Science.gov

Sample records for bone marrow microcirculation

  1. Dysfunctional Microcirculation of the Lumbar Vertebral Marrow Prior to the Bone Loss and Intervertebral Discal Degeneration

    PubMed Central

    Lu, Guang-ming

    2015-01-01

    Study Design. Descriptive study, stratified sampling. Objective. Using dynamic computed tomographic perfusion (CTP) to explore the age-related distribution patterns of the microcirculation perfusion in the vertebral marrow, the vertebral bone mineral density (BMD), and the intervertebral discal degeneration (IDD) further to discuss the possible causation between them. Summary of Background Data. A latest viewpoint deemed that reduced blood supply of the vertebral marrow was correlated with an increased incidence of IDD and loss of BMD. However, the causative relationship between them needs more investigation. Methods. One hundred eighty-six general people were randomly enrolled by stratified sampling and grouped by age: 15 years or less, 16 to 25 years, 26 to 35 years, 36 to 45 years, 46 to 55 years, 56 to 65 years, 66 to 75 years, and 76 years or more. Both CTP and BMD of the third and fourth lumbar vertebral marrow were measured, and the IDD incidence of the third-fourth vertebrae was assessed. The temporal-spatial distribution patterns of the age-related changes of CTP, BMD, and IDD were described, and the correlations between them were calculated. Results. Microcirculatory perfusion of the vertebral marrow developed to maturate by 25 years, maintained stable at 35 years, and then declined by age after 35 years. BMD grew to a peak phase in 26 to 45 years and then dropped by years. However, IDD presented a sudden increase after 45 years of age. CTP (blood flow [r = 0.806], blood volume [r = 0.685], and permeability [r = 0.619]) showed strong positive correlations and CTP (time to peak [r = −0.211], mean transit time [r = −0.598]) showed negative correlations with BMD. Meanwhile, CTP (blood flow [r = −0.815], blood volume [r = −0.753], and permeability [r = −0.690]) had strong negative correlations and CTP (time to peak [r = 0.323] and mean transit time [r = 0.628]) had positive correlations with the incidence of IDD. Conclusion. Aging-related decrease

  2. Bone marrow aspiration

    MedlinePlus

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

  3. 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; ...

  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 culture

    MedlinePlus

    ... There may be some bleeding at the puncture site. More serious risks, such as serious bleeding or infection, are very rare. Alternative Names Culture - bone marrow Images Bone marrow aspiration References ...

  6. Bone Marrow Diseases

    MedlinePlus

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

  7. 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

  8. Aspiration and Biopsy: Bone Marrow

    MedlinePlus

    ... Your 1- to 2-Year-Old Aspiration and Biopsy: Bone Marrow KidsHealth > For Parents > Aspiration and Biopsy: Bone Marrow A A A What's in this ... ósea What It Is Bone marrow aspirations and biopsies are performed to examine bone marrow, the spongy ...

  9. Aspiration and Biopsy: Bone Marrow

    MedlinePlus

    ... A Week of Healthy Breakfasts Shyness Aspiration and Biopsy: Bone Marrow KidsHealth > For Teens > Aspiration and Biopsy: Bone Marrow A A A What's in this ... Questions What It Is Bone marrow aspirations and biopsies are performed to examine bone marrow, the spongy ...

  10. Bone marrow biopsy

    MedlinePlus

    ... myelodysplastic syndrome; MDS) A nerve tissue tumor called neuroblastoma Bone marrow disease that leads to an abnormal ... Hairy cell leukemia Hodgkin lymphoma Multiple myeloma Myelofibrosis Neuroblastoma Non-Hodgkin lymphoma Platelet count Polycythemia vera Primary ...

  11. Bone and bone marrow: the same organ.

    PubMed

    Del Fattore, Andrea; Capannolo, Marta; Rucci, Nadia

    2010-11-01

    Interplays between bone and bone marrow are not limited to merely anatomic and histological connections, but include a tight functional correlation. Bone marrow resides within the medullary cavity of the bones and the process of hematopoiesis is regulated, at least in part, by bone cells. Moreover, osteoclasts and osteoblasts derive from precursors of hematopoietic and mesenchymal origin, respectively, both residing within the bone marrow. Alterations in one of these components typically cause impairment in the other, so diseases of the bone marrow compartment often affect the bone and vice versa. All these findings could make us to speculate that bone and bone marrow are not two separate districts, but can be considered as the two elements of the same unique functional unit, the bone-bone marrow organ. Here we will describe histological and functional interplays between bone and bone marrow, and will illustrate some diseases in which this tight correlation is evident.

  12. 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 ...

  13. What Are Bone Marrow Tests?

    MedlinePlus

    ... for people with certain bleeding disorders such as hemophilia. Bone marrow tests can be done in a ... reading Anemia Aplastic Anemia Blood Tests Clinical Trials Hemophilia Thrombocythemia and Thrombocytosis Thrombocytopenia Rate This Content: Updated: ...

  14. Aspiration and Biopsy: Bone Marrow

    MedlinePlus

    ... in determining treatment and prognosis) viral, bacterial, or fungal infections in the bone marrow that might be causing lasting fever or other symptoms certain genetic diseases (such as lipid storage diseases) They also ...

  15. Aspiration and Biopsy: Bone Marrow

    MedlinePlus

    ... in determining treatment and prognosis) viral, bacterial, or fungal infections in the bone marrow that might be causing a lasting fever or other symptoms certain genetic diseases (such as lipid storage diseases) They also ...

  16. [Normal bone marrow and common reactive alterations].

    PubMed

    Tzankov, A; Dirnhofer, S; Beham-Schmid, C

    2012-11-01

    Histological examination of bone marrow biopsies is an important and powerful diagnostic tool to assess various hematological and non-hematological disorders. Morphological examination of such biopsies requires knowledge of the composition of normal bone marrow and its variations, such as age-related changes. Diagnostic problems may arise due to poor specimen quality, insufficient sections or stainings and insufficient experience with reactive bone marrow changes which occasionally resemble neoplastic disorders. Reactive bone marrow processes can affect one or more hematopoietic cell lines, lead to disruption of the normal architecture and specifically affect the bone marrow stroma. Optimal bone marrow diagnosis requires adequately stained slides and, when needed, immunophenotyping and molecular examinations. Furthermore, rather than biopsy interpretation of other organs, pathologists routinely need clinical history information for correct interpretation and diagnosis of bone marrow changes. In this article, the normal features of bone marrow as well as the most frequent reactive bone marrow alterations are described.

  17. Role of bone marrow macrophages in controlling homeostasis and repair in bone and bone marrow niches.

    PubMed

    Kaur, Simranpreet; Raggatt, Liza Jane; Batoon, Lena; Hume, David Arthur; Levesque, Jean-Pierre; Pettit, Allison Robyn

    2017-01-01

    Macrophages, named for their phagocytic ability, participate in homeostasis, tissue regeneration and inflammatory responses. Bone and adjacent marrow contain multiple functionally unique resident tissue macrophage subsets which maintain and regulate anatomically distinct niche environments within these interconnected tissues. Three subsets of bone-bone marrow resident tissue macrophages have been characterised; erythroblastic island macrophages, haematopoietic stem cell niche macrophages and osteal macrophages. The role of these macrophages in controlling homeostasis and repair in bone and bone marrow niches is reviewed in detail.

  18. Methotrexate and bone marrow metaphases.

    PubMed

    Cunningham, J J; Potter, A M; Watmore, A E; Winfield, D A

    1988-07-15

    The efficacy of a methotrexate (MTX) block/thymidine release synchronization technique has been assessed in bone marrow cultures from patients with acute nonlymphocytic leukemia and myelodysplasia. In contrast to cultures of stimulated lymphocytes from normal individuals, no improvement in mitotic index (MI) or metaphase quality could be detected using this technique. Demonstration of an unchanged level of division in bone marrow cultures in the presence of MTX suggests that the technique is unsuitable for synchronization purposes in this tissue. The influence of preincubation prior to MTX exposure and duration of exposure to colcemid on MI and metaphase quality have also been examined.

  19. 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.

  20. Structural features of bone marrow

    PubMed Central

    Romaniuk, Anatolii; Lyndina, Yuliia; Sikora, Vladyslav; Lyndin, Mykola; Karpenko, Ludmyla; Gladchenko, Oksana; Masalitin, Igor

    2016-01-01

    Purpose This article is devoted to the investigation of the structural features of the bone marrow of mature rats. Materials and methods The investigation of the structural features of the bone marrow was performed on the femurs of the mature male rats. General structure of the organ was studied with hematoxylin–eosin and Van Gieson staining of samples. Certain features of the bone marrow structure were studied using immunohistochemical method (CD3, CD79α, S100, myeloperoxidase, and cyclin D1). Results We can state that stromal–parenchymal structure is typical for the bone marrow of rats as for any other organ. The stromal component is presented with bone tissue (48.8 ± 3.3% at epiphyses), the net of blood vessels (18.7 ± 2.1%), fat tissue (11 ± 2%), fibrous tissue (0.7 ± 0.2%), and the network of reticular fibers. Hematopoietic tissue covers 20.9 ± 3.7% at the femoral epiphyses and 69.6 ± 2.2% at diaphysis. Among these tissues, myelopoiesis occupies 74.2 ± 4.7%, erythropoiesis – 24.3 ± 4.7%, and lymphopoiesis – less than 5%. Megalokaryocytes take 0.1–0.3%. Conclusion Considering the lack of significant anatomical, morphological, and histological differences of red bone marrow of rats and humans, we can state that hematopoiesis in rats takes place on the basis of the same principles as in humans, although it has certain mechanisms. PMID:28203394

  1. 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.

  2. Salvianolic Acid B Prevents Bone Loss in Prednisone-Treated Rats through Stimulation of Osteogenesis and Bone Marrow Angiogenesis

    PubMed Central

    Cui, Liao; Li, Ting; Liu, Yuyu; Zhou, Le; Li, Pinghua; Xu, Bilian; Huang, Lianfang; Chen, Yan; Liu, Yanzhi; Tian, Xiaoyan; Jee, Webster S. S.; Wu, Tie

    2012-01-01

    Glucocorticoid (GC) induced osteoporosis (GIO) is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B) is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1) In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d) for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d) not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2) In vitro study: In concentration from 10−6 mol/L to 10−7 mol/L, Sal B stimulated bone marrow stromal cell (MSC) differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin mRNA expression with

  3. Salvianolic acid B prevents bone loss in prednisone-treated rats through stimulation of osteogenesis and bone marrow angiogenesis.

    PubMed

    Cui, Liao; Li, Ting; Liu, Yuyu; Zhou, Le; Li, Pinghua; Xu, Bilian; Huang, Lianfang; Chen, Yan; Liu, Yanzhi; Tian, Xiaoyan; Jee, Webster S S; Wu, Tie

    2012-01-01

    Glucocorticoid (GC) induced osteoporosis (GIO) is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B) is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1) In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d) for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d) not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2) In vitro study: In concentration from 10(-6) mol/L to 10(-7) mol/L, Sal B stimulated bone marrow stromal cell (MSC) differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin mRNA expression with

  4. 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…

  5. 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.

  6. 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.

  7. 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.

  8. Androgen, Estrogen and the Bone Marrow Microenvironment

    DTIC Science & Technology

    2009-12-01

    SUPPLEMENTARY NOTES 14. ABSTRACT We have accomplished the following: 1) Characterized androgen responsive genes in mouse bone marrow (BM) via...castration (androgen ablation) and estrogen stimulation. 2) Measurements of testosterone, dihydrotestosterone and of genes that regulate the local... gene expression in the bone marrow. In males, the main source of estrogen is through conversion of androgen by aromatase. We postulate that gene

  9. Bone marrow examination in pancytopenia.

    PubMed

    Rangaswamy, M; Prabhu; Nandini, N M; Manjunath, G V

    2012-08-01

    Pancytopenia is defined by reduction of all the three formed elements of blood below the normal reference. It may be a manifestation of a wide variety of disorders, which primarily or secondarily affect the bone marrow. Haematological investigation forms the bedrock in the management of patients with pancytopenia and therefore needs detailed study. The total number of cases studied were 100 over a period of two years in the department of pathology, JSS Hospital, Mysore. Megaloblastic anaemia (33%) was the commonest cause of pancytopenia. Other causes were nutritional anaemia (16%), aplastic anaemia (14%), hypersplenism (10%), sepsis (9%) and leukaemia (5%). Less common causes were alcoholic liver disease, haemolytic anaemia, HIV, dengue, systemic lupus erythematosus, viral hepatitis, disseminated TB and multiple myeloma. Most of the patients were in the age group of 11-30 years with a male:female ratio of 1.6:1.Generalised weakness and fatigue (88%) were the commonest presenting complaints. Haemoglobin level varied from 1-10 g/dl with majorIty (70%) of them in the range of 5.1-10 g/dI. TLC was in the range of 500-4000 cells/cmm. Most (34%) of them had 3100-4000 cells/cmm. Platelet count was in the range of 4000-1,40,000 cells/cmm. Reticulocyte count varied from 0.1%-15% with majority (82%) of them ranging from 0.1%-2%. The bone marrow cellularity was hypocellular in 14%, hypercellular in 75%, and normocellular in 11% of the patients. Pancytopenia is a relatively common entity with inadequate attention in Indian subcontinent. A comprehensive clinical and haematological study of patients with pancytopenia will usually help in the identification of the underlying cause. However in view of wide array of aetiologies, pancytopenia continues to be a diagnostic challenge for haematologists.

  10. Megakaryocytes, malignancy and bone marrow vascular niches.

    PubMed

    Psaila, B; Lyden, D; Roberts, I

    2012-02-01

    Dynamic interactions between hematopoietic cells and their specialized bone marrow microenvironments, namely the vascular and osteoblastic 'niches', regulate hematopoiesis. The vascular niche is conducive for thrombopoiesis and megakaryocytes may, in turn, regulate the vascular niche, especially in supporting vascular and hematopoietic regeneration following irradiation or chemotherapy. A role for platelets in tumor growth and metastasis is well established and, more recently, the vascular niche has also been implicated as an area for preferential homing and engraftment of malignant cells. This article aims to provide an overview of the dynamic interactions between cellular and molecular components of the bone marrow vascular niche and the potential role of megakaryocytes in bone marrow malignancy.

  11. [Increased efficacy of allogenic bone marrow transplantation].

    PubMed

    Fedotenkov, A G; Danilova, L A; Ignasheva, L P

    1982-08-01

    Experiments made in vivo and vitro have demonstrated that conservation of allogeneic hemopoietic tissue with glycerin brings about a decrease in transplatation, homologous activity of T lymphocytes. Allogeneic bone marrow conserved with glycerin compares very favourably with freshly prepared allogeneic bone marrow since the transplant-versus-host reaction is attenuated under the effect of glycerin. Moreover, it shows a higher proliferative activity. The glycerin-induced reduction of the inactivating effect of lymphocytes against non-syngeneic colony-forming units enables the conserved bone marrow to be transplanted from several donors.

  12. Pituitary abscess after autologous bone marrow transplantation.

    PubMed

    Leff, R S; Martino, R L; Pollock, W J; Knight, W A

    1989-05-01

    The first case of pituitary abscess arising in a patient during recovery from autologous bone marrow transplantation is reported. A 31-year-old man with a 9 month history of T-cell lymphoma died suddenly more than 60 days after successful treatment with high-dose cyclophosphamide, total body irradiation, and autologous bone marrow infusion. Autopsy revealed a pituitary abscess associated with clinically silent sphenoid sinusitis. Unique aspects of this case are presented and clinical and pathologic features of pituitary abscess are reviewed. Although rare, pituitary abscess may complicate recovery from bone marrow transplantation.

  13. Kinetics of erythrogenesis after bone marrow transplantation.

    PubMed

    Lazarus, H M; Chahine, A; Lacerna, K; Wamble, A; Iaffaldano, C; Straight, M; Rabinovitch, A; Schimenti, K J; Jacobberger, J

    1992-04-01

    To determine the kinetics of bone marrow erythrogenesis after bone marrow transplantation, the authors counted reticulocytes (by blood smear and flow cytometry) and compared those data with neutrophil and platelet recovery in 23 consecutive bone marrow transplant patients. The earliest indication of marrow recovery after allogeneic and autologous bone marrow transplantation was defined as the second increasing cell count after the lowest recorded count, provided that the trend continued upward. Recovery of marrow function was detected earlier in 10 of 23 patients using reticulocyte counts than by either neutrophil or platelet count alone. Specifically, in 8 of these 10 patients, recovery of erythropoiesis was determined earlier by flow cytometric examination than by the blood smear method. On the other hand, combining the data using the earliest value of platelet, neutrophil, and reticulocyte counts indicated that the mean day of recovery in our patient population was determined to be 12.1 +/- 4 days after marrow infusion. In patients undergoing autologous and allogeneic bone marrow transplantation, serial neutrophil and reticulocyte count determinations are complementary in early clinical detection of successful engraftment.

  14. [Changes in the bone marrow in cancer patients. 61 bone marrow biopsies].

    PubMed

    Marsan, C; Henon, P; Cywiner-Golenzer, C; Zitouna, M M; Girardi, P

    1976-01-01

    The authors studied 61 bone marrow biopsies carried out in cancerous patients, presumably suffering from a bone metastasis and before any treatment. They feel that quantitative and qualitative changes in the bone marrow may be considered to be an indirect diagnostic indication of metastatic spread.

  15. 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.

  16. Psycholegal issues in sibling bone marrow donation.

    PubMed

    Weisz, Victoria

    1992-01-01

    The only hope of survival for children with a number of life-threatening illnesses is a successful bone marrow transplant (BMT). Unlike the treatment source for most therapies, the raw material for transplant therapy comes from a human being. Although many BMTs are autologous, utilizing the patient's own bone marrow, a large percentage of childhood BMTs rely on bone marrow from children or adolescents who are biological siblings to the sick child. Medical and legal systems are confronted with a dilemma when healthy children are needed to undergo minimally risky, yet somewhat painful, procedures for the benefit of their critically ill siblings. This article reviews legal issues involved in sibling bone marrow donation and psychological research that is relevant to those issues. The article concludes with proposed directions for future psycholegal research and a discussion of ethical issues that are not amenable to empirical investigation.

  17. Bone marrow transplant – children - discharge

    MedlinePlus

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

  18. 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

  19. Redox Regulation in Bone Marrow Failure

    DTIC Science & Technology

    2012-06-01

    aplastic anemia patients with a p38 MAPK inhibitor can restore defective hematopoietic activity, suggesting the critical role of p38 in bone marrow...hematopoietic stem cells, and eventually leading to bone marrow failure [7, 8] [9] [10]. On the other hand, treating aplastic anemia patients with a p38...in aplastic anemia . J Immunol, 2002. 168(12): p. 5984-8. 12. Ikebuchi, K., et al., Interleukin 6 enhancement of interleukin 3-dependent

  20. The pathology of bone marrow failure.

    PubMed

    Leguit, Roos J; van den Tweel, Jan G

    2010-11-01

    An important indication for bone marrow investigation is the presence of bone marrow failure, which manifests itself as (pan)cytopenia. The causes of cytopenia are varied and differ considerably between childhood and adulthood. In the paediatric age group inherited bone marrow failure syndromes are important causes of bone marrow failure, but they play only a minor role in later life. This review gives a comprehensive overview of bone marrow failure disorders in children and adults. We classified the causes of bone marrow failure according to the main presenting haematological abnormality, i.e. anaemia, neutropenia, thrombocytopenia or pancytopenia. The following red cell disorders are discussed: red cell aplasia, sideroblastic anaemia, congenital dyserythropoietic anaemia, haemolytic anaemia, paroxysmal nocturnal haemoglobinuria, iron deficiency anaemia, anaemia of chronic disease and megaloblastic anaemia. The neutropenias occur in the context of Shwachman-Diamond syndrome (SDS), severe congenital neutropenia, cyclic neutropenia, immune-related neutropenia and non-immune neutropenia. In addition, the following causes of thrombocytopenia are discussed: congenital amegakaryocytic thrombocytopenia, thrombocytopenia with absent radii, immune-related thrombocytopenia and non-immune thrombocytopenia. Finally, we pay attention to the following pancytopenic disorders: Fanconi anaemia, dyskeratosis congenita, aplastic anaemia, myelodysplastic syndromes and human immunodeficiency virus (HIV) infection.

  1. [Bone and Stem Cells. Intravital imaging of bone marrow microenvironment].

    PubMed

    Mizuno, Hiroki; Kikuta, Junichi; Ishii, Masaru

    2014-04-01

    Various kinds of cell types, such as osteoclasts, osteoblasts, hematopoietic cells, and mesenchymal cells, have been reported to exist in the bone marrow and communicate with each other. Although there have been many previous studies about bone marrow microenvironment, most of them were analyzed by conventional methods such as histological analysis and flow cytometry. These methods could not observe the dynamic cell movement in living bone marrow. Recently rapid development of fluorescent imaging techniques enables us to understand the cellular dynamics in vivo . That's why we have originally established an advanced imaging system for visualizing living bone tissues with intravital two-photon microscopy. Here we show the latest data and the detailed methodology of intravital imaging of bone marrow microenvironment, and also discuss its further application.

  2. Abnormal bone marrow histopathology in paediatric mastocytosis.

    PubMed

    Carter, Melody C; Metcalfe, Dean D; Clark, Alicia S; Wayne, Alan S; Maric, Irina

    2015-03-01

    The diagnostic criteria for paediatric mastocytosis are largely based on adult studies and bone marrow findings are not well described in children. We evaluated use of the World Health Organization (WHO) criteria for the diagnosis of systemic disease in paediatric mastocytosis. In addition, we identified unique clinico-histopathological features within the biopsies. One hundred and thirteen children with paediatric mastocytosis were evaluated at the National Institutes of Health between 1986 and 2013. Complete bone marrow evaluations were performed in 50 cases. Seven children had repeat procedures. Bone marrows were analysed by histopathology, flow cytometry and for KIT D816V. Bone marrow biopsies displayed mild atypical haematopoietic maturation, increased haematogones and hypocellularity in a sub-set of patients with urticaria pigmentosa, diffuse cutaneous mastocytosis and indolent systemic mastocytosis. Hypocellularity was most pronounced in those with urticaria pigmentosa. Haematogones were highest, on average, in patients with diffuse cutaneous mastocytosis or mastocytomas. There was no evidence of peripheral blood cytopenias, myelodysplastic syndrome, myeloproliferative neoplasm or leukaemia within this cohort. The WHO criteria are applicable for the diagnosis of systemic mastocytosis in paediatrics. Although unsuspected bone marrow findings typically seen in myeloproliferative disorders are frequent in paediatric mastocytosis, patients within this study remained clinically stable without progression to a more aggressive variant.

  3. Radionuclide imaging of bone marrow disorders.

    PubMed

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

    2011-01-01

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

  4. Tracking Mouse Bone Marrow Monocytes In Vivo

    PubMed Central

    Hamon, Pauline; Rodero, Mathieu Paul; Combadière, Christophe; Boissonnas, Alexandre

    2015-01-01

    Real time multiphoton imaging provides a great opportunity to study cell trafficking and cell-to-cell interactions in their physiological 3-dimensionnal environment. Biological activities of immune cells mainly rely on their motility capacities. Blood monocytes have short half-life in the bloodstream; they originate in the bone marrow and are constitutively released from it. In inflammatory condition, this process is enhanced, leading to blood monocytosis and subsequent infiltration of the peripheral inflammatory tissues. Identifying the biomechanical events controlling monocyte trafficking from the bone marrow towards the vascular network is an important step to understand monocyte physiopathological relevance. We performed in vivo time-lapse imaging by two-photon microscopy of the skull bone marrow of the Csf1r-Gal4VP16/UAS-ECFP (MacBlue) mouse. The MacBlue mouse expresses the fluorescent reporters enhanced cyan fluorescent protein (ECFP) under the control of a myeloid specific promoter 1, in combination with vascular network labelling. We describe how this approach enables the tracking of individual medullar monocytes in real time to further quantify the migratory behaviour within the bone marrow parenchyma and the vasculature, as well as cell-to-cell interactions. This approach provides novel insights into the biology of the bone marrow monocyte subsets and allows to further address how these cells can be influenced in specific pathological conditions. PMID:25867540

  5. Bone marrow osteoblast vulnerability to chemotherapy.

    PubMed

    Gencheva, Marieta; Hare, Ian; Kurian, Susan; Fortney, Jim; Piktel, Debbie; Wysolmerski, Robert; Gibson, Laura F

    2013-06-01

    Osteoblasts are a major component of the bone marrow microenvironment, which provide support for hematopoietic cell development. Functional disruption of any element of the bone marrow niche, including osteoblasts, can potentially impair hematopoiesis. We have studied the effect of two widely used drugs with different mechanisms of action, etoposide (VP16) and melphalan, on murine osteoblasts at distinct stages of maturation. VP16 and melphalan delayed maturation of preosteoblasts and altered CXCL12 protein levels, a key regulator of hematopoietic cell homing to the bone marrow. Sublethal concentrations of VP16 and melphalan also decreased the levels of several transcripts which contribute to the composition of the extracellular matrix (ECM) including osteopontin (OPN), osteocalcin (OCN), and collagen 1A1 (Col1a1). The impact of chemotherapy on message and protein levels for some targets was not always aligned, suggesting differential responses at the transcription and translation or protein stability levels. As one of the main functions of a mature osteoblast is to synthesize ECM of a defined composition, disruption of the ratio of its components may be one mechanism by which chemotherapy affects the ability of osteoblasts to support hematopoietic recovery coincident with altered marrow architecture. Collectively, these observations suggest that the osteoblast compartment of the marrow hematopoietic niche is vulnerable to functional dysregulation by damage imposed by agents frequently used in clinical settings. Understanding the mechanistic underpinning of chemotherapy-induced changes on the hematopoietic support capacity of the marrow microenvironment may contribute to improved strategies to optimize patient recovery post-transplantation.

  6. Bone marrow cells and myocardial regeneration.

    PubMed

    Wang, Fu-Sheng; Trester, Cathy

    2004-05-01

    Hematopoietic stem cell (HSC) plasticity and its clinical application have been studied profoundly in the past few years. Recent investigations indicate that HSC and other bone marrow stem cells can develop into other tissues. Because of the high morbidity and mortality of myocardial infarction and other heart disorders, myocardial regeneration is a good example of the clinical application of HSC plasticity in regenerative medicine. Preclinical studies in animals suggest that the use of this kind of treatment can reconstruct heart blood vessels, muscle, and function. Some clinical study results have been reported in the past 2 years. In 2003, reports of myocardial regeneration treatment increased significantly. Other studies include observations on the cell surface markers of transplanted cells and treatment efficacy. Some investigations, such as HSC testing, have focused on clinical applications using HSC plasticity and bone marrow transplantation to treat different types of disorders. In this review, we focus on the clinical application of bone marrow cells for myocardial regeneration.

  7. National Marrow Donor Program. HLA Typing for Bone Marrow Transplantation

    DTIC Science & Technology

    2014-11-30

    event. 3. Immunogenetic Studies: Increase understanding of the immunologic factors important in HSC transplantation. 4. Clinical Research... Immunology , and Transplantation DaSH Data Standards Hackathon DC Donor Center National Marrow Donor Program® N00014-13-1-0039 HLA Typing for Bone...Management Strategy ImmPort Immunology Database and Analysis Portal IND Investigational New Drug IND Improvised Nuclear Device IPR Immunobiology Project

  8. Bone marrow-derived lung epithelial cells.

    PubMed

    Krause, Diane S

    2008-08-15

    Bone marrow-derived cells can take on the phenotype of epithelial cells and express epithelial-specific genes in multiple organs. Here, we focus on recent data on the appearance of marrow-derived epithelial cells in the adult lung. These findings have garnered significant skepticism because in most cases marrow-derived epithelial cells are very rare, the marrow cell of origin is not known, the techniques for detection have needed improvement, and there seem to be multiple mechanisms by which this occurs. Recent studies have focused on these concerns. Once these important concerns are addressed, further studies on the function(s) of these cells will need to be performed to determine whether this engraftment has any clinical significance-either beneficial or detrimental.

  9. The diagnostic value of bone marrow iron.

    PubMed

    Wulfhekel, U; Düllmann, J

    1990-01-01

    The light and electronmicroscopic representation of non-haemiron in the bone-marrow provides the unique opportunity of extensively evaluating the iron metabolism. In the bone-marrow, macrophages represent the physiological place of iron storage. The iron in the cytoplasma is stored in them in the form of free ferritin molecules and lysomally as aggregated ferritin and/or haemosiderin in siderosomes. In an equal iron balance and unimpaired internal iron exchange only erythroblasts (sideroblasts) and erythrocytes (siderocytes) of the bone-marrow besides macrophages possess siderosomes. In addition to this physiological or orthotopic iron storage a heterotopic iron storage can be observed under pathological conditions, particularly with iron overloading of the organism, in the endothelial cells of sinusoids and plasma cells. In detail, the patterns of iron storage in the bone-marrow are described in the different stages of iron deficiency, disturbance of iron utilization in chronically inflammatory processes or tumour diseases, condition after intravenous iron administration, transfusion siderosis, hereditary haemochromatosis and sideroblastic anaemia.

  10. Magnetic resonance imaging of bone marrow disease in children

    SciTech Connect

    Cohen, M.D.; Klatte, E.C.; Baehner, R.; Smith, J.A.; Martin-Simmerman, P.; Carr, B.E.; Provisor, A.J.; Weetman, R.M.; Coates, T.; Siddiqui, A.

    1984-06-01

    Seven children underwent magnetic resonance imaging (MRI) of the bone marrow: results showed that it is technically feasible to obtain good MR images of marrow in children. MR has detected abnormality in the bone marrow of a child who had metastatic neuroblastoma. The extent of abnormality in the femur correlated well with findings of a bone marrow isotope scan. In one child who had idiopathic aplastic anemia, diseased marrow could not be distinguished from normal marrow on MR images. MRI identified abnormality of the marrow in osteogenic sarcoma, and demonstrated change in response to chemotherapy. It displayed marrow spread of tumors as well as CT. MRI showed marrow abnormality in four children who had leukemia.

  11. Engineering bone grafts with enhanced bone marrow and native scaffolds.

    PubMed

    Hung, Ben P; Salter, Erin K; Temple, Josh; Mundinger, Gerhard S; Brown, Emile N; Brazio, Philip; Rodriguez, Eduardo D; Grayson, Warren L

    2013-01-01

    The translation of tissue engineering approaches to the clinic has been hampered by the inability to find suitable multipotent cell sources requiring minimal in vitro expansion. Enhanced bone marrow (eBM), which is obtained by reaming long bone medullary canals and isolating the solid marrow putty, has large quantities of stem cells and demonstrates significant potential to regenerate bone tissues. eBM, however, cannot impart immediate load-bearing mechanical integrity or maintain the gross anatomical structure to guide bone healing. Yet, its putty-like consistency creates a challenge for obtaining the uniform seeding necessary to effectively combine it with porous scaffolds. In this study, we examined the potential for combining eBM with mechanically strong, osteoinductive trabecular bone scaffolds for bone regeneration by creating channels into scaffolds for seeding the eBM. eBM was extracted from the femurs of adult Yorkshire pigs using a Synthes reamer-irrigator-aspirator device, analyzed histologically, and digested to extract cells and characterize their differentiation potential. To evaluate bone tissue formation, eBM was seeded into the channels in collagen-coated or noncoated scaffolds, cultured in osteogenic conditions for 4 weeks, harvested and assessed for tissue distribution and bone formation. Our data demonstrates that eBM is a heterogenous tissue containing multipotent cell populations. Furthermore, coating scaffolds with a collagen hydrogel significantly enhanced cellular migration, promoted uniform tissue development and increased bone mineral deposition. These findings suggest the potential for generating customized autologous bone grafts for treating critical-sized bone defects by combining a readily available eBM cell source with decellularized trabecular bone scaffolds.

  12. Bone Marrow Edema: Chronic Bone Marrow Lesions of the Knee and the Association with Osteoarthritis.

    PubMed

    Collins, Jason A; Beutel, Bryan G; Strauss, Eric; Youm, Thomas; Jazrawi, Laith

    2016-03-01

    Bone marrow edema of the knee occurs secondary to a myriad of causes. The hallmark of a bone marrow lesion (BML) is an area of decreased signal intensity on T1 weighted MRI with a corresponding area of increased signal intensity on a T2 weighted MRI. Recently, chronic bone marrow lesions have been correlated with knee pain and progression of osteoarthritis. These lesions have also been associated with other degenerative conditions such as meniscal tears, cartilage deterioration, subchondral cyst formation, mechanical malalignment, and ultimately progression to arthroplasty. Medical treatments, such as prostacyclin and bisphosphonate therapy, have shown promise. Alignment procedures, as well as core decompression and subchondroplasty, have been used as surgical treatments for chronic BMLs.

  13. Periosteum and bone marrow in bone lengthening: a DEXA quantitative evaluation in rabbits.

    PubMed

    Guichet, J M; Braillon, P; Bodenreider, O; Lascombes, P

    1998-10-01

    We quantitatively studied the role of periosteum and bone marrow-endosteum during lengthening in 18 growing rabbits, comparing four surgical procedures: 1) periosteum and bone marrow preservation, 2) periosteum preservation, bone marrow destruction, 3) periosteum destruction, bone marrow preservation, 4) periosteum and bone marrow destruction. An external fixator was set on one femur, the other serving as a control. Distraction began on day 5 and stopped on day 25 (0.25 mm/12 hours). On day 30, femora were harvested with a layer of muscle. Area, bone mineral content and density were measured by dual-energy x-ray absorptiometry. Procedure 2 showed the highest increase in bone mineral content around the elongated callus (127%) compared to procedures: 1 (81%), 3 (25%) and 4 (-8%, i.e., resorption of bone ends). A statistically significant effect on bone formation was observed when preserving (vs. destroying): 1) periosteum, 2) bone marrow (effect observed only around the distraction gap), 3) periosteum and bone marrow in combination. Periosteum alone forms a larger callus, with more mineral content than bone marrow alone, and destruction of both results in the absence of bone formation around the distraction area. Careful preservation of periosteum is essential to bone healing. Formation of bone with a large mineral content does not require bone marrow preservation, but there is an interaction effect on healing between bone marrow and periosteum.

  14. 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.

  15. Bone marrow-derived dendritic cells.

    PubMed

    Roney, Kelly

    2013-01-01

    While much is understood about dendritic cells and their role in the immune system, the study of these cells is critical to gain a more complete understanding of their function. Dendritic cell isolation from mouse body tissues can be difficult and the number of cells isolated small. This protocol describes the growth of large number of dendritic cells from the culture of mouse bone marrow cells. The dendritic cells grown in culture facilitate experiments that may require large number of dendritic cells without great expense or use of large number of mice.

  16. Androgen, Estrogen and the Bone Marrow Microenvironment

    DTIC Science & Technology

    2009-12-01

    binding protein-5 expression. Xu C, Graf LF, Fazli L, Coleman IM, Mauldin DE, Li D, Nelson PS, Gleave M, Plymate SR, Cox ME, Torok-Storb BJ, Knudsen BS...Meeting presentations: Xu C, Graf LF, Fazli L, Nelson PS, Plymate SR, Cox ME, Torok-Storb BJ, Knudsen BS (2007) Androgen-regulation of the Bone...Marrow Microenvironment targets IGFBP-5. Innovative Minds in Prostate Cancer Today (IMPaCT). Atlanta, Georgia. P8-7. Xu C, Graf LF, Fazli L

  17. [Fundamental study of blood and bone marrow].

    PubMed

    Miura, Ikuo

    2009-10-01

    The WHO classification incorporated recent advances of immunology, cytogenetics, and molecular biology, which developed from FAB classification based on cell morphology and cytochemistry. One of the most distinct changes was "AML with recurrent genetic abnormalities." The immunological and cytogenetic studies are required to apply the classification to hematopoietic and lymphoid neoplasms in addition to conventional examinations of the blood and bone marrow. The fundamentals of specimen collection, cell counts, morphologic analysis of blood cells, special stains and other laboratory studies were described in related to the management of myeloid leukemias.

  18. [Modified method for whole bone marrow adherent culture of human bone marrow mesenchymal stem cells].

    PubMed

    Wang, Xiao-Qing; Zhong, Zhao-Dong; Chen, Zhi-Chao; Zou, Ping

    2014-04-01

    This study was aimed to investigate a more convenient and efficient method to cultivate the human bone marrow mesenchymal stem cells by means of natural erythrocyte sedimentation principle, based on the whole bone marrow adherent method. The bone marrow was cultured with a six-well plate instead of the flasks.Firstly, the bone marrow specimen was cultivated with the MSC complete medium for 48 h, then the upper RBC-free supernatant layer was drawn and placed into the new wells to isolate MSC. Inverted microscope was used to observe the cell morphology and to record the adherent time of first cell passage, first passaging time. The traditional whole bone marrow adherent method was used as the control. The cell cycle and cell surface markers were detected by flow cytometry,and the differentiative capacity of MSC into osteocyte and adipocyte was identified by alkaline phosphatase kit and oil red O, respectively. Besides, the proliferative curve of P1,P3,P5 of BMSC was depicted by counting method. The results showed that MSC cultured by the modified method highly expressed CD90, CD105, CD13, CD44 and lowly expressed CD14, CD45, CD34. Concerning the cell cycle feature, it was found that most of the cells were in G0/G1 phase (88.76%) , followed by G2/M phase (3.04%) and S phase (8.2%), which was in accordance with stem cell cycle characteristics. The proliferative curve showed a typical "S" type, and both the oil red O and alkaline phosphatase staining of MSC were positive. Compared with the traditional method, the modified method had the advantage of high adherence rate (P = 0.0001) and shorter passaging time for the first passage (P = 0.001), with the statistically significant difference. It is concluded that there is a large number of adherent, active and suspended MSC in the RBC-free supernatant layer after the culture of bone marrow for 48 h. Isolating MSC by the modified method is more convenient and efficient than the traditional whole bone marrow adherent method.

