture cells which were then irradiated with a 3.7 GBq (100 mCi)57Co/Rh Mossbauer source for 4 hours. Significant inbibition has been observed on the cell growth due to hematin and irradiatron.

  7. Multiorgan WU Polyomavirus Infection in Bone Marrow Transplant Recipient

    PubMed Central

    Siebrasse, Erica A.; Nguyen, Nang L.; Willby, Melisa J.; Erdman, Dean D.; Menegus, Marilyn A.

    2016-01-01

    WU polyomavirus (WUPyV) was detected in a bone marrow transplant recipient with severe acute respiratory distress syndrome who died in 2001. Crystalline lattices of polyomavirus-like particles were observed in the patient’s lung by electron microscopy. WUPyV was detected in the lung and other tissues by real-time quantitative PCR and identified in the lung and trachea by immunohistochemistry. A subset of WUPyV-positive cells in the lung had morphologic features of macrophages. Although the role of WUPyV as a human pathogen remains unclear, these results clearly demonstrate evidence for infection of respiratory tract tissues in this patient. PMID:26691850

  8. Bone marrow mononuclears from murine tibia after spaceflight on biosatellite

    NASA Astrophysics Data System (ADS)

    Andreeva, Elena; Roe, Maria; Buravkova, Ludmila; Andrianova, Irina; Goncharova, Elena; Gornostaeva, Alexandra

    Elucidation of the space flight effects on the adult stem and progenitor cells is an important goal in space biology and medicine. A unique opportunity for this is provided by project "BION -M1". The purpose of this study was to evaluate the effects of a 30-day flight on biosatellite "BION - M1" and the subsequent 7-day recovery on the quantity, viability, immunophenotype of mononuclears from murine tibia bone marrow. Also the in vitro characterization of functional capacity of multipotent mesenchymal stromal cells (MSCs) was scheduled. Under the project, the S57black/6 mice were divided into groups: spaceflight/vivarium control, recovery after spaceflight/ vivarium control to recovery. Bone marrow mononuclears were isolated from the tibia and immunophenotyped using antibodies against CD45, CD34, CD90 on a flow cytometer Epics XL (Beckman Coulter). A part of the each pool was frozen for subsequent estimation of hematopoietic colony-forming units (CFU), the rest was used for the evaluation of fibroblast CFU (CFUf) number, MSC proliferative activity and osteogenic potency. The cell number in the flight group was significantly lower than in the vivarium control group. There were no differences in this parameter between flight and control groups after 7 days of recovery. The mononuclears viability was more than 95 percent in all examined groups. Flow cytometric analysis showed no differences in the bone marrow cell immunophenotype (CD45, CD34, CD90.1 (Thy1)), but the flight animals had more large-sized CD45+mononuclears, than the control groups of mice. There was no difference in the CFUf number between groups. After 7 days in vitro the MSC number in flight group was twice higher than in vivarium group, after 10 days - 4 times higher. These data may indicate a higher proliferative activity of MSCs after spaceflight. MSCs showed the same and high alkaline phosphatase activity, both in flight and in the control groups, suggesting no effect of spaceflight factors on early

  9. Phase I/II study of Holmium-166-DOTMP for bone marrow ablation in multiple myeloma prior to bone marrow transplantation (BMT)

    SciTech Connect

    Podoloff, D.A.; Bhadkamkar, V.H.; Kasi, L.P.

    1994-05-01

    We evaluated a bone seeking radionuclide, Ho-166 DOTMP (which has both beta and gamma energies) as an agent for bone marrow ablation prior to bone marrow transplant. Six men and 1 woman in the age range 42-59 yrs. who had previously failed conventional chemotherapy using VAD (Vincristine, Adriamycin, Dexamethasone) were treated. Each patient received a diagnostic dose (Dx) of 30 mCi of Ho-166 DOTMP and underwent serial total body images using photopeak and scatter windows. Transmission images were obtained on day O. Transmission, scatter and photopeak images were used to calculate marrow dose and skeletal uptake. Therapy dose (Tx) was established to deliver a prescribed absorbed dose to the marrow. Bone marrow biopsy samples from lilac crest were obtained to determine activity concentration and to calculate marrow dose. The Dx was followed by a Tx of 25 Gy (3 pts.), 40 Gy (3 pts.) and 50 Gy (1 pt.). Additional total body imaging was accomplished prior to each Tx and SPECT after the final Tx. Bone retention varied from 26-33%. The calculated red marrow dose varied from 11 to 48 Gy. Toxicity was minimal and included: myalgia (1), nausea (2), increased BUN (1), sore throat (1), fever (1x1 day). Bone marrow ablation was achieved in 3/7 pts. The last pt. treated at the highest dose level had greater than 75% reduction in myeloma protein. We conclude that at doses as high as 31.8 mCi/Kg no significant toxicity has been observed. Diagnostic pretherapy imaging and derived dosimetry is helpful in prescribing a red marrow dose prior to radionuclide therapy. The MTD has not yet been reached. However, thus far Ho-166 DOTMP has safely ablated bone marrow prior to BMT.

  10. The effect of bone marrow concentrate and hyperbaric oxygen therapy on bone repair.

    PubMed

    Grassmann, J P; Schneppendahl, J; Sager, M; Hakimi, A R; Herten, M; Loegters, T T; Wild, M; Hakimi, M; Windolf, J; Jungbluth, P

    2015-01-01

    Neoangiogenesis represents an essential part of bone regeneration. Therefore the improvement of neovascularization is the subject of various research approaches. In addition autologous mesenchymal stem cells concentrate in combination with bone substitute materials have been shown to support bone regeneration. In a rabbit model we examined the proposed synergistic effect of hyperbaric oxygen therapy (HBOT) and bone marrow concentrate (BMC) with porous calcium phosphate granules (CPG) on neoangiogenesis and osseous consolidation of a critical- size defect. The animal groups treated with HBOT showed a significantly higher microvessel density (MVD) by immunhistochemistry. Furthermore HBOT groups presented a significantly larger amount of new bone formation histomorphometrically as well as radiologically. We conclude that the increase in perfusion as a result of increased angiogenesis may play a key role in the effects of HBOT and consequently promotes bone healing. PMID:25577213

  11. Short-Term Effect of Estrogen on Human Bone Marrow Fat.

    PubMed

    Limonard, Eelkje J; Veldhuis-Vlug, Annegreet G; van Dussen, Laura; Runge, Jurgen H; Tanck, Michael W; Endert, Erik; Heijboer, Annemieke C; Fliers, Eric; Hollak, Carla E; Akkerman, Erik M; Bisschop, Peter H