  19. Common Cold Can Be Dangerous After Bone Marrow Transplant

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_164206.html Common Cold Can Be Dangerous After Bone Marrow Transplant Rhinovirus ... 2017 TUESDAY, March 21, 2017 (HealthDay News) -- The common cold can be deadly for patients recovering from bone ...

  20. Schwann cells induce neuronal differentiation of bone marrow stromal cells.

    PubMed

    Zurita, Mercedes; Vaquero, Jesús; Oya, Santiago; Miguel, Miriam

    2005-04-04

    Bone marrow stromal cells are multipotent stem cells that have the potential to differentiate into bone, cartilage, fat and muscle. Recently, bone marrow stromal cells have been shown to have the capacity to differentiate into neurons under specific experimental conditions, using chemical factors. We now describe how bone marrow stromal cells can be induced to differentiate into neuron-like cells when they are co-cultured with Schwann cells. When compared with chemical differentiation, expression of neuronal differentiation markers begins later, but one week after beginning co-culture, most bone marrow stromal cells showed a typical neuronal morphology. Our present findings support the transdifferentiation of bone marrow stromal cells, and the potential utility of these cells for the treatment of degenerative and acquired disorders of the nervous system.

  1. Effects of the bone marrow microenvironment on hematopoietic malignancy.

    PubMed

    Askmyr, Maria; Quach, Julie; Purton, Louise E

    2011-01-01

    The bone marrow (BM) is contained within the bone cavity and is the main site of hematopoiesis, the continuous development of blood cells from immature hematopoietic stem and progenitor cells. The bone marrow consists of developing hematopoietic cells and non-hematopoietic cells, the latter collectively termed the bone marrow microenvironment. These non-hematopoietic cells include cells of the osteoblast lineage, adipocytes and endothelial cells. For many years these bone marrow microenvironment cells were predicted to play active roles in regulating hematopoiesis, and recent studies have confirmed such roles. Importantly, more recent data has indicated that cells of the BM microenvironment may also contribute to hematopoietic diseases. In this review we provide an overview of the roles of the data suggesting that the cells of the bone marrow microenvironment may play an active role in the initiation and progression of hematopoietic malignancy.

  2. 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.

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

    PubMed

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

    2013-07-21

    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.

  4. A multiscale model of the bone marrow and hematopoiesis

    PubMed Central

    Silva, Ariosto S; Anderson, Alexander R.A.

    2013-01-01

    The bone marrow is necessary for renewal of all hematopoietic cells and critical for maintenance of a wide range of physiologic functions. Multiple human diseases result from bone marrow dysfunction. It is also the site in which “liquid” tumors, including leukemia and multiple myeloma, develop as well as a frequent site of metastases. Understanding the complex cellular and microenvironmental interactions that govern normal bone marrow function as well as diseases and cancers of the bone marrow would be a valuable medical advance. Our goal is the development of a spatially-explicit in silico model of the bone marrow to understand both its normal function and the evolutionary dynamics that govern the emergence of bone marrow malignancy. Here we introduce a multiscale computational model of the bone marrow that incorporates three distinct spatial scales, cell, hematopoietic subunit, whole marrow. Implemented as a fixed lattice 3D cellular automaton, it reproduces the spatial characteristics of the normal bone marrow and is validated against data from the daily production of mature blood cells and response of hematopoiesis after irradiation. The major mechanisms modeled in this work are: (1) replication, specialization and migration of hematopoietic cells, (2) optimized spatial configuration of sinuses and hematopoietic compartments and, (3) intravasation of mature hematopoietic cells into sinuses. Our results, using parameter estimates from literature, recapitulates normal bone marrow function and suggest an explanation for the fractal-like structure of trabeculae and sinuses in the marrow, which would be an optimization of the hematopoietic function in order to maximize the number of mature blood cells produced daily within the volumetric restrictions of the marrow. PMID:21631151

  5. [Frontiers in Live Bone Imaging Researches. In vivo imaging of bone marrow microenvironment].

    PubMed

    Mizuno, Hiroki; Ishii, Masaru

    2015-06-01

    The function of hematopoietic stem cells and leukemia stem cells depends on their interaction with complex microenvironment within the bone marrow. Conventional methods could not observe the dynamic cell movement in living bone marrow. Recently rapid development of live imaging techniques enables us to understand the cellular interaction. Intravital two-photon imaging is the ideal method to understand the nature of bone marrow because of visualizing the cellular dynamics in vivo and observing the bone marrow long time. Here we show the latest reports about bone marrow microenvironment by intravital imaging, and also discuss its further application.

  6. Enteral nutrition after bone marrow transplantation

    PubMed Central

    Papadopoulou, A; MacDonald, A; Williams, M; Darbyshire, P; Booth, I

    1997-01-01

    Accepted 16 April 1997
 Nutritional insult after bone marrow transplantation (BMT) is complex and its nutritional management challenging. Enteral nutrition is cheaper and easier to provide than parenteral nutrition, but its tolerance and effectiveness in reversing nutritional depletion after BMT is poorly defined. Nutritional status, wellbeing, and nutritional biochemistry were prospectively assessed in 21 children (mean age 7.5 years; 14 boys) who received nasogastric feeding after BMT (mean duration 17 days) and in eight children (mean age 8 years, four boys) who refused enteral nutrition and who received dietetic advice only.
 Enteral nutrition was stopped prematurely in eight patients. Greater changes in weight and mid upper arm circumference were observed in the enteral nutrition group, while positive correlations were found between the duration of feeds and increase in weight and in mid upper arm circumference. Vomiting and diarrhoea had a similar incidence in the two groups, while fever and positive blood cultures occurred more frequently in the dietetic advice group. Diarrhoea occurring during enteral nutrition was not associated with fat malabsorption, while carbohydrate malabsorption was associated with rotavirus infection only. Enteral feeding did not, however, affect bone marrow recovery, hospital stay, general wellbeing, or serum albumin concentrations. Hypomagnesaemia, hypophosphataemia, zinc and selenium deficiency were common in both groups. In conclusion, enteral nutrition, when tolerated, is effective in limiting nutritional insult after BMT. With existing regimens nutritional biochemistry should be closely monitored in order to provide supplements when required.

 PMID:9301351

  7. Aerobic nitroreduction of dehydrochloramphenicol by bone marrow.

    PubMed

    Isildar, M; Abou-Khalil, W H; Jimenez, J J; Abou-Khalil, S; Yunis, A A

    1988-06-30

    It has been previously demonstrated that dehydrochloramphenicol (DH-CAP), a bacterial metabolite of chloramphenicol, induces DNA single strand breaks in intact cells and is profoundly more cytotoxic than chloramphenicol (CAP). In view of previous observations relating genotoxicity of nitrocompounds to their nitroreduction by the target tissue, we studied the nitroreduction of DH-CAP by human and rabbit bone marrow. Nitroreduction by tissue homogenates was determined by the Bratton Marshall colorimetric assay and by high-performance liquid chromatography (HPLC). Nitroreduction of DH-CAP by bone marrow cell homogenates was observed under aerobic conditions and the reduction was both cell concentration- and time-dependent. The formation of the amino product aminodehydrochloramphenicol was confirmed by HPLC. Reduction by other tissues including human liver, Raji cells, and HL-60 tumors was also observed. These results suggest that genotoxicity of DH-CAP may be related to its nitroreduction by the target tissue with in situ production of toxic intermediates. Together with previous studies, these observations lend support to the thesis that the p-NO2 group may be the structural feature underlying aplastic anemia from CAP.

  8. The Procuring and Processing of Human Cadaveric Bone Marrow

    DTIC Science & Technology

    1990-01-01

    PROCESSING OF HUMAN CADAVERIC BONE MARROW 12. PERSONAL AUTHOR(S) Timothy R. Faloon 13a. TYPE OF REPORT 13b. TIMECiOVED 14. DATE OF REPORT (Year, Month, Day) S...CADAVERIC BONE MARROW PROCESSING PROTOCOL ................ 15 Procedure for processing and freezing . .................................. 15 CELL VIABILITY...18 Procedure . ....................................................... 18 USING THE COULTER COUNTER

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Non-myeloablative bone marrow transplantation.

    PubMed

    Ruiz-Argüelles, Guillermo J

    2003-01-01

    As a result of the evolution of knowledge in the area of allogeneic hematopoietic stem cells (HSC) transplantation, several dogmata have been broken. We now have the following information: a) successful engraftment if allogeneic HSC bone marrow ablation of the recipient is not required; b) HSC create their own space through graft-vs.-host reactions; c) several malignancies are eradicated by the graft-vs.-tumor effect; d) allografting can be conducted on an out-patient basis; e) allografting can be done in aged or debilitated individuals; f) allografting can be achieved without transfusion of blood products, and g) costs of the allografting procedures can be substantially diminished. Breaking all these dogmata has resulted in availability of HSC allografting to a larger number of individuals, thus offering true curative therapeutic options to patients who otherwise would not qualify to receive these opportunities.

  14. Bone marrow modified acrylic bone cement for augmentation of osteoporotic cancellous bone.

    PubMed

    Arens, Daniel; Rothstock, Stephan; Windolf, Markus; Boger, Andreas

    2011-11-01

    The use of polymethylmethacrylate (PMMA) cement to reinforce fragile or broken vertebral bodies (vertebroplasty) leads to extensive bone stiffening. This might be one reason for fractures at the adjacent vertebrae following this procedure. PMMA with a reduced Young's modulus may be more suitable. The goal of this study was to produce and characterize PMMA bone cements with a reduced Young's modulus by adding bone marrow. Bone cements were produced by combining PMMA with various volume fractions of freshly harvested bone marrow from sheep. Porosity, Young's modulus, yield strength, polymerization temperature, setting time and cement viscosity of different cement modifications were investigated. The samples generated comprised pores with diameters in the range of 30-250 μm leading to porosity up to 51%. Compared to the control cement, Young's modulus and yield strength decreased from 1830 to 740 MPa and from 58 to 23 MPa respectively by adding 7.5 ml bone marrow to 23 ml premixed cement. The polymerization temperature decreased from 61 to 38 ∘C for cement modification with 7.5 ml of bone marrow. Setting times of the modified cements were lower in comparison to the regular cement (28 min). Setting times increased with higher amounts of added bone marrow from around 16-25 min. The initial viscosities of the modified cements were higher in comparison to the control cement leading to a lower risk of extravasation. The hardening times followed the same trend as the setting times. In conclusion, blending bone marrow with acrylic bone cement seems to be a promising method to increase the compliance of PMMA cement for use in cancellous bone augmentation in osteoporotic patients due to its modified mechanical properties, lower polymerization temperature and elevated initial viscosity.

  15. 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)

  16. Marrow stromal fibroblastic cell cultivation in vitro on decellularized bone marrow extracellular matrix.

    PubMed

    Dutra, Timothy F; French, Samuel W

    2010-02-01

    The in vitro biocompatibility of decellularized bone marrow extracellular matrix was evaluated. Following a freeze-thaw cycle, sectioned discs of fresh frozen rat metaphyseal bone were sequentially incubated in solutions of hypertonic, then hypotonic Ringer's solution, followed by deoxycholic acid, then DNAase I. The adequacy of decellularization of marrow stroma was examined by light microscopy. Marrow stromal fibroblastic cells were harvested by dispersion of rat long bone marrow, followed by concentration by discontinuous Ficoll-Paque gradient centrifugation. The fibroblastic cells were expanded by in vitro cultivation, and second passage cells were cryopreserved until needed. Cryopreserved marrow stromal cells were applied dropwise to sections of decellularized bone marrow extracellular matrix, and cultured in BJGb medium with 20% fetal bovine serum for ten days. Mature cultures were formalin fixed, decalcified, and embedded in paraffin. Light microscopy of hematoxylin and eosin stained sections showed individual spindle cells invading the upper portion of the decellularized extracellular matrix, and also a monolayer of spindle cells on the upper surfaces of exposed trabecular and cortical bone. This experiment showed that decellularized marrow extracellular matrix is a biocompatible three dimensional in vitro substrate for marrow stromal fibroblastic cells.

  17. Primary Splenic Angiosarcoma Revealed by Bone Marrow Metastasis

    PubMed Central

    Anoun, Soumaya; Marouane, Sofia; Quessar, Asmae; Benchekroun, Said

    2014-01-01

    Primary splenic angiosarcomas are the most common malignant non-hematopoietic tumors of the spleen. Metastatic diseases were found in 69% of patients in a reported series but the incidence of bone marrow involvement is unclear. We report a rare case of a 25-years-old Moroccan woman with unsuspected primary splenic angiosarcoma revealed by bone marrow metastasis. She presented with serious anemia and splenomegaly. Bone marrow biopsy revealed proliferating spindle cells. Computed tomography scanning showed an enlarged spleen with heterogeneous lesions. Splenectomy was performed and retrospective histological study of the spleen confirmed the diagnosis. She died 1 year after splenectomy. PMID:25541659

  18. Primary splenic angiosarcoma revealed by bone marrow metastasis.

    PubMed

    Anoun, Soumaya; Marouane, Sofia; Quessar, Asmae; Benchekroun, Said

    2014-12-05

    Primary splenic angiosarcomas are the most common malignant non-hematopoietic tumors of the spleen. Metastatic diseases were found in 69% of patients in a reported series but the incidence of bone marrow involvement is unclear. We report a rare case of a 25-years-old Moroccan woman with unsuspected primary splenic angiosarcoma revealed by bone marrow metastasis. She presented with serious anemia and splenomegaly. Bone marrow biopsy revealed proliferating spindle cells. Computed tomography scanning showed an enlarged spleen with heterogeneous lesions. Splenectomy was performed and retrospective histological study of the spleen confirmed the diagnosis. She died 1 year after splenectomy.

  19. 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.

  20. Infections and immunodeficiency in bone marrow transplantation.

    PubMed

    Tutschka, P J

    1988-05-01

    After allogeneic bone marrow transplantation certain patterns of infectious complications emerge that follow the clinical course, are correlated to the immunobiology of transplantation and are almost predictable in their character and expression. The preparative regimen, designed to generate complete aplasia, will be associated with severe and sometimes life-threatening bacterial infections, predominantly with Gram-negative organisms derived from bowel flora, but also Gram-positive skin saprophytes. In this early aplastic phase, life-threatening viral infections are less common, consisting mainly of herpes simplex and possibly Epstein-Barr stomatitis and BK papovavirus cystitis. Systemic infections with invasive filamentous fungi are rare and are seen only when the induced aplasia is markedly prolonged. Once early marrow recovery has been achieved, systemic infections will generally disappear unless acute graft-vs.-host disease develops. This complication, which will lead to the breakdown of natural barriers such as skin and gastrointestinal epithelium and the marked impairment of all systemic defense mechanisms, can cause polymicrobial infections as well as set the stage for life-threatening viral infections. Such opportunistic viral infections, leading to either interstitial pneumonia or hemorrhagic gastroenteritis, are the major threat in the early recovery phase after engraftment has taken place. Usually caused by cytomegalovirus and rotavirus, respectively, these infections are the primary expression of the severe combined immunodeficiency post transplant, statistically associated with the presence of acute graft-vs.-host disease and amenable to immunologic manipulations. With the recovery of cellular and humoral immune function derived from transplanted donor lymphoid cells, the third phase of infectious complications is reached, covering 3 months to 2 years post grafting.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. 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.

  2. 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 ...

  3. Bone marrow infection with Mycobacterium fortuitum in a diabetic patient.

    PubMed

    Satti, Luqman; Abbasi, Shahid; Sattar, Abdul; Ikram, Aamer; Manzar, Muhammad Adnan; Khalid, Malik Muhammad

    2011-08-01

    Incidence and prevalence of Mycobacterium fortuitum infection vary greatly by location and death is very rare except in disseminated disease in immunocompromised individuals. We present what we believe is the first case of bone marrow infection with Mycobacterium fortuitum in an HIV negative patient. Bone marrow examination revealed presence of numerous acid fast bacilli which were confirmed as Mycobacterium fortuitum on culture and by molecular analysis. Patient was managed successfully with amikacin and ciprofloxacin.

  4. Radioimmune imaging of bone marrow in patients with suspected bone metastases from primary breast cancer

    SciTech Connect

    Duncker, C.M.; Carrio, I.; Berna, L.; Estorch, M.; Alonso, C.; Ojeda, B.; Blanco, R.; Germa, J.R.; Ortega, V. )

    1990-09-01

    Radioimmune imaging of bone marrow was performed by technetium-99m- (99mTc) labeled antigranulocyte monoclonal antibody BW 250/183 (AGMoAb) scans in 32 patients with suspected bone metastases from primary breast cancer. AGMoAb scans showed bone marrow defects in 25/32 (78%) patients; bone invasion was subsequently confirmed in 23 (72%) patients. Conventional bone scans performed within the same week detected bone metastases in 17/32 (53%) patients (p less than 0.001). AGMoAb scans detected more sites indicating metastatic disease than bone scans in 12 of these 17 patients (71%). All patients with bone metastases in the axial skeleton had bone marrow defects at least at the sites of bone metastases. Of 15 patients with normal, or indicative of, benign disease bone scans, 8 patients (53%) presented with bone marrow defects in the AGMoAb scans. Bone invasion was confirmed in six of them. AGMoAb bone marrow scans provide a method for the early detection of bone metastatic invasion in patients with breast cancer and suspected bone metastases.

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

    PubMed

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

    2013-03-01

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

  6. Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment

    PubMed Central

    Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Fahey, Frederic; Daley, George Q.

    2009-01-01

    Osteoblasts and endothelium constitute functional niches that support hematopoietic stem cells (HSC) in mammalian bone marrow (BM) 1,2,3 . Adult BM also contains adipocytes, whose numbers correlate inversely with the hematopoietic activity of the marrow. Fatty infiltration of hematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia 4. To explore whether adipocytes influence hematopoiesis or simply fill marrow space, we compared the hematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. By flow cytometry, colony forming activity, and competitive repopulation assay, HSCs and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 “fatless” mice, which are genetically incapable of forming adipocytes8, and in mice treated with the PPARγ inhibitor Bisphenol-A-DiGlycidyl-Ether (BADGE), which inhibits adipogenesis9, post-irradiation marrow engraftment is accelerated relative to wild type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone marrow microenvironment, and suggest that antagonizingmarrow adipogenesis may enhance hematopoietic recovery in clinical bone marrow transplantation. PMID:19516257

  7. 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

  8. 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.

  9. Effects of Spaceflight on Cells of Bone Marrow Origin

    PubMed Central

    Özçivici, Engin

    2013-01-01

    Once only a subject for science fiction novels, plans for establishing habitation on space stations, the Moon, and distant planets now appear among the short-term goals of space agencies. This article reviews studies that present biomedical issues that appear to challenge humankind for long-term spaceflights. With particularly focus on cells of bone marrow origin, studies involving changes in bone, immune, and red blood cell populations and their functions due to extended weightlessness were reviewed. Furthermore, effects of mechanical disuse on primitive stem cells that reside in the bone marrow were also included in this review. Novel biomedical solutions using space biotechnology will be required in order to achieve the goal of space exploration without compromising the functions of bone marrow, as spaceflight appears to disrupt homeostasis for all given cell types. Conflict of interest:None declared. PMID:24385745

  10. 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.

  11. 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.

  12. Spatial mapping of functional pelvic bone marrow using FLT PET.

    PubMed

    McGuire, Sarah M; Menda, Yusuf; Boles Ponto, Laura L; Gross, Brandie; TenNapel, Mindi; Smith, Brian J; Bayouth, John E

    2014-07-08

    The purpose of this study was to determine the ability of regions identified with bony landmarks on CT imaging to accurately represent active bone marrow when compared to FLT PET imaging. These surrogate regions could then be used to create a bone marrow sparing radiation therapy plan when FLT PET imaging is not available. Whole body (WB) FLT PET images were obtained of 18 subjects prior to chemoradiation therapy. The FLT image of each subject was registered to a CT image acquired for that subject to obtain anatomic information of the pelvis. Seventeen regions were identified based on features of the pelvic bones, sacrum, and femoral heads. The probability of FLT uptake being located in each of 17 different CT-based regions of the bony pelvis was calculated using Tukey's multiple comparison test. Statistical analysis of FLT uptake in the pelvis indicated four distinct groups within the 17 regions that had similar levels of activity. Regions located in the central part of the pelvis, including the superior part of the sacrum, the inner halves of the iliac crests, and the L5 vertebral body, had greater FLT uptake than those in the peripheral regions (p-value < 0.05). We have developed a method to use CT-defined pelvic bone regions to represent FLT PET-identified functional bone marrow. Individual regions that have a statistically significant probability of containing functional bone marrow can be used as avoidance regions to reduce radiation dose to functional bone marrow in radiation therapy planning. However, because likely active bone marrow regions and pelvic targets typically overlap, patient-specific spatial detail may be advantageous in IMRT planning scenarios and may best be provided using FLT PET imaging.

  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. Cells derived from young bone marrow alleviate renal aging.

    PubMed

    Yang, Hai-Chun; Rossini, Michele; Ma, Li-Jun; Zuo, Yiqin; Ma, Ji; Fogo, Agnes B

    2011-11-01

    Bone marrow-derived stem cells may modulate renal injury, but the effects may depend on the age of the stem cells. Here we investigated whether bone marrow from young mice attenuates renal aging in old mice. We radiated female 12-mo-old 129SvJ mice and reconstituted them with bone marrow cells (BMC) from either 8-wk-old (young-to-old) or 12-mo-old (old-to-old) male mice. Transfer of young BMC resulted in markedly decreased deposition of collagen IV in the mesangium and less β-galactosidase staining, an indicator of cell senescence. These changes paralleled reduced expression of plasminogen activator inhibitor-1 (PAI-1), PDGF-B (PDGF-B), the transdifferentiation marker fibroblast-specific protein-1 (FSP-1), and senescence-associated p16 and p21. Tubulointerstitial and glomerular cells derived from the transplanted BMC did not show β-galactosidase activity, but after 6 mo, there were more FSP-1-expressing bone marrow-derived cells in old-to-old mice compared with young-to-old mice. Young-to-old mice also exhibited higher expression of the anti-aging gene Klotho and less phosphorylation of IGF-1 receptor β. Taken together, these data suggest that young bone marrow-derived cells can alleviate renal aging in old mice. Direct parenchymal reconstitution by stem cells, paracrine effects from adjacent cells, and circulating anti-aging molecules may mediate the aging of the kidney.

  16. 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.

  17. Spine fusion using cell matrix composites enriched in bone marrow-derived cells.

    PubMed

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

    2003-02-01

    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.

  18. Bone marrow endothelium-targeted therapeutics for metastatic breast cancer.

    PubMed

    Mai, Junhua; Huang, Yi; Mu, Chaofeng; Zhang, Guodong; Xu, Rong; Guo, Xiaojing; Xia, Xiaojun; Volk, David E; Lokesh, Ganesh L; Thiviyanathan, Varatharasa; Gorenstein, David G; Liu, Xuewu; Ferrari, Mauro; Shen, Haifa

    2014-08-10

    Effective treatment of cancer metastasis to the bone relies on bone marrow drug accumulation. The surface proteins in the bone marrow vascular endothelium provide docking sites for targeted drug delivery. We have developed a thioaptamer that specifically binds to E-selectin that is overexpressed in the vasculature of tumor and inflammatory tissues. In this study, we tested targeted delivery of therapeutic siRNA loaded in the E-selectin thioaptamer-conjugated multistage vector (ESTA-MSV) drug carrier to bone marrow for the treatment of breast cancer bone metastasis. We evaluated tumor type- and tumor growth stage-dependent targeting in mice bearing metastatic breast cancer in the bone, and carried out studies to identify factors that determine targeting efficiency. In a subsequent study, we delivered siRNA to knock down expression of the human STAT3 gene in murine xenograft models of human MDA-MB-231 breast tumor, and assessed therapeutic efficacy. Our studies revealed that the CD31(+)E-selectin(+) population accounted for 20.8%, 26.4% and 29.9% of total endothelial cells respectively inside the femur of mice bearing early, middle and late stage metastatic MDA-MB-231 tumors. In comparison, the double positive cells remained at a basal level in mice with early stage MCF-7 tumors, and jumped to 23.9% and 28.2% when tumor growth progressed to middle and late stages. Accumulation of ESTA-MSV inside the bone marrow correlated with the E-selectin expression pattern. There was up to 5-fold enrichment of the targeted MSV in the bone marrow of mice bearing early or late stage MDA-MB-231 tumors and of mice with late stage, but not early stage, MCF-7 tumors. Targeted delivery of STAT3 siRNA in ESTA-MSV resulted in knockdown of STAT3 expression in 48.7% of cancer cells inside the bone marrow. Weekly systemic administration of ESTA-MSV/STAT3 siRNA significantly extended survival of mice with MDA-MB-231 bone metastasis. In conclusion, targeting the overexpressed E

  19. Composite vascularized skin/bone transplantation models for bone marrow-based tolerance studies.

    PubMed

    Ozmen, Selahattin; Ulusal, Betul G; Ulusal, Ali E; Izycki, Dariusz; Siemionow, Maria

    2006-03-01

    There is an ongoing need to understand the mechanisms of bone marrow-based allograft tolerance. This is important in clarifying the diverse variables influencing the ultimate outcome of the solid organ and composite tissue transplants. To establish bone marrow transplantation as a routine clinical application, further experimental studies should be conducted to overcome the obstacles related to the bone marrow transplantation. These obstacles include graft versus host disease, immunocompetence, and toxicity of the conditioning regimens. For these purposes, novel experimental models are needed. In an attempt to provide a reliable research tool for bone marrow-based tolerance induction studies, we introduced different experimental models of modified vascularized skin/bone marrow (VSBM) transplantation technique for tolerance induction, monitoring, and maintenance studies. In this skin/bone transplantation model, the technical feasibility of concurrent or consecutive transplantation of the combination of bilateral vascularized skin, vascularized bone marrow, or vascularized skin/bone marrow transplants was investigated. Isograft transplantations were performed between genetically identical Lewis (LEW, RT1) rats. Five different experimental designs in 5 groups of 5 animals each were studied. Group I: Bilateral vascularized skin (VS) transplantation; group II: bilateral vascularized skin/bone transplantation; group III: vascularized skin transplantation on one side and vascularized skin/bone transplantation on the contralateral side; group IV: vascularized bone transplantation on one side and vascularized skin/bone transplantation on the contralateral side; group V: vascularized bone transplantation on one side and vascularized skin transplantation on the contralateral side. Successful transplantations were performed in all groups. The survival of the isograft transplants was evaluated clinically and histologically. All skin flaps remained pink and pliable and grew new

  20. 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.

  1. 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

  2. Qualitative Aspects of Bone Marrow Adiposity in Osteoporosis

    PubMed Central

    Pino, Ana María; Miranda, Melissa; Figueroa, Carolina; Rodríguez, Juan Pablo; Rosen, Clifford J.

    2016-01-01

    The function of marrow adipocytes and their origin has not been defined although considerable research has centered on their presence in certain conditions, such as osteoporosis. Less work has focused on the qualitative aspects of marrow fat. Bone marrow serum is composed of multiple nutrients that almost certainly relate to functional aspects of the niche. Previous studies using non-invasive techniques have shown that osteoporotic individuals have more marrow fat and that the ratio of saturated: unsaturated fatty acid is high. We recently reported that bone marrow sera from osteoporotic patients with fracture showed a switch toward decreased content of total saturated versus unsaturated fatty acids, compared to patients without fracture highlighting a dynamic relationship between the composition of fatty acids in the bone microenvironment and the metabolic requirements of cells. The relative distribution of fatty acids differed considerably from that in the serum providing further evidence that energy utilization is high and that marrow adipocytes may contribute to this pool. Whether these lipids can affect osteoblast function in a positive or negative manner is still not certain but will require further investigation. PMID:27826285

  3. Modeling selective elimination of quiescent cancer cells from bone marrow.

    PubMed

    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

    2015-08-01

    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.

  4. 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.

  5. Risk factors in interstitial pneumonitis following allogenic bone marrow transplantation

    SciTech Connect

    Pino Y Torres, J.L.; Bross, D.S.; Lam, W.C.; Wharam, M.D.; Santos, G.W.; Order, S.E.

    1982-08-01

    Total body irradiation is part of the preparatory regimen for allogeneic bone marrow transplantation because of its cytotoxic and immunosuppressive properties. A major toxicity of bone marrow transplantation has been interstitial pneumonitis, which may be, in part, related to the lung irradiation. One hundred and sixty-one consecutive patients receiving allogeneic bone marrow transplantation for leukemia and aplastic anemia at Johns Hopkins Hospital (1968-1979) were retrospectively studied. The present study demonstrated that lung shielding to 600 rad maximum in single dose total body irradiation, fractionation of total body irradiation in comparison to single dose total body irradiation, and absence of graft versus host disease in the leukemia patients, each reduced the risk of interstitial pneumonitis. Total body irradiation significantly reduced the leukemia recurrence rate and/or the failure of remission induction.

  6. Bones of contention: marrow-derived cells in myocardial regeneration.

    PubMed

    Sussman, Mark A; Murry, Charles E

    2008-06-01

    Almost 7 years have passed since the initial publication reporting that bone marrow cells regenerate infarcted myocardium. The subsequent years produced hundreds of investigations that ran the gamut of findings from validation to disproof. Undeterred by the concurrent debate, clinical trials ensued to test the safety and efficacy of bone marrow-derived cell population for autologous therapy in clinical treatment of myocardial disease. In the following conversational exchange, two scientists with distinct perspectives weigh the pros and cons of pursuing bone marrow stem cell therapy and look toward finding a consensus of where the future lies for regenerative medicine and the heart. The conclusion is that the two camps may not be as far apart as it may seem from the rancor in literature and at meetings, and the potential of one day achieving regenerative therapy is indeed a vision that both parties enthusiastically share.

  7. Advances in bone marrow stem cell therapy for retinal dysfunction.

    PubMed

    Park, Susanna S; Moisseiev, Elad; Bauer, Gerhard; Anderson, Johnathon D; Grant, Maria B; Zam, Azhar; Zawadzki, Robert J; Werner, John S; Nolta, Jan A

    2017-01-01

    The most common cause of untreatable vision loss is dysfunction of the retina. Conditions, such as age-related macular degeneration, diabetic retinopathy and glaucoma remain leading causes of untreatable blindness worldwide. Various stem cell approaches are being explored for treatment of retinal regeneration. The rationale for using bone marrow stem cells to treat retinal dysfunction is based on preclinical evidence showing that bone marrow stem cells can rescue degenerating and ischemic retina. These stem cells have primarily paracrine trophic effects although some cells can directly incorporate into damaged tissue. Since the paracrine trophic effects can have regenerative effects on multiple cells in the retina, the use of this cell therapy is not limited to a particular retinal condition. Autologous bone marrow-derived stem cells are being explored in early clinical trials as therapy for various retinal conditions. These bone marrow stem cells include mesenchymal stem cells, mononuclear cells and CD34(+) cells. Autologous therapy requires no systemic immunosuppression or donor matching. Intravitreal delivery of CD34(+) cells and mononuclear cells appears to be tolerated and is being explored since some of these cells can home into the damaged retina after intravitreal administration. The safety of intravitreal delivery of mesenchymal stem cells has not been well established. This review provides an update of the current evidence in support of the use of bone marrow stem cells as treatment for retinal dysfunction. The potential limitations and complications of using certain forms of bone marrow stem cells as therapy are discussed. Future directions of research include methods to optimize the therapeutic potential of these stem cells, non-cellular alternatives using extracellular vesicles, and in vivo high-resolution retinal imaging to detect cellular changes in the retina following cell therapy.

  8. Genotoxicity of ibuprofen in mouse bone marrow cells in vivo.

    PubMed

    Tripathi, Rina; Pancholi, Shyam S; Tripathi, Pankaj

    2012-10-01

    Genotoxicity of ibuprofen was evaluated by employing the mouse in vivo chromosomal aberration (CA) test. Ibuprofen administered orally at doses of 10, 20, 40, and 60 mg/kg body weight to mice resulted in mitotic depression and induction of CAs. A dose-related decrease in mitotic index (MI) and an increase in the frequencies of chromosomal aberrations per cell (CAs/cell) were recorded in bone marrow cells. However, a statistically significant reduction in MI and an increase in CAs/cell were found for both the higher doses. The results obtained indicate that ibuprofen is capable of inducing dose-dependent genotoxicity in bone marrow cells of mice.

  9. Systemic bone marrow disorders: Characterization with proton chemical shift imaging

    SciTech Connect

    Gueckel, F.B.; Brix, G.; Semmler, W.; Zuna, I.; Knauf, W.; Ho, A.D.; van Kaick, G. )

    1990-07-01

    In a prospective clinical study, 26 patients (22 with malignant lymphoma and 4 with myelofibrosis) and 9 healthy volunteers were examined by conventional magnetic resonance and proton chemical shift imaging (CSI; modified Dixon method). On the basis of the CSI data, a quantitative evaluation of the relative fat and water signal fractions in regions of interest of the femur, pelvis, and spine was performed. In 16 of 17 patients with biopsy-proven bone marrow disorders, CSI revealed a significant reduction in the fat fraction of the bone marrow relative to that of normal volunteers. The visual assessment could detect only 14 of the 17 pathological cases.

  10. 18F-FDG super bone marrow uptake

    PubMed Central

    Alam, Mohammed Shah; Fu, Lilan; Ren, Yun-Yan; Wu, Hu-Bing; Wang, Quan-Shi; Han, Yan-Jiang; Zhou, Wen-Lan; Li, Hong-Sheng; Wang, Zhen

    2016-01-01

    Abstract The present study was performed to investigate whether the markedly 2-deoxy-2-(fluorine-18) fluoro-D-glucose (18F-FDG) uptake in the bone marrow (BM) is a presentation of malignant infiltration (MI). Super bone marrow uptake (super BMU) was used to name the markedly 18F-FDG uptake on BM, which was similar to or higher than that of the brain. From April 2008 to December 2015, 31 patients with such presentation were retrospectively reviewed. The 18F-FDG uptake was semiquantified using SUVmax and BM to cerebellum (BM/C) ratio. The origin of super BMU was diagnosed by pathology. Some blood parameters, as well as fever, were also collected and analyzed. For comparison, 106 patients with mildly and moderately uptake in BM and 20 healthy subjects were selected as the control group. Bone marrow MI was diagnosed in 93.5% (29/31) patients with super BMU, which mostly originated from acute leukemia and highly aggressive lymphoma. The super BMU group had markedly higher 18F-FDG uptake in the BM than those of mildly and moderately uptake, and the control subjects (all P = 0.000) and the BM/C ratio reached a high of 1.24 ± 0.36. The incidence of bone marrow MI in the super BMU group was markedly higher than that of mildly and moderately uptake (93.5% vs 36.8%, P = 0.000). Based on the receiver operating characteristic analysis, when cut-off values of BM/C and SUVmax were set at 0.835 and 6.560, the diagnostic specificity for bone marrow MI reached the high levels of 91.4% and 95.7%, respectively. In 15 patients with bone marrow MI, the extra-BM malignant lesions were simultaneously detected by 18F-FDG PET/CT. The liver and the nasal cavity involvements were only found in the patients with lymphoma, but not in those with leukemia. A decrease of leukocyte, hemoglobin, and platelet counts was noted in 48.4%, 86.2%, and 51.5% of patients with bone marrow MI, respectively. The present study revealed that super BMU was a highly potent indicator for the bone

  11. 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

  12. Bone marrow chimera experiments to determine the contribution of hematopoietic stem cells to cerebral angiogenesis.

    PubMed

    Machein, Marcia Regina; Plate, Karl H

    2014-01-01

    The generation of bone marrow chimera in mice is a valuable tool to study a variety of cellular processes. Donor bone marrow cells expressing reporter genes have been used to study the process of cell differentiation and the mechanisms involved in bone marrow cell recruitment. Bone marrow cells bearing genetic manipulation have been used in bone marrow chimeras to elucidate the role of molecules in different physiological and pathological settings. Since in the normal adult brain angiogenesis does not occur, models of brain injury like ischemia and tumor growth have been used to study the contribution of bone marrow-derived cells to the cerebral vasculature. This chapter describes the procedures to perform bone marrow transplantation in order to study the contribution of bone marrow-derived cells to vascularization in an orthotopic glioma model.

  13. Hematopoietic Stem Cells in Neural-crest Derived Bone Marrow

    PubMed Central

    Jiang, Nan; Chen, Mo; Yang, Guodong; Xiang, Lusai; He, Ling; Hei, Thomas K.; Chotkowski, Gregory; Tarnow, Dennis P.; Finkel, Myron; Ding, Lei; Zhou, Yanheng; Mao, Jeremy J.

    2016-01-01

    Hematopoietic stem cells (HSCs) in the endosteum of mesoderm-derived appendicular bones have been extensively studied. Neural crest-derived bones differ from appendicular bones in developmental origin, mode of bone formation and pathological bone resorption. Whether neural crest-derived bones harbor HSCs is elusive. Here, we discovered HSC-like cells in postnatal murine mandible, and benchmarked them with donor-matched, mesoderm-derived femur/tibia HSCs, including clonogenic assay and long-term culture. Mandibular CD34 negative, LSK cells proliferated similarly to appendicular HSCs, and differentiated into all hematopoietic lineages. Mandibular HSCs showed a consistent deficiency in lymphoid differentiation, including significantly fewer CD229 + fractions, PreProB, ProB, PreB and B220 + slgM cells. Remarkably, mandibular HSCs reconstituted irradiated hematopoietic bone marrow in vivo, just as appendicular HSCs. Genomic profiling of osteoblasts from mandibular and femur/tibia bone marrow revealed deficiencies in several HSC niche regulators among mandibular osteoblasts including Cxcl12. Neural crest derived bone harbors HSCs that function similarly to appendicular HSCs but are deficient in the lymphoid lineage. Thus, lymphoid deficiency of mandibular HSCs may be accounted by putative niche regulating genes. HSCs in craniofacial bones have functional implications in homeostasis, osteoclastogenesis, immune functions, tumor metastasis and infections such as osteonecrosis of the jaw. PMID:28000662

  14. Impaired Function of Bone Marrow Stromal Cells in Systemic Mastocytosis

    PubMed Central

    Nemeth, K.; Wilson, T.M.; Ren, J.J.; Sabatino, M.; Stroncek, D.F.; Krepuska, M.; Bai, Y.; Robey, P.G.; Metcalfe, D.D.; Mezey, E.

    2015-01-01

    Patients with systemic mastocytosis (SM) have a wide variety of problems, including skeletal abnormalities. The disease results from a mutation of the stem cell receptor (c-kit) in mast cells and we wondered if the function of bone marrow stromal cells (BMSCs; also known as MSCs or mesenchymal stem cells) might be affected by the invasion of bone marrow by mutant mast cells. As expected, BMSCs from SM patients do not have a mutation in c-kit, but they proliferate poorly. In addition, while osteogenic differentiation of the BMSCs seems to be deficient, their adipogenic potential appears to be increased. Since the hematopoietic supportive abilities of BMSCs are also important, we also studied the engraftment in NSG mice of human CD34+ hematopoietic progenitors, after being co-cultured with BMSCs of healthy volunteers vs. BMSCs derived from patients with SM. BMSCs derived from the bone marrow of patients with SM could not support hematopoiesis to the extent that healthy BMSCs do. Finally, we performed an expression analysis and found significant differences between healthy and SM derived BMSCs in the expression of genes with a variety of functions, including the WNT signaling, ossification, and bone remodeling. We suggest that some of the symptoms associated with SM might be driven by epigenetic changes in BMSCs caused by dysfunctional mast cells in the bone marrow of the patients. PMID:26001169

  15. 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

  16. Regulation of vitamin C transporter in the type 1 diabetic mouse bone and bone marrow.

    PubMed

    Sangani, Rajnikumar; Naime, Mohammad; Zakhary, Ibrahim; Ahmad, Saif; Chutkan, Norman; Zhu, Andy; Ha, Yonju; Hamrick, Mark; Isales, Carlos; Elsalanty, Mohammed; Smith, Sylvia; Liou, Gregory I; Fulzele, Sadanand

    2013-12-01

    A number of studies have revealed that Type I diabetes (T1D) is associated with bone loss and an increased risk of fractures. T1D induces oxidative stress in various tissues and organs. Vitamin C plays an important role in the attenuation of oxidative stress; however, little is known about the effect of T1D induced oxidative stress on the regulation of vitamin C transporter in bone and bone marrow cells. To investigate this, T1D was induced in mice by multiple low dose injections of streptozotocin. We have demonstrated that endogenous antioxidants, glutathione peroxidase (GPx) and superoxide dismutase (SOD) are down-regulated in the bone and bone marrow of T1D. The vitamin C transporter isoform SVCT2, the only known transporter expressed in bone and bone marrow stromal cells (BMSCs), is negatively regulated in the bone and bone marrow of T1D. The μCT imaging of the bone showed significantly lower bone quality in the 8 week T1D mouse. The in-vitro study in BMSCS showed that the knockdown of SVCT2 transporter decreases ascorbic acid (AA) uptake, and increases oxidative stress. The significant reversing effect of antioxidant vitamin C is only possible in control cells, not in knockdown cells. This study suggested that T1D induces oxidative stress and decreases SVCT2 expression in the bone and bone marrow environment. Furthermore, this study confirms that T1D increases bone resorption, decreases bone formation and changes the microstructure of bones. This study has provided evidence that the regulation of the SVCT2 transporter plays an important role not only in T1D osteoporosis but also in other oxidative stress-related musculoskeletal complications.

  17. HLA Typing for Bone Marrow Transplantation

    DTIC Science & Technology

    2007-10-31

    storage of the first product at the apheresis center. It is also common, particularly if products arrive late in the business day, for either PBSC or marrow...over time with products stored at 20°C whereas no notable change was observed with products stored at 4’C (p ɘ.0003). However for BM, platelet

  18. 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.

  19. 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...

  20. 40 CFR 798.5385 - In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 33 2012-07-01 2012-07-01 false In vivo mammalian bone marrow... Genetic Toxicity § 798.5385 In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis. (a) Purpose. The in vivo bone marrow cytogenetic test is a mutagenicity test for the detection of...

  1. 40 CFR 798.5385 - In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 32 2014-07-01 2014-07-01 false In vivo mammalian bone marrow... Genetic Toxicity § 798.5385 In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis. (a) Purpose. The in vivo bone marrow cytogenetic test is a mutagenicity test for the detection of...

  2. Identification of Bone Marrow-Derived Soluble Factors Regulating Human Mesenchymal Stem Cells for Bone Regeneration.

    PubMed

    Tsai, Tsung-Lin; Li, Wan-Ju

    2017-02-14

    Maintaining properties of human bone marrow-derived mesenchymal stem cells (BMSCs) in culture for regenerative applications remains a great challenge. An emerging approach of constructing a culture environment mimicking the bone marrow niche to regulate BMSC activities has been developed. In this study, we have demonstrated a systematic approach to identify soluble factors of interest extracted from human bone marrow and used them in BMSC culture for tissue regeneration. We have found that lipocalin-2 and prolactin are key factors in bone marrow, involved in regulating BMSC activities. Treating the cell with lipocalin-2 and prolactin delays cellular senescence of BMSCs and primes the cell for osteogenesis and chondrogenesis. We have also demonstrated that BMSCs pretreated with lipocalin-2 and prolactin can enhance the repair of calvarial defects in mice. Together, our study provides research evidence of using a viable approach to prime BMSC properties in vitro for improving cell-based tissue regeneration in vivo.

  3. Histochemistry of blood and bone marrow cells in pangolins.

    PubMed

    Caxton-Martins, A E

    1977-04-01

    Blood and bone marrow cells of pangolins have been examined histochemically. Sudanophilia, PAS positivity and acid phosphatase and alkaline phosphatase reactivity were confined to cells of the granulocytic and monocytic series, while peroxidase reactivity was confined to cells of the erythroid series. In this latter respect the pangolin is unique among mammals so far studied.

  4. 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.

  5. 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.

  6. 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

  7. Usefulness of bone marrow transplantation in the Hurler syndrome.

    PubMed

    Braunlin, Elizabeth A; Stauffer, Nanci R; Peters, Charles H; Bass, John L; Berry, James M; Hopwood, John J; Krivit, William

    2003-10-01

    The Hurler syndrome, an autosomal recessive storage disease of childhood, leads to death within the first decade of life from progressive deposition of glycosaminoglycans within the myointima of the coronary arteries and airways. Cardiac ultrasound findings of patients with this syndrome >10 years after successful bone marrow transplantation are described.

  8. Activation of Myeloid-Derived Suppressor Cells in Bone Marrow

    DTIC Science & Technology

    2013-12-01

    antigen in situ and in vitro. Atherosclerosis 135(1): 19–27. 21. Chow A, et al. (2011) Bone marrow CD169+ macrophages promote the retention of hematopoietic...renal injury-acceleration of atherosclerosis . Arterioscler Thromb Vasc Biol 31(12):2856–2864. 30. Lin SL, et al. (2010) Macrophage Wnt7b is critical for

  9. 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)

  10. Oestrogen-induced bone marrow aplasia in a dog.

    PubMed

    Bland-van den Berg, P; Bomzon, L; Lurie, A

    1978-12-01

    A case of oestrogen toxicity in the dog is described. The bone marrow was primarily affected with resultant non-regenerative anaemia, leukocytosis followed by leukopaenia, and thrombocytopaenia. Endometritis, toxaemia and disseminate intravascular coagulation were complicating factors. The case terminated fatally intensive therapy.

  11. Anaplasma platys in Bone Marrow Megakaryocytes of Young Dogs

    PubMed Central

    De Tommasi, A. Sara; Baneth, Gad; Breitschwerdt, Edward B.; Stanneck, Dorothee; Dantas-Torres, Filipe; Otranto, Domenico

    2014-01-01

    Anaplasma platys is an obligate intracellular rickettsial pathogen that infects platelets of dogs, forming basophilic intracellular morulae. In the present report, cellular inclusions were documented in bone marrow thrombocyte precursors of two young naturally infected dogs, indicating that A. platys can infect megakaryocytes and promegakaryocytes. PMID:24622106

  12. 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.

  13. 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.

  14. 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

  15. Low-frequency vibration treatment of bone marrow stromal cells induces bone repair in vivo

    PubMed Central

    He, Shengwei; Zhao, Wenzhi; Zhang, Lu; Mi, Lidong; Du, Guangyu; Sun, Chuanxiu; Sun, Xuegang

    2017-01-01

    Objective(s): To study the effect of low-frequency vibration on bone marrow stromal cell differentiation and potential bone repair in vivo. Materials and Methods: Forty New Zealand rabbits were randomly divided into five groups with eight rabbits in each group. For each group, bone defects were generated in the left humerus of four rabbits, and in the right humerus of the other four rabbits. To test differentiation, bones were isolated and demineralized, supplemented with bone marrow stromal cells, and implanted into humerus bone defects. Varying frequencies of vibration (0, 12.5, 25, 50, and 100 Hz) were applied to each group for 30 min each day for four weeks. When the bone defects integrated, they were then removed for histological examination. mRNA transcript levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor κ-B ligan, and pre-collagen type 1 α were measured. Results: Humeri implanted with bone marrow stromal cells displayed elevated callus levels and wider, more prevalent, and denser trabeculae following treatment at 25 and 50 Hz. The mRNA levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor κ-B ligand, and pre-collagen type 1 α were also markedly higher following 25 and 50 Hz treatment. Conclusion: Low frequency (25–50 Hz) vibration in vivo can promote bone marrow stromal cell differentiation and repair bone injury. PMID:28133520

  16. 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.

  17. Bone marrow necrosis in a cat infected with feline leukemia virus.

    PubMed

    Shimoda, T; Shiranaga, N; Mashita, T; Hasegawa, A

    2000-01-01

    A one-year old castrated male cat was admitted to the hospital with vomiting and diarrhea. Laboratory examination revealed pancytopenia and positive for FeLV antigen. A bone marrow examination indicated necrosis of the nucleated cells. Based on these findings, the cat was diagnosed as bone marrow necrosis. Pancytopenia was effectively treated with corticosteroids. Re-examination of the bone marrow confirmed a recovery of normal hematopoietic cells with a infiltration of many macrophages. It is strongly suspected that the bone marrow necrosis in this case could be associated with a bone marrow suppression due to FeLV infection.

  18. Stem cell niche failure concerns bone marrow failure--a diagnostic and therapeutic consideration.

    PubMed

    Law, Sujata; Chaudhuri, Samaresh

    2011-01-01

    Diseases of the bone marrow often referred to as "Bone marrow failure" have complicated pathophysiological picture with respect to hematopoietic systemic function. The reason for such bone marrow disorder is not well understood till date, although some sporadic etiological sources have been described earlier. With the advent of current investigations, hematopoietic stem cell involvement together with the failure of signaling interaction within the bone marrow niche has been found to reveal interesting correlations with the disease onset. The present review furnishes justification for bone marrow failure as a concern of stem cell niche failure and hints at providing important clues for disease diagnosis and therapeutic maneuver.

  19. Bone marrow to liver: the blood of Prometheus.

    PubMed

    Theise, Neil D; Krause, Diane S

    2002-12-01

    The existence of hepatic stem or progenitor cells has been controversial for decades, though it was presumed that if such cells existed, they would lie within the liver. There is now consensus, however, that not only do facultative hepatic stem cells exist within the liver, but also that cells from extra-hepatic sites, in particular the bone marrow, can contribute to hepatocyte and cholangiocyte regeneration. Despite confidence that engraftment of marrow cells in the liver occurs, the mechanistic details of this process remain poorly understood. Moreover, the physiological importance and therapeutic utility of this phenomenon remains controversial.

  20. 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.

  1. Bone marrow regeneration following fractionated radiation therapy. [/sup 60/Co or HMV linear accelerator

    SciTech Connect

    Hill, D.R.; Benak, S.B.; Phillips, T.L.; Price, D.C.

    1980-09-01

    Eight patients were studied with /sup 99m/Tc-S colloid bone marrow scans prior to or at various intervals following megavoltage irradiation. None had marrow tumor involvement and none had chemotherapy during the study period. If reticuloendothelial marrow activity reflects hematopoietic activity, there appears to be maximal depression of marrow activity 6 months post irradiation. Total nodal irradiated patients regenerated marrow as well as local field patients despite the larger marrow volume irradiated.

  2. Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone.

    PubMed

    Prisby, Rhonda D

    2014-07-01

    Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4-6 month; n=8) and old (22-24 month; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner's Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via μCT to quantify microvascular ossification. Bone marrow blood vessels from the rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and "normal" vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (p<0.05) in the old vs. young rats. Calcified and ossified vessel volumes per tissue volume and calcified vessel volume per patent vessel volume were augmented (p<0.05) 262%, 375% and 263%, respectively, in the old vs. young rats. Ossified and patent vessel number was higher (171%) and lower (40%), respectively, in the old vs. young rats. Finally, adipocyte volume per patent vessel volume was higher (86%) with age. This study is the first to report ossification of bone marrow blood vessels in rats and humans. Ossification presumably results in "microvascular dead space" in regard to loss of patency and vasomotor function as opposed to necrosis. Progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the

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

    PubMed Central

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

    2013-01-01

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

  4. [Bone and Stem Cells. Immune cell regulation by the bone marrow niche].

    PubMed

    Terashima, Asuka; Takayanagi, Hiroshi

    2014-04-01

    Adult hematopoietic stem cells (HSCs) are maintained in the bone marrow and give rise to all blood cell types. The maintenance and the differentiation of blood cells including immune cells are essential for host defense and oxygen delivery. HSCs are maintained in microenvironments called stem cell niches, which consists of various cell types in bone marrow. Recently, new visualization technologies and assay systems brought advances in studies on the stem cell niche. In addition, several reports demonstrated that osteoblasts and osteocytes regulate not only HSC homeostasis but also immune cell differentiation, suggesting a close relationship between bone cells and HSCs.

  5. 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

  6. [Bone and Stem Cells. Bone marrow microenvironment niches for hematopoietic stem and progenitor cells].

    PubMed

    Nagasawa, Takashi

    2014-04-01

    In bone marrow, the special microenvironments known as niches control proliferation and differentiation of hematopoietic stem and progenitor cells (HSPCs) . However, the identity and functions of the niches has been a subject of longstanding debate. Although it has been reported previously that osteoblasts lining the bone surface act as HSC niches, their precise role in HSC maintenance remains unclear. On the other hand, the adipo-osteogenic progenitors with long processes, termed CXCL12-abundant reticular (CAR) cells, which preferentially express the chemokine CXCL12, stem cell factor (SCF) , leptin receptor and PDGF receptor-β were identified in the bone marrow. Recent studies revealed that endothelial cells of bone marrow vascular sinuses and CAR cells provided niches for HSCs. The identity and functions of various other candidate HSC niche cells, including nestin-expressing cells and Schwann cells would also be discussed in this review.

  7. Discoidin Receptor 2 Controls Bone Formation and Marrow Adipogenesis.

    PubMed

    Ge, Chunxi; Wang, Zhengyan; Zhao, Guisheng; Li, Binbin; Liao, Jinhui; Sun, Hanshi; Franceschi, Renny T

    2016-12-01

    Cell-extracellular matrix (ECM) interactions play major roles in controlling progenitor cell fate and differentiation. The receptor tyrosine kinase, discoidin domain receptor 2 (DDR2), is an important mediator of interactions between cells and fibrillar collagens. DDR2 signals through both ERK1/2 and p38 MAP kinase, which stimulate osteoblast differentiation and bone formation. Here we show that DDR2 is critical for skeletal development and differentiation of marrow progenitor cells to osteoblasts while suppressing marrow adipogenesis. Smallie mice (Ddr2(slie/slie) ), which contain a nonfunctional Ddr2 allele, have multiple skeletal defects. A progressive decrease in tibial trabecular bone volume/total volume (BV/TV) was observed when wild-type (WT), Ddr2(wt/slie) , and Ddr2(slie/slie) mice were compared. These changes were associated with reduced trabecular number (Tb.N) and trabecular thickness (Tb.Th) and increased trabecular spacing (Tb.Sp) in both males and females, but reduced cortical thickness only in Ddr2(slie/slie) females. Bone changes were attributed to decreased bone formation rather than increased osteoclast activity. Significantly, marrow fat and adipocyte-specific mRNA expression were significantly elevated in Ddr2(slie/slie) animals. Additional skeletal defects include widened calvarial sutures and reduced vertebral trabecular bone. To examine the role of DDR2 signaling in cell differentiation, bone marrow stromal cells (BMSCs) were grown under osteogenic and adipogenic conditions. Ddr2(slie/slie) cells exhibited defective osteoblast differentiation and accelerated adipogenesis. Changes in differentiation were related to activity of runt-related transcription factor 2 (RUNX2) and PPARγ, transcription factors that are both controlled by MAPK-dependent phosphorylation. Specifically, the defective osteoblast differentiation in calvarial cells from Ddr2(slie/slie) mice was associated with reduced ERK/MAP kinase and RUNX2-S319 phosphorylation and could

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

    PubMed

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

    2011-12-01

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

  9. Osteogenic activity of bone marrow-derived mesenchymal stem cells (BMSCs) seeded on irradiated allogenic bone.

    PubMed

    Tohma, Yasuaki; Dohi, Yoshiko; Ohgushi, Hajime; Tadokoro, Mika; Akahane, Manabu; Tanaka, Yasuhito

    2012-02-01

    Allogenic bone grafting, a technique used in orthopaedic surgery, has several problems, including low osteogenic activity. To overcome the problem, this study aimed to determine whether in vivo osteogenesis could be enhanced using allogenic irradiated bone grafts after seeding with autologous bone marrow-derived mesenchymal stem cells (BMSCs). The allogenic bone cylinders were extracted from ACI rats and sterilized by irradiation. Donor BMSCs were obtained from fresh Fischer 344 (F344) rat bone marrow by cell culture. The allogenic bone with or without BMSCs were transplanted subcutaneously into syngeneic F344 rats. At 4 weeks after transplantation, high alkaline phosphatase (ALP) activity, bone-specific osteocalcin mRNA expression and newly formed bone were detected in the allogenic bone with BMSCs. The origin of the newly formed bone was derived from cultured donor BMSCs. However, none of these identifiers of osteogenesis were detected in either the fresh or the irradiated allogenic bone without BMSCs. These results indicate the availability of autologous BMSCs to heighten the osteogenic response of allogenic bone. Our present tissue-engineering method might contribute to a wide variety of allogenic bone grafting techniques in clinical settings.

  10. 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.

  11. Bone Marrow Blood Vessels: Normal and Neoplastic Niche

    PubMed Central

    Shahrabi, Saeid; Rezaeeyan, Hadi; Ahmadzadeh, Ahmad; Shahjahani, Mohammad; Saki, Najmaldin

    2016-01-01

    Blood vessels are among the most important factors in the transport of materials such as nutrients and oxygen. This study will review the role of blood vessels in normal bone marrow hematopoiesis as well as pathological conditions like leukemia and metastasis. Relevant literature was identified by a Pubmed search (1992-2016) of English-language papers using the terms bone marrow, leukemia, metastasis, and vessel. Given that blood vessels are conduits for the transfer of nutrients, they create a favorable situation for cancer cells and cause their growth and development. On the other hand, blood vessels protect leukemia cells against chemotherapy drugs. Finally, it may be concluded that the vessels are an important factor in the development of malignant diseases. PMID:27994770

  12. 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.

  13. Juvenile xanthogranuloma with clonal proliferation in the bone marrow.

    PubMed

    Mały, Ewa; Przyborska, Marta; Rybczyńska, Aleksandra; Konatkowska, Benigna; Nowak, Jerzy; Januszkiewicz, Danuta

    2012-04-01

    The triple association between juvenile xanthogranuloma (JXG), juvenile myelomonocytic leukemia and neurofibromatosis was described in literature in about 20 cases. In this paper, the case of an 11-month-old infant boy with a disseminated JXG with unusual cytogenetic representation in the bone marrow was reported. Neurofibromatosis and juvenile myelomonocytic leukemia were excluded, just the same as other leukemias. Bone marrow and peripheral blood cytogenetic analysis revealed a karyotype with many rearrangements 46,XY,-6,der(12)t(6;12)(p21;p13),del(7)(p13p22),+9 once described in the literature as a B-acute lymphoblastic leukemia case. On the contrary, in our patient immunologic testing demonstrated a high activity of T lymphocytes, however, inflammation was excluded. To the best of our knowledge this is the first described case of systemic JXG with determined karyotype representing unusual chromosomal aberrations.

  14. Bone marrow-derived stem cells initiate pancreatic regeneration.

    PubMed

    Hess, David; Li, Li; Martin, Matthew; Sakano, Seiji; Hill, David; Strutt, Brenda; Thyssen, Sandra; Gray, Douglas A; Bhatia, Mickie

    2003-07-01

    We show that transplantation of adult bone marrow-derived cells expressing c-kit reduces hyperglycemia in mice with streptozotocin-induced pancreatic damage. Although quantitative analysis of the pancreas revealed a low frequency of donor insulin-positive cells, these cells were not present at the onset of blood glucose reduction. Instead, the majority of transplanted cells were localized to ductal and islet structures, and their presence was accompanied by a proliferation of recipient pancreatic cells that resulted in insulin production. The capacity of transplanted bone marrow-derived stem cells to initiate endogenous pancreatic tissue regeneration represents a previously unrecognized means by which these cells can contribute to the restoration of organ function.

  15. 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.

  16. Isolation, characterization, and biologic features of bone marrow endothelial cells.

    PubMed

    Almeida-Porada, G; Ascensão, J L

    1996-10-01

    Bone marrow endothelial cells (BMECs) are an integral part of the bone marrow microenvironment and are likely to play an important role in the regulation of hematopoiesis, either by producing growth factors or inhibitory cytokines or by displaying adhesion molecules that can interact with hematopoietic progenitors. In the present study we demonstrate the isolation, propagation, and characterization of BMECs with regard to morphology, growth characteristics, phenotype, and production of cytokines. Furthermore, we report the creation of a cell line with "BMEC-like" characteristics and compare the characteristics of primary BMEC cultures to those of the immortalized cell line. In addition, we demonstrate that BMECs are susceptible to infection by a laboratory strain of human cytomegalovirus (CMV), suggesting that CMV infection of endothelial cells in vivo could potentially play a role in the hematologic abnormalities observed during CMV infection.

  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.

  18. Haemopoietic recovery in spleen and marrow after transplantation of bone marrow from either normal or hydroxyurea treated mice.

    PubMed

    Hasthorpe, S; Hodgson, G S

    1977-09-01

    Haemopoietic regeneration was studied following x-irradiation and transplantation of bone marrow from either normal or hydroxyurea-treated donor mice, to ascertain the contribution of proliferating progenitor cells to regeneration. With transplantation of equivalent numbers of CFU-S, total DNA and 3HTdR uptake into DNA in spleen and femoral bone marrow and the erythroid, granulocytic and mononuclear cell populations were not significantly different between normal (NBM) and hydroxyurea-treated (HUBM) marrow. The response of hypertransfused x-irradiated mice to erythropoietin (EPO) administration was also not significantly different in spleens of mice receiving normal or hydroxyurea-treated marrow.

  19. 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

  20. 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

  1. [Functional activity of bone marrow-derived peptides (myelopeptides)].

    PubMed

    Mikhaĭlova, A A; Petrov, R V

    2009-12-01

    The review describes structure and functions of bone marrow-derived peptides (myelopeptides). The final biological effects of these endogenous bioregulators (antitumor, antiviral, anti-infectious, antileukemia etc.) are due to their immunocorrecting and differentiating activity. Myelopeptides are the integral parts of the immune homeostasis maintenance system. Nowadays, medical preparations with no side effects and natural mechanisms of action are being developed on the basis of synthesized myelopeptides.

  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. Bone marrow stromal stem cells: nature, biology, and potential applications.

    PubMed

    Bianco, P; Riminucci, M; Gronthos, S; Robey, P G

    2001-01-01

    Bone marrow stromal cells are progenitors of skeletal tissue components such as bone, cartilage, the hematopoiesis-supporting stroma, and adipocytes. In addition, they may be experimentally induced to undergo unorthodox differentiation, possibly forming neural and myogenic cells. As such, they represent an important paradigm of post-natal nonhematopoietic stem cells, and an easy source for potential therapeutic use. Along with an overview of the basics of their biology, we discuss here their potential nature as components of the vascular wall, and the prospects for their use in local and systemic transplantation and gene therapy.

  4. 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

  5. CNS Inflammation and Bone Marrow Neuropathy in Type 1 Diabetes

    PubMed Central

    Hu, Ping; Thinschmidt, Jeffrey S.; Yan, Yuanqing; Hazra, Sugata; Bhatwadekar, Ashay; Caballero, Sergio; Salazar, Tatiana; Miyan, Jaleel A.; Li, Wencheng; Derbenev, Andrei; Zsombok, Andrea; Tikhonenko, Maria; Dominguez, James M.; McGorray, Susan P.; Saban, Daniel R.; Boulton, Michael E.; Busik, Julia V.; Raizada, Mohan K.; Chan-Ling, Tailoi; Grant, Maria B.

    2014-01-01

    By using pseudorabies virus expressing green fluorescence protein, we found that efferent bone marrow–neural connections trace to sympathetic centers of the central nervous system in normal mice. However, this was markedly reduced in type 1 diabetes, suggesting a significant loss of bone marrow innervation. This loss of innervation was associated with a change in hematopoiesis toward generation of more monocytes and an altered diurnal release of monocytes in rodents and patients with type 1 diabetes. In the hypothalamus and granular insular cortex of mice with type 1 diabetes, bone marrow–derived microglia/macrophages were activated and found at a greater density than in controls. Infiltration of CD45+/CCR2+/GR-1+/Iba-1+ bone marrow–derived monocytes into the hypothalamus could be mitigated by treatment with minocycline, an anti-inflammatory agent capable of crossing the blood-brain barrier. Our studies suggest that targeting central inflammation may facilitate management of microvascular complications. PMID:24160325

  6. 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.

  7. Gene therapy for monogenic disorders of the bone marrow.

    PubMed

    Ghosh, Sujal; Thrasher, Adrian J; Gaspar, H Bobby

    2015-06-05

    Ex-vivo gene transfer of autologous haematopoietic stem cells in patients with monogenic diseases of the bone marrow has emerged as a new therapeutic approach, mainly in patients lacking a suitable donor for transplant. The encouraging results of initial clinical trials of gene therapy for primary immunodeficiencies were tempered by the occurrence of genotoxicity in a number of patients. Over the last decade, safer viral vectors have been developed to overcome the risk of insertional mutagenesis and have led to impressive clinical outcomes with considerably improved safety. We review the efforts in specific immunodeficiencies including adenosine deaminase deficiency, X-linked severe combined immunodeficiency, chronic granulomatous disease and Wiskott Aldrich syndrome. Major recent progress has also been made in haemoglobinopathies, such as beta-thalassaemia, sickle cell disease and Fanconi anaemia, and also specific lysosomal storage diseases, which, although not strictly bone marrow specific conditions, have been effectively treated by bone marrow-based treatment. The success of these recent studies and the advent of new technologies, such as gene editing, suggest that gene therapy could become a more generally applied treatment modality for a number of haematopoietic disorders.

  8. [Effect of aclacinomycin A on bone marrow (author's transl)].

    PubMed

    Ohmori, K; Shirai, M; Kiyosaki, T; Hori, S; Tone, H

    1980-04-01

    Japan White rabbits were treated with aclacinomycin A, a new anthracycline antitumor antibiotic, at a dose of 6.25 or 25.0 mg/kg by single intravenous, or 12.5 or 50.0 mg/kg by single oral administration, respectively. Beagle dogs were treated at a dose of 3.0 or 6.0 mg/kg by single intravenous injection. In rabbits in higher dose groups, RBC and WBC counts as well as lymphocyte ratio in peripheral blood decreased on day 1. Nucleated cell counts and erythroid elements in bone marrow decreased to raise M/E ratio (Myeloid/Erythroid ratio) on day 3. In a dog given at 6.0 mg/kg, WBC and platelet counts, lymphocyte and neutrocyte per cents in peripheral blood and also nucleated cells, particularly erythroid elements in bone marrow remarkably decreased on day 3 accompanied with an increase in M/E ratio. These changes were almost completely recovered by day 14 in both animals. No abnormalities were found in lower dose groups. Male Wistar rats, treated with the drug at a dose of 1.5 mg/kg by daily intraperitoneal injection for 30 days, showed slight decreases in peripheral WBC and RBC counts and M/E ratio in bone marrow. No change was observed in rats treated at 0.75 mg/kg and less for 30 days.

  9. 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.

  10. 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

  11. FANCD2 protects against bone marrow injury from ferroptosis.

    PubMed

    Song, Xinxin; Xie, Yangchun; Kang, Rui; Hou, Wen; Sun, Xiaofang; Epperly, Michael W; Greenberger, Joel S; Tang, Daolin

    2016-11-18

    Bone marrow injury remains a serious concern in traditional cancer treatment. Ferroptosis is an iron- and oxidative-dependent form of regulated cell death that has become part of an emerging strategy for chemotherapy. However, the key regulator of ferroptosis in bone marrow injury remains unknown. Here, we show that Fanconi anemia complementation group D2 (FANCD2), a nuclear protein involved in DNA damage repair, protects against ferroptosis-mediated injury in bone marrow stromal cells (BMSCs). The classical ferroptosis inducer erastin remarkably increased the levels of monoubiquitinated FANCD2, which in turn limited DNA damage in BMSCs. FANCD2-deficient BMSCs were more sensitive to erastin-induced ferroptosis (but not autophagy) than FANCD2 wild-type cells. Knockout of FANCD2 increased ferroptosis-associated biochemical events (e.g., ferrous iron accumulation, glutathione depletion, and malondialdehyde production). Mechanically, FANCD2 regulated genes and/or expression of proteins involved in iron metabolism (e.g., FTH1, TF, TFRC, HAMP, HSPB1, SLC40A1, and STEAP3) and lipid peroxidation (e.g., GPX4). Collectively, these findings indicate that FANCD2 plays a novel role in the negative regulation of ferroptosis. FANCD2 could represent an amenable target for the development of novel anticancer therapies aiming to reduce the side effects of ferroptosis inducers.

  12. Mobilised bone marrow-derived cells accelerate wound healing.

    PubMed

    Wang, Yu; Sun, Yu; Yang, Xiao-Yan; Ji, Shi-Zhao; Han, Shu; Xia, Zhao-Fan

    2013-08-01

    Massive skin defects caused by severe burn and trauma are a clinical challenge to surgeons. Timely and effective wound closure is often hindered by the lack of skin donor site. Bone marrow-derived cells (BMDCs) have been shown to 'differentiate' into multiple tissue cells. In this study we focused on the direct manipulation of endogenous BMDCs, avoiding the immunocompatibility issues and complicated cell isolation, purification, identification and amplification procedures in vitro on wound repair. We found that mobilisation of the BMDCs into the circulation significantly increased the amount of BMDCs at the injury site which in turn accelerated healing of large open wound. We used a chimeric green fluorescent protein (GFP) mouse model to track BMDCs and to investigate their role in full-thickness skin excisional wounds. We have shown that bone marrow mobilisation by granulocyte colony stimulating factor (G-CSF) exerted multiple beneficial effects on skin repair, both by increasing the engraftment of BMDCs into the skin to differentiate into multiple skin cell types and by upregulating essential cytokine mRNAs critical to wound repair. The potential trophic effects of G-CSF on bone marrow stem cells to accelerate wound healing could have a significant clinical impact.

  13. Bone Marrow Microenvironment Modulation of Acute Lymphoblastic Leukemia Phenotype

    PubMed Central

    Moses, Blake S; Slone, William L; Thomas, Patrick; Evans, Rebecca; Piktel, Debbie; Angel, Peggi M; Walsh, Callee M; Cantrell, Pamela S; Rellick, Stephanie L; Martin, Karen H; Simpkins, James W; Gibson, Laura F

    2015-01-01

    Acute lymphoblastic leukemia (ALL) treatment regimens have dramatically improved the survival of ALL patients. However, chemoresistant minimal residual disease (MRD) that persists following cessation of therapy contributes to aggressive relapse. The bone marrow microenvironment (BMM) is an established “site of sanctuary” for ALL as well as myeloid lineage hematopoietic disease, with signals in this unique anatomical location contributing to drug resistance. Several models have been developed to recapitulate the interactions between the BMM and ALL cells. However, many in vitro models fail to accurately reflect the level of protection afforded to the most resistant sub-set of leukemic cells during co-culture with BMM elements. Pre-clinical in vivo models have advantages, but can be costly, and are often not fully informed by optimal in vitro studies. In the current report we describe an innovative extension of 2D co-culture wherein ALL cells uniquely interact with bone marrow derived stromal cells. Tumor cells in this model bury beneath primary human bone marrow derived stromal cells or osteoblasts, termed “phase dim” (PD) ALL, and exhibit a unique phenotype characterized by altered metabolism, distinct protein expression profiles, increased quiescence, and pronounced chemotherapy resistance. Investigation focused on the PD subpopulation may more efficiently inform pre-clinical design and investigation of MRD and relapse that arises from BMM supported leukemic tumor cells. PMID:26407636

  14. Bone marrow-derived cells are present in Mooren's ulcer.

    PubMed

    Ye, Juan; Chen, Jian; Kim, Jae Chan; Yao, Ke

    2004-01-01

    To investigate whether bone marrow-derived cells are present in Mooren's ulcer and involved in its destructive and regenerative disease course, tissue specimens were collected from 3 eyes of 3 patients with Mooren's ulcer that underwent lamellar keratectomy. Three normal donor limbal corneoscleras served as controls. Immunohistochemical staining patterns were analyzed by using the following antibodies: CD34 (a marker of hematopoietic progenitor cells and endothelium), c-kit (a marker of hematopoietic and stromal progenitor cells) and STRO-1 (a differentiation antigen present on bone marrow fibroblast cells and on various nonhematopoietic progenitor cells). Strong positive CD34, c-kit and STRO-1 cells were revealed in Mooren's ulcer specimens, especially in the superficial stroma. A few weakly expressed CD34 stromal cells were seen in normal limbal cornea, but no immunoreactivity for c-kit and STRO-1 was found. Bone marrow-derived cells are present in Mooren's ulcer and contribute to its destructive and regeneration process by synergizing with other factors. Specific therapeutic strategies that target the role of these cells in Mooren's ulcer are anticipated.

  15. 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.

  16. An Enzymatic Method to Rescue Mesenchymal Stem Cells from Clotted Bone Marrow Samples

    PubMed Central

    Malonzo, Cherry; Poetzel, Tobias; Baur, Martin; Steffen, Frank; Stoyanov, Jivko

    2015-01-01

    Mesenchymal stem cells (MSCs) - usually obtained from bone marrow - often require expansion culture. Our protocol uses clinical grade urokinase to degrade clots in the bone marrow and release MSCs for further use. This protocol provides a rapid and inexpensive alternative to bone marrow resampling. Bone marrow is a major source of MSCs, which are interesting for tissue engineering and autologous stem cell therapies. Upon withdrawal bone marrow may clot, as it comprises all of the hematopoietic system. The resulting clots contain also MSCs that are lost for expansion culture or direct stem cell therapy. We experienced that 74% of canine bone marrow samples contained clots and yielded less than half of the stem cell number expected from unclotted samples. Thus, we developed a protocol for enzymatic digestion of those clots to avoid labor-intense and costly bone marrow resampling. Urokinase - a clinically approved and readily available thrombolytic drug – clears away the bone marrow clots almost completely. As a consequence, treated bone marrow aspirates yield similar numbers of MSCs as unclotted samples. Also, after urokinase treatment the cells kept their metabolic activity and the ability to differentiate into chondrogenic, osteogenic and adipogenic lineages. Our protocol salvages clotted blood and bone marrow samples without affecting the quality of the cells. This obsoletes resampling, considerably reduces sampling costs and enables the use of clotted samples for research or therapy. PMID:25938767

  17. Use of autologous bone marrow mononuclear cells and cultured bone marrow stromal cells in dogs with orthopaedic lesions.

    PubMed

    Crovace, A; Favia, A; Lacitignola, L; Di Comite, M S; Staffieri, F; Francioso, E

    2008-09-01

    The aim of the study is to evaluate the clinical application in veterinary orthopedics of bone marrow mononuclear cells (BMMNCs) and cultured bone marrow stromal cells (cBMSCs) for the treatment of some orthopaedic lesions in the dog. The authors carried out a clinical study on 14 dogs of different breed, age and size with the following lesions: 1 bone cyst of the glenoid rime; 2 nonunion of the tibia; 3 nonunion of the femur; 2 lengthening of the radius; 1 large bone defect of the distal radius;1 nonunion with carpus valgus; 4 Legg-Calvé-Perthés disease. In 9 cases the BMMCNs were used in combination with a three dimensional resorbable osteogenic scaffold the chemical composition and size of which facilitates the ingrowth of bone. In these cases the BMMNCs were suspended in an adequate amount of fibrin glue and then distribuited uniformly on a Tricalcium-Phosphate (TCP) scaffold onto which were also added some drops of thrombin. In 1 case of nonunion of the tibia and in 3 cases of Legg-Calvè-Perthés (LCP) disease the cultured BMSCs were used instead because of the small size of the dogs and of the little amount of aspirated bone marrow. X-ray examinations were performed immediately after the surgery. Clinical, ultrasounds and X-ray examinations were performed after 20 days and then every month. Until now the treated dogs have shown very good clinical and X-ray results. One of the objectives of the study was to use the BMMNCs in clinical application in orthopaedic lesions in the dog. The advantages of using the cells immediately after the bone marrow is collected, are that the surgery can be performed the same day, the cells do not need to be expanded in vitro, they preserve their osteogenic potential to form bone and promote the proper integration of the implant with the bone and lastly, the technique is easier and the costs are lower.

  18. Long-term cryopreservation of bone marrow for autologous transplantation.

    PubMed

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

    1996-03-01

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

  19. Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice

    PubMed Central

    Govey, Peter M.; Zhang, Yue; Donahue, Henry J.