    2015-11-01

    Bone marrow fat, an unique component of the bone marrow cavity increases with aging and menopause and is inversely related to bone mass. Sex steroids may be involved in the regulation of bone marrow fat, because men have higher bone marrow fat than women and clinical observations have suggested that the variation in bone marrow fat fraction is greater in premenopausal compared to postmenopausal women and men. We hypothesized that the menstrual cycle and/or estrogen affects the bone marrow fat fraction. First, we measured vertebral bone marrow fat fraction with Dixon Quantitative Chemical Shift MRI (QCSI) twice a week during 1 month in 10 regularly ovulating women. The vertebral bone marrow fat fraction increased 0.02 (95% CI, 0.00 to 0.03) during the follicular phase (p = 0.033), and showed a nonsignificant decrease of 0.02 (95% CI, -0.01 to 0.04) during the luteal phase (p = 0.091). To determine the effect of estrogen on bone marrow fat, we measured vertebral bone marrow fat fraction every week for 6 consecutive weeks in 6 postmenopausal women before, during, and after 2 weeks of oral 17-β estradiol treatment (2 mg/day). Bone marrow fat fraction decreased by 0.05 (95% CI, 0.01 to 0.09) from 0.48 (95% CI, 0.42 to 0.53) to 0.43 (95% CI, 0.34 to 0.51) during 17-β estradiol administration (p < 0.001) and increased again after cessation. During 17-β estradiol administration the bone formation marker procollagen type I N propeptide (P1NP) increased (p = 0.034) and the bone resorption marker C-terminal crosslinking telopeptides of collagen type I (CTx) decreased (p < 0.001). In conclusion, we described the variation in vertebral bone marrow fat fraction among ovulating premenopausal women. And among postmenopausal women, we demonstrated that 17-β estradiol rapidly reduces the marrow fat fraction, suggesting that 17-β estradiol regulates bone marrow fat independent of bone mass. PMID:25982922

  12. Bone marrow as a metastatic niche for disseminated tumor cells from solid tumors

    PubMed Central

    Shiozawa, Yusuke; Eber, Matthew R; Berry, Janice E; Taichman, Russell S

    2015-01-01

    Bone marrow is a heterogeneous organ containing diverse cell types, and it is a preferred metastatic site for several solid tumors such as breast and prostate cancer. Recently, it has been shown that bone metastatic cancer cells interact with the bone marrow microenvironment to survive and grow, and thus this microenvironment is referred to as the ‘metastatic niche'. Once cancer cells spread to distant organs such as bone, the prognosis for the patient is generally poor. There is an urgent need to establish a greater understanding of the mechanisms whereby the bone marrow niche influences bone metastasis. Here we discuss insights into the contribution of the bone marrow ‘metastatic niche' to progression of bone metastatic disease, with a particular focus on cells of hematopoietic and mesenchymal origin. PMID:26029360

  13. 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. PMID:23519534

  14. Ethnic and sex differences in bone marrow adipose tissue and bone mineral density relationship

    PubMed Central

    Chen, J.; Gantz, M.; Punyanitya, M.; Heymsfield, S. B.; Gallagher, D.; Albu, J.; Engelson, E.; Kotler, D.; Pi-Sunyer, X.; Shapses, S.

    2012-01-01

    Summary The relationship between bone marrow adipose tissue and bone mineral density is different between African Americans and Caucasians as well as between men and women. This suggests that the mechanisms that regulate the differentiation and proliferation of bone marrow stromal cells may differ in these populations. Introduction It has long been established that there are ethnic and sex differences in bone mineral density (BMD) and fracture risk. Recent studies suggest that bone marrow adipose tissue (BMAT) may play a role in the pathogenesis of osteoporosis. It is unknown whether ethnic and sex differences exist in the relationship between BMAT and BMD. Methods Pelvic BMAT was evaluated in 455 healthy African American and Caucasian men and women (age 18–88 years) using whole-body T1-weighted magnetic resonance imaging. BMD was measured using whole-body dual-energy X-ray absorptiometry. Results A negative correlation was observed between pelvic BMAT and total body BMD or pelvic BMD (r=−0.533, −0.576, respectively; P<0.001). In multiple regression analyses with BMD as the dependent variable, ethnicity significantly entered the regression models as either an individual term or an interaction with BMAT. Menopausal status significantly entered the regression model with total body BMD as the dependent variable. African Americans had higher total body BMD than Caucasians for the same amount of BMAT, and the ethnic difference for pelvic BMD was greater in those participants with a higher BMAT. Men and premeno-pausal women had higher total body BMD levels than postmenopausal women for the same amount of BMAT. Conclusions An inverse relationship exists between BMAT and BMD in African American and Caucasian men and women. The observed ethnic and sex differences between BMAT and BMD in the present study suggest the possibility that the mechanisms regulating the differentiation and proliferation of bone marrow stromal cells may differ in these populations. PMID

  15. Bone reconstruction of large defects using bone marrow derived autologous stem cells.

    PubMed

    Lucarelli, Enrico; Donati, Davide; Cenacchi, Annarita; Fornasari, Pier Maria

    2004-04-01

    Bone is a tissue that has the ability to heal itself when fractured. Occasionally, a critical defect can be formed when part of the bone is lost or excised, in this case the bone fails to heal and requires bone reconstruction to prevent a non-union defect. Autogenous cancellous bone is the current gold standard treatment in bone loss. Because the amount of autogenous cancellous bone that can be harvested is limited, the expanding need for bone reconstruction is paired by the growth of interest in the discipline of tissue engineering. Labs worldwide are working to provide the right carrier and the right set of cells that, once retransplanted, will ensure bone repair. Several investigators have focused their attention on a subset of autologous non-hematopoietic stem/progenitor cells contained in the adult bone marrow stroma, referred to as stromal stem cells (SSC), as the appropriate cells to be transplanted. The use of autologous cells is facilitated by less stringent ethical and regulatory issues and does not require the patient to be immunologically suppressed. In pre-clinical and clinical protocols of critical defects in which SSC are employed, two approaches are mainly used: in the first, SSC are derived from bone marrow and directly introduced at the lesion site, in the second, SSC are derived from several sites and are expanded ex vivo before being implanted. Both approaches, equally correct in principle, will have to demonstrate, with definitive evidence of their efficacy, their capability of solving a critical clinical problem such as non-union. In this report we outline the difficulties of working with SSC. PMID:15062758

  16. Cutaneous mast cell maturation does not depend on an intact bone marrow microenvironment

    SciTech Connect

    Charley, M.R.; Mikhael, A.; Sontheimer, R.D.; Gilliam, J.N.; Bennett, M.

    1984-01-01

    A study was made to determine whether the maturation of murine cutaneous mast cells from stem cells depends on an intact bone marrow microenvironment. Normal bone marrow cells (+/+) were infused into 2 groups of mast cell-deficient mice: WBB6F1-W/Wv mice and /sup 89/Sr-pretreated W/Wv mice. /sup 89/Sr is a long-lived bone-seeking radioisotope which provides continuous irradiation of the marrow and thereby ablates the marrow microenvironment. Skin biopsies revealed that the /sup 89/Sr-pretreated mice and the controls had repopulated their skin with mast cells equally well. Natural killer cell function was significantly depressed in the /sup 89/Sr-treated mice, confirming that the marrow microenvironment had been functionally altered. It appears that, although the precursors for cutaneous mast cells are marrow derived, they do not need an intact marrow microenvironment for maturation.