    2016-01-01

    Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone’s capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p<0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure. PMID:27936104

  20. 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

  1. Comparison of solid and fluid constitutive models of bone marrow during trabecular bone compression.

    PubMed

    Metzger, Thomas A; Niebur, Glen L

    2016-10-03

    The mechanical environment and mechanobiology of bone marrow may play essential roles in bone adaptation, cancer metastasis, and immune cell regulation. However, the location of marrow within the trabecular pore space complicates experimental measurement of marrow mechanics. Computational models provide a means to assess the shear stress and pressure in the marrow during physiological loading, but they rely on accurate inputs for the marrow and the physics assumed for the interaction of bone and marrow. Elastic, viscoelastic, and fluid constitutive properties have all been reported from experimental measurements of marrow properties. It is unclear whether this ambiguity reflects the various length-scales, loading rates, and boundary conditions of the experiments, or if the material models are sufficiently similar as to be interchangeable. To address this question, we analyzed both the mean shear stress and its spatial distribution induced in marrow during compression of trabecular bone cubes when using linear elastic, neo-Hookean, viscoelastic, and power-law fluid constitutive models. Experimentally reported parameters were initially applied for all four constitutive models, resulting in poor agreement. The parameters of the soft solid models were calibrated by linear interpolation so that the volume averaged shear stress agreed with the fluid model for each, but this could only be accomplished on a specimen-by-specimen basis. Following calibration, the root-mean-squared (RMS) difference between the solid and fluid constitutive models was still greater than 26% even when the overall mean shear stress was in close agreement, indicating that the spatial distribution of stress is also sensitive to the constitutive model. As such, the choice of constitutive model should be backed by a strong rationale, and results should be interpreted with care.

  2. Bone marrow adsorbed dose of rhenium-186-HEDP and the relationship with decreased platelet counts

    SciTech Connect

    Klerk, J.M.H. de; Dieren, E.B. van; Schip, A.D. van het

    1996-01-01

    Rhenium-186(Sn)-1,1-hydroxyethylidene diphosphonate ({sup 186}Re-HEDP) has been used for palliation of metastatic bone pain. The purpose of this study was to find a relationship between the bone marrow absorbed dose and the toxicity, expressed as the percentage decrease in the peripheral blood platelet count. The bone marrow absorbed dose was calculated according to the MIRD model using data obtained from ten treatments of patients suffering from metastatic prostate cancer; noninvasive and pharmacokinetic method were used. The bone marrow doses were related to toxicity using the pharmacodynamic sigmoid E{sub max} model. The mean bone marrow absorbed doses using the noninvasive and pharmacokinetic methods were in a close range to each other (1.07 mGy/MBq and 1.02 mGy/MBq, respectively). There was a good relationship between the toxicity and the bone marrow absorbed dose (r = 0.80). Furthermore, the EDrm{sub 50} (i.e., the bone marrow absorbed dose producing a 50% platelet decrease) to bone marrow for {sup 186}Re-HEDP was on the order of 2 Gy. Although the function of normal bone marrow is affected by metastases in patients with metastatic bone disease, the MIRD model can be used to relate toxicity to the bone marrow absorbed dose after a therapeutic dosage of {sup 186}Re-HEDP. 33 refs., 1 fig., 1 tab.

  3. 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.

  4. Haemophilus influenzae type b (HIB)-conjugate immunization before bone marrow harvest in autologous bone marrow transplantation.

    PubMed

    Molrine, D C; Guinan, E C; Antin, J H; Wheeler, C; Parsons, S K; Weinstein, H J; McGarigle, C; Blanding, P; Phillips, N R; Ciamarra, A; George, S; Ambrosino, D M

    1996-06-01

    Immune reconstitution following autologous bone marrow transplantation (ABMT) is characterized by defects in B cell and T cell function and loss of specific antibody. In the late post-transplant period, patients are at risk for infections with polysaccharide encapsulated organisms and respond poorly to polysaccharide vaccines. We examined whether immunizing ABMT patients before bone marrow (BM) harvest enhanced the early recovery of specific antibody. Twelve patients were immunized before BM harvest with Haemophilus influenzae type b (HIB)-conjugate, tetanus toxoid and polysaccharide pneumococcal vaccines. Forty-one comparable ABMT patients not immunized prior to BM harvest were also studied. Following ABMT, both groups of patients were immunized with HIB-conjugate and tetanus toxoid vaccines at 3, 6, 12 and 24 months and with pneumococcal vaccine at 12 and 24 months. Patients immunized before BM harvest had higher HIB antibody concentrations during the first 2 years post-transplant, the differences reaching significance at 3 months (P = 0.0001) and following the 24-month dose (P = 0.048). Tetanus toxoid antibody concentrations were also significantly higher at 3 months (P = 0.001) and 6 months (P = 0.032) in patients immunized before BM harvest. There were no differences in pneumococcal antibody concentrations between the two groups. Immunization of patients before bone marrow harvest resulted in higher anti-HIB antibody concentrations following ABMT and may be an effective strategy to prevent infectious complications.

  5. Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow.

    PubMed

    Park, Min Hee; Jin, Hee Kyung; Min, Woo-Kie; Lee, Won Woo; Lee, Jeong Eun; Akiyama, Haruhiko; Herzog, Herbert; Enikolopov, Grigori N; Schuchman, Edward H; Bae, Jae-sung

    2015-06-12

    Many reports have revealed the importance of the sympathetic nervous system (SNS) in the control of the bone marrow environment. However, the specific role of neuropeptide Y (NPY) in this process has not been systematically studied. Here we show that NPY-deficient mice have significantly reduced hematopoietic stem cell (HSC) numbers and impaired regeneration in bone marrow due to apoptotic destruction of SNS fibers and/or endothelial cells. Furthermore, pharmacological elevation of NPY prevented bone marrow impairments in a mouse model of chemotherapy-induced SNS injury, while NPY injection into conditional knockout mice lacking the Y1 receptor in macrophages did not relieve bone marrow dysfunction. These results indicate that NPY promotes neuroprotection and restores bone marrow dysfunction from chemotherapy-induced SNS injury through the Y1 receptor in macrophages. They also reveal a new role of NPY as a regulator of the bone marrow microenvironment and highlight the potential therapeutic value of this neuropeptide.

  6. Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow

    PubMed Central

    Park, Min Hee; Jin, Hee Kyung; Min, Woo-Kie; Lee, Won Woo; Lee, Jeong Eun; Akiyama, Haruhiko; Herzog, Herbert; Enikolopov, Grigori N; Schuchman, Edward H; Bae, Jae-sung

    2015-01-01

    Many reports have revealed the importance of the sympathetic nervous system (SNS) in the control of the bone marrow environment. However, the specific role of neuropeptide Y (NPY) in this process has not been systematically studied. Here we show that NPY-deficient mice have significantly reduced hematopoietic stem cell (HSC) numbers and impaired regeneration in bone marrow due to apoptotic destruction of SNS fibers and/or endothelial cells. Furthermore, pharmacological elevation of NPY prevented bone marrow impairments in a mouse model of chemotherapy-induced SNS injury, while NPY injection into conditional knockout mice lacking the Y1 receptor in macrophages did not relieve bone marrow dysfunction. These results indicate that NPY promotes neuroprotection and restores bone marrow dysfunction from chemotherapy-induced SNS injury through the Y1 receptor in macrophages. They also reveal a new role of NPY as a regulator of the bone marrow microenvironment and highlight the potential therapeutic value of this neuropeptide. PMID:25916827

  7. On a mathematical model of bone marrow metastatic niche.

    PubMed

    Munoz, Ana Isabel; Tello, J Ignacio

    2017-02-01

    We propose a mathematical model to describe tumor cells movement towards a metastasis location into the bone marrow considering the influence of chemotaxis inhibition due to the action of a drug. The model considers the evolution of the signaling molecules CXCL-12 secreted by osteoblasts (bone cells responsible of the mineralization of the bone) and PTHrP (secreted by tumor cells) which activates osteoblast growth. The model consists of a coupled system of second order PDEs describing the evolution of CXCL-12 and PTHrP, an ODE of logistic type to model the Osteoblasts density and an extra equation for each cancer cell. We also simulate the system to illustrate the qualitative behavior of the solutions. The numerical method of resolution is also presented in detail.

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

    SciTech Connect

    Schepelmann, K. )

    1990-01-01

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

  9. The use of bone marrow stromal cells (bone marrow-derived multipotent mesenchymal stromal cells) for alveolar bone tissue engineering: basic science to clinical translation.

    PubMed

    Kagami, Hideaki; Agata, Hideki; Inoue, Minoru; Asahina, Izumi; Tojo, Arinobu; Yamashita, Naohide; Imai, Kohzoh

    2014-06-01

    Bone tissue engineering is a promising field of regenerative medicine in which cultured cells, scaffolds, and osteogenic inductive signals are used to regenerate bone. Human bone marrow stromal cells (BMSCs) are the most commonly used cell source for bone tissue engineering. Although it is known that cell culture and induction protocols significantly affect the in vivo bone forming ability of BMSCs, the responsible factors of clinical outcome are poorly understood. The results from recent studies using human BMSCs have shown that factors such as passage number and length of osteogenic induction significantly affect ectopic bone formation, although such differences hardly affected the alkaline phosphatase activity or gene expression of osteogenic markers. Application of basic fibroblast growth factor helped to maintain the in vivo osteogenic ability of BMSCs. Importantly, responsiveness of those factors should be tested under clinical circumstances to improve the bone tissue engineering further. In this review, clinical application of bone tissue engineering was reviewed with putative underlying mechanisms.

  10. 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.

  11. [Bone metabolism and cardiovascular function update. Inter-communication between bone marrow hematopoiesis and skeletal/vascular network].

    PubMed

    Katayama, Yoshio

    2014-07-01

    The hematopoiesis takes place in the bone marrow. Because bone marrow is the "marrow" of the bone, bone marrow does not exist without bone. The specialized microenvironment for hematopoietic stem cells (HSCs) to be appropriately functional is called "niche" . In the recent ten years since the bone-forming osteoblast was identified as a HSC niche, the entire mesenchymal lineage cells from mesenchymal stem cells to end-terminal osteocytes have been recognized as niche cells or niche-modulators. Among these, mesenchymal stem/progenitor cells are located at perivascular area. The very recent study showed the difference between arteriolar and sinusoidal niches. It is likely that the vascular network and the bone tissue are connected by the mesenchymal lineage cells as a complex of bone forming system, and HSCs utilize this complex as a series of niche.

  12. The bone marrow microenvironment contributes to type I diabetes induced osteoblast death.

    PubMed

    Coe, Lindsay M; Irwin, Regina; Lippner, Dennean; McCabe, Laura R

    2011-02-01

    Type I diabetes increases an individual's risk for bone loss and fracture, predominantly through suppression of osteoblast activity (bone formation). During diabetes onset, levels of blood glucose and pro-inflammatory cytokines (including tumor necrosis factor α (TNFα)) increased. At the same time, levels of osteoblast markers are rapidly decreased and stay decreased chronically (i.e., 40 days later) at which point bone loss is clearly evident. We hypothesized that early bone marrow inflammation can promote osteoblast death and hence reduced osteoblast markers. Indeed, examination of type I diabetic mouse bones demonstrates a greater than twofold increase in osteoblast TUNEL staining and increased expression of pro-apoptotic factors. Osteoblast death was amplified in both pharmacologic and spontaneous diabetic mouse models. Given the known signaling and inter-relationships between marrow cells and osteoblasts, we examined the role of diabetic marrow in causing the osteoblast death. Co-culture studies demonstrate that compared to control marrow cells, diabetic bone marrow cells increase osteoblast (MC3T3 and bone marrow derived) caspase 3 activity and the ratio of Bax/Bcl-2 expression. Mouse blood glucose levels positively correlated with bone marrow induced osteoblast death and negatively correlated with osteocalcin expression in bone, suggesting a relationship between type I diabetes, bone marrow and osteoblast death. TNF expression was elevated in diabetic marrow (but not co-cultured osteoblasts); therefore, we treated co-cultures with TNFα neutralizing antibodies. The antibody protected osteoblasts from bone marrow induced death. Taken together, our findings implicate the bone marrow microenvironment and TNFα in mediating osteoblast death and contributing to type I diabetic bone loss.

  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. Necroptosis in spontaneously-mutated hematopoietic cells induces autoimmune bone marrow failure in mice

    PubMed Central

    Xin, Junping; Breslin, Peter; Wei, Wei; Li, Jing; Gutierrez, Rafael; Cannova, Joseph; Ni, Allen; Ng, Grace; Schmidt, Rachel; Chen, Haiyan; Parini, Vamsi; Kuo, Paul C.; Kini, Ameet R.; Stiff, Patrick; Zhu, Jiang; Zhang, Jiwang

    2017-01-01

    Acquired aplastic anemia is an autoimmune-mediated bone marrow failure syndrome. The mechanism by which such an autoimmune reaction is initiated is unknown. Whether and how the genetic lesions detected in patients cause autoimmune bone marrow failure have not yet been determined. We found that mice with spontaneous deletion of the TGFβ-activated kinase-1 gene in a small subset of hematopoietic cells developed bone marrow failure which resembled the clinical manifestations of acquired aplastic anemia patients. Bone marrow failure in such mice could be reversed by depletion of CD4+ T lymphocytes or blocked by knockout of interferon-γ, suggesting a Th1-cell-mediated autoimmune mechanism. The onset and progression of bone marrow failure in such mice were significantly accelerated by the inactivation of tumor necrosis factor-α signaling. Tumor necrosis factor-α restricts autoimmune bone marrow failure by inhibiting type-1 T-cell responses and maintaining the function of myeloid-derived suppressor cells. Furthermore, we determined that necroptosis among a small subset of mutant hematopoietic cells is the cause of autoimmune bone marrow failure because such bone marrow failure can be prevented by deletion of receptor interacting protein kinase-3. Our study suggests a novel mechanism to explain the pathogenesis of autoimmune bone marrow failure. PMID:27634200

  15. 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.

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

    PubMed

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

    2014-05-01

    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 × 10(6) 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.

  17. 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.

  18. Muscle-specific kinase antibody associated myasthenia gravis after bone marrow transplantation.

    PubMed

    Heidarzadeh, Zeinab; Mousavi, Seyyed-Asadollah; Ostovan, Vahid Reza; Nafissi, Shahriar

    2014-02-01

    Myasthenia gravis is a rare complication of bone marrow transplantation and graft versus host disease. We report a 30-year-old woman presented with oculobulbar and proximal limb weakness after allogeneic bone marrow transplantation for chronic myelogenous leukemia. Also, she developed graft versus host disease following bone marrow transplantation. Investigations led to the diagnosis of muscle specific kinase antibody related myasthenia gravis. There have been only two case reports of muscle specific kinase antibody positive myasthenia gravis after bone marrow transplantation in the literature, but none of the previously reported cases had graft versus host disease.

  19. Kaposi's sarcoma-associated herpesvirus infection of bone marrow dendritic cells from multiple myeloma patients.

    PubMed

    Rettig, M B; Ma, H J; Vescio, R A; Põld, M; Schiller, G; Belson, D; Savage, A; Nishikubo, C; Wu, C; Fraser, J; Said, J W; Berenson, J R

    1997-06-20

    Kaposi's sarcoma-associated herpesvirus (KSHV) was found in the bone marrow dendritic cells of multiple myeloma patients but not in malignant plasma cells or bone marrow dendritic cells from normal individuals or patients with other malignancies. In addition the virus was detected in the bone marrow dendritic cells from two out of eight patients with monoclonal gammopathy of undetermined significance (MGUS), a precursor to myeloma. Viral interleukin-6, the human homolog of which is a growth factor for myeloma, was found to be transcribed in the myeloma bone marrow dendritic cells. KSHV may be required for transformation from MGUS to myeloma and perpetuate the growth of malignant plasma cells.

  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. 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

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

    PubMed

    Hardaway, Aimalie L; Herroon, Mackenzie K; Rajagurubandara, Erandi; Podgorski, Izabela

    2014-09-01

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

  3. Monitoring microcirculation.

    PubMed

    Ocak, Işık; Kara, Atila; Ince, Can

    2016-12-01

    The clinical relevance of microcirculation and its bedside observation started gaining importance in the 1990s since the introduction of hand-held video microscopes. From then, this technology has been continuously developed, and its clinical relevance has been established in more than 400 studies. In this paper, we review the different types of video microscopes, their application techniques, the microcirculation of different organ systems, the analysis methods, and the software and scoring systems. The main focus of this review will be on the state-of-art technique, CytoCam-incident dark-field imaging, and the most recent technological and technical updates concerning microcirculation monitoring.

  4. Osteoblastic Wnts differentially regulate bone remodeling and the maintenance of bone marrow mesenchymal stem cells.

    PubMed

    Wan, Yong; Lu, Cheng; Cao, Jingjing; Zhou, Rujiang; Yao, Yiyun; Yu, Jian; Zhang, Lingling; Zhao, Haixia; Li, Hanjun; Zhao, Jianzhi; Zhu, Xuming; He, Lin; Liu, Yongzhong; Yao, Zhengju; Yang, Xiao; Guo, Xizhi

    2013-07-01

    Wnt signaling has important roles in embryonic bone development and postnatal bone remodeling, but inconsistent impact on bone property is observed in different genetic alterations of Lrp5 and β-catenin. More importantly, it is still controversial whether Lrp5 regulate bone formation locally or globally through gut-derived serotonin. Here we explored the function of Wnt proteins in osteoblastic niche through inactivation of the Wntless (Wls) gene, which abrogates the secretion of Wnts. The depletion of Wls in osteoblast progenitor cells resulted in severe osteopenia with more profound defects in osteoblastogenesis, osteoclastogenesis and maintenance of bone marrow mesenchymal stem cells (BMSCs) compared to that observed in Lrp5 and β-catenin mutants. These findings support the point of view that Wnt/Lrp5 signaling locally regulates bone mass accrual through multiple effects of osteoblastic Wnts on osteoblastic bone formation and osteoclastic bone resorption. Moreover, osteoblastic Wnts confer a niche role for maintenance of BMSCs, providing novel cues for the definition of BMSCs niche in bone marrow.

  5. Dissecting the role of bone marrow stromal cells on bone metastases.

    PubMed

    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.

  6. Bone marrow derived stem cells in joint and bone diseases: a concise review.

    PubMed

    Marmotti, Antonio; de Girolamo, Laura; Bonasia, Davide Edoardo; Bruzzone, Matteo; Mattia, Silvia; Rossi, Roberto; Montaruli, Angela; Dettoni, Federico; Castoldi, Filippo; Peretti, Giuseppe

    2014-09-01

    Stem cells have huge applications in the field of tissue engineering and regenerative medicine. Their use is currently not restricted to the life-threatening diseases but also extended to disorders involving the structural tissues, which may not jeopardize the patients' life, but certainly influence their quality of life. In fact, a particularly popular line of research is represented by the regeneration of bone and cartilage tissues to treat various orthopaedic disorders. Most of these pioneering research lines that aim to create new treatments for diseases that currently have limited therapies are still in the bench of the researchers. However, in recent years, several clinical trials have been started with satisfactory and encouraging results. This article aims to review the concept of stem cells and their characterization in terms of site of residence, differentiation potential and therapeutic prospective. In fact, while only the bone marrow was initially considered as a "reservoir" of this cell population, later, adipose tissue and muscle tissue have provided a considerable amount of cells available for multiple differentiation. In reality, recently, the so-called "stem cell niche" was identified as the perivascular space, recognizing these cells as almost ubiquitous. In the field of bone and joint diseases, their potential to differentiate into multiple cell lines makes their application ideally immediate through three main modalities: (1) cells selected by withdrawal from bone marrow, subsequent culture in the laboratory, and ultimately transplant at the site of injury; (2) bone marrow aspirate, concentrated and directly implanted into the injury site; (3) systemic mobilization of stem cells and other bone marrow precursors by the use of growth factors. The use of this cell population in joint and bone disease will be addressed and discussed, analysing both the clinical outcomes but also the basic research background, which has justified their use for the

  7. [Distribution of compact bone mesenchymal stem cells in lung tissue and bone marrow of mouse].

    PubMed

    Wang, Rui-Ping; Wu, Ren-Na; Guo, Yu-Qing; Zhang, Bin; Chen, Hu

    2014-02-01

    This study was aimed to investigate the distribution of compact bone mesenchymal stem cells(MSC) marked with lentiviral plasmid pGC FU-RFP-LV in lung tissue and bone marrow of mouse. The MSC were infected by lentivirus with infection efficiency 78%, the infected MSC were injected into BALB/c mice via tail veins in concentration of 1×10(6) /mouse. The mice were randomly divided into 4 group according to 4 time points as 1, 2, 5 and 7 days. The lung tissue and bone marrow were taken and made of frozen sections and smears respectively in order to observed the distributions of MSC. The results indicated that the lentiviral infected MSC displayed phenotypes and biological characteristics which conformed to MSC by immunophenotyping analysis and induction differentiation detection. After the MSC were infected with optimal viral titer MOI = 50, the cell growth no significantly changed; the fluorescent microscopy revealed that the distributions of MSC in bone marrow on day 1, 2, 5 and 7 were 0.50 ± 0.20, 0.67 ± 0.23, 0.53 ± 0.14, 0.33 ± 0.16; those in lung tissue were 0.55 ± 0.15, 0.47 ± 0.13, 0.29 ± 0.13, 0.26 ± 0.08. It is concluded that the distribution of MSC in lung tissue reaches a peak on day 1, while distribution of MSC in bone marrow reaches a peak on day 2. The distribution of mouse MSC relates with RFP gene expression and implantation of MSC in lung tissue and bone marrow.

  8. [Suitability of autologous blood donation before bone marrow donation].

    PubMed

    Gouëzec, H; Ferré, N; Hervé, F; Lapart, C; Leberre, C; Bernard, M; Dauriac, C; Nimubona, S

    2015-06-01

    We assessed the benefit of predeposite autologous blood donation (PAD) before bone marrow (BM) donation on transfusion requirements, haemoglobin concentrations (Hb) and the occurrence of adverse events (AE). We collected data retrospectively from 50 donors of BM with PAD from 2010 to 2014. An autologous transfusion (AT) was given to 50% of the donors (group 1). In the group 2, the products from PAD were not used. The total volume median of marrow harvested was 17.7 mL/k (range 12.3-21.4) in the group 1 and 13.3 mL/k (8.6-22.6) in the group 2. The female ratio was higher in the group 1 (60%) than in the group 2 (16%). Bone marrow harvest led to a decline in Hb (from PAD to first day after BM donation) by 2.9 g/dL (1.5-5.5) in the group 1 and by 3.5 g/dL (1.2-5) in the group 2. The post-harvest Hb (D+1) median was identical in the two groups: 10.9 g/dL (7.6-13.5) in the group 1 versus 11.5 g/dL (9.3-13.4) in the group 2. Six AE were reported in each group. In the group with AE, the median weight was lower: 58 k (50-71) versus 75 k (52-110); and the median total volume of marrow harvested was higher: 20.1 mL/k (9.9-21.4) versus 14.3 mL/k (8.6-22.6). All post-harvest Hb were ≥ 7.6g/dL. This study shows the high loss of Hb after BM donation but not enough to prove a blood transfusion in BM donors with median age of 36 years (16-62) and without comorbidity. The occurrence of AE (25% of BM donors) justifies a careful surveillance after the BM donation. The PAD should not be routinely offered to bone marrow donors.

  9. Stromal cell-derived factor-1 mediates changes of bone marrow stem cells during the bone repair process.

    PubMed

    Okada, Kiyotaka; Kawao, Naoyuki; Yano, Masato; Tamura, Yukinori; Kurashimo, Shinzi; Okumoto, Katsumi; Kojima, Kotarou; Kaji, Hiroshi

    2016-01-01

    Osteoblasts, osteoclasts, chondrocytes, and macrophages that participate in the bone repair process are derived from hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). However, the roles of these stem cells during the repair of injured bone tissue are still unclear. In the present study, we examined the effects of bone defect on HSCs and MSCs in bone marrow and spleen in 75 mice and its mechanism. We analyzed the HSC and MSC populations in these tissues of a mouse with femoral bone damage by using flow cytometry. The number of HSCs in the bone marrow of mice with damaged femurs was significantly lower than the number of these cells in the bone marrow of the contralateral intact femurs on day 2 after injury. Meanwhile, the number of MSCs in the bone marrow of mice with damaged femurs was significantly higher than that of the contralateral femurs. Both intraperitoneal administration of AMD3100, a C-X-C chemokine receptor 4 (CXCR4) antagonist, and local treatment with an anti-stromal cell-derived factor-1 (SDF-1) antibody blunted the observed decrease in HSC and increase in MSC populations within the bone marrow of injured femurs. In conclusion, the present study revealed that there is a concurrent decrease and increase in the numbers of HSCs and MSCs, respectively, in the bone marrow during repair of mouse femoral bone damage. Furthermore, the SDF-1/CXCR4 system was implicated as contributing to the changes in these stem cell populations upon bone injury.

  10. 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

  11. Mouse bone marrow cytogenetic damage produced by residues of tequila.

    PubMed

    Madrigal-Bujaidar, E; Rojas, A; Ramos, A; Rosas, E; Díaz Barriga-Arceo, S

    1990-06-01

    Five concentrations (50-860 mg/kg) of residues obtained after distillation and lyophilization of commercial tequila were injected into mice for evaluation of chromosome aberrations, sister-chromatid exchanges, and proliferation kinetics in mouse bone marrow cells. Appropriate positive and negative controls were included. Our results showed significant dose-related increases of chromosomal aberrations starting at 50 mg/kg and for sister-chromatid exchanges at 430 mg/kg. Cellular proliferation kinetics showed no alterations. With these data we demonstrated that the residues of tequila are genotoxic in vivo.

  12. 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

  13. Ehrlichiosis: a cause of bone marrow hypoplasia in humans.

    PubMed

    Pearce, C J; Conrad, M E; Nolan, P E; Fishbein, D B; Dawson, J E

    1988-05-01

    Infection with Ehrlichia canis should be suspected in patients with fever, headache, malaise, leukopenia, thrombocytopenia, and a history of recent exposure to ticks. The cytopenia is caused by bone marrow hypoplasia which may be severe. The disease may be confused with spotless Rocky Mountain spotted fever but can be differentiated from this infection serologically with acute and convalescent sea. In humans, recovery has occurred with and without antibiotic therapy. However, prompt antibiotic therapy is advised prior to serologic studies, especially in immunocompromised individuals, splenectomized persons, and patients with AIDS-who may develop a more overwhelming rickettsial infection.

  14. Tuberculosis in pediatric oncology and bone marrow transplantation patients.

    PubMed

    Cruz, Andrea T; Airewele, Gladstone; Starke, Jeffrey R

    2014-08-01

    Five children with malignancies (3 hematologic, 1 medulloblastoma, 1 hepatoblastoma) and one bone marrow transplant patient were treated for tuberculosis over a 30-year period. Three had pulmonary disease, 3 disseminated tuberculosis, and 1 had scrofula. Four of five had positive tuberculin skin tests, cultures were positive in 5/6 children. One child died of disseminated TB after engraftment, and one child had hepatotoxicity likely related to tuberculosis therapy. All cases were potentially preventable had they been screened due to established risk factors of foreign birth (4/6) or parental foreign birth (2/6). All children should be screened for latent tuberculosis before chemotherapy.

  15. Multiorgan WU Polyomavirus Infection in Bone Marrow Transplant Recipient.

    PubMed

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

    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.

  16. Mouse Models in Bone Marrow Transplantation and Adoptive Cellular Therapy

    PubMed Central

    Arber, Caroline; Brenner, Malcolm K.; Reddy, Pavan

    2014-01-01

    Mouse models of transplantation have been indispensable to the development of bone marrow transplantation (BMT). Their role in the generation of basic science knowledge is invaluable and is subject to discussion below. However, this article focuses on the direct role and relevance of mouse models towards the clinical development and advances in BMT and adoptive T-cell therapy for human diseases. The authors aim to present a thoughtful perspective on the pros and cons of mouse models while noting that despite imperfections these models are obligatory for the development of science-based medicine. PMID:24216170

  17. Inhibition of PPARgamma prevents type I diabetic bone marrow adiposity but not bone loss.

    PubMed

    Botolin, Sergiu; McCabe, Laura R

    2006-12-01

    Diabetes type I is associated with bone loss and increased bone adiposity. Osteoblasts and adipocytes are both derived from mesenchymal stem cells located in the bone marrow, therefore we hypothesized that if we could block adipocyte differentiation we might prevent bone loss in diabetic mice. Control and insulin-deficient diabetic BALB/c mice were chronically treated with a peroxisomal proliferator-activated receptor gamma (PPARgamma) antagonist, bisphenol-A-diglycidyl ether (BADGE), to block adipocyte differentiation. Effects on bone density, adiposity, and gene expression were measured. BADGE treatment did not prevent diabetes-associated hyperglycemia or weight loss, but did prevent diabetes-induced hyperlipidemia and effectively blocked diabetes type I-induced bone adiposity. Despite this, BADGE treatment did not prevent diabetes type I suppression of osteoblast markers (runx2 and osteocalcin) and bone loss (as determined by micro-computed tomography). BADGE did not suppress osteoblast gene expression or bone mineral density in control mice, however, chronic (but not acute) BADGE treatment did suppress osteocalcin expression in osteoblasts in vitro. Taken together, our findings suggest that BADGE treatment is an effective approach to reduce serum triglyceride and free fatty acid levels as well as bone adiposity associated with type I diabetes. The inability of BADGE treatment to prevent bone loss in diabetic mice suggests that marrow adiposity is not linked to bone density status in type I diabetes, but we cannot exclude the possibility of additional BADGE effects on osteoblasts or other bone cells, which could contribute to preventing the rescue of the bone phenotype.

  18. 40 CFR 798.5385 - In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Genetic Toxicity § 798.5385 In vivo mammalian bone marrow cytogenetics tests: Chromosomal analysis. (a... intralaboratory variation with the in vivo bone morrow metaphase procedure,” Handbook of mutagenicity...

  19. CHANGES IN OUTLYING BONE MARROW ACCOMPANYING A LOCAL INCREASE OF TEMPERATURE WITHIN PHYSIOLOGICAL LIMITS

    PubMed Central

    Huggins, Charles; Blocksom, B. H.

    1936-01-01

    A great difference exists in the adult bone marrow of central bones as compared with outlying bones of the mammalia and avia, the distal bones being at a great disadvantage from the standpoint of blood cell production. Several experimental procedures are reported by which this disadvantage is overcome and in consequence fatty marrow of outlying bones is replaced by red marrow occurring chiefly at the epiphyseal regions, unless a low oxygen stimulus is also provided when marrow of the diaphysis becomes involved. A common factor in all of the experiments was an elevation of temperature beyond that prevailing in these distal regions, and it is felt that the evidence warrants the opinion that the cause of improvement is thermal. In some experiments, blood cell formation was increasing while the heat was adversely affecting the testis. The experiments permit construction of a general theory of fat distribution in bone marrow. In certain grafts of precartilage to other rats, normal differentiation into bone, cartilage, and marrow occurred, while in others cartilage and very small amounts of primitive marrow developed with slight, or no bone formation. Cartilage was always successfully engrafted. The capacity to form sinusoids in bone marrow is determined by the nature of the tissue rather than by the ingrowing endothelium. PMID:19870534

  20. 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.

  1. Extensive bone marrow necrosis associated with antiphospholipid antibodies.

    PubMed

    Bulvik, S; Aronson, I; Ress, S; Jacobs, P

    1995-06-01

    Bone marrow necrosis (BMN), defined morphologically by destruction of hematopoietic tissue, including the stroma, with preservation of the bone, is a rare syndrome. The conditions in which it is seen include sickle cell disease, acute leukemia, metastatic neoplasia, and bacterial infection, particularly when hypovolemia and septic shock are present. BMN is also associated with disseminated intravascular coagulation (DIC) following irradiation and antineoplastic therapy. The antiphospolipid syndrome (APS) is characterized by antibodies directed against the antiphospolipid substrate. Because this substrate is prominently involved in the coagulation cascade and widely distributed on cell walls, patients present with venous or arterial thromboses, recurrent abortion, thrombocytopenia, and Coombs' positive hemolytic anemia, typically with raised anticardiolipin antibodies or a diagnostic lupus anticoagulant test. BMN does not appear to have been previously recognized in this context. We report what we believe to be the first such case and suggest that the high titers of antibodies present may have played a central role in its pathogenesis.

  2. Repair of orbital bone defects in canines using grafts of enriched autologous bone marrow stromal cells

    PubMed Central

    2014-01-01

    Backgroud Bone tissue engineering is a new approach for the repair of orbital defects. The aim of the present study was to explore the feasibility of tissue-engineered bone constructed using bone marrow stromal cells (BMSCs) that were rapidly isolated and concentrated from bone marrow (BM) by the red cell lysis method, then combined with β-tricalcium phosphate (β-TCP) to create grafts used to restore orbital bone defects in canines. Methods In the experimental group, grafts were constructed using BMSCs obtained by red cell lysis from 20 ml bone marrow, combined with β-TCP and BM via the custom-made stem cell-scaffold device, then used to repair 10 mm diameter medial orbital wall bony defects in canines. Results were compared with those in groups grafted with BM/β-TCP or β-TCP alone, or with defects left untreated as controls. The enrichment of BMSCs and nucleated cells (NCs) in the graft was calculated from the number in untreated bone marrow and in suspensions after red cell lysis. Spiral computed tomography (CT) scans were performed 1, 4, 12 and 24 weeks after implantation in all groups. Gross examination, micro-CT and histological measurements were performed 24 weeks after surgery. The results were analyzed to evaluate the efficacy of bone repair. Results The number of NCs and of colony-forming units within the scaffolds were increased 54.8 times and 53.4 times, respectively, compared with untreated bone marrow. In the BMSC-BM/β-TCP group, CT examination revealed that the scaffolds were gradually absorbed and the bony defects were restored. Micro-CT and histological examination confirmed that the implantations led to good repair of the defects, with 6 out 8 orbital defects completely restored in the experimental group, while by contrast, the grafts in the control groups did not fully repair the bony defects, a difference which was statistically significant (p < 0.05). Conclusions Tissue-engineered bone, constructed using BMSCs isolated by red cell

  3. 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.

  4. Granulomatous bone marrow disease. A review of the literature and clinicopathologic analysis of 58 cases.

    PubMed

    Bodem, C R; Hamory, B H; Taylor, H M; Kleopfer, L

    1983-11-01

    We have reviewed 58 cases of bone marrow granuloma at a single institution over a 20-year time span, and have summarized the available English literature. We conclude that bone marrow granulomas are an infrequent pathologic finding which, when found, require definition as to an underlying etiology. Undoubtedly, the illnesses associated with marrow granuloma are similar to those causing granulomatous hepatitis. The following additional statements may justifiably be made based on this review. There are no morphologic features which allow reliable differentiation between the causes of bone marrow granuloma. By combining careful histologic, microbiologic, and serologic techniques, an etiology can be documented in most (87%) patients with marrow granulomas. A medication history is an important element of this evaluation. Rocky Mountain spotted fever, cytomegalovirus infection, ibuprofen, acute lymphocytic leukemia, and various collagen vascular diseases should be added to the list of causes of marrow granuloma. The prognostic significance of marrow granuloma in patients without an ascertainable underlying illness remains unclear.

  5. 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

  6. Coping patterns among bone marrow transplant patients: a hermeneutical inquiry.

    PubMed

    Shuster, G F; Steeves, R H; Onega, L; Richardson, B

    1996-08-01

    Bone marrow transplantation (BMT) has recently become the treatment of choice for a number of malignancies. This procedure is highly technical, involving the use of radiation and chemotherapy to destroy the patient's diseased bone marrow and with it functions of the entire immune system. It is a process with toxic effects that are experienced by all patients to varying degrees. A great deal of research related to the physiological aspects of this procedure has already been done, but considerably fewer studies have examined the psychosocial aspects of the BMT procedure from the patient's perspective. Knowledge about how BMT patients understand this process and cope with its effects is important information for nurses taking care of these patients. The purpose of the study was to describe in depth the patterns of meaning employed by patients in the hospital as they coped with the experience of their BMT. Eleven patients were interviewed from one to four times a week throughout their hospitalization. Hermeneutic analysis was used to identify five major themes: physiological functioning, alertness, attitude, social relationships, and spirituality. Implications from the findings for nursing practice are discussed.

  7. Prevention of diabetes in rats by bone marrow transplantation.

    PubMed

    Alinaji; Silvers, W K; Bellgrau, D; Anderson, A O; Plotkin, S; Barker, C F

    1981-09-01

    Hyperglycemia, hypoinsulinemia and ketonemia often develop abruptly in previously normal young "BB" rats. The syndrome mimics human juvenile diabetes closely and is, thus, appropriate for assessing pancreatic transplantation. Transplantation of islet cells from closely histocompatible Wistar Furth (WF) donor resulted in permanent normoglycemia when immunosuppression with ALS was given. However, when islet cells from nondiabetic "BB" donors were transplanted to nonimmunosuppressed diabetic "BB" recipients, only transient normoglycemia followed. Transplantation of WF islets cells also failed in diabetic "BB" rats which were tolerant of WF antigens, again suggesting destruction of transplanted islet cells by the original disease process-possibly autoimmunity. Evidence for autoimmunity was strengthened by the finding that newly diabetic "BB" rats could be rendered normoglycemic by immunosuppression. Since genetic susceptibility to spontaneous autoimmune diabetes is unique to some members of the "BB" stock, an attempt was made to alter their vulnerability by modifying their cellular immune system. Accordingly, 50 million bone marrow cells from WF donors were inoculated into half the newborn members of "BB" litters, leaving the littermates as unmodified controls. Most bone marrow recipients were protected, only four of 37 (10.8%) ever becoming diabetic, while the incidence of diabetes in noninoculated littermates was 22 of 39 (56.4%). The ultimate goal in human diabetes, which also seems very likely to be an autoimmune disease, may not be replacement of destroyed islet cells but identification of potentially susceptible children and prevention of islet destruction by immunologic manipulation.