  17. Gluteal Compartment Syndrome following an Iliac Bone Marrow Aspiration

    PubMed Central

    Vega-Najera, Carlos; Leal-Contreras, Carlos; Leal-Berumen, Irene

    2013-01-01

    The compartment syndrome is a condition characterized by a raised hydraulic pressure within a closed and non expandable anatomical space. It leads to a vascular insufficiency that becomes critical once the vascular flow cannot return the fluids back to the venous system. This causes a potential irreversible damage of the contents of the compartment, especially within the muscle tissues. Gluteal compartment syndrome (GCS) secondary to hematomas is seldom reported. Here we present a case of a 51-year-old patient with history of a non-Hodgkin lymphoma who underwent a bone marrow aspiration from the posterior iliac crest that had excessive bleeding at the puncture zone. The patient complained of increasing pain, tenderness, and buttock swelling. Intraoperative pressure validation of the gluteal compartment was performed, and a GCS was diagnosed. The patient was treated with a gluteal region fasciotomy. The patient recovered from pain and swelling and was discharged shortly after from the hospital. We believe clotting and hematologic disorders are a primary risk factor in patients who require bone marrow aspirations or biopsies. It is important to improve awareness of GCS in order to achieve early diagnosis, avoid complications, and have a better prognosis. PMID:24392235

  18. Spleen and bone marrow megakaryocytes as targets for inhaled vanadium.

    PubMed

    Fortoul, Teresa I; Piñón-Zarate, Gabriela; Diaz-Bech, Maria Eugenia; González-Villalva, Adriana; Mussali-Galante, Patricia; Rodriguez-Lara, Vianey; Colin-Barenque, Laura; Martinez-Pedraza, Michelle; Montaño, Luis F

    2008-11-01

    An increased incidence in ischemic and thromboembolic events in the population of cities with rising air suspended particle pollution has suggested the interaction of some of the components of these particles in the coagulation system. A previous report from our laboratory identified thrombocytosis as a consequence of the subacute and chronic inhalation of vanadium. With this preceding information we decided to evaluate the effects of this element in the spleen and bone marrow in a mouse experimental model. CD-1 male mice inhaled V2O5 0.02 M for one hour twice a week for twelve weeks. The spleen and bone marrow were processed for light microscopy. The increase in quantity and size of megakaryocytes (MKs) in the exposed group in both organs was striking. Also, modifications in the cytoplasm, granule content and nuclear ultrastructure were evident. Our results indicate the influence of vanadium on megakaryopoyesis, an effect which could be the onset of the thrombocytosis previously reported by our group. The modifications in MKs described here suggest that inhaled vanadium could induce megakaryocytic proliferation, which may result in increased production of platelets and increased risk for thromboembolic events. PMID:18785114

  19. Adipose lineage specification of bone marrow-derived myeloid cells

    PubMed Central

    Majka, Susan M.; Miller, Heidi L.; Sullivan, Timothy; Erickson, Paul F.; Kong, Raymond; Weiser-Evans, Mary; Nemenoff, Raphael; Moldovan, Radu; Morandi, Shelley A.; Davis, James A.; Klemm, Dwight J.

    2012-01-01

    We have reported the production of white adipocytes in adipose tissue from hematopoietic progenitors arising from bone marrow. However, technical challenges have hindered detection of this adipocyte population by certain other laboratories. These disparate results highlight the need for sensitive and definitive techniques to identify bone marrow progenitor (BMP)-derived adipocytes. In these studies we exploited new models and methods to enhance detection of this adipocyte population. Here we showed that confocal microscopy with spectrum acquisition could effectively identify green fluorescent protein (GFP) positive BMP-derived adipocytes by matching their fluorescence spectrum to that of native GFP. Likewise, imaging flow cytometry made it possible to visualize intact unilocular and multilocular GFP-positive BMP-derived adipocytes and distinguished them from non-fluorescent adipocytes and cell debris in the cytometer flow stream. We also devised a strategy to detect marker genes in flow-enriched adipocytes from which stromal cells were excluded. This technique also proved to be an efficient means for detecting genetically labeled adipocytes and should be applicable to models in which marker gene expression is low or absent. Finally, in vivo imaging of mice transplanted with BM from adipocyte-targeted luciferase donors showed a time-dependent increase in luciferase activity, with the bulk of luciferase activity confined to adipocytes rather than stromal cells. These results confirmed and extended our previous reports and provided proof-of-principle for sensitive techniques and models for detection and study of these unique cells. PMID:23700536

  20. Bone Marrow Gene Therapy for HIV/AIDS

    PubMed Central

    Herrera-Carrillo, Elena; Berkhout, Ben

    2015-01-01

    Bone marrow gene therapy remains an attractive option for treating chronic immunological diseases, including acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV). This technology combines the differentiation and expansion capacity of hematopoietic stem cells (HSCs) with long-term expression of therapeutic transgenes using integrating vectors. In this review we summarize the potential of bone marrow gene therapy for the treatment of HIV/AIDS. A broad range of antiviral strategies are discussed, with a particular focus on RNA-based therapies. The idea is to develop a durable gene therapy that lasts the life span of the infected individual, thus contrasting with daily drug regimens to suppress the virus. Different approaches have been proposed to target either the virus or cellular genes encoding co-factors that support virus replication. Some of these therapies have been tested in clinical trials, providing proof of principle that gene therapy is a safe option for treating HIV/AIDS. In this review several topics are discussed, ranging from the selection of the antiviral molecule and the viral target to the optimal vector system for gene delivery and the setup of appropriate preclinical test systems. The molecular mechanisms used to formulate a cure for HIV infection are described, including the latest antiviral strategies and their therapeutic applications. Finally, a potent combination of anti-HIV genes based on our own research program is described. PMID:26193303

  1. A novel metric for bone marrow cells chromosome pairing.

    PubMed

    Khmelinskii, Artem; Ventura, Rodrigo; Sanches, João

    2010-06-01

    Karyotyping is a set of procedures, in the scope of the cytogenetics, that produces a visual representation of the 46 chromosomes observed during the metaphase step of the cellular division, called mitosis, paired and arranged in decreasing order of size. Automatic pairing of bone marrow cells is a difficult task because these chromosomes appear distorted, overlapped, and their images are usually blurred with undefined edges and low level of detail. In this paper, a new metric is proposed to compare this type of chromosome images toward the design of an automatic pairing algorithm for leukemia diagnostic purposes. Besides the features used in the traditional karyotyping procedures, a new feature, based on mutual information , is proposed to increase the discriminate power of the G-banding pattern dissimilarity between chromosomes and improve the performance of the classifier. The pairing algorithm is formulated as a combinatorial optimization problem where the distances between homologous chromosomes are minimized and the distances between nonhomologous ones are maximized. The optimization task is solved by using an integer programming approach. A new bone marrow chromosome dataset--Lisbon-K1 (LK1) chromosome dataset with 9200 chromosomes---was build for this study. These chromosomes have much lower quality than the classic Copenhagen, Edinburgh, and Philadelphia datasets, and its classification and pairing is therefore more difficult. Experiments using real images from the LK(1) and Grisan et al. datasets based on a leave-one-out cross-validation strategy are performed to test and validate the pairing algorithm. PMID:20172790

  2. The effects of simulated hypogravity on murine bone marrow cells

    NASA Technical Reports Server (NTRS)

    Lawless, Desales

    1989-01-01

    Mouse bone marrow cells grown in complete medium at unit gravity were compared with a similar population cultured in conditions that mimic some aspects of microgravity. After the cells adjusted to the conditions that simulated microgravity, they proliferated as fetal or oncogenic populations; their numbers doubled in twelve hour periods. Differentiated subpopulations were depleted from the heterogeneous mixture with time and the undifferentiated hematopoietic stem cells increased in numbers. The cells in the control groups in unit gravity and those in the bioreactors in conditions of microgravity were monitored under a number of parameters. Each were phenotyped as to cell surface antigens using a panel of monoclonal antibodies and flow cytometry. Other parameters compared included: pH, glucose uptake, oxygen consumption and carbon-dioxide production. Nuclear DNA was monitored by flow cytometry. Functional responses were studied by mitogenic stimulation by various lectins. The importance of these findings should have relevance to the space program. Cells should behave predictably in zero gravity; specific populations can be eliminated from diverse populations and other populations isolated. The availability of stem cell populations will enhance both bone marrow and gene transplant programs. Stem cells will permit developmental biologists study the paths of hematopoiesis.

  3. Current insights into inherited bone marrow failure syndromes.

    PubMed

    Chung, Nack-Gyun; Kim, Myungshin

    2014-08-01

    Inherited bone marrow failure syndrome (IBMFS) encompasses a heterogeneous and complex group of genetic disorders characterized by physical malformations, insufficient blood cell production, and increased risk of malignancies. They often have substantial phenotype overlap, and therefore, genotyping is often a critical means of establishing a diagnosis. Current advances in the field of IBMFSs have identified multiple genes associated with IBMFSs and their pathways: genes involved in ribosome biogenesis, such as those associated with Diamond-Blackfan anemia and Shwachman-Diamond syndrome; genes involved in telomere maintenance, such as dyskeratosis congenita genes; genes encoding neutrophil elastase or neutrophil adhesion and mobility associated with severe congenital neutropenia; and genes involved in DNA recombination repair, such as those associated with Fanconi anemia. Early and adequate genetic diagnosis is required for proper management and follow-up in clinical practice. Recent advances using new molecular technologies, including next generation sequencing (NGS), have helped identify new candidate genes associated with the development of bone marrow failure. Targeted NGS using panels of large numbers of genes is rapidly gaining potential for use as a cost-effective diagnostic tool for the identification of mutations in newly diagnosed patients. In this review, we have described recent insights into IBMFS and how they are advancing our understanding of the disease's pathophysiology; we have also discussed the possible implications they will have in clinical practice for Korean patients. PMID:25210520

  4. Ion channels in mesenchymal stem cells from rat bone marrow.

    PubMed

    Li, Gui-Rong; Deng, Xiu-Ling; Sun, Haiying; Chung, Stephen S M; Tse, Hung-Fat; Lau, Chu-Pak

    2006-06-01

    Mesenchymal stem cells (MSCs) from bone marrow are believed to be an ideal cell source for cardiomyoplasty; however, cellular electrophysiology is not understood. The present study was designed to investigate ion channels in undifferentiated rat MSCs. It was found that three types of outward currents were present in rat MSCs, including a small portion of Ca(2+)-activated K(+) channel (I(KCa)) sensitive to inhibition by iberiotoxin and/or clotromazole, a delayed rectifier K(+) current (IK(DR)), and a transient outward K(+) current (I(to)). In addition, tetrodotoxin (TTX)-sensitive sodium current (I(Na.TTX)) and nifedipine-sensitive L-type Ca(2+) current (I(Ca.L)) were found in a small population of rat MSCs. Moreover, reverse transcription-polymerase chain reaction revealed the molecular evidence of mRNA for the functional ionic currents, including Slo and KCNN4 for I(KCa); Kv1.4 for I(to); Kv1.2 and Kv2.1 for IK(DR); SCN2a1 for I(Na.TTX); and CCHL2a for I(Ca.L). These results demonstrate for the first time that multiple functional ion channel currents (i.e., I(KCa), I(to), IK(DR), I(Na.TTX), and I(Ca.L)) are present in rat MSCs from bone marrow; however, physiological roles of these ion channels remain to be studied. PMID:16484345

  5. Bone Marrow Graft in Man after Conditioning by Antilymphocytic Serum*

    PubMed Central

    Mathé, G.; Amiel, J. L.; Schwarzenberg, L.; Choay, J.; Trolard, P.; Schneider, M.; Hayat, M.; Schlumberger, J. R.; Jasmin, Cl.

    1970-01-01

    Allogeneic bone marrow grafts carried out after previous administration of antilymphocytic serum alone were attempted in 16 patients. Of these, six had acute myeloblastic leukaemia, four acute lymphoblastic leukaemia, and one a blast cell crisis in polycythaemia vera. Ten of these patients were in an overt phase of the disease and resistant to chemotherapy, while nine had complete agranulocytosis. In five of these patients erythrocyte and leucocyte antigenic markers demonstrated the establishment of the graft. One patient had thalassaemia major, and four others had aplasia of the bone marrow, in one case due to chloramphenicol poisoning and in another to virus hepatitis. The grafts were successful in the last two patients and transformed their clinical condition. No signs of early acute secondary disease were noted in any of the patients, either when the donor had been given antilymphocytic serum or when he was untreated. The grafts had no adoptive immunotherapeutic effect on the acute leukaemia. These observations have clearly shown that antilymphocytic serum has an immunosuppressive effect in man when it is used alone. PMID:4909449

  6. Current insights into inherited bone marrow failure syndromes

    PubMed Central

    Chung, Nack-Gyun

    2014-01-01

    Inherited bone marrow failure syndrome (IBMFS) encompasses a heterogeneous and complex group of genetic disorders characterized by physical malformations, insufficient blood cell production, and increased risk of malignancies. They often have substantial phenotype overlap, and therefore, genotyping is often a critical means of establishing a diagnosis. Current advances in the field of IBMFSs have identified multiple genes associated with IBMFSs and their pathways: genes involved in ribosome biogenesis, such as those associated with Diamond-Blackfan anemia and Shwachman-Diamond syndrome; genes involved in telomere maintenance, such as dyskeratosis congenita genes; genes encoding neutrophil elastase or neutrophil adhesion and mobility associated with severe congenital neutropenia; and genes involved in DNA recombination repair, such as those associated with Fanconi anemia. Early and adequate genetic diagnosis is required for proper management and follow-up in clinical practice. Recent advances using new molecular technologies, including next generation sequencing (NGS), have helped identify new candidate genes associated with the development of bone marrow failure. Targeted NGS using panels of large numbers of genes is rapidly gaining potential for use as a cost-effective diagnostic tool for the identification of mutations in newly diagnosed patients. In this review, we have described recent insights into IBMFS and how they are advancing our understanding of the disease's pathophysiology; we have also discussed the possible implications they will have in clinical practice for Korean patients. PMID:25210520

  7. Bone marrow transplantation in subjects with mental disorders.

    PubMed

    Akaho, Rie; Sasaki, Tsukasa; Yoshino, Miyo; Hagiya, Katsuko; Akiyama, Hideki; Sakamaki, Hisashi