  8. Anemia of immobility: caused by adipocyte accumulation in bone marrow.

    PubMed

    Payne, Michael W C; Uhthoff, Hans K; Trudel, Guy

    2007-01-01

    Anemia of chronic disease has long been used to classify a non-regenerative, low-grade, chronic, normocytic, normochromic anemia that presents with no obvious etiology. Within this group, some patients have a chronic inflammatory condition that limits erythrocyte generation or access to iron stores. This specific type of anemia has been termed anemia of chronic inflammation. However, a substantial remainder of patients diagnosed with anemia of chronic disease present with no active inflammation. These include many clinical populations with reduced limb loading, such as spinal cord injured patients, astronauts, elderly people with limited mobility and experimental bed-rest subjects. In some populations with decreased mobility, accumulation of fat in the bone marrow has been demonstrated. We hypothesize that adipocyte accumulation in bone marrow both passively and actively impairs erythropoiesis and thus defines a new type of anemia called anemia of immobility. The non-specific umbrella term anemia of chronic disease thus becomes obsolete in favour of either the diagnosis of anemia of immobility or anemia of chronic inflammation according to the distinct mechanism involved.

  9. ICSH guidelines for the standardization of bone marrow immunohistochemistry.

    PubMed

    Torlakovic, E E; Brynes, R K; Hyjek, E; Lee, S-H; Kreipe, H; Kremer, M; McKenna, R; Sadahira, Y; Tzankov, A; Reis, M; Porwit, A

    2015-08-01

    Bone marrow (BM) tissue biopsy evaluation, including trephine biopsy and clot section, is an integral part of BM investigation and is often followed by ancillary studies, in particular immunohistochemistry (IHC). IHC provides in situ coupling of morphological assessment and immunophenotype. The number of different IHC tests that can be applied to BM trephine biopsies and the number of indications for IHC testing is increasing concurrently with the development of flow cytometry and molecular diagnostic methods. An international Working Party for the Standardization of Bone Marrow IHC was formed by the International Council for Standardization in Hematology (ICSH) to prepare a set of guidelines for the standardization of BM IHC based on currently available published evidence and modern understanding of quality assurance principles as applied to IHC in general. The guidelines were discussed at the ICSH General Assemblies and reviewed by an international panel of experts to achieve further consensus and represent further development of the previously published ICSH guidelines for the standardization of BM specimens handling and reports.

  10. 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.

  11. Registered bone marrow donors' views on bodily donations.

    PubMed

    Sanner, M A

    1997-01-01

    The attitudes of 463 potential bone marrow donors toward blood donation, kidney donation in life, organ donation after death, autopsy, and donation of the whole body for anatomic dissection were surveyed, using a questionnaire that had previously been employed for assessing the attitudes of the public. The response rate was 96%. Three quarters of the respondents were blood donors and recruited via the blood center. The proportion that accepted the procedures varied between 24% for anatomic dissection and 97% for autopsy. Differences were small between individuals with positive attitudes and individuals who had also actively taken steps to activate these attitudes. Compared with the public, the bone marrow donors were more positive to all kinds of bodily donations. The conclusion is that if one is prepared to give from the body in life, one is also prepared to give after death. The results may indicate less death anxiety and fear of physical injury, and less fear of chaos either with or without altruism compared to the public.

  12. 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

  13. Bone Marrow Gene Therapy for HIV/AIDS.

    PubMed

    Herrera-Carrillo, Elena; Berkhout, Ben

    2015-07-17

    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.

  14. 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

  15. Busulfan and total body irradiation as antihematopoietic stem cell agents in the preparation of patients with congenital bone marrow disorders for allogenic bone marrow transplantation

    SciTech Connect

    Parkman, R.; Rappeport, J.M.; Hellman, S.; Lipton, J.; Smith, B.; Geha, R.; Nathan, D.G.

    1984-10-01

    The capacity of busulfan and total body irradiation to ablate hematopoietic stem cells as preparation for the allogeneic bone marrow transplantation of patients with congenital bone marrow disorders was studied. Fourteen patients received 18 transplants; busulfan was used in the preparatory regimen of eight transplants and total body irradiation in the regimens of six transplants. Sustained hematopoietic ablation was achieved in six of eight patients prepared with busulfan and in all six patients prepared with total body irradiation. Three patients prepared with total body irradiation died with idiopathic interstitial pneumonitis, whereas no patients receiving busulfan developed interstitial pneumonitis. The optimal antihematopoietic stem cell agent to be used for the preparation of patients with congenital bone marrow disorder for bone marrow transplantation is not certain.

  16. Roles of bone marrow cells in skeletal metastases: no longer bystanders.

    PubMed

    Park, Serk In; Soki, Fabiana N; McCauley, Laurie K

    2011-12-01

    Bone serves one of the most congenial metastatic microenvironments for multiple types of solid tumors, but its role in this process remains under-explored. Among many cell populations constituting the bone and bone marrow microenvironment, osteoblasts (originated from mesenchymal stem cells) and osteoclasts (originated from hematopoietic stem cells) have been the main research focus for pro-tumorigenic roles. Recently, increasing evidence further elucidates that hematopoietic lineage cells as well as stromal cells in the bone marrow mediate distinct but critical functions in tumor growth, metastasis, angiogenesis and apoptosis in the bone microenvironment. This review article summarizes the key evidence describing differential roles of bone marrow cells, including hematopoietic stem cells (HSCs), megakaryocytes, macrophages and myeloid-derived suppressor cells in the development of metastatic bone lesions. HSCs promote tumor growth by switching on angiogenesis, but at the same time compete with metastatic tumor cells for occupancy of osteoblastic niche. Megakaryocytes negatively regulate the extravasating tumor cells by inducing apoptosis and suppressing proliferation. Macrophages and myeloid cells have pro-tumorigenic roles in general, suggesting a similar effect in the bone marrow. Hematopoietic and stromal cell populations in the bone marrow, previously considered as simple by-standers in the context of tumor metastasis, have distinct and active roles in promoting or suppressing tumor growth and metastasis in bone. Further investigation on the extended roles of bone marrow cells will help formulate better approaches to treatment through improved understanding of the metastatic bone microenvironment.

  17. Bone-like nodules formed by human bone marrow stromal cells: comparative study and characterization.

    PubMed

    Schecroun, N; Delloye, C h

    2003-03-01

    Autologous bone marrow stromal cells have been proposed as an adjuvant in the treatment of bone nonunion. This cell therapy would require the establishment of culture conditions that permit the rapid expansion of these cells ex vivo while retaining their potential for further differentiation. Our aim was to achieve a full differentiation process using human bone marrow aspirates. We first analyzed the effects of mineralization medium (with ascorbic acid and phosphate) and dexamethasone (dex) during the primary culture of human bone marrow stromal (HBMS) cells on the proliferation/differentiation behavior of first-passage cells. The most appropriate schedule was then selected to further characterize this differentiation model. We showed that primary culture of HBMS cells in proliferation medium (DMEM supplemented with 10% fetal calf serum), with a 48-h treatment by mineralization medium and dex resulted in a better osteoblastic differentiation of first-passage cells than primary culture carried out in mineralization medium with or without dex. We showed that culture of HBMS cells under these conditions (primary culture in proliferation medium, followed by subculture in mineralization medium) led to the formation of specifically mineralized bone-like nodules similar to the ones observed with rat bone marrow stromal cells. Our nodules exhibited three distinct cell types, reproducing in vitro a tissue-like structure. This treatment demonstrated an optimal proliferation and expression of osteoblastic markers such as alkaline phosphatase, osteocalcin, and type I collagen. The primary culture allowed the multiplication of the number of adherent progenitor cells at the initial time of plating by a mean factor of 44,000, which was found to be negatively correlated with age. Thus, this differentiation model could provide a new tool to elaborate an autologous cell therapy designed to enhance osteogenesis.

  18. Bone marrow examination for identifying malaria in fever of unknown origin.

    PubMed

    Mirdha, B R; Samantray, J C; Mishra, B; Xess, I

    1999-02-01

    To determine the utility of bone marrow examination for the diagnosis of malaria in patients with persistent fever for prolonged duration, we prospectively studied individuals undergoing diagnostic bone marrow examinations between January 1992 to December 1996. All marrow examinations of patients were examined microbiologically and resulted in diagnosis of malaria in 6.6% of the total patients studied. No case of bacterial, mycobacterial or fungal infection was diagnosed. The diagnostic efficacy of bone marrow for evidence of malaria was very useful in febrile individuals for whom the diagnosis was otherwise unknown.

  19. Electrostimulation and morphologic study of the nerves to the bone marrow of the albino rat.

    PubMed

    DePace, D M; Webber, R H

    1975-01-01

    The innervation of the bone marrow of the albino rat was investigated by electrostimulation and morphological methods. Stimulation of the lumbar sympathetic trunks resulted in the release of reticulocytes and neutrophils into the circulating blood. The effects of stimulation on other cell types in the bone marrow could not be definitely established. It was concluded that the nerve fibers to the bone marrow were distributed to the arteries. It is postulated that the transmitter substance released at the autonomic nerve endings may have an effect upon the permeability of the venous sinusiods and the mobility of the blood cells in the marrow parenchyma resulting in their release into the circulating blood.

  20. Osteoprogenitor cells from bone marrow and cortical bone: understanding how the environment affects their fate.

    PubMed

    Corradetti, Bruna; Taraballi, Francesca; Powell, Sebastian; Sung, David; Minardi, Silvia; Ferrari, Mauro; Weiner, Bradley K; Tasciotti, Ennio

    2015-05-01

    Bone is a dynamic organ where skeletal progenitors and hematopoietic cells share and compete for space. Presumptive mesenchymal stem cells (MSC) have been identified and harvested from the bone marrow (BM-MSC) and cortical bone fragments (CBF-MSC). In this study, we demonstrate that despite the cells sharing a common ancestor, the differences in the structural properties of the resident tissues affect cell behavior and prime them to react differently to stimuli. Similarly to the bone marrow, the cortical portion of the bone contains a unique subset of cells that stains positively for the common MSC-associated markers. These cells display different multipotent differentiation capability, clonogenic expansion, and immunosuppressive potential. In particular, when compared with BM-MSC, CBF-MSC are bigger in size, show a lower proliferation rate at early passages, have a greater commitment toward the osteogenic lineage, constitutively produce nitric oxide as a mediator for bone remodeling, and more readily respond to proinflammatory cytokines. Our data suggest that the effect of the tissue's microenvironment makes the CBF-MSC a superior candidate in the development of new strategies for bone repair.

  1. 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

  2. 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

  3. Microdosimetry of astatine-211 using histological images: application to bone marrow.

    PubMed

    Akabani, G; Zalutsky, M R

    1997-12-01

    A method is presented for calculating the small-scale dosimetry of 211At in red bone marrow using chord-length distributions obtained from digitized histological images. This study used histological samples of bone marrow from beagle dogs to convey morphological information about cell conglomerations within bone marrow. Two 211At activity distributions were considered within the extracellular fluid and the surface of red bone marrow cells. Results confirmed the influence of cell conglomeration and activity distribution in determining the microdosimetry of red bone marrow. Average S* values of 1.6 x 10(-9) and 1.90 x 10(-9) Gy g Bq(-1) s(-1) were calculated for activity distributions located within the extracellular fluid and the surface of red bone marrow cells, respectively. The cumulated activity required to reduce survival probability to 0.37 also was calculated as a function of cell sensitivity for both activity distributions. The activity distribution on the cell surface resulted in a higher cell-killing efficiency, requiring a lower activity concentration of approximately 25% when compared with activity located in the extracellular fluid. Of relevance to potential clinical studies with 211At, the probability for zero hits for red bone marrow cells was > 10% for cumulated activities of less than 5.5 x 10(8) Bq s g(-1) in bone marrow.

  4. Multiple Myeloma Impairs Bone Marrow Localization of Effector Natural Killer Cells by Altering the Chemokine Microenvironment.

    PubMed

    Ponzetta, Andrea; Benigni, Giorgia; Antonangeli, Fabrizio; Sciumè, Giuseppe; Sanseviero, Emilio; Zingoni, Alessandra; Ricciardi, Maria Rosaria; Petrucci, Maria Teresa; Santoni, Angela; Bernardini, Giovanni

    2015-11-15

    Natural killer (NK) cells are key innate immune effectors against multiple myeloma, their activity declining in multiple myeloma patients with disease progression. To identify the mechanisms underlying NK cell functional impairment, we characterized the distribution of functionally distinct NK cell subsets in the bone marrow of multiple myeloma-bearing mice. Herein we report that the number of KLRG1(-) NK cells endowed with potent effector function rapidly and selectively decreases in bone marrow during multiple myeloma growth, this correlating with decreased bone marrow NK cell degranulation in vivo. Altered NK cell subset distribution was dependent on skewed chemokine/chemokine receptor axes in the multiple myeloma microenvironment, with rapid downmodulation of the chemokine receptor CXCR3 on NK cells, increased CXCL9 and CXCL10, and decreased CXCL12 expression in bone marrow. Similar alterations in chemokine receptor/chemokine axes were observed in patients with multiple myeloma. Adoptive transfer experiments demonstrated that KLRG1(-) NK cell migration to the bone marrow was more efficient in healthy than multiple myeloma-bearing mice. Furthermore, bone marrow localization of transferred CXCR3-deficient NK cells with respect to wild type was enhanced in healthy and multiple myeloma-bearing mice, suggesting that CXCR3 restrains bone marrow NK cell trafficking. Our results indicate that multiple myeloma-promoted CXCR3 ligand upregulation together with CXCL12 downmodulation act as exit signals driving effector NK cells outside the bone marrow, thus weakening the antitumor immune response at the primary site of tumor growth.

  5. Postradiation recovery of human bone marrow and morphological dynamics of undifferentiated cell pool

    SciTech Connect

    Suvorova, L.A.; Vyalova, N.A.; Barabanoya, A.V.; Gruzdev, G.P.

    1982-01-01

    The postradiation repair of the hemopoietic function in human beings and of changes observed in bone marrow and peripheral blood is described. The processes of damage and recovery of bone marrow from acute radiation sickness induced by external radiation are described, based on observations of 77 samples made from the first to the forty-third day after irradiation.

  6. 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

  7. 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

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

    PubMed

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

    2016-05-01

    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.

  9. 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.

  10. Chlorpromazine-induced liver and bone marrow granulomas associated with agranulocytosis.

    PubMed

    Ben-Yehuda, A; Bloom, A; Lijovetzky, G; Flusser, D; Tur-Kaspa, R

    1990-08-01

    Chlorpromazine-induced liver damage is usually manifested by intrahepatic cholestasis. Hypoplastic bone marrow associated with agranulocytosis is a well-known side effect of chlorpromazine treatment. A 35-year-old woman with liver and bone marrow granulomas associated with agranulocytosis induced by chlorpromazine treatment is described.

  11. Regulatory pathways associated with bone loss and bone marrow adiposity caused by aging, chemotherapy, glucocorticoid therapy and radiotherapy.

    PubMed

    Georgiou, Kristen R; Hui, Susanta K; Xian, Cory J

    2012-01-01

    The bone marrow is a complex environment that houses haematopoietic and mesenchymal cell populations and regulates bone turnover throughout life. The high proliferative capacity of these cell populations however, makes them susceptible to damage and injury, altering the steady-state of the bone marrow environment. Following cancer chemotherapy, irradiation and long-term glucocorticoid use, reduced bone and increased fat formation of marrow stromal progenitor cells results in a fatty marrow cavity, reduced bone mass and increased fracture risk. These bone and marrow defects are also observed in age-related complications such as estrogen deficiency and increased oxidative stress. Although the underlying mechanisms are yet to be clarified, recent investigations have suggested a switch in lineage commitment of bone marrow mesenchymal stem cells down the adipogenic lineage at the expense of osteogenic differentiation following such stress or injury. The Wnt/β-catenin signalling pathway is however has been recognized the key mechanism regulating stromal commitment, and its involvement in the osteogenic and adipogenic lineage commitment switch under the damaging conditions has been of great interest. This article reviews the effects of various types of stress or injury on the commitment to the adipogenic and osteogenic lineages of bone marrow stromal progenitor cells, and summarizes the roles of the Wnt/β-catenin and associated signalling pathways in the lineage commitment, switch, and recovery after damage, and as a therapeutic target.

  12. 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

  13. 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

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

    PubMed

    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.

  15. Primary bone marrow B-cell non-Hodgkin's lymphoma successfully treated with R-CHOP.

    PubMed

    Qian, Liren; Zhang, Zhi; Shen, Jianliang; Liu, Yi

    2013-01-01

    Primary isolated bone marrow disease as a presenting feature of lymphoma is very rare. We describe the case of a Chinese with isolated bone marrow small B-cell lymphoma as a first manifestation. A 55-year old woman was admitted to our hospital with fever. Her peripheral blood smear and laboratory findings were suggestive of bicytopenia. Bone marrow specimen showed diffusely distributed small-sized lymphocytes. Combined with immunophenotypic and chromosomal analysis, a diagnosis of primary bone marrow B-cell non-Hodgkin's lymphoma was made. The patient was treated with R-CHOP (rituximab and cyclophosphamide, epirubicin, vindesine, and prednisone) regimen for six cycles. She had complete remission and is still alive without relapse. We concluded that primary bone marrow mature small B-cell lymphoma is a rare but distinctive subtype of lymphoma. The prognosis for this entity is poor but rituximab-based treatment is promising for improving its outcomes.

  16. 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.

  17. Composite vascularized skin/bone graft model: a viable source for vascularized bone marrow transplantation.

    PubMed

    Siemionow, Maria; Ulusal, Betul G; Ozmen, Selahattin; Ulusal, Ali E; Ozer, Kagan

    2004-01-01

    In this study, we introduce a new model for vascularized skin and bone marrow transplantation. Twenty-five Lewis (RT1(1)) rats were studied. Anatomic dissection studies were performed in 5 animals. In the experimental group, 10 isograft transplantations were performed between Lewis rats. Combined groin skin and femoral bone flaps were transplanted based on the femoral artery and vein. Transplants were evaluated on a daily basis. All flaps survived without problems over 100 days posttransplant. The skin component remained pink and pliable, and grew new hair. Histological examination of the femoral bone (except the femoral head) revealed active hematopoiesis with a viable compact and cancellous bone components on day 100 posttransplant. This model can be applied to tolerance induction studies across the major Histocompatibility (MHC) barrier, where bone will serve as donor of stem and progenitor cells, and the skin flap will serve as a monitor of graft rejection.

  18. Allogenous bone grafts improved by bone marrow stem cells and platelet growth factors: clinical case reports.

    PubMed

    Filho Cerruti, Humberto; Kerkis, Irina; Kerkis, Alexandre; Tatsui, Nelson Hidekazu; da Costa Neves, Adriana; Bueno, Daniela Franco; da Silva, Marcelo Cavenaghi Pereira

    2007-04-01

    In order to increase the amount of available bone where dental implants must be placed, the present study has associated platelet-rich plasma (PRP) and mononuclear cells (MNCs) from bone marrow aspirate and bone scaffold (BS) in 32 patients aged between 45 and 75 years old. The MNC attainment and the adherence to the BS were confirmed through histology, cell culture, and scanning electron microscopy. The clinical results, analyzed by computed tomography, have showed that the scaffolds were well integrated and adapted to the cortical bone. We can conclude that the process of healing observed in the patients was due to the presence of mesenchymal stem cell in MNC fraction in the bone grafts.

  19. Bone marrow segmentation based on a combined consideration of transverse relaxation processes and Dixon oscillations.

    PubMed

    Balasubramanian, Mukund; Jarrett, Delma Y; Mulkern, Robert V

    2016-05-01

    The aim of this study was to demonstrate that gradient-echo sampling of single spin echoes can be used to isolate the signal from trabecular bone marrow, with high-quality segmentation and surface reconstructions resulting from the application of simple post-processing strategies. Theoretical expressions of the time-domain single-spin-echo signal were used to simulate signals from bone marrow, non-bone fatty deposits and muscle. These simulations were compared with and used to interpret signals obtained by the application of the gradient-echo sampling of a spin-echo sequence to image the knee and surrounding tissues at 1.5 T. Trabecular bone marrow has a much higher reversible transverse relaxation rate than surrounding non-bone fatty deposits and other musculoskeletal tissues. This observation, combined with a choice of gradient-echo spacing that accentuates Dixon-type oscillations from chemical-shift interference effects, enabled the isolation of bone marrow signal from surrounding tissues through the use of simple image subtraction and thresholding. Three-dimensional renderings of the marrow surface were then readily generated with this approach - renderings that may prove useful for bone morphology assessment, e.g. for the measurement of femoral anteversion. In conclusion, understanding the behavior of signals from bone marrow and surrounding tissue as a function of time through a spin echo facilitates the segmentation and reconstruction of bone marrow surfaces using straightforward post-processing strategies that are typically available on modern radiology workstations.

  20. 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.

  1. Bone turnover markers in peripheral blood and marrow plasma reflect trabecular bone loss but not endocortical expansion in aging mice.

    PubMed

    Shahnazari, Mohammad; Dwyer, Denise; Chu, Vivian; Asuncion, Frank; Stolina, Marina; Ominsky, Michael; Kostenuik, Paul; Halloran, Bernard

    2012-03-01

    We examined age-related changes in biochemical markers and regulators of osteoblast and osteoclast activity in C57BL/6 mice to assess their utility in explaining age-related changes in bone. Several recently discovered regulators of osteoclasts and osteoblasts were also measured to assess concordance between their systemic levels versus their levels in marrow plasma, to which bone cells are directly exposed. MicroCT of 6-, 12-, and 24-month-old mice indicated an early age-related loss of trabecular bone volume and surface, followed by endocortical bone loss and periosteal expansion. Trabecular bone loss temporally correlated with reductions in biomarkers of bone formation and resorption in both peripheral blood and bone marrow. Endocortical bone loss and periosteal bone gain were not reflected in these protein biomarkers, but were well correlated with increased expression of osteocalcin, rank, tracp5b, and cathepsinK in RNA extracted from cortical bone. While age-related changes in bone turnover markers remained concordant in blood versus marrow, aging led to divergent changes in blood versus marrow for the bone cell regulators RANKL, OPG, sclerostin, DKK1, and serotonin. Bone expression of runx2 and osterix increased progressively with aging and was associated with an increase in the number of osteoprogenitors and osteoclast precursors. In summary, levels of biochemical markers of bone turnover in blood and bone marrow plasma were predictive of an age-related loss of trabecular surfaces in adult C57BL/6 mice, but did not predict gains in cortical surfaces resulting from cortical expansion. Unlike these turnover markers, a panel of bone cell regulatory proteins exhibited divergent age-related changes in marrow versus peripheral blood, suggesting that their circulating levels may not reflect local levels to which osteoclasts and osteoblasts are directly exposed.

  2. Blood and Bone Marrow Hematopoietic Stem Cells for Transplantation: A Comparative Review.

    PubMed

    Janssen; Hiemenz; Fields; Zorsky; Ballester; Goldstein; Elfenbein

    1994-05-01

    Classical bone marrow transplantation collects bone marrow from a normal individual. This is infused into a patient rendered aplastic by high-dose chemoradiotherapy. Shortcomings include a limited donor pool and morbidity and mortality from graft-vs-host and graft rejection phenomena. Autologous marrow transplantation, in which the marrow of the patient to be transplanted is harvested, cryopreserved, and stored until needed, is not so constrained. Although marrow cannot be collected from some individuals due to hypocellularity, fibrosis, or infiltration with malignant disease, the presence of peripheral blood stem cells in the circulation allows these individuals to be treated with autologous transplantation therapy. It has been postulated that these hematopoietic progenitors have advantages over bone marrow collected stem cells, including safer and less expensive collections and accelerated rates of hematopoietic recovery following high-dose therapy and stem cell reinfusion.

  3. [Hematopoietic growth factors in primary and therapy-related bone marrow insufficiency].

    PubMed

    Hansen, B; Hippe, E; Jacobsen, G K; Johnsen, H E

    1992-06-08

    This investigation is retrospective and comprises 20 patients with bone-marrow insufficiency. During the period 1.4.1988-1.3.1991, these patients were treated with erythropoietin (Epo), the granulocyte-macrophage-colony-stimulating factor (GM-CSF) or the granulocyte-colony-stimulating factor (G-CSF). Thirteen patients had primary bone-marrow insufficiency: six had the myelodysplastic syndrome, three had primary myelofibrosis, two aplastic anemia and two myelomatosis. On account of dominating symptoms of anemia, five patients received Epo while eight received GM-CSF as part of an extensive clinical trial of this preparation. Seven patients with relapse of the haematological malignant disease had bone-marrow insufficiency and pancytopenia secondary to intensive chemotherapy/irradiation: four of these patients received GM-CSF and two received G-CSF with the object of increasing bone-marrow regeneration and to render further chemotherapy possible. One patient received GM-CSF with the object of improving bone-marrow function after autologous bone-marrow transplantation. Treatment with Epo for ten months combined with treatment with interferon for six months resulted in normalization of the haemoglobin concentration in one patient with bone-marrow insufficiency on account of primary myelofibrosis. Treatment with Epo for briefer periods in lower doses was without effect in four other patients with primary bone-marrow insufficiency. Treatment with GM-CSF and G-CSF resulted in neutrophil leukocytosis in 12 out of 15 patients (80%) and, in six out of 14 patients (43%), increased marrow cellularity was demonstrated by means of histological examination of the bone-marrow. One patient showed normal haemoglobin levels during treatment with GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Ectopic bone regeneration by human bone marrow mononucleated cells, undifferentiated and osteogenically differentiated bone marrow mesenchymal stem cells in beta-tricalcium phosphate scaffolds.

    PubMed

    Ye, Xinhai; Yin, Xiaofan; Yang, Dawei; Tan, Jian; Liu, Guangpeng

    2012-07-01

    Tissue engineering approaches using the combination of porous ceramics and bone marrow mesenchymal stem cells (BMSCs) represent a promising bone substitute for repairing large bone defects. Nevertheless, optimal conditions for constructing tissue-engineered bone have yet to be determined. It remains unclear if transplantation of predifferentiated BMSCs is superior to undifferentiated BMSCs or freshly isolated bone marrow mononucleated cells (BMNCs) in terms of new bone formation in vivo. The aim of this study was to investigate the effect of in vitro osteogenic differentiation (β-glycerophosphate, dexamethasone, and l-ascorbic acid) of human BMSCs on the capability to form tissue-engineered bone in unloaded conditions after subcutaneous implantation in nude mice. After isolation from human bone marrow aspirates, BMNCs were divided into three parts: one part was seeded onto porous beta-tricalcium phosphate ceramics immediately and transplanted in a heterotopic nude mice model; two parts were expanded in vitro to passage 2 before cell seeding and in vivo transplantation, either under osteogenic conditions or not. Animals were sacrificed for micro-CT and histological evaluation at 4, 8, 12, 16, and 20 weeks postimplantation. The results showed that BMSCs differentiated into osteo-progenitor cells after induction, as evidenced by the altered cell morphology and elevated alkaline phosphatase activity and calcium deposition, but their clonogenicity, proliferating rate, and seeding efficacy were not significantly affected by osteogenic differentiation, compared with undifferentiated cells. Extensive new bone formed in the pores of all the scaffolds seeded with predifferentiated BMSCs at 4 weeks after implantation, and maintained for 20 weeks. On the contrary, scaffolds containing undifferentiated BMSCs revealed limited bone formation only in 1 out of 6 cases at 8 weeks, and maintained for 4 weeks. For scaffolds with BMNCs, woven bone was observed sporadically only in one

  5. Treatment of simple bone cysts with aspiration and a single bone marrow injection.

    PubMed

    Docquier, Pierre-Louis; Delloye, Christian

    2003-01-01

    The authors report the results of percutaneous aspiration and injection of marrow into active, simple bone cyst in 17 cases. Slow regression of the cyst and progressive healing were obtained in 13 cases (76%), no response was observed in 2 cases (12%), and recurrence was observed in 2 others (12%) after a follow-up of 33.9 months. Cyst evolution was monitored by a cyst index, cyst diameter, and computer-assisted densitometric image analysis of serial radiographs.

  6. Simple bone cysts treated with aspiration and a single bone marrow injection. A preliminary report.

    PubMed

    Delloye, C; Docquier, P L; Cornu, O; Poilvache, P; Peters, M; Woitrin, B; Rombouts, J J; De Nayer, P

    1998-01-01

    The results of a single percutaneous aspiration and injection of marrow into active, simple bone cysts are reported in 8 cases. Slow regression of the cyst was consistently observed except in one lesion in the distal tibia. All the patients have been free of symptoms after this treatment after a mean follow up of 31 months. The evolution of the cysts was monitored by a cyst index, cyst diameter measurements and computer assisted densitometric image analysis of serial radiographs.

  7. Bone marrow features of diagnostic impact in erythrocytosis.

    PubMed

    Thiele, Juergen; Kvasnicka, Hans Michael; Diehl, Volker

    2005-06-01

    Controversy continues to persist about the role of histopathology regarding diagnosis of polycythemia vera (PV). For this reason, a clinicopathological study was performed on 334 patients presenting with a sustained borderline to marked erythrocytosis (hemoglobin >17 g/dl in men and >15 g/dl in women). The aim was to elucidate the discriminating impact of bone marrow biopsy examinations in an independent fashion from laboratory parameters. According to morphological findings based on a semiquantitative evaluation of standardized features, cellularity, megakaryocytes (quantity, size, pleomorphous aspect, clustering, nuclear lobulation), eosinophils, cellular debris, perivascular plasmacytosis and iron-laden macrophages exerted a distinctive value. Comparison with clinical data and follow-up revealed that in only 13 patients (4%), histopathology failed to differentiate clearly between PV (208 patients) and secondary polycythemias (113 patients). In conclusion, certain sets of morphological parameters allow a distinction between autonomous and reactive polycythemias and therefore enhance significantly diagnostic validity.

  8. Pericardial Tamponade: a Rare Complication of Sternal Bone Marrow Biopsy

    PubMed Central

    Santavy, Petr; Troubil, Martin; Lonsky, Vladimir

    2013-01-01

    Injury of the heart with concomitant pericardial tamponade as a result of sternal bone marrow biopsy is rare. An 80-year-old man was admitted with dehydration and non-specified abdominal pain to the regional hospital. Sternal aspiration biopsy was performed because of anemia and thrombocytopenia. Later on, because of the back pain, general weakness and blood pressure drop, an echocardiography examination was indicated. Pericardial fluid collection was found. Anticipated ascending aortic dissection was excluded on computed tomography scan, but pericardial fluid collection was confirmed. Transfer to our cardiac surgical facility ensued. Limited heart tamponade was affirmed on echocardiography and surgery was immediately indicated. Blood effusion was found in upper mediastinal fat tissue and 300 mL of blood were evacuated from opened pericardial space. Stab wound by sternal biopsy needle at the upper part of ascending aorta was repaired by pledgeted suture. Postoperative course was uneventful. PMID:24179668

  9. Reversible posterior leucoencephalopathy syndrome associated with bone marrow transplantation.

    PubMed

    Teive, H A; Brandi, I V; Camargo, C H; Bittencourt, M A; Bonfim, C M; Friedrich, M L; de Medeiros, C R; Werneck, L C; Pasquini, R

    2001-09-01

    Reversible posterior leucoencephalopathy syndrome (RPLS) has previously been described in patients who have renal insufficiency, eclampsia, hypertensive encephalopathy and patients receiving immunosuppressive therapy. The mechanism by which immunosuppressive agents can cause this syndrome is not clear, but it is probably related with cytotoxic effects of these agents on the vascular endothelium. We report eight patients who received cyclosporine A (CSA) after allogeneic bone marrow transplantation or as treatment for severe aplastic anemia (SSA) who developed posterior leucoencephalopathy. The most common signs and symptoms were seizures and headache. Neurological dysfunction occurred preceded by or concomitant with high blood pressure and some degree of acute renal failure in six patients. Computerized tomography studies showed low-density white matter lesions involving the posterior areas of cerebral hemispheres. Symptoms and neuroimaging abnormalities were reversible and improvement occurred in all patients when given lower doses of CSA or when the drug was withdrawn. RPLS may be considered an expression of CSA neurotoxicity.

  10. Neonatal manifestations of inherited bone marrow failure syndromes.

    PubMed

    Khincha, Payal P; Savage, Sharon A

    2016-02-01

    The inherited bone marrow failure syndromes (IBMFS) are a rare yet clinically important cause of neonatal hematological and non-hematological manifestations. Many of these syndromes, such as Fanconi anemia, dyskeratosis congenita and Diamond-Blackfan anemia, confer risks of multiple medical complications later in life, including an increased risk of cancer. Some IBMFS may present with cytopenias in the neonatal period whereas others may present only with congenital physical abnormalities and progress to pancytopenia later in life. A thorough family history and detailed physical examination are integral to the work-up of any neonate in whom there is a high index of suspicion for an IBMFS. Correct detection and diagnosis of these disorders is important for appropriate long-term medical surveillance and counseling not only for the patient but also for appropriate genetic counselling of their families regarding recurrence risks in future children and generations.

  11. Wolman disease successfully treated by bone marrow transplantation.

    PubMed

    Krivit, W; Peters, C; Dusenbery, K; Ben-Yoseph, Y; Ramsay, N K; Wagner, J E; Anderson, R

    2000-09-01

    Wolman disease is characterized by severe diarrhea and malnutrition leading to death during infancy. Lysosomal acid lipase deficiency is the cause of the symptoms and signs. It is inherited in an autosomal recessive manner. All Wolman disease patients have adrenal gland calcification. Previous therapeutic attempts have failed to provide remission. We report successful long-term bone marrow engraftment in a patient with Wolman disease resulting in continued normalization of peripheral leukocyte lysosomal acid lipase enzyme activity. Diarrhea is no longer present. Now, at 4 years of age, this patient is gaining developmental milestones. Cholesterol and triglyceride levels are normal. Liver function is normal. This is the first long-term continued remission reported for Wolman disease.

  12. Neonatal manifestations of inherited bone marrow failure syndromes

    PubMed Central

    Khincha, Payal P.; Savage, Sharon A.

    2015-01-01

    SUMMARY The inherited bone marrow failure syndromes (IBMFS) are a rare yet clinically important cause of neonatal hematological and non-hematological manifestations. Many of these syndromes, such as Fanconi anemia, dyskeratosis congenita and Diamond–Blackfan anemia, confer risks of multiple medical complications later in life, including an increased risk of cancer. Some IBMFS may present with cytopenias in the neonatal period whereas others may present only with congenital physical abnormalities and progress to pancytopenia later in life. A thorough family history and detailed physical examination are integral to the work-up of any neonate in whom there is a high index of suspicion for an IBMFS. Correct detection and diagnosis of these disorders is important for appropriate long-term medical surveillance and counseling not only for the patient but also for appropriate genetic counselling of their families regarding recurrence risks in future children and generations. PMID:26724991

  13. Flow Dynamics and HSPC Homing in Bone Marrow Microvessels.

    PubMed

    Bixel, M Gabriele; Kusumbe, Anjali P; Ramasamy, Saravana K; Sivaraj, Kishor K; Butz, Stefan; Vestweber, Dietmar; Adams, Ralf H

    2017-02-14

    Measurements of flow velocities at the level of individual arterial vessels and sinusoidal capillaries are crucial for understanding the dynamics of hematopoietic stem and progenitor cell homing in the bone marrow vasculature. We have developed two complementary intravital two-photon imaging approaches to determine blood flow dynamics and velocities in multiple vessel segments by capturing the motion of red blood cells. High-resolution spatiotemporal measurements through a cranial window to determine short-time dynamics of flowing blood cells and repetitive centerline scans were used to obtain a detailed flow-profile map with hemodynamic parameters. In addition, we observed the homing of individual hematopoietic stem and progenitor cells and obtained detailed information on their homing behavior. With our imaging setup, we determined flow patterns at cellular resolution, blood flow velocities and wall shear stress in small arterial vessels and highly branched sinusoidal capillaries, and the cellular dynamics of hematopoietic stem and progenitor cell homing.

  14. Prevention and treatment of fungal infections in bone marrow transplantation.

    PubMed

    Mossad, Sherif B

    2003-07-01

    There has not been as much success in the prevention and treatment of invasive fungal infections, particularly aspergillosis, compared to the prevention and treatment of cytomegalovirus infection and graft-versus-host disease in bone marrow transplant (BMT) recipients. Allogeneic BMT recipients who develop graft-versus-host disease and remain immunosuppressed for long periods are at major risk for development of these infections. Prevention of environmental exposure, antifungal chemoprophylaxis, and attempts at early diagnosis are essential for the reduction of mortality from invasive fungal infections. Chest computerized axial tomography is extremely useful in diagnosing pulmonary aspergillosis. However, microbiologic or histologic identification of infection remains essential. Unfortunately, the response to therapy in BMT recipients remains suboptimal. With the development of the lipid formulations of amphotericin B, the newer azoles, and the echinocandins, safer and more efficacious options have become available. The optimal use of antifungal agents or their combinations remains to be determined.

  15. Protecting the interests of the child bone marrow donor.

    PubMed

    Terry, Louise M; Campbell, Anne

    2004-01-01

    At a time when designer babies have been created to act as cord blood donors to sick siblings, ethical debate has focused predominantly on the extent to which it is acceptable to create one human being to assist another. However, children are frequently used this way, by their families and doctors who extract their bone marrow, to try to save the life of another, usually a sibling. With any life-threatening illness, there is the possibility that the urgency of the sick sibling's need means that the short-term welfare of the donor child receives less attention than it should by parents and doctors. This article suggests ways to protect the interests of such children and empower them within the decision-making process and concludes that the drive to save life must be tempered by recognition of the intrinsic worth of donor children and their rights not to be exploited.