    2003-06-01

    Bone marrow transplantation (BMT) is a critical treatment of malignant illnesses including leukemia and others. Successful achievement of BMT requires the patients to tolerate isolation for several weeks to avoid infections. They are also required to follow several regulations and instructions to survive the treatment because the patients' physical condition is complicated due to the malignant illness, preparatory treatment and transplant of bone marrow from other subjects. These could be a significant challenge for patients with mental disorders. Here the cases are reported of seven leukemia patients who were referred to the Metropolitan Komagome Hospital for BMT from April 1996 through May 2000, who had been suffering from mental disorders, including schizophrenia, bipolar I mood disorder, panic disorder, dysthymic disorder, autistic disorder, and borderline personality disorder, prior to the treatment. The BMT was achieved in six out of the seven subjects; the exception was a subject with borderline personality disorder. Psychiatric treatments, including medication, to improve and maintain mental status appeared to be critical for the achievement of BMT in several patients. Understanding of the status of the malignant disease and the role of BMT was another significant issue. Test admission seemed to be helpful to reduce concerns and anxiety both in the patients and hospital staff. PMID:12753572

  8. Autologous bone marrow stem cells--properties and advantages.

    PubMed

    Rice, Claire M; Scolding, Neil J

    2008-02-15

    The properties of self-renewal and multi-lineage differentiation make stem cells attractive candidates for use in cellular reparative therapy, particularly in neurological diseases where there is a paucity of treatment options. However, clinical trials using foetal material in Parkinson's disease have been disappointing and highlighted problems associated with the use of embryonic stem cells, including ethical issues and practical concerns regarding teratoma formation. Understandably, this has led investigators to explore alternative sources of stem cells for transplantation. The expression of neuroectodermal markers by cells of bone marrow origin focused attention on these adult stem cells. Although early enthusiasm has been tempered by dispute regarding the validity of reports of in vitro (trans)differentiation, the demonstration of functional benefit in animal models of neurological disease is encouraging. Here we will review some of the required properties of stem cells for use in transplantation therapy with specific reference to the development of bone marrow-derived cells as a source of cells for repair in demyelination. PMID:17669432

  9. Bone marrow capacity for bone cells and trabecular bone turnover in immobilized tibia after sciatic neurectomy in mice.

    PubMed

    Sakai, A; Nakamura, T; Tsurukami, H; Okazaki, R; Nishida, S; Tanaka, Y; Norimura, T; Suzuki, K

    1996-05-01

    Trabecular bone turnover and bone marrow capacity for the development of bone cells in the tibia were assessed after sciatic neurectomy (NX) in mice. The right hindlimbs of 6-week-old DDY mice were neurectomized and left hindlimbs were sham-operated and served as NX controls. Histomorphometrical analyses of the trabecular bone of the proximal tibia demonstrated the initial decrease in bone formation rate for the first 14 days and the subsequent increase in osteoclast surface for the next 14 days. The number of adherent stromal cells per tibia obtained for the NX limbs was reduced on days 7 and 10 postsurgically, and then recovered on day 12. However, the alkaline phosphatase activity of the cells was persistently depressed. The formation of osteoclast-like multinucleated cells in the marrow cultures obtained from NX limbs at days 10, 12, and 14 showed a significant increase in the medium containing parathyroid hormone (PTH). The number of colonies cultured for colony forming units-fibroblastic (CFU-f) that developed from the marrow cells did not differ in the NX and the contralateral limbs at any time during the period. On the other hand, the number of colonies cultured of colony forming units for granulocytes and macrophages (CFU-GM) was markedly increased for both the NX and the contralateral tibiae at days 12 and 14. This study clearly demonstrates that there are two stages in the development of osteopenia after NX. During the first 14 days, trabecular bone formation and number of marrow stromal cells are reduced. In the second 14 day period, the trabecular osteoclast number is increased and osteoclast formation from the bone marrow cells is enhanced in the presence of PTH. However, neither the CFU-f nor the CFU-GM assay could identify the changes in osteogenic or osteoclastogenic potential of the bone marrow. These in vitro assays provide limited information on the shifts in bone marrow cell lineages and the local environment producing osteopenia in the

  10. Expression of proteoglycan core proteins in human bone marrow stroma.

    PubMed Central

    Schofield, K P; Gallagher, J T; David, G

    1999-01-01

    Heparan sulphate proteoglycans (HSPGs) present on the surface of bone marrow stromal cells and in the extracellular matrix (ECM) have important roles in the control of adhesion and growth of haemopoietic stem and progenitor cells. The two main groups of proteoglycans which contain heparan sulphate chains are members of the syndecan and glypican families. In this study we have identified the main surface membrane and matrix-associated HSPGs present in normal human bone marrow stroma formed in long-term culture. Proteoglycans were extracted from the adherent stromal layers and treated with heparitinase and chondroitinase ABC. The core proteins were detected by Western blotting using antibodies directed against syndecans-1-4, glypican-1 and the ECM HSPG, perlecan. Stromal cell expression at the RNA level was detected by Northern blotting and by reverse transcription PCR. Glypican-1, syndecan-3 and syndecan-4 were the major cell-membrane HSPG species and perlecan was the major ECM proteoglycan. There was no evidence for expression of syndecan-1 protein. Syndecan-3 was expressed mainly as a variant or processed 50-55 kDa core protein and in lower amounts as the characteristic 125 kDa core protein. These results suggest that syndecan-3, syndecan-4 and glypican-1 present on the surface of marrow stromal cells, together with perlecan in the ECM, may be responsible for creating the correct stromal 'niche' for the maintenance and development of haemopoietic stem and progenitor cells. The detection of a variant form of syndecan-3 as a major stromal HSPG suggests a specific role for this syndecan in haemopoiesis. PMID:10527946

  11. Myxomatous stromal changes and necrosis of bone marrow--a retrospective study of 3 years.

    PubMed

    Gupta, Nalini; Kumar, Vijay; Varma, Neelam; Garewal, Gurjeevan; Das, Reena; Ahluwalia, Jasmina; Dash, Sumitra

    2004-07-01

    Myxomatous stromal changes and bone marrow necrosis (BMN) are uncommon histologic findings. These changes have been found in various conditions like disseminated carcinomatosis, postchemotherapy cases, chronic infections, infiltrative disorders of the marrow etc. The present study is a retrospective study of 3 years (Jan, 1999 to Dec. 2001) from Deptt. Of Hematology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh (India). During this period, 3740 bone marrow samples were examined. Myxomatous stromal changes and bone marrow necrosis were noted in 0.43% (16/3740) and 0.45% (17/3740) samples respectively. In addition to common causes of myxomatous stromal changes and bone marrow necrosis as described in the literature, this study highlights the association of these conditions with some of the rarer entities like hyperoxalosis, leishmaniasis, parvovirus induced marrow aplasia and cryptococcal infection. There is paucity of such associations in the literature. PMID:16295422

  12. A T Cell View of the Bone Marrow

    PubMed Central

    Bonomo, Adriana; Monteiro, Ana Carolina; Gonçalves-Silva, Triciana; Cordeiro-Spinetti, Eric; Galvani, Rômulo Gonçalves; Balduino, Alex

    2016-01-01

    The majority of T cells present in the bone marrow (BM) represent an activated/memory phenotype and most of these, if not all, are circulating T cells. Their lodging in the BM keeps them activated, turning the BM microenvironment into a “memory reservoir.” This article will focus on how T cell activation in the BM results in both direct and indirect effects on the hematopoiesis. The hematopoietic stem cell niche will be presented, with its main components and organization, along with the role played by T lymphocytes in basal and pathologic conditions and their effect on the bone remodeling process. Also discussed herein will be how “normal” bone mass peak is achieved only in the presence of an intact adaptive immune system, with T and B cells playing critical roles in this process. Our main hypothesis is that the partnership between T cells and cells of the BM microenvironment orchestrates numerous processes regulating immunity, hematopoiesis, and bone remodeling. PMID:27242791

  13. Detection of micrometastatic prostate cancer cells in the bone marrow of patients with prostate cancer.

    PubMed Central

    Deguchi, T.; Yang, M.; Ehara, H.; Ito, S.; Nishino, Y.; Takahashi, Y.; Ito, Y.; Shimokawa, K.; Tanaka, T.; Imaeda, T.; Doi, T.; Kawada, Y.

    1997-01-01

    Thirty-five patients with prostate cancer were examined for micrometastases to the bone marrow using reverse transcription-polymerase chain reaction (RT-PCR) with primers specific for the prostate-specific antigen (PSA) gene. Of nine patients with bone metastases detectable by bone scan imaging, five patients had PSA mRNA expression in the bone marrow detectable by RT-PCR. Of 26 patients with negative bone scan findings, seven patients had PSA mRNA expression detectable in the bone marrow. RT-PCR could detect micrometastatic prostate cancer cells in the bone marrow that were not detectable by bone scan imaging. Of 16 patients with a serum PSA concentration of 25 ng ml(-1) or greater, only nine (56.3%) had bone metastases detected by bone scans. Of the remaining seven patients, five had micrometastases to the bone marrow detected by RT-PCR. Overall, 14 of 16 patients (87.5%) with a serum PSA concentration of 25 ng ml(-1) or greater had metastatic bone diseases including bone marrow micrometastases. Of 19 patients with a serum PSA concentration of less than 25 ng ml(-1), two (10.5%) had only micrometastatic disease detected by RT-PCR. A significant correlation was observed between the incidence of bone involvement and the serum PSA concentration. This study suggests that RT-PCR will potentially develop into a relevant tool to assess bone involvement including bone marrow micrometastases and establish a precise correlation between serum PSA concentration and metastatic bone disease in patients with prostate cancer. Images Figure 1 PMID:9043017

  14. Blockage of caspase-1 activation ameliorates bone marrow inflammation in mice after hematopoietic stem cell transplantation.

    PubMed

    Qiao, Jianlin; Wu, Jinyan; Li, Yuanyuan; Xia, Yuan; Chu, Peipei; Qi, Kunming; Yan, Zhiling; Yao, Haina; Liu, Yun; Xu, Kailin; Zeng, Lingyu

    2016-01-01

    Conditioning regimens before hematopoietic stem cell transplantation (HSCT), cause damage to bone marrow and inflammation. Whether inflammasomes are involved in bone marrow inflammation remains unclear. The study aims to evaluate the role of inflammasomes in bone marrow inflammation after HSCT. On days 7, 14, 21 and 28 after HSCT, mice were sacrificed for analysis of bone marrow inflammation, pro-inflammatory cytokines secretion, inflammasomes expression and caspase-1 activation. Bone marrow inflammation with neutrophils and macrophages infiltration was observed after HSCT. Secretion of IL-1β, IL-18, TNF-α and IL-6 were elevated, with increased caspase-1 activation and inflammasomes expression. Caspase-1 inhibitor administration after HSCT significantly reduced infiltration of neutrophils and macrophages into bone marrow and increased the numbers of megakaryocytes and platelets. In conclusion, inflammasomes activation is involved in bone marrow inflammation after HSCT and caspase-1 inhibition attenuates bone marrow inflammation and promoted hematopoietic reconstitution, suggesting targeting caspase-1 might be beneficial for improving HSCT outcomes. PMID:26639193

  15. Knowledge and attitude of Lublin universities students' toward the opportunity of becoming unrelated bone marrow donor.

    PubMed

    Sikora, Agnieszka; Wiorkowski, Krzysztof; Szara, Paulina; Drabko, Katarzyna

    2014-01-01

    Hematopoietic Stem Cell Transplantation (HSCT) is a very important life-saving procedure to treat many disorders. In August 2014, there were more than 24.5 million donor registered in the Worldwide Bone Marrow Donor Register. In the Polish Register of Unrelated Bone Marrow and Umbilical Cord Blood Donors at the end of 2013 there were almost 540 thousand registered bone marrow donors. Despite increasing numbers of registered donors, the amount of requests also increased. It shows that the number of donors is still insufficient. The analysis of knowledge and attitude of Lublin universities students' toward the opportunity to become an unrelated bone marrow donor was the aim of our study. 1609 Lublin students from non-medical universities from different years and specializations of study, of both sexes, aged 19-35 took part in the survey. It consisted of 16 questions. There were knowledge-testing questions, and also personal ones. Among interviewees, 16% were registered as potential bone marrow donors. The reason for not being registered registration chosen most often was that the surveyed did not take this into consideration. Correct answers to all of the questions were given by 21% of students. The biggest number of incorrect answers was given to the question about a place from bone marrow is harvested - nearly 49%. Registered students showed a better level of knowledge than the unregistered. We noted a low level of knowledge about bone marrow donation and possibility of becoming potential bone marrow donor among Lublin universities students. PMID:25648307

  16. Rare Bone Marrow Biopsy Complication: A Challenging Case of Sacroiliitis and Staphilococcus Aureus Sepsis

    PubMed Central

    Morotti, Alessandro; Barozzino, Maria Consiglio; Guerrasio, Angelo

    2016-01-01

    Bone marrow biopsy is a mandatory procedure to diagnose several hematological disorders. This invasive analysis is generally safe and the procedure-related risks are rare and include bleeding at the site of puncture and, very occasionally, local infections. Here, we describe a case of sacroiliitis that occurred as a consequence of bone marrow biopsy. PMID:27162606

  17. Recovery of hair coat color in Gray Collie (cyclic neutropenia)-normal bone marrow transplant chimeras.

    PubMed Central

    Yang, T. J.

    1978-01-01

    Gray Collie-normal bone marrow transplantation chimeras showed normal coloration of the hair coat on tails and several other areas 2 years after successful transplantation of bone marrow to correct cyclic neutropenia of the Gray Collie syndrome. Images Figures 1-2 PMID:347941

  18. A Novel Approach for Performing Bone Marrow Aspiration at the Time of Radical Prostatectomy

    PubMed Central

    Tosoian, Jeffrey J.; Reyes, Diane K.; Gorin, Michael A.; Hortopan, Steven; Partin, Alan W.; Pienta, Kenneth J.; Ross, Ashley E.; Schaeffer, Edward M.

    2016-01-01

    The bone marrow microenvironment represents a “metastatic niche” in which prostate cancer cells may persist and evade cytotoxic therapy. In order to study the biology of prostate cancer dissemination, we have established a safe and efficient method for performing pubic bone marrow aspiration at the time of radical prostatectomy. We herein describe our experience with this technique. PMID:27175343

  19. Abnormal bone marrow distribution following unsuccessful hip replacement: a potential confusion on white cell scanning.