  16. The Challenge and the Promise of Bone Marrow Cells for Human Cartilage Repair.

    PubMed

    Chu, Constance R

    2015-04-01

    The cartilage repair potential of bone marrow-derived stem cells has been well described. Harnessing this potential for human articular cartilage repair remains challenging. Accessing bone marrow repair cells through marrow stimulation techniques such as microfracture is readily achieved with generally good but inconsistent results. Animal and human studies show feasibility for ex vivo processing of bone marrow to isolate, concentrate, and culture mesenchymal stem cells. Nevertheless, it has been difficult to show consistent and clinically meaningful improvement using bone marrow cell preparations above what has been achieved with microfracture. Consequently, microfracture continues to be the simplest and most commonly used method to enhance repair of focal articular cartilage defects. Emerging preclinical work in the equine model suggests a role for enhancing marrow-stimulation techniques through the use of natural scaffolds such as autologous platelet enriched fibrin as well as optimization of joint biology through localized gene therapy to support cartilage repair. In contrast to joint replacement where inert materials of known mechanical properties are used, host biology determines the relative success, failure, and durability of cartilage repair. As such, development of personalized strategies to improve the quality and durability of bone marrow cell-based articular cartilage repair represent exciting new areas of inquiry. Continued advances in stem cell biology, scaffold technologies, and methods to delineate and enhance host biology, both systemically and within the joint, hold promise for harnessing the full power of bone marrow cells to facilitate cartilage repair and regeneration.

  17. Bone marrow-derived cell regulation of skeletal muscle regeneration

    PubMed Central

    Sun, Dongxu; Martinez, Carlo O.; Ochoa, Oscar; Ruiz-Willhite, Lourdes; Bonilla, Jose R.; Centonze, Victoria E.; Waite, Lindsay L.; Michalek, Joel E.; McManus, Linda M.; Shireman, Paula K.

    2009-01-01

    Limb regeneration requires the coordination of multiple stem cell populations to recapitulate the process of tissue formation. Therefore, bone marrow (BM) -derived cell regulation of skeletal muscle regeneration was examined in mice lacking the CC chemokine receptor 2 (CCR2). Myofiber size, numbers of myogenic progenitor cells (MPCs), and recruitment of BM-derived cells and macrophages were assessed after cardiotoxin-induced injury of chimeric mice produced by transplanting BM from wild-type (WT) or CCR2−/− mice into irradiated WT or CCR2−/− host mice. Regardless of the host genotype, muscle regeneration and recruitment of BM-derived cells and macrophages were similar in mice replenished with WT BM, whereas BM-derived cells and macrophage accumulation were decreased and muscle regeneration was impaired in all animals receiving CCR2−/− BM. Furthermore, numbers of MPCs (CD34+/Sca-1−/CD45− cells) were significantly increased in mice receiving CCR2−/− BM despite the decreased size of regenerated myofibers. Thus, the expression of CCR2 on BM-derived cells regulated macrophage recruitment into injured muscle, numbers of MPC, and the extent of regenerated myofiber size, all of which were independent of CCR2 expression on host-derived cells. Future studies in regenerative medicine must include consideration of the role of BM-derived cells, possibly macrophages, in CCR2-dependent events that regulate effective skeletal muscle regeneration.—Sun, D., Martinez, C. O., Ochoa, O., Ruiz-Willhite, L., Bonilla, J. R., Centonze, V. E., Waite, L. L., Michalek, J. E., McManus, L. M., Shireman, P. K. Bone marrow-derived cell regulation of skeletal muscle regeneration. PMID:18827026

  18. Aspergillus antigen testing in bone marrow transplant recipients

    PubMed Central

    Williamson, E; Oliver, D; Johnson, E; Foot, A; Marks, D; Warnock, D

    2000-01-01

    Aims—To assess the clinical usefulness of a commercial aspergillus antigen enzyme linked immunosorbent assay (ELISA) in the diagnosis of invasive aspergillosis (IA) in bone marrow transplant recipients, and to compare it with a commercial latex agglutination (LA) test. Methods—In total, 2026 serum samples from 104 bone marrow transplant recipients were tested. These comprised 67 sera from seven patients who had died with confirmed IA, 268 sera from nine patients who had died with suspected IA, and 1691 sera from 88 patients with no clinical, radiological, or microbiological signs of IA. Results—The ELISA was more sensitive than the LA test. All patients who were ELISA positive were also LA positive, and a positive LA result never preceded a positive ELISA. Twelve of 16 patients with confirmed or suspected IA were ELISA positive on two or more occasions, compared with 10 of 15 who were LA positive. ELISA was positive before LA in five patients (range, 2–14 days), and became positive on the same day in the remainder. Aspergillus antigen was detected by ELISA a median of 15 days before death (range, 4–233). Clinical and/or radiological evidence of IA was noted in all patients, and a positive ELISA was never the sole criterion for introduction of antifungal treatment. Two samples (one from each of two patients without IA) gave false positive results. Conclusions—The aspergillus ELISA is a specific indicator of invasive aspergillosis if the criterion of two positive samples is required to confirm the diagnosis. However, the test is insufficiently sensitive to diagnose aspergillosis before other symptoms or signs are apparent, and hence is unlikely to lead to earlier initiation of antifungal treatment. It is therefore unsuitable for screening of asymptomatic patients at risk of invasive aspergillosis, but does have a useful role in confirming the diagnosis in symptomatic patients. Key Words: invasive aspergillosis • aspergillus antigen • Platelia enzyme

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

    PubMed

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

    2015-01-01

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

  20. Induction of allogeneic unresponsiveness by supralethal irradiation and bone marrow reconstitution. [Dogs

    SciTech Connect

    Rapaport, F.T.; Bachvaroff, R.J.; Akiyama, N.; Sato, T.

    1980-09-01

    Supralethally irradiated dogs were reconstituted wth their own stored bone marrow and were challenged at various time intervals with a kidney allograft. The data suggest that transplanted bone marrow cells may participate directly in the events leading to allogenic unresponsiveness. The time interval between marrow cell replacement and kidney allotransplantation required for optimal results suggest that at least one cycle of cell turnover by the replaced stem cells is needed in order to produce unresponsiveness. Host irradiation and reconstitution with stored autologous marrow may be useful in the treatment of certain forms of cancer.

  1. Elastic intramedullary nailing and DBM-Bone marrow injection for the treatment of simple bone cysts

    PubMed Central

    Kanellopoulos, Anastasios D; Mavrogenis, Andreas F; Papagelopoulos, Panayiotis J; Soucacos, Panayotis N

    2007-01-01

    Background Simple or unicameral bone cysts are common benign fluid-filled lesions usually located at the long bones of children before skeletal maturity. Methods We performed demineralized bone matrix and iliac crest bone marrow injection combined with elastic intramedullary nailing for the treatment of simple bone cysts in long bones of 9 children with a mean age of 12.6 years (range, 4 to 15 years). Results Two of the 9 patients presented with a pathological fracture. Three patients had been referred after the failure of previous treatments. Four patients had large lesions with impending pathological fractures that interfered with daily living activities. We employed a ratio to ascertain the severity of the lesion. The extent of the lesion on the longitudinal axis was divided with the normal expected diameter of the long bone at the site of the lesion. The mean follow-up was 77 months (range, 5 to 8 years). All patients were pain free and had full range of motion of the adjacent joints at 6 weeks postoperatively. Review radiographs showed that all 7 cysts had consolidated completely (Neer stage I) and 2 cysts had consolidated partially (Neer stage II). Until the latest examination there was no evidence of fracture or re-fracture. Conclusion Elastic intramedullary nailing has the twofold benefits of continuous cyst decompression, and early immediate stability to the involved bone segment, which permits early mobilization and return to the normal activities of the pre-teen patients. PMID:17916249

  2. Murine leukemia virus infects early bone marrow progenitors in immunocompetent mice.

    PubMed

    Tumas-Brundage, K M; Garret, W; Blank, K; Prystowsky, M B

    1996-10-15

    Chronic murine leukemia viruses (MuLVs) are retroviruses which induce leukemias/lymphomas after long latency periods. The induction of leukemia by MuLVs is complex, requiring multiple steps beginning with infection of an appropriate target cell. A number of investigators have proposed a bone marrow-thymus axis in the development of retrovirus induced T-cell lymphoma in which cells are initially infected in the bone marrow. These bone marrow cells or their progeny migrate to the thymus during the disease process. In our system using adult, immunocompetent BALB.K mice infected with E-55(+) MuLV, a similar pattern is seen; integrated virus is initially detectable in the bone marrow and spleen and only later in the thymus. In order to better understand the leukemic process, we analyzed the bone marrow from adult, immunocompetent BALB.K mice infected with the E-55(+) MuLV in bone marrow colony assays. The results from these assays demonstrate that either a pluripotent progenitor cell or an early progenitor cell is a target in the bone marrow for the virus.

  3. Effects of ionizing radiation on differentiation of murine bone marrow cells into mast cells.

    PubMed

    Murakami, Sho; Yoshino, Hironori; Ishikawa, Junya; Yamaguchi, Masaru; Tsujiguchi, Takakiyo; Nishiyama, Ayaka; Yokoyama, Kouki; Kashiwakura, Ikuo

    2015-11-01

    Mast cells, immune effector cells produced from bone marrow cells, play a major role in immunoglobulin E-mediated allergic responses. Ionizing radiation affects the functions of mast cells, which are involved in radiation-induced tissue damage. However, whether ionizing radiation affects the differential induction of mast cells is unknown. Here we investigated whether bone marrow cells of X-irradiated mice differentiated into mast cells. To induce mast cells, bone marrow cells from X-irradiated and unirradiated mice were cultured in the presence of cytokines required for mast cell induction. Although irradiation at 0.5 Gy and 2 Gy decreased the number of bone marrow cells 1 day post-irradiation, the cultured bone marrow cells of X-irradiated and unirradiated mice both expressed mast cell-related cell-surface antigens. However, the percentage of mast cells in the irradiated group was lower than in the unirradiated group. Similar decreases in the percentage of mast cells induced in the presence of X-irradiation were observed 10 days post irradiation, although the number of bone marrow cells in irradiated mice had recovered by this time. Analysis of mast cell function showed that degranulation of mast cells after immunoglobulin E-mediated allergen recognition was significantly higher in the X-irradiated group compared with in the unirradiated group. In conclusion, bone marrow cells of X-irradiated mice differentiated into mast cells, but ionizing radiation affected the differentiation efficiency and function of mast cells.

  4. Molecular evidence for the localization of Plasmodium falciparum immature gametocytes in bone marrow

    PubMed Central

    Aguilar, Ruth; Magallon-Tejada, Ariel; Achtman, Ariel H.; Moraleda, Cinta; Joice, Regina; Cisteró, Pau; Li Wai Suen, Connie S. N.; Nhabomba, Augusto; Macete, Eusebio; Mueller, Ivo; Marti, Matthias; Alonso, Pedro L.; Menéndez, Clara; Schofield, Louis

    2014-01-01

    Plasmodium falciparum immature gametocytes are not observed in peripheral blood. However, gametocyte stages in organs such as bone marrow have never been assessed by molecular techniques, which are more sensitive than optical microscopy. We quantified P falciparum sexual stages in bone marrow (n = 174) and peripheral blood (n = 70) of Mozambican anemic children by quantitative polymerase chain reaction targeting transcripts specific for early (PF14_0748; PHISTa), intermediate (PF13_0247; Pfs48/45), and mature (PF10_0303; Pfs25) gametocytes. Among children positive for the P falciparum housekeeping gene (PF08_0085; ubiquitin-conjugating enzyme gene) in bone marrow (n = 136) and peripheral blood (n = 25), prevalence of immature gametocytes was higher in bone marrow than peripheral blood (early: 95% vs 20%, P < .001; intermediate: 80% vs 16%; P < .001), as were transcript levels (P < .001 for both stages). In contrast, mature gametocytes were more prevalent (100% vs 51%, P < .001) and abundant (P < .001) in peripheral blood than in the bone marrow. Severe anemia (3.57, 95% confidence interval 1.49-8.53) and dyserythropoiesis (6.21, 95% confidence interval 2.24-17.25) were independently associated with a higher prevalence of mature gametocytes in bone marrow. Our results highlight the high prevalence and abundance of early sexual stages in bone marrow, as well as the relationship between hematological disturbances and gametocyte development in this tissue. PMID:24335496

  5. Evidence for transdifferentiation of human bone marrow-derived stem cells: recent progress and controversies.

    PubMed

    Tao, Helen; Ma, David D F

    2003-02-01

    Adult bone marrow-derived stem cells have traditionally been known as tissue-specific stem cells capable of producing blood cells. This concept is being challenged by a series of recent discoveries. It has been demonstrated that there are heterogeneous stem cell populations in adult bone marrow compartment. Under appropriate experimental conditions, a certain type of bone marrow stem cells appears to differentiate (or transdifferentiate) into a variety of non-haemopoietic cells of ectodermal, mesodermal and endodermal origins (such as myocytes, neural cells and hepatocytes). The plasticity, that is, the ability to regenerate cells belonging to different organs and tissues of adult (postnatal) stem cells, has raised the therapeutic possibility of using these stem cells for tissue repair and regeneration. Presently, definitive evidence for plasticity or transdifferentiation of bone marrow stem cells is lacking. Despite controversies concerning the plasticity of bone marrow-derived stem cells, early clinical trials are being conducted in patients suffering from myocardial infarct, arthritic and neurological diseases using autologous bone marrow stem cells. This review summarises recent progresses and controversies in transdifferentiation of adult bone marrow-derived stem cells to non-haemopoietic tissues.

  6. Effect of bone marrow-derived stem cells on chondrocytes from patients with osteoarthritis.

    PubMed

    Zhang, Qiangzhi; Chen, Yong; Wang, Qiang; Fang, Chaoyong; Sun, Yu; Yuan, Tao; Wang, Yuebei; Bao, Rongni; Zhao, Ningjian

    2016-02-01

    Increasing numbers of individuals are suffering from osteoarthritis every year, and the directed intra-articular injection of bone marrow stem cells has provided a promising treatment strategy for osteoarthritis. Although a number of studies have demonstrated that intra-articular injection of bone marrow stem cells produced desirable results, the mechanism underlying this effect has not been elucidated. In the current study, the effect of bone marrow stem cells on chondrocytes from patients with osteoarthritis was observed in a co-culture system. Human chondrocytes were obtained from patients with osteoarthritis who underwent surgical procedures and bone marrow stem cells were obtained from bone marrow aspirates, and then the chondrocytes were then cultured alone or cocultured with bone marrow stem cells in 0.4-µm Transwell inserts. The differentiation and biological activity of chondrocytes in the culture system were measured, and the inflammatory factors and OA-associated markers were also measured. The results indicated that coculture with human bone marrow stem cells increases cell proliferation of chondrocytes and inhibits inflammatory activity in osteoarthritis.

  7. Bone marrow metastases in small cell lung cancer: detection with magnetic resonance imaging and monoclonal antibodies.

    PubMed Central

    Trillet, V.; Revel, D.; Combaret, V.; Favrot, M.; Loire, R.; Tabib, A.; Pages, J.; Jacquemet, P.; Bonmartin, A.; Mornex, J. F.

    1989-01-01

    The detection of bone marrow involvement might be of prognostic value and may influence therapeutic decisions in small cell lung cancer. By unilateral bone marrow aspiration and biopsy, evidence of bone marrow metastases is seen in 15-30% of patients with this disease. Since magnetic resonance imaging of the lower body and immunostaining with monoclonal antibodies have recently been shown to be very sensitive detection methods, we investigated the value of these two techniques in detecting bone marrow involvement in 35 consecutive patients with small cell lung cancer. The results were compared to those obtained with conventional cytohistological analysis. In all cases when cytology and/or bone marrow biopsy were positive, monoclonal antibodies immunostaining and magnetic resonance imaging also detected malignant cells. Furthermore, evidence of bone marrow involvement was shown with magnetic resonance imaging and/or immunostaining in 10 of 26 cases (38%) where routine procedures were unable to detect malignant cells. In one of these 26 patients, magnetic resonance imaging and immunostaining provided the only evidence of metastatic disease. These data suggest that the rate of bone marrow metastases is underestimated by routine procedures. Further investigation is needed to determine whether or not these new non-invasive methods have prognostic value or affect therapeutic choices in small cell lung carcinoma. Images Figure 1 Figure 2 PMID:2553088

  8. Mesenchymal progenitors residing close to the bone surface are functionally distinct from those in the central bone marrow.

    PubMed

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

    2013-04-01

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

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

    PubMed Central

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

    2017-01-01

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

  10. Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow.

    PubMed

    Zhou, Bo O; Yue, Rui; Murphy, Malea M; Peyer, James G; Morrison, Sean J

    2014-08-07

    Studies of the identity and physiological function of mesenchymal stromal cells (MSCs) have been hampered by a lack of markers that permit both prospective identification and fate mapping in vivo. We found that Leptin Receptor (LepR) is a marker that highly enriches bone marrow MSCs. Approximately 0.3% of bone marrow cells were LepR(+), 10% of which were CFU-Fs, accounting for 94% of bone marrow CFU-Fs. LepR(+) cells formed bone, cartilage, and adipocytes in culture and upon transplantation in vivo. LepR(+) cells were Scf-GFP(+), Cxcl12-DsRed(high), and Nestin-GFP(low), markers which also highly enriched CFU-Fs, but negative for Nestin-CreER and NG2-CreER, markers which were unlikely to be found in CFU-Fs. Fate-mapping showed that LepR(+) cells arose postnatally and gave rise to most bone and adipocytes formed in adult bone marrow, including bone regenerated after irradiation or fracture. LepR(+) cells were quiescent, but they proliferated after injury. Therefore, LepR(+) cells are the major source of bone and adipocytes in adult bone marrow.

  11. In vivo bone metabolism and ex vivo bone marrow osteoprogenitors in vitamin D-deprived pigs.

    PubMed

    Denis, I; Cournot, G; Lacroix, H; Colin, C; Zerath, E; Pointillart, A

    2000-05-01

    Vitamin D insufficiency is still a concern in countries where there is no routine food supplementation, such as France. A low vitamin D status is clearly associated with an increased risk of fracture in the elderly, but the long-term consequences of latent vitamin D insufficiency in young people and adults are not known. We fed 26 growing pigs a high calcium diet (1.1%) with a 1000 IU cholecalciferol/kg diet (controls), or without vitamin D (0D) for 4 months. We then analyzed the overall impact of low vitamin D status on osteotropic hormones (calcitriol and immunoreactive parathyroid hormone), plasma markers of bone remodeling (alkaline phosphatase [ALP] activity, carboxyterminal propeptide of type I procollagen [PICP], osteocalcin, hydroxyproline), whole bone parameters (ash content, bending moment), histomorphometry, and the populations of marrow osteoblastic and osteoclastic precursors by ex vivo cultures. The fall in plasma 25-dihydroxyvitamin [25(OH)D] in the 0D pigs indicated severe depletion of their vitamin D stores. However, they remained normocalcemic, were mildly hyperparathyroid after 2 months of vitamin D deprivation, and showed only a slight decrease in plasma calcitriol. The bone mineral content and bending moment of metatarsals decreased and they had increased osteoblastic (+59%, p < 0.05 0D vs. controls) and osteoclastic (+31%, p < 0.1 0D vs. controls) surfaces. This was not paralleled by increased bone turnover, because plasma hydroxyproline and ALP were unchanged and PICP and osteocalcin were decreased. The adherent fraction of bone marrow cells showed a great increase in the number of total stromal colony-forming units (CFU-F; +93%, p < 0.05 0D vs. controls) and in the percent of ALP(+) CFU-F (+58%, p < 0.01 0D vs. controls) in cultures from 0D pigs. More tartrate-resistant acid phosphatase-positive (TRAP(+)) multinucleated cells were generated in cultures of nonadherent marrow cells from 0D pigs, and the area of resorption was 345% greater than

  12. JAK3/STAT6 Stimulates Bone Marrow-Derived Fibroblast Activation in Renal Fibrosis.

    PubMed

    Yan, Jingyin; Zhang, Zhengmao; Yang, Jun; Mitch, William E; Wang, Yanlin

    2015-12-01

    Renal fibrosis is a final common manifestation of CKD resulting in progressive loss of kidney function. Bone marrow-derived fibroblast precursors contribute significantly to the pathogenesis of renal fibrosis. However, the signaling mechanisms underlying the activation of bone marrow-derived fibroblast precursors in the kidney are not fully understood. In this study, we investigated the role of the Janus kinase 3 (JAK3)/signal transducer and activator of transcription (STAT6) signaling pathway in the activation of bone marrow-derived fibroblasts. In cultured mouse monocytes, IL-4 or IL-13 activated STAT6 and induced expression of α-smooth muscle actin and extracellular matrix proteins (fibronectin and collagen I), which was abolished by a JAK3 inhibitor (CP690,550) in a dose-dependent manner or blocked in the absence of STAT6. In vivo, STAT6 was activated in interstitial cells of the obstructed kidney, an effect that was abolished by CP690,550. Mice treated with CP690,550 accumulated fewer bone marrow-derived fibroblasts in the obstructed kidneys compared with vehicle-treated mice. Treatment with CP690,550 also significantly reduced myofibroblast transformation, matrix protein expression, fibrosis development, and apoptosis in obstructed kidneys. Furthermore, STAT6-deficient mice accumulated fewer bone marrow-derived fibroblasts in the obstructed kidneys, produced less extracellular matrix protein, and developed much less fibrosis. Finally, wild-type mice engrafted with STAT6(-/-) bone marrow cells displayed fewer bone marrow-derived fibroblasts in the obstructed kidneys and showed less severe renal fibrosis compared with wild-type mice engrafted with STAT6(+/+) bone marrow cells. Our results demonstrate that JAK3/STAT6 has an important role in bone marrow-derived fibroblast activation, extracellular matrix production, and interstitial fibrosis development.

  13. Formation of pancreatic duct epithelium from bone marrow during neonatal development.

    PubMed

    Wang, Xiuli; Ge, Shundi; Gonzalez, Ignacio; McNamara, George; Rountree, C Barth; Xi, Kenny Kezhe; Huang, Grace; Bhushan, Anil; Crooks, Gay M

    2006-02-01

    Recent reports suggest that bone marrow-derived cells engraft and differentiate into pancreatic tissue at very low frequency after pancreatic injury. All such studies have used adult recipients. The aim of our studies was to investigate the potential of bone marrow to contribute to the exocrine and endocrine components of the pancreas during the normal rapid growth of the organ that occurs during the neonatal period. Five to ten million bone marrow cells from adult, male, transgenic, green fluorescent protein (GFP) mice were injected into neonatal nonobese diabetic/severely compromised immunodeficient/beta2microglobulin-null mice 24 hours after birth. Two months after bone marrow transplantation, pancreas tissue was analyzed with fluorescence immunohistochemistry and fluorescence in situ hybridization (FISH). Co-staining of GFP, with anticytokeratin antibody, and with FISH for the presence of donor Y chromosome indicated that up to 40% of ducts (median 4.6%) contained epithelial cells derived from donor bone marrow. In some of these donor-derived ducts, there were clusters of large and small ducts, all comprised of GFP+ epithelium, suggesting that whole branching structures were derived from donor bone marrow. In addition, rare cells that coexpressed GFP and insulin were found within islets. Unlike pancreatic damage models, no bone marrow-derived vascular endothelial cells were found. In contrast to the neonatal recipients, bone marrow transplanted into adult mice rarely generated ductal epithelium or islet cells (p<.05 difference between adult and neonate transplants). These findings demonstrate the existence in bone marrow of pluripotent stem cells or epithelial precursors that can migrate to the pancreas and differentiate into complex organ-specific structures during the neonatal period.

  14. Anticonvulsant activity of bone marrow cells in electroconvulsive seizures in mice

    PubMed Central

    2013-01-01

    Background Bone marrow is an accessible source of progenitor cells, which have been investigated as treatment for neurological diseases in a number of clinical trials. Here we evaluated the potential benefit of bone marrow cells in protecting against convulsive seizures induced by maximum electroconvulsive shock (MES), a widely used model for screening of anti-epileptic drugs. Behavioral and inflammatory responses were measured after MES induction in order to verify the effects promoted by transplantation of bone marrow cells. To assess the anticonvulsant effects of bone marrow cell transplantation, we measured the frequency and duration of tonic seizure, the mortality rate, the microglial expression and the blood levels of cytokine IL-1, IL-6, IL-10 and TNF-α after MES induction. We hypothesized that these behavioral and inflammatory responses to a strong stimulus such as a convulsive seizure could be modified by the transplantation of bone marrow cells. Results Bone marrow transplanted cells altered the convulsive threshold and showed anticonvulsant effect by protecting from tonic seizures. Bone marrow cells modified the microglial expression in the analyzed brain areas, increased the IL-10 and attenuate IL-6 levels. Conclusions Bone marrow cells exert protective effects by blocking the course of electroconvulsive seizures. Additionally, electroconvulsive seizures induced acute inflammatory responses by altering the pattern of microglia expression, as well as in IL-6 and IL-10 levels. Our findings also indicated that the anticonvulsant effects of these cells can be tested with the MES model following the same paradigm used for drug testing in pharmacological screening. Studies on the inflammatory reaction in response to acute seizures in the presence of transplanted bone marrow cells might open a wide range of discussions on the mechanisms relevant to the pathophysiology of epilepsies. PMID:24011127

  15. Treatment with a sclerostin antibody increases cancellous bone formation and bone mass regardless of marrow composition in adult female rats.

    PubMed

    Tian, XiaoYan; Setterberg, Rebecca B; Li, Xiaodong; Paszty, Chris; Ke, Hua Zhu; Jee, Webster S S

    2010-09-01

    The current report describes the skeletal effects of a sclerostin monoclonal antibody (Scl-AbIII) treatment at a yellow (fatty) marrow skeletal site in adult female rats. Ten-month-old female Sprague-Dawley rats were treated with vehicle or Scl-AbIII at 5 or 25 mg/kg, twice per week by s.c. injection for 4 weeks. Trabecular bone from a yellow (fatty) marrow site, the 5th caudal vertebral body (CVB), was processed undecalcified for quantitative bone histomorphometric analysis. Compared to vehicle controls, Scl-AbIII at both doses significantly increased bone formation parameters and trabecular bone volume and thickness and decreased bone resorption parameter in the trabecular bone of the CVB. As a reference, we also found that the Scl-AbIII at both doses significantly decreased bone resorption and increased bone formation and bone volume in a red (hematopoietic) marrow site, the 4th lumber vertebral body (LVB). It appears that the percentage of increase in trabecular bone volume induced by Scl-AbIII treatment was slightly larger in the LVB than in the CVB. In summary, these preclinical findings show that antibody-mediated sclerostin inhibition has significant bone anabolic effects at both red and yellow marrow skeletal sites.

  16. Rectal Cancer With Disseminated Carcinomatosis of the Bone Marrow: Report of a Case

    PubMed Central

    Nakashima, Yuichiro; Takeishi, Kazuki; Guntani, Atsushi; Tsujita, Eiji; Yoshinaga, Keiji; Matsuyama, Ayumi; Hamatake, Motoharu; Maeda, Takashi; Tsutsui, Shinichi; Matsuda, Hiroyuki; Fujihara, Megumu; Ishida, Teruyoshi

    2014-01-01

    We report a rare case of disseminated carcinomatosis of the bone marrow from rectal cancer with disseminated intravascular coagulation (DIC). A 65-year-old man was admitted with melena and low back pain at rest. X-ray examination showed rectal cancer with multiple bone metastases. Laboratory examination showed severe anemia and DIC. Histologic examination showed disseminated carcinomatosis of the bone marrow. The DIC was considered to be caused by disseminated carcinomatosis of the bone marrow from rectal cancer, and we immediately started treatment with anti-DIC therapy and anticancer chemotherapy with the modified FOLFOX6 regimen (mFOLFOX6). After some response to therapy, the patient's general condition deteriorated, and he died 128 days after admission. This is the first English report showing disseminated carcinomatosis of the bone marrow from colorectal cancer treated with mFOLFOX6. PMID:25216414

  17. Effect of autologous bone marrow-derived cells associated with guided bone regeneration or not in the treatment of peri-implant defects.

    PubMed

    Ribeiro, F V; Suaid, F F; Ruiz, K G S; Rodrigues, T L; Carvalho, M D; Nociti, F H; Sallum, E A; Casati, M Z

    2012-01-01

    This study investigated the effect of bone marrow-derived cells associated with guided bone regeneration in the treatment of dehiscence bone defects around dental implants. Iliac-derived bone marrow cells were harvested from dogs and phenotypically characterized with regard to their osteogenic properties. After teeth extraction, three implant sites were drilled, dehiscences created and implants placed. Dehiscences were randomly assigned to: bone marrow-derived cells, bone marrow-derived cells+guided bone regeneration, and control (no treatment). After 3 months, implants with adjacent tissues were processed histologically, bone-to-implant contact, bone fill within the threads, new bone area in a zone lateral to the implant, new bone height, and new bone weight at the bottom of the defect were determined. Phenotypic characterization demonstrated that bone marrow-derived cells presented osteogenic potential. Statistically higher bone fill within the threads was observed in both bone marrow-derived cells+guided bone regeneration bone marrow-derived cell groups compared with the control group (P<0.05), with no difference between the groups treated with cells (P>0.05). For the other parameters (new bone area, bone-to-implant contact, new bone height and new bone weight), only the bone marrow-derived cells+guided bone regeneration group presented higher values compared with the non-treated control (P<0.05). Bone marrow-derived cells provided promising results for peri-implantar bone regeneration, although the combined approach seems to be relevant, especially to bone formation out of the implant threads.

  18. Asiatic acid inhibits adipogenic differentiation of bone marrow stromal cells.

    PubMed

    Li, Zheng-Wei; Piao, Cheng-dong; Sun, Hong-hui; Ren, Xian-Sheng; Bai, Yun-Shen

    2014-03-01

    Bone marrow mesenchymal stromal cells (BMSCs) are the common precursors for both osteoblasts and adipocytes. With aging, BMSC osteoblast differentiation decreases whereas BMSC differentiation into adipocytes increases, resulting in increased adipogenesis and bone loss. In the present study, we investigated the effect of asiatic acid (AA) on adipocytic differentiation of BMSCs. AA inhibited the adipogenic induction of lipid accumulation, activity of glycerol-3-phosphate dehydrogenase, and expression of marker genes in adipogenesis: peroxisome proliferation-activated receptor (PPAR)γ, adipocyte fatty acid-binding protein (ap) 2, and adipsin. Further, we found that AA did not alter clonal expansion rate and expression of C/EBPβ, upstream key regulator of PPARγ, and binding activity of C/EBPβ to PPARγ promoter was not affected by AA as well. These findings suggest that AA may modulate differentiation of BMSCs to cause a lineage shift away from the adipocytes, and inhibition of PPARγ by AA is through C/EBPβ-independent mechanisms. Thus, AA could be a potential candidate for a novel drug against osteoporosis.

  19. Repair of segmental bone defects with bone marrow and BMP-2 adenovirus in the rabbit radius

    NASA Astrophysics Data System (ADS)

    Cheng, Lijia; Lu, Xiaofeng; Shi, Yujun; Li, Li; Xue, Jing; Zhang, Li; Xia, Jie; Wang, Yujia; Zhang, Xingdong; Bu, Hong

    2012-12-01

    Bone tissue engineering (BTE) is approached via implantation of autogenous mesenchymal stem cells (MSCs), marrow cells, or platelet-rich plasma, etc. To the contrary, gene therapy combining with the bone marrow (BM) has not been often reported. This study was performed to investigate whether a modified BTE method, that is, the BM and a recombinant human bone morphogenetic protein-2 adenovirus (Ad.hBMP-2) gene administering in hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) ceramics could accelerate the healing of segmental defects in the rabbit radius. In our study, ceramics were immersed in the adenovirus overnight, and half an hour before surgery, autologous BM aspirates were thoroughly mixed with the ceramics; at the same time, a 15-mm radius defect was introduced in the bilateral forelimbs of all animals, after that, this defect was filled with the following: (1) Ad.hBMP-2 + HA/β-TCP + autologous BM (group 1); (2) HA/β-TCP + Ad.hBMP-2 (group 2); (3) HA/β-TCP alone (group 3); (4) an empty defect as a control (group 4). Histological observation and μ-CT analyses were performed on the specimens at weeks 2, 4, 8, and 12, respectively. In group 1, new bone was observed at week 4 and BM appeared at week 12, in groups 2 and 3, new bone was observed at week 8 and it was more mature at week 12, in contrast, the defect was not bridged in group 4 at week 12. The new bone area percentage in group 1 was significantly higher than that in groups 2 and 3. Our study indicated that BM combined with hBMP-2 adenovirus and porous ceramics could significantly increase the amount of newly formed bone. And this modified BTE method thus might have potentials in future clinical application.

  20. Bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in five painted storks.

    PubMed

    Weber, Martha A; Terrell, Scott P; Neiffer, Donald L; Miller, Michele A; Mangold, Barbara J

    2002-08-01

    Five painted storks were treated with fenbendazole for 5 days for internal parasitism. Four birds died following treatment. Profound heteropenia was a consistent finding in all samples evaluated; additionally, the 1 surviving bird had progressive anemia. Consistent necropsy findings in the 4 birds that died were small intestinal crypt cell necrosis and severe bone marrow depletion and necrosis. Fenbendazole has been associated with bone marrow hypoplasia and enteric damage in mammals and other species of birds. The dosages of fenbendazole used in birds are often substantially higher than those recommended for mammals, which may contribute to bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in birds.

  1. Stress responses after pediatric bone marrow transplantation: preliminary results of a prospective longitudinal study.

    PubMed

    Stuber, M L; Nader, K; Yasuda, P; Pynoos, R S; Cohen, S

    1991-11-01

    This paper reports the preliminary findings of a longitudinal prospective study of young children undergoing bone marrow transplantation. Symptoms of post-traumatic stress were seen in these children up to 12 months after transplant. The bone marrow transplantation survivors demonstrated more denial and avoidance and fewer arousal symptoms than has been noted in children traumatized by a violent life threat, such as a sniper attack. These data suggest the use of post-traumatic stress as a model in understanding some of the symptoms of pediatric bone marrow transplantation survivors and may be applicable to other children exposed to the double life threat of serious illness and intensive medical intervention.

  2. Bone marrow origin of Ia-positive cells in the medulla rat thymus

    SciTech Connect

    Barclay, A.N.; Mayrhofer, G.

    1981-06-01

    Irradiated rats were reconstituted with bone marrow from F1 hybrids. Ia antigen of donor-bone marrow origin was detected by an immunoperoxidase technique on cryostat sections and found predominantly in the medulla of rat thymus 2 wk after reconstitution. These Ia-bearing cells increased in number with time after reconstitution, but the Ia on the cortical epithelial cells remained of host origin. The nature of the bone marrow-derived cells and their implication for major histocompatibility complex restriction are discussed.

  3. Antitumor immunomodulatory activity of allogenic bone marrow cells on TiNi scaffold

    NASA Astrophysics Data System (ADS)

    Kokorev, O. V.; Hodorenko, V. N.; Cherdyntseva, N. V.; Gunther, V. E.

    2016-08-01

    The present study was undertaken to evaluate the feasibility of modulation of anti-tumor response by allogenic bone marrow cell transplantation into porous TiNi-based scaffold. Transplantation of bone marrow cells into porous TiNi-based scaffold leads to antitumor (35%) and antimetastatic (55%) effects. The lifetime of tumor-bearing animals and implanted allogenic bone marrow cells in incubator of TiNi increases up to 60%. The possible mechanisms of the effect of allogenic cells on tumor process are the stimulation of endogenous effectors of antitumor immunity.

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

    NASA Astrophysics Data System (ADS)

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

    2012-11-01

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

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

    PubMed

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

    2016-10-01

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

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

    PubMed Central

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

    2016-01-01

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

  7. A potential reference point for assessment of condylar bone marrow of the temporomandibular joint on proton density weighted images.

    PubMed

    Yamamoto, Aya; Sano, Tsukasa; Otonari-Yamamoto, Mika; Nishikawa, Keiichi; Kwok, Edmund

    2008-10-01

    The purpose of this research was to determine a potential reference point for measurement of signal intensity of bone marrow of the condyle on proton density-weighted images (PDW) prior to analysis of bone marrow abnormality related to symptomatic osteoarthritis of the temporomandibular joint (TMJ). The study was based on 79 joints in 41 patients. The regions of interest (ROI) were placed over the bone marrow of the condyle and four other structures, It was hypothesized that a correlation between signal intensity of ROI over bone marrow and that of another structure would provide a potential reference point4or measurement of signal intensity of bone marrow. A significant positive linear correlation was found in the group for gray matter-1 and bone marrow. The correlation coefficient was 0.3 (Pearson correlation coefficient; p < 0.05). It was determined that gray matter is a potential reference point in evaluating the signal intensity of bone marrow in the mandibular condyle.