    PubMed

    Cunningham, D A

    1991-01-01

    A case is presented in which a grossly abnormal distribution of bone marrow following failed hip replacement would have led to the false diagnosis of osteomyelitis. The value of combining bone marrow scanning with indium white cell scanning in possible osteomyelitis is emphasised. PMID:2019282

  20. The Role of Bone Marrow Cells in the Phenotypic Changes Associated with Diabetic Nephropathy

    PubMed Central

    Yang, Guang; Cheng, Qingli; Liu, Sheng; Zhao, Jiahui

    2015-01-01

    The aim of our study was to investigate the role of bone marrow cells in the phenotypic changes that occur in diabetic nephropathy. Bone marrow cells were obtained from either streptozotocin-induced diabetic or untreated control C3H/He mice and transplanted into control C3H/He mice. Eight weeks after bone marrow cell transplantation, renal morphologic changes and clinical parameters of diabetic nephropathy, including the urine albumin/creatinine ratio and glucose tolerance, were measured in vivo. Expression levels of the genes encoding α1 type IV collagen and transforming growth factor-β1 in the kidney were assayed. Our results demonstrated that glucose tolerance was normal in the recipients of bone marrow transplants from both diabetic and control donors. However, compared with recipients of the control bone marrow transplant, the urinary albumin/creatinine ratio, glomerular size, and the mesangial/glomerular area ratio increased 3.3-fold (p < 0.01), 1.23-fold (p < 0.01), and 2.13-fold (p < 0.001), respectively, in the recipients of the diabetic bone marrow transplant. Expression levels of the genes encoding glomerular α1 type IV collagen and transforming growth factor-β1 were also significantly increased (p < 0.01) in the recipients of the diabetic bone marrow transplant. Our data suggest that bone marrow cells from the STZ-induced diabetic mice can confer a diabetic phenotype to recipient control mice without the presence of hyperglycemia. PMID:26340671

  1. Combination therapies prevent the neuropathic, proinflammatory characteristics of bone marrow in streptozotocin-induced diabetic rats.

    PubMed

    Dominguez, James M; Yorek, Mark A; Grant, Maria B

    2015-02-01

    We previously showed that peripheral neuropathy of the bone marrow was associated with loss of circadian rhythmicity of stem/progenitor cell release into the circulation. Bone marrow neuropathy results in dramatic changes in hematopoiesis that lead to microvascular complications, inflammation, and reduced endothelial repair. This series of events represents early pathogenesis before development of diabetic retinopathy. In this study we characterized early alterations within the bone marrow of streptozotocin (STZ)-induced diabetic rats following treatments that prevent experimental peripheral neuropathy. We asked whether bone marrow neuropathy and the associated bone marrow pathology were reversed with treatments that prevent peripheral neuropathy. Three strategies were tested: inhibition of neutral endopeptidase, inhibition of aldose reductase plus lipoic acid supplementation, and insulin therapy with antioxidants. All strategies prevented loss of nerve conduction velocity resulting from STZ-induced diabetes and corrected the STZ-induced diabetes-associated increase of immunoreactivity of neuropeptide Y, tyrosine hydroxylase, and somatostatin. The treatments also reduced concentrations of interleukin-1β, granulocyte colony-stimulating factor, and matrix metalloproteinase 2 in STZ-induced diabetic bone marrow supernatant and decreased the expression of NADPH oxidase 2, nitric oxide synthase 2, and nuclear factor-κB1 mRNA in bone marrow progenitor cells. These therapies represent novel approaches to attenuate the diabetic phenotype within the bone marrow and may constitute an important therapeutic strategy for diabetic microvascular complications. PMID:25204979

  2. Transplanted Bone Marrow Cells Repair Heart Tissue and Reduce Myocarditis in Chronic Chagasic Mice

    PubMed Central

    Soares, Milena B. P.; Lima, Ricardo S.; Rocha, Leonardo L.; Takyia, Christina M.; Pontes-de-Carvalho, Lain; Campos de Carvalho, Antonio C.; Ribeiro-dos-Santos, Ricardo

    2004-01-01

    A progressive destruction of the myocardium occurs in ∼30% of Trypanosoma cruzi-infected individuals, causing chronic chagasic cardiomyopathy, a disease so far without effective treatment. Syngeneic bone marrow cell transplantation has been shown to cause repair and improvement of heart function in a number of studies in patients and animal models of ischemic cardiopathy. The effects of bone marrow transplant in a mouse model of chronic chagasic cardiomyopathy, in the presence of the disease causal agent, ie, the T. cruzi, are described herein. Bone marrow cells injected intravenously into chronic chagasic mice migrated to the heart and caused a significant reduction in the inflammatory infiltrates and in the interstitial fibrosis characteristics of chronic chagasic cardiomyopathy. The beneficial effects were observed up to 6 months after bone marrow cell transplantation. A massive apoptosis of myocardial inflammatory cells was observed after the therapy with bone marrow cells. Transplanted bone marrow cells obtained from chagasic mice and from normal mice had similar effects in terms of mediating chagasic heart repair. These results show that bone marrow cell transplantation is effective for treatment of chronic chagasic myocarditis and indicate that autologous bone marrow transplant may be used as an efficient therapy for patients with chronic chagasic cardiomyopathy. PMID:14742250

  3. 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

  4. High-fat diet causes bone loss in young mice by promoting osteoclastogenesis through alteration of the bone marrow environment.

    PubMed

    Shu, Lei; Beier, Eric; Sheu, Tzong; Zhang, Hengwei; Zuscik, Michael J; Puzas, Edward J; Boyce, Brendan F; Mooney, Robert A; Xing, Lianping

    2015-04-01

    Obesity is a severe health problem in children, afflicting several organ systems including bone. However, the role of obesity on bone homeostasis and bone cell function in children has not been studied in detail. Here we used young mice fed a high-fat diet (HFD) to model childhood obesity and investigate the effect of HFD on the phenotype of cells within the bone marrow environment. Five-week-old male mice were fed a HFD for 3, 6, and 12 weeks. Decreased bone volume was detected after 3 weeks of HFD treatment. After 6 and 12 weeks, HFD-exposed mice had less bone mass and increased osteoclast numbers. Bone marrow cells, but not spleen cells, from HFD-fed mice had increased osteoclast precursor frequency, elevated osteoclast formation, and bone resorption activity, as well as increased expression of osteoclastogenic regulators including RANKL, TNF, and PPAR-gamma. Bone formation rate and osteoblast and adipocyte numbers were also increased in HFD-fed mice. Isolated bone marrow cells also had a corresponding elevation in the expression of positive regulators of osteoblast and adipocyte differentiation. Our findings indicate that in juvenile mice, HFD-induced bone loss is mainly due to increased osteoclast bone resorption by affecting the bone marrow microenvironment. Thus, targeting osteoclast formation may present a new therapeutic approach for bone complications in obese children. PMID:25673503