  8. Combined autologous bone marrow mononuclear cell and gene therapy as the last resort for patients with critical limb ischemia

    PubMed Central

    Skóra, Jan; Pupka, Artur; Janczak, Dariusz; Barć, Piotr; Dawiskiba, Tomasz; Korta, Krzysztof; Baczyńska, Dagmara; Garcarek, Jerzy

    2014-01-01

    Introduction Our study was designed to investigate the safety and efficacy of combined autologous bone marrow mononuclear cell (MNC) and gene therapy in comparison to conventional drug therapy in patients with critical limb ischemia (CLI). Material and methods Thirty-two patients with CLI persisting for 12–48 months (average time 27.5 months) were randomized into 2 groups, each group consisting of 16 patients. In the first group, administration of autologous bone marrow MNC and vascular endothelial growth factor (VEGF) plasmid was performed. The patients from the second group were treated pharmacologically with pentoxifylline. Ankle-brachial index (ABI) was measured and angiography was performed before and finally 3 months after treatment. The pain was evaluated using the Visual Analog Scale (VAS) before and after 3 months. Results Ankle-brachial index improved significantly from 0.29 ±0.21 to 0.52 ±0.23 (p < 0.001) in 12 patients (75.0%) 3 months after the experimental therapy in group 1. In this group angiography showed the development of collateral vessels. Ischemic ulcers healed completely in 11 patients (68.75%). In group 2 the ABI did not improve in any patient; moreover the complete healing of skin ulcers was not found in any of the patients of this group. Amputation was performed in 4 (25.0%) patients in group 1, and in 8 patients (50%) from group 2. Conclusions These data after 3-month follow-up indicate that intramuscular injection of MNC combined with gene therapy in patients with chronic CLI is safe, and a more feasible and effective method of treatment than the conventional therapy. However, both therapies are limited by the degree of microcirculation damage. PMID:25995748

  9. Strain energy density gradients in bone marrow predict osteoblast and osteoclast activity: a finite element study.

    PubMed

    Webster, Duncan; Schulte, Friederike A; Lambers, Floor M; Kuhn, Gisela; Müller, Ralph

    2015-03-18

    Huiskes et al. hypothesized that mechanical strains sensed by osteocytes residing in trabecular bone dictate the magnitude of load-induced bone formation. More recently, the mechanical environment in bone marrow has also been implicated in bone׳s response to mechanical stimulation. In this study, we hypothesize that trabecular load-induced bone formation can be predicted by mechanical signals derived from an integrative µFE model, incorporating a description of both the bone and marrow phase. Using the mouse tail loading model in combination with in vivo micro-computed tomography (µCT) we tracked load induced changes in the sixth caudal vertebrae of C57BL/6 mice to quantify the amount of newly mineralized and eroded bone volumes. To identify the mechanical signals responsible for adaptation, local morphometric changes were compared to micro-finite element (µFE) models of vertebrae prior to loading. The mechanical parameters calculated were strain energy density (SED) on trabeculae at bone forming and resorbing surfaces, SED in the marrow at the boundary between bone forming and resorbing surfaces, along with SED in the trabecular bone and marrow volumes. The gradients of each parameter were also calculated. Simple regression analysis showed mean SED gradients in the trabecular bone matrix to significantly correlate with newly mineralized and eroded bone volumes R(2)=0.57 and 0.41, respectively, p<0.001). Nevertheless, SED gradients in the marrow were shown to be the best predictor of osteoblastic and osteoclastic activity (R(2)=0.83 and 0.60, respectively, p<0.001). These data suggest that the mechanical environment of the bone marrow plays a significant role in determining osteoblast and osteoclast activity.

  10. Efficacy of aspiration and autogenous bone marrow injection in the treatment of simple bone cysts

    PubMed Central

    Abak, Alshahid A.; Bakarman, Khalid A.; Al-Jassir, Fawzi F.; Khoshhal, Khalid I.; Zamzami, Marwan M.

    2008-01-01

    Twenty eight patients with simple bone cyst that were treated by aspiration and percutaneous autogenous bone marrow injection were reviewed to evaluate the treatment outcome. There were 18 boys and ten girls. Their mean age was 10.9 ± 2.75 years. Single injection was performed for 16 patients; the rest had double or triple injections. There were no operative complications. The mean follow-up was 34.7 ± 6.87 months. The procedure succeeded in obtaining healing in 23 cysts (82%). Cysts with index of more than five and cortical thickness of less than 1 mm were significantly prone to pathological fractures and had significant poor results after treatment. Our results suggested that autogenous bone marrow injection is a safe and effective treatment method for simple bone cysts, but sometimes repeated injections are necessary. Cyst index and cortical thickness are good indicators for cyst aggressiveness and good predictors for treatment outcome. PMID:18622614

  11. Mice deficient in 11beta-hydroxysteroid dehydrogenase type 1 lack bone marrow adipocytes, but maintain normal bone formation.

    PubMed

    Justesen, Jeannette; Mosekilde, Lis; Holmes, Megan; Stenderup, Karin; Gasser, Jürg; Mullins, John J; Seckl, Jonathan R; Kassem, Moustapha

    2004-04-01

    Glucocorticoids (GCs) exert potent, but poorly characterized, effects on the skeleton. The cellular activity of GCs is regulated at a prereceptor level by 11beta-hydroxysteroid dehydrogenases (11betaHSDs). The type 1 isoform, which predominates in bone, functions as a reductase in intact cells and regenerates active cortisol (corticosterone) from circulating inert 11-keto forms. The aim of the present study was to investigate the role of this intracrine activation of GCs on normal bone physiology in vivo using mice deficient in 11betaHSD1 (HSD1(-/-)). The HSD1(-/-) mice exhibited no significant changes in cortical or trabecular bone mass compared with wild-type (Wt) mice. Aged HSD1(-/-) mice showed age-related bone loss similar to that observed in Wt mice. Histomorphometric analysis showed similar bone formation and bone resorption parameters in HSD1(-/-) and Wt mice. However, examination of bone marrow composition revealed a total absence of marrow adipocytes in HSD1(-/-) mice. Cells from Wt and HSD1(-/-) mice exhibited similar growth rates as well as similar levels of production of osteoblastic markers. The adipocyte-forming capacity of in vitro cultured bone marrow stromal cells and trabecular osteoblasts was similar in HSD1(-/-) and Wt mice. In conclusion, our results suggest that 11betaHSD1 amplification of intracellular GC actions in mice may be required for bone marrow adipocyte formation, but not for bone formation. The clinical relevance of this observation remains to be determined.

  12. Effects of OK-432 on murine bone marrow and the production of natural killer cells

    SciTech Connect

    Pollack, S.B.; Rosse, C.

    1985-01-01

    The streptococcal preparation, OK-432, which augments anti-tumor responses in humans and mice, has been shown to be a potent immunomodulator. Among its effects is a pronounced augmentation of natural killer (NK) activity. The hypothesis that OK-432 alters the rates of production and maturation of NK cells in the bone marrow was tested. Studies to determine the kinetic parameters of NK cell production in normal C57BL/6J mice using tritiated thymidine, /sup 3/H-TdR, as a DNA marker are described. We are now extending those studies to determine the effect of OK-432 on the bone marrow and on the production of NK cells in the marrow. Initial observations are reported which indicate that OK-432 has profound effects on the cellularity and mitotic activity of the bone marrow, and in particular, on cells with the characteristics of natural killer cells within the marrow. 17 refs., 3 figs., 4 tabs.

  13. Comparison of manual and automated cultures of bone marrow stromal cells for bone tissue engineering.

    PubMed

    Akiyama, Hirokazu; Kobayashi, Asako; Ichimura, Masaki; Tone, Hiroshi; Nakatani, Masaru; Inoue, Minoru; Tojo, Arinobu; Kagami, Hideaki

    2015-11-01

    The development of an automated cell culture system would allow stable and economical cell processing for wider clinical applications in the field of regenerative medicine. However, it is crucial to determine whether the cells obtained by automated culture are comparable to those generated by manual culture. In the present study, we focused on the primary culture process of bone marrow stromal cells (BMSCs) for bone tissue engineering and investigated the feasibility of its automation using a commercially available automated cell culture system in a clinical setting. A comparison of the harvested BMSCs from manual and automated cultures using clinically acceptable protocols showed no differences in cell yields, viabilities, surface marker expression profiles, and in vivo osteogenic abilities. Cells cultured with this system also did not show malignant transformation and the automated process was revealed to be safe in terms of microbial contamination. Taken together, the automated procedure described in this report provides an approach to clinical bone tissue engineering.

  14. Structure and function of bone marrow hemopoiesis: mechanisms of response to ionizing radiation exposure.

    PubMed

    Fliedner, T M; Graessle, D; Paulsen, C; Reimers, K

    2002-08-01

    It is the purpose of this presentation to review the unique structure and function of bone marrow anchored hematopoiesis in their significance for its response mechanisms to an exposure to ionizing radiation. The ultimate objective of bone marrow hematopoiesis is to maintain in the peripheral blood a constant level of the different blood cell types (erythrocytes, granulocytes, platelets, lymphocytes, etc.). All of them have their particular turnover kinetics (such as granulocytes 120 x 10(9)/d, erythrocytes 200 x 10(9)/d or thrombocytes 150 x 10(9)/d), are semi-autonomous in their steady state regulatory mechanisms and dependent on a life-long supply of mature cells from a stem cell pool with unlimited replicative and pluripotent differentiative potential. The present knowledge of hematopoietic cellular renewal is the result of years of basic experimental and clinical studies using radionuclides in various metabolic forms including (59)Fe, (32)P (DF (32)P), (51)Cr, (131)I, (60)Co, (3)H ((3)HTdR) and (14)C ((14)CTdR). To understand the physiology but in particular the radiation-pathophysiology, it is essential to recognize in detail the infrastructure of the bone marrow as a distinct unit. Indispensable for a life-long cell production is the capsule of the marrow - the bone cortex -, the arterial supply of blood connected to the sinusoidal microvascular architecture with its sinusoids contorti and recti as well as the central (cell collecting) sinusoids. It is further of importance to recognize the significance of nerval regulation of blood flow, characterized by myelinated and unmyelinated nerve fibers. The type of unique lining cells of the sinusoids is the prerequisite for the cell traffic between the hemopoietic parenchyma and the blood. This in turn cannot be achieved without an alternative opening and closing of the sinusoidal segments which - in turn - requires a rigid long capsule to assure an - in toto - constant volume of each bone marrow unit. If a bone

  15. Bone Marrow Transplantation for Recessive Dystrophic Epidermolysis Bullosa

    PubMed Central

    Wagner, John E.; Ishida-Yamamoto, Akemi; McGrath, John A.; Hordinsky, Maria; Keene, Douglas R.; Riddle, Megan J.; Osborn, Mark J.; Lund, Troy; Dolan, Michelle; Blazar, Bruce R.; Tolar, Jakub

    2010-01-01

    Background Recessive dystrophic epidermolysis bullosa is an incurable, often fatal mucocutaneous blistering disease caused by mutations in COL7A1, the gene encoding type VII collagen (C7). On the basis of preclinical data showing biochemical correction and prolonged survival in col7−/− mice, we hypothesized that allogeneic marrow contains stem cells capable of ameliorating the manifestations of recessive dystrophic epidermolysis bullosa in humans. Methods Between October 2007 and August 2009, we treated seven children who had recessive dystrophic epidermolysis bullosa with immunomyeloablative chemotherapy and allogeneic stem-cell transplantation. We assessed C7 expression by means of immunofluorescence staining and used transmission electron microscopy to visualize anchoring fibrils. We measured chimerism by means of competitive polymerase-chain-reaction assay, and documented blister formation and wound healing with the use of digital photography. Results One patient died of cardiomyopathy before transplantation. Of the remaining six patients, one had severe regimen-related cutaneous toxicity, with all having improved wound healing and a reduction in blister formation between 30 and 130 days after transplantation. We observed increased C7 deposition at the dermal–epidermal junction in five of the six recipients, albeit without normalization of anchoring fibrils. Five recipients were alive 130 to 799 days after transplantation; one died at 183 days as a consequence of graft rejection and infection. The six recipients had substantial proportions of donor cells in the skin, and none had detectable anti-C7 antibodies. Conclusions Increased C7 deposition and a sustained presence of donor cells were found in the skin of children with recessive dystrophic epidermolysis bullosa after allogeneic bone marrow transplantation. Further studies are needed to assess the long-term risks and benefits of such therapy in patients with this disorder. (Funded by the National

  16. Healing of segmental bone defects with granular porous hydroxyapatite augmented with recombinant human osteogenic protein-1 or autologous bone marrow.

    PubMed

    den Boer, Frank C; Wippermann, Burkhard W; Blokhuis, Taco J; Patka, Peter; Bakker, Fred C; Haarman, Henk J Th M

    2003-05-01

    Hydroxyapatite is a synthetic bone graft, which is used for the treatment of bone defects and nonunions. However, it is a rather inert material with no or little intrinsic osteoinductive activity. Recombinant human osteogenic protein-1 (rhOP-1) is a very potent biological agent, that enhances osteogenesis during bone repair. Bone marrow contains mesenchymal stem cells, which are capable of new bone formation. Biosynthetic bone grafts were created by the addition of rhOP-1 or bone marrow to granular porous hydroxyapatite. The performance of these grafts was tested in a sheep model and compared to the results of autograft, which is clinically the standard treatment of bone defects and nonunions. A 3 cm segmental bone defect was made in the tibia and fixed with an interlocking intramedullary nail. There were five treatment groups: no implant (n=6), autograft (n=8), hydroxyapatite alone (n=8), hydroxyapatite loaded with rhOP-1 (n=8), and hydroxyapatite loaded with autologous bone marrow (n=8). At 12 weeks, healing of the defect was evaluated with radiographs, a torsional test to failure, and histological examination of longitudinal sections through the defect. Torsional strength and stiffness of the healing tibiae were about two to three times higher for autograft and hydroxyapatite plus rhOP-1 or bone marrow compared to hydroxyapatite alone and empty defects. The mean values of both combination groups were comparable to those of autograft. There were more unions in defects with hydroxyapatite plus rhOP-1 than in defects with hydroxyapatite alone. Although the differences were not significant, histological examination revealed that there was more often bony bridging of the defect in both combination groups and the autograft group than in the group with hydroxyapatite alone. Healing of bone defects, treated with porous hydroxyapatite, can be enhanced by the addition of rhOP-1 or autologous bone marrow. The results of these composite biosynthetic grafts are equivalent to

  17. Comparison of methodologies in determining bone marrow fat percentage under different environmental conditions.

    PubMed

    Murden, David; Hunnam, Jaimie; De Groef, Bert; Rawlin, Grant; McCowan, Christina

    2017-01-01

    The use of bone marrow fat percentage has been recommended in assessing body condition at the time of death in wild and domestic ruminants, but few studies have looked at the effects of time and exposure on animal bone marrow. We investigated the utility of bone marrow fat extraction as a tool for establishing antemortem body condition in postmortem specimens from sheep and cattle, particularly after exposure to high heat, and compared different techniques of fat extraction for this purpose. Femora were collected from healthy and "skinny" sheep and cattle. The bones were either frozen or subjected to 40°C heat; heated bones were either wrapped in plastic to minimize desiccation or were left unwrapped. Marrow fat percentage was determined at different time intervals by oven-drying, or by solvent extraction using hexane in manual equipment or a Soxhlet apparatus. Extraction was performed, where possible, on both wet and dried tissue. Multiple samples were tested from each bone. Bone marrow fat analysis using a manual, hexane-based extraction technique was found to be a moderately sensitive method of assessing antemortem body condition of cattle up to 6 d after death. Multiple replicates should be analyzed where possible. Samples from "skinny" sheep showed a different response to heat from those of "healthy" sheep; "skinny" samples were so reduced in quantity by day 6 (the first sampling day) that no individual testing could be performed. Further work is required to understand the response of sheep marrow.

  18. Copper deficiency-related bone marrow changes secondary to long-term total parenteral nutrition.

    PubMed

    Oo, Thein Hlaing; Hu, Shimin

    2017-02-01

    Total parenteral nutrition can be complicated by the marrow sea-blue histiocytes as well as copper deficiency-related bone marrow changes. Cytoplasmic vacuoles in the erythroid and myeloid precursors raise the possibility of copper deficiency anemia. If the diagnosis is delayed, the clinical course can be complicated by neurologic deficits.

  19. In vivo osteoinductive effect and in vitro isolation and cultivation bone marrow mesenchymal stem cells.

    PubMed

    Redzić, Amira; Smajilagić, Amer; Aljicević, Mufida; Berberović, Ljubomir

    2010-12-01

    Bone marrow contains cell type termed mesenchymal stem cells (MSC), first recognized in bone marrow by a German pathologist, Julius Cohnheim in 1867. That MSCs have potential to differentiate in vitro in to the various cells lines as osteoblast, chondroblast, myoblast and adipoblast cells lines. Aims of our study were to show in vivo capacity of bone marrow MSC to produce bone in surgically created non critical size mandible defects New Zeland Rabbits, and then in second part of study to isolate in vitro MSC from bone marrow, as potential cell transplantation model in bone regeneration. In vivo study showed new bone detected on 3D CT reconstruction day 30, on all 3 animals non critical size defects, treated with bone marrow MSC exposed to the human Bone Morphogenetic Protein 7 (rhBMP-7). Average values of bone mineral density (BMD), was 530 mg/cm3, on MSC treated animals, and 553 mg/cm3 on control group of 3 animals where non critical size defects were treated with iliac crest autologue bone graft. Activity of the Alkaline Phosphatase enzyme were measurement on 0.5, 14, 21, 30 day and increased activity were detected day 14 on animals treated with bone marrow MSCs compared with day 30 on iliac crest treated animals. That results indicates strong osteoinduction activity of the experimental bone marrow MSCs models exposed to the rhBMP-7 factor Comparing ALP activity, that model showed superiorly results than control group. That result initiates us in opinion that MSCs alone should be alternative for the autolologue bone transplantation and in vitro study we isolated singles MSCs from the bone marrow of rat's tibia and femora and cultivated according to the method of Maniatopoulos et all. The small initial colonies of fibroblast like cells were photo-documented after 2 days of primary culture. Such isolated and cultivated MSCs in future studies will be exposed to the growth factors to differentiate in osteoblast and indicate their clinically potential as alternative

  20. Sideroblastic changes of the bone marrow can be predicted by the erythrogram of peripheral blood

    PubMed Central

    ROVÓ, A; STÜSSI, G; MEYER-MONARD, S; FAVRE, G; TSAKIRIS, D; HEIM, D; HALTER, J; ARBER, C; PASSWEG, J; GRATWOHL, A; TICHELLI, A

    2010-01-01

    The diagnosis of sideroblastic anemia is based on bone marrow aspiration, and the detection of ring sideroblasts (RS) in iron staining. The finding of laboratory parameters to approach this diagnosis still remains a great challenge. In this study, we analyzed the value of a specific erythrogram pattern from peripheral blood, produced by the ADVIA®120 cell counter, to predict sideroblastic changes in the bone marrow. In a two step-design study, we first showed that 32/38 consecutive patients reporting ≥15% RS had such a pattern in the erythrogram. In the second step, we prospectively identified over a period of 32 months 21 patients with this typical erythrogram; 20/21 had ≥15% RS in the bone marrow. Hence, by this validation, we confirm that the erythrogram is highly predictive of RS in the bone marrow. The interpretation of the erythrogram should become daily practice in hematology to improve the efficacy to detect sideroblastic changes. PMID:19706066

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

    PubMed

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

    2009-06-01

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

  2. Bone-marrow imaging with indium-111 chloride in aplastic anemia and myelofibrosis: concise communication

    SciTech Connect

    Sayle, B.A.; Helmer, R.E.; Birdsong, B.A.; Balachandran, S.; Gardner, F.H.

    1982-02-01

    Twenty-nine patients with aplastic anemia and 11 patients with myelofibrosis were evaluated with indium-111 chloride bone-marrow imaging, ferrokinetics, and bone-marrow core biopsies. There was good correlation between the erythrocyte cellularity of the marrow and the In-111 bone-marrow scan grades in most patients. In some, the overall scan grade tended to underestimate the erythroid elements because the core biopsy had been taken from the area of the greatest radionuclide concentration on the scan. In patients with aplastic anemia, there was good correlation between the plasma iron clearance t1/2 and the scan grade. Less agreement was found in the comparison between the Fe-59 sacral and organ counts and the red-cell iron utilization. In patients with myelofibrosis, there was poor correlation between the surface counts over the sacrum and the red-cell iron utilization. Plasma iron clearances were abnormally short and were unrelated to the transferrin saturation levels. Eighteen patients were studied several times to evaluate their responses to steroid therapy. In all, there was good correlation between the bone-marrow imaging, the erythrocyte cellularity, ferrokinetics, and the patient's response to therapy. Indium-111 bone-marrow imaging is useful both in evaluating marrow erythroid activity and in following the response to therapy in patients with these diseases.

  3. Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration.

    PubMed

    Park, Dongsu; Spencer, Joel A; Koh, Bong Ihn; Kobayashi, Tatsuya; Fujisaki, Joji; Clemens, Thomas L; Lin, Charles P; Kronenberg, Henry M; Scadden, David T

    2012-03-02

    Mesenchymal stem cells (MSCs) commonly defined by in vitro functions have entered clinical application despite little definition of their function in residence. Here, we report genetic pulse-chase experiments that define osteoblastic cells as short-lived and nonreplicative, requiring replenishment from bone-marrow-derived, Mx1(+) stromal cells with "MSC" features. These cells respond to tissue stress and migrate to sites of injury, supplying new osteoblasts during fracture healing. Single cell transplantation yielded progeny that both preserve progenitor function and differentiate into osteoblasts, producing new bone. They are capable of local and systemic translocation and serial transplantation. While these cells meet current definitions of MSCs in vitro, they are osteolineage restricted in vivo in growing and adult animals. Therefore, bone-marrow-derived MSCs may be a heterogeneous population with the Mx1(+) population, representing a highly dynamic and stress responsive stem/progenitor cell population of fate-restricted potential that feeds the high cell replacement demands of the adult skeleton.

  4. Overcoming Bone Marrow Stroma-Mediated Chemoresistance in Metastatic Breast Cancer Cells

    DTIC Science & Technology

    2004-08-01

    AD Award Number: DAMD17-03- 1 -0524 .TITLE: Overcoming Bone Marrow Stroma- Mediated Chemoresistance in Metastatic Breast Cancer Cells PRINCIPAL...SUBTITLE 5. FUNDING NUMBERS Overcoming Bone Marrow Stroma- Mediated Chemoresistance in DAMD17-03- 1 -0524 Metastatic Breast Cancer Cells 6. AUTHOR(S) Robert...the compound (Figure 1 ). The inhibitor was slightly more effective in T-47D cells than in MCF-7 cells, but did not eradicate dormant clones much past

  5. Serum lipoproteins during bone marrow hyperplasia after phenylhydrazine administration in rats.

    PubMed Central

    Dessì, S.; Batetta, B.; Spano, O.; Pulisci, D.; Anchisi, C.; Pani, P.; Broccia, G.

    1990-01-01

    In the present study, lipoprotein metabolism was investigated during compensatory hyperplasia of bone marrow after haemolysis induced by phenylhydrazine (20 mg/kg b.w.) administration in rats. The rats were sacrificed at different time intervals (0, 1, 2 and 5 days) after phenylhydrazine treatment. Analysis of the different fractions of lipoproteins has shown that during bone marrow hyperplasia there is an alteration of lipoprotein profiles, mainly due to a decrease of HDL2 and HDL3 subfractions. PMID:2206988

  6. Inhibition of human lysosomal elastase by the cartilage bone marrow extract Rumalon.

    PubMed

    Baici, A; Salgam, P; Fehr, K; Böni, A

    1981-01-01

    Human lysosomal elastase from polymorphonuclear leucocytes is inhibited by the cartilage bone marrow extract Rumalon. Separately, both the cartilage and the bone marrow extracts are able to inhibit the enzymatic activity by 73%, under saturating conditions. The mixture of the two extracts inhibits elastase by 93%. It is suggested that the two partners act as a cumulative inhibition mechanism and this phenomenon is emphasized in a general theoretical model for synergy of proteinase-directed inhibitors.

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

    PubMed Central

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

    2009-01-01

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

  8. Bone marrow fibrosis with fibrocytic and immunoregulatory responses induced by β-catenin activation in osteoprogenitors.

    PubMed

    Yu, Jian; Cao, Jingjing; Li, Hanjun; Liu, Pei; Xu, Shuqin; Zhou, Rujiang; Yao, Zhengju; Guo, Xizhi

    2016-03-01

    Wnt/β-catenin signaling has been reported to contribute to the development of bone fibrous dysplasia. However, it remains unclear whether fibrocytes and immune cells are involved in this β-catenin-mediated bone marrow fibrosis. In this study, we showed that constitutive activation of β-catenin by Col1a1-Cre (3.6-kb) exhibited bone marrow fibrosis, featured with expanded populations of fibrocytes, myofibroblasts and osteoprogenitors. Lineage tracing and IHC examinations showed that Col3.6-Cre display Cre recombinase activity not only in osteoprogenitors, but also in monocyte-derived fibrocytes in the endosteal niches of bones. Additionally, β-catenin stimulated the secretion of cytokines and pro-fibrotic signals in bone marrow, including GM-CSF, TGFβ1 and VEGF. Consequently, the frequency of differentiated immature monocyte-derived dendritic cells and naïve T cells was markedly increased in the mutant bone marrow. These phenotypes were quite different from those following β-catenin activation in mature osteoblasts driven by Col1a1-Cre (2.3-kb). Our findings suggested that a conserved pro-fibrotic signal cascade might underlie β-catenin-mediated bone marrow fibrosis, involving TGFβ1-enhanced fibrocyte activation and immunoregulatory responses. This study might shed new light on the understanding and development of a therapeutic strategy for bone fibrous dysplasia.

  9. Bone marrow fat is increased in chronic kidney disease by magnetic resonance spectroscopy

    PubMed Central

    Fadel, W.; Eckert, G. J.; Ponsler-Sipes, K.; Moe, S. M.; Lin, C.

    2015-01-01

    Summary In aging, the bone marrow fills with fat and this may lead to higher fracture risk. We show that a bone marrow fat measurement by magnetic resonance spectroscopy (MRS), a newer technique not previously studied in chronic kidney disease (CKD), is useful and reproducible. CKD patients have significantly higher bone marrow fat than healthy adults. Introduction Renal osteodystrophy leads to increased morbidity and mortality in patients with CKD. Traditional bone biopsy histomorphometry is used to study abnormalities in CKD, but the bone marrow, the source of osteoblasts, has not been well characterized in patients with CKD. Methods To determine the repeatability of bone marrow fat fraction assessment by MRS and water-fat imaging (WFI) at four sites in patients with CKD, testing was performed to determine the coefficients of reproducibility and intraclass coefficients (ICCs). We further determined if this noninvasive technique could be used to determine if there are differences in the percent bone marrow fat in patients with CKD compared to matched controls using paired t tests. Results The mean age of subjects with CKD was 59.8±7.2 years, and the mean eGFR was 24±8 ml/min. MRS showed good reproducibility at all sites in subjects with CKD and controls, with a coefficient of reproducibilities ranging from 2.4 to 13 %. MRS and WFI assessment of bone marrow fat showed moderate to strong agreement (ICC 0.6–0.7) at the lumbar spine, with poorer agreement at the iliac crest and no agreement at the tibia. The mean percent bone marrow fat at L2–L4 was 13.8 % (95 % CI 8.3–19.7) higher in CKD versus controls (p<0.05). Conclusions MRS is a useful and reproducible technique to study bone marrow fat in CKD. Patients with CKD have significantly higher bone marrow fat than healthy adults; the relationship with bone changes requires further analyses. PMID:25701052

  10. The influence of Sm-153 therapy on bone marrow function

    PubMed Central

    Małkowski, Bogdan; Dudek, Anna; Wędrowski, Mateusz; Szefer, Jarosław

    2016-01-01

    Aim of the study Studies about possible risks connected with β-emitterradiotherapy concentrate mainly on potential myelotoxicity. Results of previously published analysis based on white blood cells (WBC) and platelet (PLT) counts – before and after radionuclide treatment – are quite varied. The aim of our study was to present the greatest possible impact of Samarium-153 on bone marrow function in clinical practice. Material and methods The study included the blood test results of 175 patients with bone metastases treated with Sm-153 in the years 2012–2014. We compared levels of WBC, PLT, red blood cells (RBC), and haemoglobin (HGB) from two blood tests – one performed directly before the therapy and the other 2–6 weeks after isotope injection. Results and conclusions The study showed decreased mean level of WBC in a control test performed after therapy in comparison to output results at about 27.1%. In our study 1.1% of patients developed the third-grade toxicity in CTCAE (Common Terminology Criteria for Adverse Events). Mean decrease of PLT was about 18%. Three patients (1.7% of all) result qualified as third-grade toxicity in a control test, one as fourth-grade. Analysis of RBC level showed 5.7% reduction of output values. The same calculation was seen for HGB – 5.1%. The greatest but acceptable decrease in haematological parameters was observed in WBC and PLT. Analysis of changes in WBC and PLT level showed them to be similar or smaller than was proven in previously published studies. PMID:28373820

  11. Different radiosensitivities of mast-cell precursors in the bone marrow and skin of mice

    SciTech Connect

    Kitamura, Y.; Yokoyama, M.; Sonoda, T.; Mori, K.J.

    1983-01-01

    Although tissue mast cells are derived from the bone marrow, some descendants of bone marrow-derived precursors retain the ability to proliferate and differentiate into mast cells even after localization in the skin. The purpose of the present study was to determine the D/sub 0/ values for mast-cell precursors in the bone marrow and those localized in the skin. Bone marrow cells were removed from (WB X C57BL/6)F/sub 1/+/+ mice after various doses of irradiation and injected into the skin of the congenic W/W/sup v/ mice which were genetically without mast cells. Radiosensitivity of mast-cell precursors in the bone marrow was evaluated by determining the proportion of the injection sites at which mast cells did not appear. For the assay of the radiosensitivity of mast-cell precursors localized in the skin, pieces of skin were removed from beige C57BL/6 (bg/sup J//bg/sup J/, Chediak-Higashi syndrome) mice after various doses of irradiation and grafted onto the backs of the normal C57BL/6 mice. Radiosensitivity of mast-cell precursors in the skin was evaluated by determining the decrease of beige-type mast cells which possessed giant granules. Mast-cell precursors in the bone marrow were much more radiosenitive than those localized in the skin. D/sup 0/ value was about 100 rad for the former and about 800 rad for the latter.

  12. Different radiosensitivities of mast-cell precursors in the bone marrow and skin of mice

    SciTech Connect

    Kitamura, Y.; Yokoyama, M.; Sonoda, T.; Mori, K.J.

    1983-01-01

    Although tissue mast cells are derived from the bone marrow, some descendants of bone marrow-derived precursors retain the ability to proliferate and differentiate into mast cells even after localization in the skin. The purpose of the present study was to determine the D0 values for mast-cell precursors in the bone marrow and those localized in the skin. Bone marrow cells were removed from (WB X C57BL/6)F1-+/+ mice after various doses of irradiation and injected into the skin of the congenic W/Wv mice which were genetically without mast cells. Radiosensitivity of mast-cell precursors in the bone marrow was evaluated by determining the proportion of the injection sites at which mast cells did not appear. For the assay of the radiosensitivity of mast-cell precursors localized in the skin, pieces of skin were removed from beige C57BL/6 (bgJ/bgJ. Chediak-Higashi syndrome) mice after various doses of irradiation and grafted onto the back of the normal C57BL/6 mice. Radiosensitivity of mast-cell precursors in the skin was evaluated by determining the decrease of beige-type mast cells which possessed giant granules. Mast-cell precursors in the bone marrow were much more radiosensitive than those localized in the skin. D0 value was about 100 rad for the former and about 800 rad for the latter.

  13. Morphological changes in the bone marrow of the dogs with visceral leishmaniasis.

    PubMed

    Momo, Claudia; Jacintho, Ana Paula Prudente; Moreira, Pamela Rodrigues Reina; Munari, Danísio Prado; Machado, Gisele Fabrino; Vasconcelos, Rosemeri de Oliveira

    2014-01-01

    The aim of this study was to evaluate the most frequent lesions in the bone marrow of dogs naturally infected by Leishmania (Leishmania) chagasi. Thirty-three dogs sacrificed at the Zoonosis Control Center of Araçatuba, a municipality endemic for visceral leishmaniasis (VL), were used. The animals were classified as asymptomatic, oligosymptomatic, and symptomatic groups. At the necropsy, bone marrow samples were collected from the femur, fixed, processed, and stained with hematoxylin and eosin. The lesion intensity was classified as mild, moderate, or severe. The parasite load was determined using immunohistochemistry. The most important lesions consisted of multifocal to diffuse granulomas, megakaryocytic dysplasia, and medullary aplasia. There were no statistical differences between the three clinical groups regarding parasite load and lesion intensity. Asymptomatic dogs also presented high parasitism in the bone marrow as dogs with clinical signs of VL. It was concluded that, regardless of clinical group, the bone marrow is a site for multiplication of Leishmania chagasi. Possibly, the bone marrow dysplasia may arise from the presence of many parasitized and activated macrophages in this organ. Consequently, it affects the profile of hematopoietic cells in the bone marrow and systemic circulation.

  14. Concise review: diabetes, the bone marrow niche, and impaired vascular regeneration.

    PubMed

    Fadini, Gian Paolo; Ferraro, Francesca; Quaini, Federico; Asahara, Takayuki; Madeddu, Paolo

    2014-08-01

    Diabetes mellitus is a global health problem that results in multiorgan complications leading to high morbidity and mortality. Until recently, the effects of diabetes and hyperglycemia on the bone marrow microenvironment-a site where multiple organ systems converge and communicate-have been underappreciated. However, several new studies in mice, rats, and humans reveal that diabetes leads to multiple bone marrow microenvironmental defects, such as small vessel disease (microangiopathy), nerve terminal pauperization (neuropathy), and impaired stem cell mobilization (mobilopathy). The discovery that diabetes involves bone marrow-derived progenitors implicated in maintaining cardiovascular homeostasis has been proposed as a bridging mechanism between micro- and macroangiopathy in distant organs. Herein, we review the physiological and molecular bone marrow abnormalities associated with diabetes and discuss how bone marrow dysfunction represents a potential root for the development of the multiorgan failure characteristic of advanced diabetes. The notion of diabetes as a bone marrow and stem cell disease opens new avenues for therapeutic interventions ultimately aimed at improving the outcome of diabetic patients.

  15. Role of neuropeptide Y in the bone marrow hematopoietic stem cell microenvironment.

    PubMed

    Park, Min Hee; Min, Woo-Kie; Jin, Hee Kyung; Bae, Jae-Sung

    2015-12-01

    The sympathetic nervous system (SNS) or neurotransmitters in the bone marrow microenvironment has been known to regulate hematopoietic stem cell (HSC) functions such as self-renewal, proliferation and differentiation. However, the specific role of neuropeptide Y (NPY) in this process remains relatively unexplored. In this study, we demonstrated that NPY deficient mice have significantly reduced HSC numbers and impaired bone marrow regeneration due to apoptotic destruction of SNS fibers and/or endothelial cells. Moreover, NPY treatment prevented bone marrow impairments in a mouse model of chemotherapy-induced SNS injury, while conditional knockout mice lacking the Y1 receptor in macrophages did not restore bone marrow dysfunction in spite of NPY injection. Transforming growth factor-beta (TGF-β) secreted by NPY-mediated Y1 receptor stimulation in macrophages plays a key role in neuroprotection and HSC survival in the bone marrow. Therefore, this study reveals a new role of NPY in bone marrow HSC microenvironment, and provides an insight into the therapeutic application of this neuropeptide.

  16. Morphological Changes in the Bone Marrow of the Dogs with Visceral Leishmaniasis

    PubMed Central

    Jacintho, Ana Paula Prudente; Moreira, Pamela Rodrigues Reina; Munari, Danísio Prado; Machado, Gisele Fabrino; Vasconcelos, Rosemeri de Oliveira

    2014-01-01

    The aim of this study was to evaluate the most frequent lesions in the bone marrow of dogs naturally infected by Leishmania (Leishmania) chagasi. Thirty-three dogs sacrificed at the Zoonosis Control Center of Araçatuba, a municipality endemic for visceral leishmaniasis (VL), were used. The animals were classified as asymptomatic, oligosymptomatic, and symptomatic groups. At the necropsy, bone marrow samples were collected from the femur, fixed, processed, and stained with hematoxylin and eosin. The lesion intensity was classified as mild, moderate, or severe. The parasite load was determined using immunohistochemistry. The most important lesions consisted of multifocal to diffuse granulomas, megakaryocytic dysplasia, and medullary aplasia. There were no statistical differences between the three clinical groups regarding parasite load and lesion intensity. Asymptomatic dogs also presented high parasitism in the bone marrow as dogs with clinical signs of VL. It was concluded that, regardless of clinical group, the bone marrow is a site for multiplication of Leishmania chagasi. Possibly, the bone marrow dysplasia may arise from the presence of many parasitized and activated macrophages in this organ. Consequently, it affects the profile of hematopoietic cells in the bone marrow and systemic circulation. PMID:24744957

  17. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation.

    PubMed

    Theise, N D; Badve, S; Saxena, R; Henegariu, O; Sell, S; Crawford, J M; Krause, D S

    2000-01-01

    Following a report of skeletal muscle regeneration from bone marrow cells, we investigated whether hepatocytes could also derive in vivo from bone marrow cells. A cohort of lethally irradiated B6D2F1 female mice received whole bone marrow transplants from age-matched male donors and were sacrificed at days 1, 3, 5, and 7 and months 2, 4, and 6 posttransplantation (n = 3 for each time point). Additionally, 2 archival female mice of the same strain who had previously been recipients of 200 male fluorescence-activated cell sorter (FACS)-sorted CD34(+)lin(-) cells were sacrificed 8 months posttransplantation under the same protocol. Fluorescence in situ hybridization (FISH) for the Y-chromosome was performed on liver tissue. Y-positive hepatocytes, up to 2.2% of total hepatocytes, were identified in 1 animal at 7 days posttransplantation and in all animals sacrificed 2 months or longer posttransplantation. Simultaneous FISH for the Y-chromosome and albumin messenger RNA (mRNA) confirmed male-derived cells were mature hepatocytes. These animals had received lethal doses of irradiation at the time of bone marrow transplantation, but this induced no overt, histologically demonstrable, acute hepatic injury, including inflammation, necrosis, oval cell proliferation, or scarring. We conclude that hepatocytes can derive from bone marrow cells after irradiation in the absence of severe acute injury. Also, the small subpopulation of CD34(+)lin(-) bone marrow cells is capable of such hepatic engraftment.

  18. Glycophorin A as a biological dosimeter for radiation dose to the bone marrow from iodine-131

    SciTech Connect

    Jensen, R.H.; Bigbee, W.L.; Grant, S.G.