  5. Adult bone marrow: which stem cells for cellular therapy protocols in neurodegenerative disorders?

    PubMed

    Wislet-Gendebien, Sabine; Laudet, Emerence; Neirinckx, Virginie; Rogister, Bernard

    2012-01-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs). In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy. PMID:22319243

  6. Adult Bone Marrow: Which Stem Cells for Cellular Therapy Protocols in Neurodegenerative Disorders?

    PubMed Central

    Wislet-Gendebien, Sabine; Laudet, Emerence; Neirinckx, Virginie; Rogister, Bernard

    2012-01-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs). In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy. PMID:22319243

  7. Expression of bone morphogenetic proteins in stromal cells from human bone marrow long-term culture.

    PubMed

    Martinovic, Snjezana; Mazic, Sanja; Kisic, Veronika; Basic, Nikolina; Jakic-Razumovic, Jasminka; Borovecki, Fran; Batinic, Drago; Simic, Petra; Grgurevic, Lovorka; Labar, Boris; Vukicevic, Slobodan

    2004-09-01

    Highly purified primitive hemopoietic stem cells express BMP receptors but do not synthesize bone morphogenetic proteins (BMPs). However, exogenously added BMPs regulate their proliferation, differentiation, and survival. To further explore the mechanism by which BMPs might be involved in hemopoietic differentiation, we tested whether stromal cells from long-term culture (LTC) of normal human bone marrow produce BMPs, BMP receptors, and SMAD signaling molecules. Stromal cells were immunohistochemically characterized by the presence of lyzozyme, CD 31, factor VIII, CD 68, S100, alkaline phosphatase, and vimentin. Gene expression was analyzed by RT-PCR and the presence of BMP protein was confirmed by immunohistochemistry (IHC). The supportive role of the stromal cell layer in hemopoiesis in vitro was confirmed by a colony assay of clonogenic progenitors. Bone marrow stromal cells express mRNA and protein for BMP-3, -4, and -7 but not for BMP-2, -5, and -6 from the first to the eighth week of culture. Furthermore, stromal cells express the BMP type I receptors, activin-like kinase-3 (ALK-3), ALK-6, and the downstream transducers SMAD-1, -4, and -5. Thus, human bone marrow stromal cells synthesize BMPs, which might exert their effects on hemopoietic stem cells in a paracrine manner through specific BMP receptors. PMID:15314083

  8. [Inhibitory effect of 8-prenylnaringenin on osteoclastogensis of bone marrow cells and bone resorption activity].

    PubMed

    Lü, Xiang; Zhou, Ying; Chen, Ke-Ming; Zhao, Zhi; Zhou, Jian; Ma, Xiao-Ni

    2013-03-01

    This study is to investigate the effect of 8-prenylnaringenin (8-PNG) on osteoclastogensis of bone marrow cells and bone resorption activity of osteoclasts. Osteoclasts were separated from long bone marrow of newborn rabbits and cultured in alpha-MEM containing 10% FBS. 8-PNG was added into culture media at 1 x 10(-7), 1 x 10(-6), 1 x 10(-5) mol xL(-1), separately. 17beta-Estradiol (E2, 1 x 10(-7) mol x L(-7)) was used as positive control. T RAP staining and TRAP activity measurement were performed after 5 days, and the bone resorption pits were analyzed after 7 days. Annexin V staining for the detection of apoptotic osteoclasts was performed after 2, 4, 8, 12, 24, 36 and 48 h separately. The mRNA expression level of TRAP and cathepsin K (CTSK) was measured by real-time RT-PCR. 8-PNG significantly reduced the number of osteoclasts which was TRAP staining positive and with more than three nucleus, the area and number of bone resorption pits decreased obviously in 8-PNG-supplemented groups. The apoptosis rate peaked earlier in the 8-PNG-supplemented groups and the mRNA expression level of TRAP and CTSK decreased significantly. All these inhibitory effects were in a dose dependent manner, the highest effect was obtained by 1 x 10(-5) mol x L(-1) 8-PNG. 8-PNG inhibits bone resorption activity of osteoclasts by inducing osteoclast apoptosis and inhibiting the gene expression and enzyme activity including TRAP and CTSK, and restrains bone marrow cells to osteoclast differentiation. PMID:23724646

  9. Route of delivery influences biodistribution of human bone marrow-derived mesenchymal stromal cells following experimental bone marrow transplantation

    PubMed Central

    Wang, Fangjing; Eid, Saada; Dennis, James E; Cooke, Kenneth R; Auletta, Jeffery J; Lee, Zhenghong

    2015-01-01

    Mesenchymal stromal cells (MSCs) have shown promise as treatment for graft-versus-host disease (GvHD) following allogeneic bone marrow transplantation (alloBMT). Mechanisms mediating in vivo effects of MSCs remain largely unknown, including their biodistribution following infusion. To this end, human bone-marrow derived MSCs (hMSCs) were injected via carotid artery (IA) or tail vein (TV) into allogeneic and syngeneic BMT recipient mice. Following xenogeneic transplantation, MSC biodistribution was measured by bioluminescence imaging (BLI) using hMSCs transduced with a reporter gene system containing luciferase and by scintigraphic imaging using hMSCs labeled with [99mTc]-HMPAO. Although hMSCs initially accumulated in the lungs in both transplant groups, more cells migrated to organs in alloBMT recipient as measured by in vivo BLI and scintigraphy and confirmed by ex vivo BLI imaging, immunohistochemistry and quantitative RT-PCR. IA injection resulted in persistent whole–body hMSC distribution in alloBMT recipients, while hMSCs were rapidly cleared in the syngeneic animals within one week. In contrast, TV-injected hMSCs were mainly seen in the lungs with fewer cells traveling to other organs. Summarily, these results demonstrate the potential use of IA injection to alter hMSC biodistribution in order to more effectively deliver hMSCs to targeted tissues and microenvironments. PMID:27330253

  10. Mycobacterium tuberculosis Contaminant Risk on Bone Marrow Aspiration Material from Iliac Bone Patients with Active Tuberculous Spondylitis

    PubMed Central

    Rahyussalim, Ahmad Jabir; Kurniawati, Tri; Rukmana, Andriansjah

    2016-01-01

    There was a concern on Mycobacterium tuberculosis spreading to the bone marrow, when it was applied on tuberculous spine infection. This research aimed to study the probability of using autologous bone marrow as a source of mesenchymal stem cell for patients with tuberculous spondylitis. As many as nine patients with tuberculous spondylitis were used as samples. During the procedure, the vertebral lesion material and iliac bone marrow aspirates were obtained for acid fast staining, bacteria culture, and PCR (polymerase chain reaction) tests for Mycobacterium tuberculosis at the Clinical Microbiology Laboratory of Faculty of Medicine Universitas Indonesia. This research showed that there was a relationship between diagnostic confirmation of tuberculous spondylitis based on the PCR test and bacterial culture on the solid vertebral lesion material with the PCR test and bacterial culture from the bone marrow aspirates. If the diagnostic confirmation concluded positive results, then there was a higher probability that there would be a positive result for the bone marrow aspirates, so that it was not recommended to use autologous bone marrow as a source of mesenchymal stem cell for patients with tuberculous spondylitis unless the PCR and culture examination of the bone marrow showed a negative result. PMID:27294117