    1997-06-01

    The frequency of peripheral blood erythrocyte variants exhibiting allelic loss of glycophorin A (N/M antigen) has been used previously as a biological dosimeter to assess somatic mutations in bone marrow cells from external whole-body irradiation. The aim of the present study was to determine whether this marker could be used as a measure of bone marrow genotoxicity induced by {sup 131}I in the treatment of thyroid cancer. Flow cytometry of immunolabeled erythrocytes was performed to enumerate glycophorin A variants before and after eight therapy doses of {sup 131}I administered to five patients with differentiated thyroid carcinoma. Bone marrow radiation exposure from each dose was calculated from the integrated retention of {sup 131}I in the whole body and in the blood. In addition, the accumulated dose to the bone marrow received from earlier {sup 131}I therapy was calculated for each patient. Regression analysis was performed on the frequency of two glycophorin A variant cell types (N/O and N/N) as a function of accumulated dose to the bone marrow. Frequency of N/O variant cells showed a significant dose-related increase with a slope of 10.9 x 10{sup -6} per sievert. This dose effect is about one-half that previously observed after whole-body external irradiation at high dose rate. This decreased response could be explained by the low dose rate of the radiation to the bone marrow from {sup 131}I. 24 refs., 2 figs., 2 tabs.

  19. Distribution of Lipid Formulations of Amphotericin B into Bone Marrow and Fat Tissue in Rabbits

    PubMed Central

    Groll, Andreas H.; Mickiene, Diana; Piscitelli, Stephen C.; Walsh, Thomas J.

    2000-01-01

    The distribution of the three currently available lipid formulations of amphotericin B (AmB) into bone marrow and fat tissue was evaluated in noninfected rabbits. Groups of four animals each received either 1 mg of AmB deoxycholate (D-AmB) per kg of body weight per day or 5 mg of AmB colloidal dispersion, AmB lipid complex, or liposomal AmB per kg per day for seven doses. Plasma, bone marrow, fat, and liver were collected at autopsy, and AmB concentrations were determined by high-performance liquid chromatography. At the investigated dosages of 5 mg/kg/day, all AmB lipid formulations achieved at least fourfold-higher concentrations in bone marrow than did standard D-AmB at a dosage of 1 mg/kg/day. Concentrations in bone marrow were 62 to 76% of concurrent AmB concentrations in the liver. In contrast, all AmB formulations accumulated comparatively poorly in fat tissue. The results of this study show that high concentrations of AmB can be achieved in the bone marrow after administration of lipid formulations, suggesting their particular usefulness against disseminated fungal infections involving the bone marrow and against visceral leishmaniasis. PMID:10639371

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

    PubMed

    Fujii, M; Ishikawa, M; Toki, H

    1984-03-01

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

  1. Noninvasive optical measurement of bone marrow lesions: a Monte Carlo study on visible human dataset

    NASA Astrophysics Data System (ADS)

    Su, Yu; Li, Ting

    2016-03-01

    Bone marrow is both the main hematopoietic and important immune organ. Bone marrow lesions (BMLs) may cause a series of severe complications and even myeloma. The traditional diagnosis of BMLs rely on mostly bone marrow biopsy/ puncture, and sometimes MRI, X-ray, and etc., which are either invasive and dangerous, or ionizing and costly. A diagnosis technology with advantages in noninvasive, safe, real-time continuous detection, and low cost is requested. Here we reported our preliminary exploration of feasibility verification of using near-infrared spectroscopy (NIRS) in clinical diagnosis of BMLs by Monte Carlo simulation study. We simulated and visualized the light propagation in the bone marrow quantitatively with a Monte Carlo simulation software for 3D voxelized media and Visible Chinese Human data set, which faithfully represents human anatomy. The results indicate that bone marrow actually has significant effects on light propagation. According to a sequence of simulation and data analysis, the optimal source-detector separation was suggested to be narrowed down to 2.8-3.2cm, at which separation the spatial sensitivity distribution of NIRS cover the most region of bone marrow with high signal-to-noise ratio. The display of the sources and detectors were optimized as well. This study investigated the light transport in spine addressing to the BMLs detection issue and reported the feasibility of NIRS detection of BMLs noninvasively in theory. The optimized probe design of the coming NIRS-based BMLs detector is also provided.

  2. [Therapeutic potential of bone marrow stem cells in cerebral infarction].

    PubMed

    Sánchez-Cruz, Gilberto; Milián-Rodríguez, Lismary

    2015-05-16

    Introduccion. Las celulas madre constituyen una alternativa terapeutica que se encuentra en fase de experimentacion para el infarto cerebral. Objetivo. Mostrar la evidencia cientifica existente sobre el potencial terapeutico de las celulas madre de la medula osea en esta enfermedad. Desarrollo. El infarto cerebral representa el 80% de las enfermedades cerebrovasculares. La trombolisis constituye la unica terapia aprobada, pero, por su estrecha ventana terapeutica, solo se aplica a un bajo porcentaje de los pacientes. De manera alternativa, los tratamientos neurorrestauradores, como el de celulas madre, pueden aplicarse en periodos mas prolongados. Por esta razon se efectuo una busqueda bibliografica en PubMed con el empleo de las palabras clave 'stem cells', 'bone marrow derived mononuclear cells' y 'stroke'. Se encontraron evidencias de seguridad y eficacia de dichas celulas en diferentes momentos evolutivos del infarto cerebral. Se identificaron estudios que en clinica y preclinica las recolectaron por puncion medular y en sangre periferica, y las trasplantaron directamente en el area infartada o por via intravascular. El efecto terapeutico se relaciona con sus propiedades de plasticidad celular y liberacion de factores troficos. Conclusiones. El concentrado de celulas mononucleares autologas, obtenido en sangre periferica o por puncion de la medula osea, y trasplantado por via intravenosa, es una factible opcion metodologica que permitira rapidamente incrementar el numero de ensayos clinicos en diferentes etapas evolutivas del infarto cerebral. Esta terapia muestra seguridad y eficacia; sin embargo, deben ampliarse las evidencias que avalen su generalizacion en humanos.

  3. Chemosensitizing AML cells by targeting bone marrow endothelial cells.

    PubMed

    Bosse, Raphael C; Wasserstrom, Briana; Meacham, Amy; Wise, Elizabeth; Drusbosky, Leylah; Walter, Glenn A; Chaplin, David J; Siemann, Dietmar W; Purich, Daniel L; Cogle, Christopher R

    2016-05-01

    Refractory disease is the greatest challenge in treating patients with acute myeloid leukemia (AML). Blood vessels may serve as sanctuary sites for AML. When AML cells were co-cultured with bone marrow endothelial cells (BMECs), a greater proportion of leukemia cells were in G0/G1. This led us to a strategy of targeting BMECs with tubulin-binding combretastatins, causing BMECs to lose their flat phenotype, degrade their cytoskeleton, cease growth, and impair migration despite unchanged BMEC viability and metabolism. Combretastatins also caused downregulation of BMEC adhesion molecules known to tether AML cells, including vascular cell adhesion molecule (VCAM)-1 and vascular endothelial (VE)-cadherin. When AML-BMEC co-cultures were treated with combretastatins, a significantly greater proportion of AML cells dislodged from BMECs and entered the G2/M cell cycle, suggesting enhanced susceptibility to cell cycle agents. Indeed, the combination of combretastatins and cytotoxic chemotherapy enhanced additive AML cell death. In vivo mice xenograft studies confirmed this finding by revealing complete AML regression after treatment with combretastatins and cytotoxic chemotherapy. Beyond highlighting the pathologic role of BMECs in the leukemia microenvironment as a protective reservoir of disease, these results support a new strategy for using vascular-targeting combretastatins in combination with cytotoxic chemotherapy to treat AML.

  4. Inherited aplastic anaemias/bone marrow failure syndromes.

    PubMed

    Dokal, Inderjeet; Vulliamy, Tom

    2008-05-01

    The inherited aplastic anaemias/bone marrow (BM) failure syndromes are a heterogeneous group of disorders characterized by BM failure usually in association with one or more somatic abnormality. The BM failure often presents in childhood but this may not be until adulthood in some cases highlighting the need for the adult haematologist to be aware of these disorders. Indeed some patients initially labelled as "idiopathic aplastic anaemia" are cryptic presentations of these genetic syndromes. Since 1992, when the first Fanconi anaemia (FA) gene was cloned there have been considerable advances in the genetics of these syndromes. These advances are beginning to provide a better understanding of normal haemopoiesis and how this might be disrupted in patients with BM failure. They have also provided important insights into some fundamental biological pathways: DNA repair-FA/BRCA pathway; telomere maintenance- dyskeratosis congenita related genes; ribosome biogenesis-Shwachman Diamond syndrome and Diamond-Blackfan anaemia genes. Additionally, as these disorders are usually associated with developmental abnormalities and an increased risk of cancer they are providing new insights into human development and the genesis of cancer. These advances have led to improved diagnosis of patients with these disorders. They may now also provide the platform for developing new treatments.

  5. Bone marrow-derived pancreatic stellate cells in rats.

    PubMed

    Sparmann, Gisela; Kruse, Marie-Luise; Hofmeister-Mielke, Nicole; Koczan, Dirk; Jaster, Robert; Liebe, Stefan; Wolff, Daniel; Emmrich, Jörg

    2010-03-01

    Origin and fate of pancreatic stellate cells (PSCs) before, during and after pancreatic injury are a matter of debate. The crucial role of PSCs in the pathogenesis of pancreatic fibrosis is generally accepted. However, the turnover of the cells remains obscure. The present study addressed the issue of a potential bone marrow (BM) origin of PSCs. We used a model of stable hematopoietic chimerism by grafting enhanced green fluorescence protein (eGFP)-expressing BM cells after irradiation of acceptor rats. Chimerism was detected by FACS analysis of eGFP-positive cells in the peripheral blood. Dibutyltin dichloride (DBTC) was used to induce acute pancreatic inflammation with subsequent recovery over 4 weeks. Investigations have been focused on isolated cells to detect the resting PSC population. The incidence of eGFP-positive PSC obtained from the pancreas of chimeric rats was approximately 7% in healthy pancreatic tissue and increased significantly to a mean of 18% in the restored pancreas 4 weeks after DBTC-induced acute inflammation. Our results suggest that BM-derived progenitor cells represent a source of renewable stellate cells in the pancreas. Increased numbers of resting PSCs after regeneration point toward enhanced recruitment of BM-derived cells to the pancreas and/or re-acquisition of a quiescent state after inflammation-induced activation.

  6. Bone marrow cells adopt the cardiomyogenic fate in vivo

    PubMed Central

    Rota, Marcello; Kajstura, Jan; Hosoda, Toru; Bearzi, Claudia; Vitale, Serena; Esposito, Grazia; Iaffaldano, Grazia; Padin-Iruegas, M. Elena; Gonzalez, Arantxa; Rizzi, Roberto; Small, Narissa; Muraski, John; Alvarez, Roberto; Chen, Xiongwen; Urbanek, Konrad; Bolli, Roberto; Houser, Steven R.; Leri, Annarosa; Sussman, Mark A.; Anversa, Piero

    2007-01-01

    The possibility that adult bone marrow cells (BMCs) retain a remarkable degree of developmental plasticity and acquire the cardiomyocyte lineage after infarction has been challenged, and the notion of BMC transdifferentiation has been questioned. The center of the controversy is the lack of unequivocal evidence in favor of myocardial regeneration by the injection of BMCs in the infarcted heart. Because of the interest in cell-based therapy for heart failure, several approaches including gene reporter assay, genetic tagging, cell genotyping, PCR-based detection of donor genes, and direct immunofluorescence with quantum dots were used to prove or disprove BMC transdifferentiation. Our results indicate that BMCs engraft, survive, and grow within the spared myocardium after infarction by forming junctional complexes with resident myocytes. BMCs and myocytes express at their interface connexin 43 and N-cadherin, and this interaction may be critical for BMCs to adopt the cardiomyogenic fate. With time, a large number of myocytes and coronary vessels are generated. Myocytes show a diploid DNA content and carry, at most, two sex chromosomes. Old and new myocytes show synchronicity in calcium transients, providing strong evidence in favor of the functional coupling of these two cell populations. Thus, BMCs transdifferentiate and acquire the cardiomyogenic and vascular phenotypes restoring the infarcted heart. Together, our studies reveal that locally delivered BMCs generate de novo myocardium composed of integrated cardiomyocytes and coronary vessels. This process occurs independently of cell fusion and ameliorates structurally and functionally the outcome of the heart after infarction. PMID:17965233

  7. Bone marrow cells adopt the cardiomyogenic fate in vivo.

    PubMed

    Rota, Marcello; Kajstura, Jan; Hosoda, Toru; Bearzi, Claudia; Vitale, Serena; Esposito, Grazia; Iaffaldano, Grazia; Padin-Iruegas, M Elena; Gonzalez, Arantxa; Rizzi, Roberto; Small, Narissa; Muraski, John; Alvarez, Roberto; Chen, Xiongwen; Urbanek, Konrad; Bolli, Roberto; Houser, Steven R; Leri, Annarosa; Sussman, Mark A; Anversa, Piero

    2007-11-06

    The possibility that adult bone marrow cells (BMCs) retain a remarkable degree of developmental plasticity and acquire the cardiomyocyte lineage after infarction has been challenged, and the notion of BMC transdifferentiation has been questioned. The center of the controversy is the lack of unequivocal evidence in favor of myocardial regeneration by the injection of BMCs in the infarcted heart. Because of the interest in cell-based therapy for heart failure, several approaches including gene reporter assay, genetic tagging, cell genotyping, PCR-based detection of donor genes, and direct immunofluorescence with quantum dots were used to prove or disprove BMC transdifferentiation. Our results indicate that BMCs engraft, survive, and grow within the spared myocardium after infarction by forming junctional complexes with resident myocytes. BMCs and myocytes express at their interface connexin 43 and N-cadherin, and this interaction may be critical for BMCs to adopt the cardiomyogenic fate. With time, a large number of myocytes and coronary vessels are generated. Myocytes show a diploid DNA content and carry, at most, two sex chromosomes. Old and new myocytes show synchronicity in calcium transients, providing strong evidence in favor of the functional coupling of these two cell populations. Thus, BMCs transdifferentiate and acquire the cardiomyogenic and vascular phenotypes restoring the infarcted heart. Together, our studies reveal that locally delivered BMCs generate de novo myocardium composed of integrated cardiomyocytes and coronary vessels. This process occurs independently of cell fusion and ameliorates structurally and functionally the outcome of the heart after infarction.

  8. Bone marrow scintigraphy and computed tomography in myloproliferative disease

    SciTech Connect

    Goldsmith, S.J.; Gilbert, H.S.; Hermann, G.

    1985-05-01

    Peripheral bone marrow (BM) expansion in myeloproliferative disease (MPD) is demonstrated by scintigraphy (scint) with Technetium 99m sulfur colloid (TSC) or Indium III chloride (In). Computed tomography (CT) of the normal adult medullary cavity yields negative attenuation coefficients (AC) which become positive when BM fat is replaced. BM scint and CT of the medullary cavity are obtained in 23 studies in 21 pts: 6 polycythemia vera (PCV), 6 post PCV myeloid metaplasis (MyM), 4 agnogenic MyM, 3 myelodysplasia with refractory anemia, 1 acute myelocytic leukemia and 1 chronic myelocytic with acute leukemic transformation. AC were measured for BM cavity of lower extremities at each third of the femur and tibia. Values ranged from -89 to +289 Hounsfield units. The results are presented in this paper. There was agreement between SCINT and CT in 83% pts and segments. 80% of MB segments with + AC had scint identified BM. BM biopsy of the iliac crest demonstrated fibrosis or blast proliferation in pts with +AC rather than hypercellularity or osteosclerosis. The highest AC values (>200) were seen in pts with blast proliferation and fibrosis. Decreased BM scint visualization and +CT AC correlated with BM fibrosis and may reflect replacement of BM elements or decreased RES function. BM scint and CT are useful to monitor MPD and select BM sites for biopsy.

  9. Bone marrow-derived progenitor cells in pulmonary fibrosis.

    PubMed

    Hashimoto, Naozumi; Jin, Hong; Liu, Tianju; Chensue, Stephen W; Phan, Sem H

    2004-01-01

    The origin of fibroblasts in pulmonary fibrosis is assumed to be intrapulmonary, but their extrapulmonary origin and especially derivation from bone marrow (BM) progenitor cells has not been ruled out. To examine this possibility directly, adult mice were durably engrafted with BM isolated from transgenic mice expressing enhanced GFP. Induction of pulmonary fibrosis in such chimera mice by endotracheal bleomycin (BLM) injection caused large numbers of GFP(+) cells to appear in active fibrotic lesions, while only a few GFP(+) cells could be identified in control lungs. Flow-cytometric analysis of lung cells confirmed the BLM-induced increase in GFP(+) cells in chimera mice and revealed a significant increase in GFP(+) cells that also express type I collagen. GFP(+) lung fibroblasts isolated from chimera mice expressed collagen and telomerase reverse transcriptase but not alpha-smooth muscle actin. Treatment of isolated GFP(+) fibroblasts with TGF-beta failed to induce myofibroblast differentiation. Cultured lung fibroblasts expressed the chemokine receptors CXCR4 and CCR7 and responded chemotactically to their cognate ligands, stromal cell-derived factor-1 alpha and secondary lymphoid chemokine, respectively. Thus the collagen-producing lung fibroblasts in pulmonary fibrosis can also be derived from BM progenitor cells.

  10. NKT cells, Treg, and their interactions in bone marrow transplantation

    PubMed Central

    Kohrt, Holbrook E.; Pillai, Asha B.; Lowsky, Robert; Strober, Samuel

    2010-01-01

    Bone marrow transplantation (BMT) is a potentially curative treatment for patients with leukemia and lymphoma. Tumor eradication is promoted by the anti-tumor activity of donor T cells contained in the transplant; however, donor T cells also mediate the serious side effect of graft-versus-host disease (GVHD). Separation of GVHD from graft anti-tumor activity is an important goal of research in improving transplant outcome. One approach is to take advantage of the immunomodulatory activity of regulatory NKT cells and CD4+ CD25+ Treg of host and/or donor origin. Both host and donor NKT cells and donor Treg are able to prevent GVHD in murine models. In this review, we summarize the mechanisms of NKT cell- and Treg-mediated protection against GVHD in mice while maintaining graft anti-tumor activity. In addition, we also examine the interactions between NKT cells and Treg in the context of BMT, and integrate the data from murine experimental models with the observations made in humans. PMID:20583031

  11. [Liver regenerative therapy using glycoside-modified bone marrow].

    PubMed

    Ise, Hirohiko; Takahashi, Masafumi; Ikeda, Uichi

    2005-12-01

    Recent studies have reported that bone marrow cells (BMCs) have the ability to generate functional hepatocytes. However, the efficiency with which BMC transplantation generates functional hepatocytes is rather low. We assumed that if BMCs accumulated directly in liver, the functional BMC-derived hepatocytes should increase more efficiently. An attempt was made to increase the accumulation of BMCs directly in liver through the interaction between hepatic asialoglycoprotein receptor (ASGPR) and galactose-exposing BMCs. Galactose-exposing BMCs that expressed green fluorescent protein (GFP) were injected into Long-Evans-Cinnamon (LEC) rats, a Wilson's disease (WD) model, via the tail vein. The WD is an autosomal-recessive disorder characterized by impaired biliary copper excretion and copper toxicosis, all due to mutations in the atp7b gene. At 5 months after transplantation, GFP-expressing hepatocyte nodules accounted for 2.4% of total liver mass, and the normal ceruloplasmin was detectable in the sera of these LEC rats. These findings suggest that the functional BMC-derived hepatocytes can be generated and the new genes derived from BMCs, such as ATP7B and GFP, can be transferred to LEC rats by the direct accumulation of BMCs in liver without hematopoietic reconstitution in need of preparative lethal irradiation.

  12. LRBA is Essential for Allogeneic Responses in Bone Marrow Transplantation

    PubMed Central

    Park, Mi Young; Sudan, Raki; Srivastava, Neetu; Neelam, Sudha; Youngs, Christie; Wang, Jia-Wang; Engelman, Robert W.; Kerr, William G.

    2016-01-01

    The PH-BEACH-WD40 (PBW) protein family members play a role in coordinating receptor signaling and intracellular vesicle trafficking. LPS-Responsive-Beige-like Anchor (LRBA) is a PBW protein whose immune function remains elusive. Here we show that LRBA-null mice are viable, but exhibit compromised rejection of allogeneic, xenogeneic and missing self bone-marrow grafts. Further, we demonstrate that LRBA-null Natural Killer (NK) cells exhibit impaired signaling by the key NK activating receptors, NKp46 and NKG2D. However, induction of IFN-γ by cytokines remains intact, indicating LRBA selectively facilitates signals by receptors for ligands expressed on the surface of NK targets. Surprisingly, LRBA limits immunoregulatory cell numbers in tissues where GvHD is primed or initiated, and consistent with this LRBA-null mice also demonstrate resistance to lethal GvHD. These findings demonstrate that LRBA is redundant for host longevity while being essential for both host and donor-mediated immune responses and thus represents a unique and novel molecular target in transplant immunology. PMID:27824136

  13. Mutagenic activity of isoxazolylnaphthoquinoneimines assayed by micronucleus bone marrow test.

    PubMed

    Sicardi, S M; Ferrato, E

    1995-05-01

    Studies were undertaken to evaluate the ability of various quinoneimines to induce micronuclei in bone marrow cells as a measure of their genotoxicity. Accordingly, 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone-4-imine (I), its 2-acetyl derivative (II) and 2-[(5-methyl-3-isoxazolyl)amino]-N-(5-methyl-3-isoxazolyl)-1 ,4- naphthoquinone-4-imine (III), as well as two of their precursors, 2-hydroxynaphthoquinone (NQ-2-OH) and 3,4-dimethyl-5-aminoisoxazole (DMAI) were given by intraperitoneal injection at 5, 50, 100 and 200 mg/Kg doses to S.J.L. Swiss mice with 24 h sampling time. Compounds I and II displayed highly significant differences at 50, 100 and 200 mg/kg doses (p < 0.01) and their mutagenic dose response curves correlated closely with an inverted U-shaped form whose interpretation is still the subject of controversy. NQ-2-OH only produced a significant increase in micronucleus frequency at 50 mg/kg, whereas no mutagenic activity was found for compound III and DMAI at the doses assayed. At 50 mg/kg the order of relative mutagenic potencies was I > II > NQ-2-OH. Mechanisms advanced to explain loss of drug activity at high doses include capture saturation, enzymatic induction during metabolism and participation of an independent defense system.

  14. Characterization of bone marrow mesenchymal stromal cells in aplastic anaemia.

    PubMed

    Hamzic, Edita; Whiting, Karen; Gordon Smith, Edward; Pettengell, Ruth

    2015-06-01

    In aplastic anaemia (AA), haemopoietic activity is significantly reduced and generally attributed to failure of haemopoietic stem cells (HSC) within the bone marrow (BM). The regulation of haemopoiesis depends on the interaction between HSC and various cells of the BM microenvironment, including mesenchymal stromal cells (MSC). MSC involvement in the functional restriction of HSC in AA is largely unknown and therefore, the physical and functional properties of AA MSC were studied in vitro. MSC were characterized by their phenotype and ability to form adherent stromal layers. The functional properties of AA MSC were assessed through proliferative, clonogenic and cross-over culture assays. Results indicate that although AA MSC presented typical morphology and distinctive mesenchymal markers, stromal formation was reduced, with 50% of BM samples failing to produce adherent layers. Furthermore, their proliferative and clonogenic capacity was markedly decreased (P = 0·03 and P = 0·04 respectively) and the ability to sustain haemopoiesis was significantly reduced, as assessed by total cell proliferation (P = 0·032 and P = 0·019 at Week 5 and 6, respectively) and clonogenic potential of HSC (P = 0·02 at Week 6). It was concluded that the biological characteristics of AA MSC are different from those of control MSC and their in vitro haemopoiesis-supporting ability is significantly reduced.

  15. Bone Marrow-Derived Mesenchymal Stem Cells Drive Lymphangiogenesis

    PubMed Central

    Maertens, Ludovic; Erpicum, Charlotte; Detry, Benoit; Blacher, Silvia; Lenoir, Bénédicte; Carnet, Oriane; Péqueux, Christel; Cataldo, Didier; Lecomte, Julie; Paupert, Jenny; Noel, Agnès

    2014-01-01

    It is now well accepted that multipotent Bone-Marrow Mesenchymal Stem Cells (BM-MSC) contribute to cancer progression through several mechanisms including angiogenesis. However, their involvement during the lymphangiogenic process is poorly described. Using BM-MSC isolated from mice of two different backgrounds, we demonstrate a paracrine lymphangiogenic action of BM-MSC both in vivo and in vitro. Co-injection of BM-MSC and tumor cells in mice increased the in vivo tumor growth and intratumoral lymphatic vessel density. In addition, BM-MSC or their conditioned medium stimulated the recruitment of lymphatic vessels in vivo in an ear sponge assay, and ex vivo in the lymphatic ring assay (LRA). In vitro, MSC conditioned medium also increased the proliferation rate and the migration of both primary lymphatic endothelial cells (LEC) and an immortalized lymphatic endothelial cell line. Mechanistically, these pro-lymphangiogenic effects relied on the secretion of Vascular Endothelial Growth Factor (VEGF)-A by BM-MSC that activates VEGF Receptor (VEGFR)-2 pathway on LEC. Indeed, the trapping of VEGF-A in MSC conditioned medium by soluble VEGF Receptors (sVEGFR)-1, -2 or the inhibition of VEGFR-2 activity by a specific inhibitor (ZM 323881) both decreased LEC proliferation, migration and the phosphorylation of their main downstream target ERK1/2. This study provides direct unprecedented evidence for a paracrine lymphangiogenic action of BM-MSC via the production of VEGF-A which acts on LEC VEGFR-2. PMID:25222747

  16. Bone marrow-derived fibrocytes contribute to liver fibrosis

    PubMed Central

    Xu, Jun

    2015-01-01

    Chronic liver injury often leads to hepatic fibrosis, a condition associated with increased levels of circulating TGF-β1 and lipopolysaccharide, activation of myofibroblasts, and extensive deposition of extracellular matrix, mostly collagen Type I. Hepatic stellate cells are considered to be the major1 but not the only source of myofibroblasts in the injured liver.2 Hepatic myofibroblasts may also originate from portal fibroblasts, mesenchymal cells, and fibrocytes.3 Since the discovery of fibrocytes in 1994 by Dr. Bucala and colleagues, this bone marrow (BM)-derived collagen Type I-producing CD45+ cells remain the most fascinating cells of the hematopoietic system. Due to the ability to differentiate into collagen Type I producing cells/myofibroblasts, fibrocytes were implicated in the pathogenesis of liver, skin, lung, and kidney fibrosis. However, studies of different organs often contain controversial results on the number of fibrocytes recruited to the site of injury and their biological function. Furthermore, fibrocytes were implicated in the pathogenesis of sepsis and were shown to possess antimicrobial activity. Finally, in response to specific stimuli, fibrocytes can give rise to fully differentiated macrophages, suggesting that in concurrence with the high plasticity of hematopoietic cells, fibrocytes exhibit progenitor properties. Here, we summarize our current understanding of the role of CD45+Collagen Type I+ BM-derived cells in response to fibrogenic liver injury and septicemia and discuss the most recent evidence supporting the critical role of fibrocytes in the mediation of pro-fibrogenic and/or pro-inflammatory responses. PMID:25966982

  17. Autologous Pancreatic Islet Transplantation in Human Bone Marrow

    PubMed Central

    Maffi, Paola; Balzano, Gianpaolo; Ponzoni, Maurilio; Nano, Rita; Sordi, Valeria; Melzi, Raffaella; Mercalli, Alessia; Scavini, Marina; Esposito, Antonio; Peccatori, Jacopo; Cantarelli, Elisa; Messina, Carlo; Bernardi, Massimo; Del Maschio, Alessandro; Staudacher, Carlo; Doglioni, Claudio; Ciceri, Fabio; Secchi, Antonio; Piemonti, Lorenzo

    2013-01-01

    The liver is the current site of choice for pancreatic islet transplantation, even though it is far from being ideal. We recently have shown in mice that the bone marrow (BM) may be a valid alternative to the liver, and here we report a pilot study to test feasibility and safety of BM as a site for islet transplantation in humans. Four patients who developed diabetes after total pancreatectomy were candidates for the autologous transplantation of pancreatic islet. Because the patients had contraindications for intraportal infusion, islets were infused in the BM. In all recipients, islets engrafted successfully as shown by measurable posttransplantation C-peptide levels and histopathological evidence of insulin-producing cells or molecular markers of endocrine tissue in BM biopsy samples analyzed during follow-up. Thus far, we have recorded no adverse events related to the infusion procedure or the presence of islets in the BM. Islet function was sustained for the maximum follow-up of 944 days. The encouraging results of this pilot study provide new perspectives in identifying alternative sites for islet infusion in patients with type 1 diabetes. Moreover, this is the first unequivocal example of successful engraftment of endocrine tissue in the BM in humans. PMID:23733196

  18. Neuropeptide y and neuropeptide y y5 receptor interaction restores impaired growth potential of aging bone marrow stromal cells.

    PubMed

    Igura, Koichi; Haider, Husnain Kh; Ahmed, Rafeeq P H; Sheriff, Sulaiman; Ashraf, Muhammad

    2011-08-01

    Abstract improved growth characteristics of the aging bone marrow cells subsequent to neuropeptide Y (NPY)/neuropeptide Y Y5 receptor (NPY Y5R) ligand-receptor interaction. Bone marrow cells were isolated from neonatal (2-3 weeks), young (8-12 weeks), and old (24-28 months) rats on the basis of their preferential adherence to plastic surface. After culturing the cells at initial seeding density of 1×10(4) cells/cm(2), we found that the proliferation potential of bone marrow cells declined with age. Real-time polymerase chain reaction (PCR) and Western blotting showed that bone marrow cells in different age groups constitutively expressed NPY and NPY receptor subtypes (Y1R, Y2R, and Y5R). However, NPY and Y5R expression increased by more than 130-fold and decreased by 28-fold, respectively, in old bone marrow cells as compared to young bone marrow cells. NPY (10 nM) stimulated the proliferation of all bone marrow cells age groups, and their proliferation was blocked by Y5R antagonist. However, the pro-proliferative effect of NPY on old bone marrow cells was weaker than other cell groups due to lower Y5R expression. Y5R gene transfection of old bone marrow cells with subsequent NPY(3-36) (10 nM) treatment significantly increased proliferation of old bone marrow cells (>56%) as compared to green fluorescence protein-transfected control old bone marrow cells. Stimulation of old bone marrow cells by NPY treatment rejuvenated the growth characteristics of aging bone marrow cells as a result of Y5R overexpression.

  19. Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains

    PubMed Central

    Weimann, James M.; Charlton, Carol A.; Brazelton, Timothy R.; Hackman, Robert C.; Blau, Helen M.

    2003-01-01

    We show here that cells within human adult bone marrow can contribute to cells in the adult human brain. Cerebellar tissues from female patients with hematologic malignancies, who had received chemotherapy, radiation, and a bone marrow transplant, were analyzed. Brain samples were obtained at autopsy from female patients who received male (sex-mismatched) or female (sex-matched, control) bone marrow transplants. Cerebella were evaluated in 10-μm-thick, formaldehyde-fixed, paraffin-embedded sections that encompassed up to ≈50% of a human Purkinje nucleus. A total of 5,860 Purkinje cells from sex-mismatched females and 3,202 Purkinje cells from sex-matched females were screened for Y chromosomes by epifluorescence. Confocal laser scanning microscopy allowed definitive identification of the sex chromosomes within the morphologically distinct Purkinje cells. In the brains of females who received male bone marrow, four Purkinje neurons were found that contained an X and a Y chromosome and two other Purkinje neurons contained more than a diploid number of sex chromosomes. No Y chromosomes were detected in the brains of sex-matched controls. The total frequency of male bone marrow contribution to female Purkinje cells approximated 0.1%. This study demonstrates that although during human development Purkinje neurons are no longer generated after birth, cells within the bone marrow can contribute to these CNS neurons even in adulthood. The underlying mechanism may be caused either by generation de novo of Purkinje neurons from bone marrow-derived cells or by fusion of marrow-derived cells with existing recipient Purkinje neurons. PMID:12576546

  20. G-CSF-Associated Bone Marrow Necrosis in AML after Induction Chemotherapy.

    PubMed

    Osuorji, Ikenna; Goldman, Lyle

    2012-01-01

    Bone marrow necrosis (BMN) is defined as necrosis of the myeloid tissues and stroma without involvement of the cortical bone. We report a case of 66-year-old male with AML-M4 (FAB classification) who was given induction chemotherapy with cytarabine and daunorubicin. Filgrastim at 480 micrograms was administered on days 15-19 to shorten the duration of neutropenia. Consequently patient developed severe pelvic bone pain, leukoerythroblastosis, and severe leukocytosis. Repeat bone marrow aspiration and biopsy on day 21 confirmed bone marrow necrosis. These manifestations responded quickly to discontinuation of filgrastim. Subsequently, he recovered full myelopoiesis. We suggest that there may be more cases of BMN associated with G-CSF that are undiagnosed.

  1. Early and late bone-marrow changes after irradiation: MR evaluation

    SciTech Connect

    Stevens, S.K.; Moore, S.G.; Kaplan, I.D. )

    1990-04-01

    Knowledge of the chronologic evolution of bone-marrow changes during and after radiation therapy is essential in differentiating normal postradiation changes from other marrow abnormalities. The appearance of the lumbar vertebral bone marrow was studied on 55 serial spin-echo and short-T1 inversion-recovery (STIR) MR images obtained in 14 patients receiving radiation therapy for Hodgkin disease, seminoma, or prostate carcinoma. Images were obtained before, at weekly intervals during, and at various monthly intervals up to 14 months after a 3- to 6-week course of fractionated paravertebral lymph-node irradiation of 1500-5000 rad (15-50 Gy). During the first 2 weeks of therapy, there was no definite change in the appearance of the marrow on spin-echo images; however, there was an increase in signal intensity on the STIR images, apparently reflecting early marrow edema and necrosis. Between weeks 3 and 6, the marrow showed an increasingly heterogenous signal and prominence of the signal from central marrow fat, shown best on T1-weighted images. Late marrow patterns (6 weeks to 14 months after therapy) varied and consisted of either homogenous fatty replacement or a band pattern of peripheral intermediate signal intensity, possibly representing hematopoietic marrow surrounding the central marrow fat. No focal marrow lesions or soft-tissue edema were identified during the course of radiation therapy; their presence should raise the possibility of the presence of a pathologic process other than radiation change. These data suggest that MR can detect radiation-induced marrow changes as early as 2 weeks after starting therapy, and that there are at least two distinct types of late marrow MR patterns.

  2. PET/CT Scanner and Bone Marrow Biopsy in Detection of Bone Marrow Involvement in Diffuse Large B-Cell Lymphoma

    PubMed Central

    El Karak, Fadi; Bou-Orm, Ibrahim R.; Ghosn, Marwan; Kattan, Joseph; Farhat, Fadi; Ibrahim, Toni; Jreige, Mario; El Cheikh, Jean

    2017-01-01

    Evaluation of bone marrow involvement (BMI) is paramount in diffuse large B-cell lymphoma (DLBCL) for prognostic and therapeutic reasons. PET/CT scanner (PET) is now a routine examination for the staging of DLBCL with prognostic and therapeutic implications. This study evaluates the role of PET for detecting marrow involvement compared to bone marrow biopsy (BMB). This monocentric study included 54 patients diagnosed with DLBCL between 2009 and 2013 and who had FDG PET/CT in a pre-treatment setting. A correlation analysis of the detection of BMI by PET and BMB was performed. A prognostic evaluation of BMI by BMB and/or PET/CT and correlation with an overall 2-year survival were analyzed. PET was more sensitive for the detection of BMI than BMB (92.3% vs. 38.5%). It can be considered a discriminatory Pre-BMB test with a negative predictive value of 97.6%. In addition, BMI by PET had a prognostic value with strong correlation with progression-free survival (PFS) (HR = 3.81; p = 0.013) and overall survival (OS) (HR = 4.12; p = 0.03) while the BMB had not. PET shows superior performance to the BMB for the detection of marrow involvement in DLBCL. It may be considered as the first line examination of bone marrow instead of the biopsy. PMID:28099514

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

    PubMed

    Boraschi-Diaz, Iris; Komarova, Svetlana V

    2016-01-01

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

  4. Determination of pesticides in postmortem blood and bone marrow of pesticide treated rabbits.

    PubMed

    Akcan, Ramazan; Hilal, Ahmet; Daglioglu, Nebile; Cekin, Necmi; Gulmen, Mete K

    2009-08-10

    Forensic toxicological analyses have traditionally focused on the use of blood, body fluids, and certain organs in examinations of deaths due to intoxication. However, in some situations, putrefaction and contamination make proper sampling from tissues impossible, such as in exhumation cases. In these cases, bone marrow might be useful as an alternative specimen since it is a potential depot for drugs. This study aims to determine pesticides in postmortem and putrefied bone marrow of pesticide treated rabbits, so as to reveal the diagnostic value of toxicological analysis of bone marrow in exhumation cases. Out of thirteen rabbits, a 110 mg/kg dose of endosulfan was orally given to six through a gavage tool, and a 2500 mg/kg dose of diazinon was given to six using the same method. One rabbit was not treated with anything and served as a control sample. Venous blood, liver, lung, kidney, brain, and bone marrow samples were collected just after spontaneous death or cervical dislocation. After this, the rabbits were buried in soil. All of them were exhumed 1 month later, and putrefied viscera and bone marrow were sampled. Blood and tissue samples underwent solvent extraction and solid phase extraction, and then the samples were analyzed by GC-MS. Mean residue levels of diazinon in early postmortem samples were 85 mg/kg, 71 mg/kg, 23 mg/kg, 21 mg/kg, 19 mg/kg, and 0.4 mg/l in the liver, bone marrow, kidney, lung, brain, and blood, respectively. Mean residue levels of diazinon in the putrefied body were 3327 mg/kg in putrefied viscera and 1783 mg/kg in the bone marrow. Mean residue levels of endosulfan isomers and metabolites in early postmortem samples (blood, liver, lung, kidney, brain, and bone marrow) were 0.46 mg/kg (endosulfan sulfate), 0.32 mg/kg (alpha and beta isomers of endosulfan), and 0.14 mg/kg (endosulfan ether) while the same levels were 0.26 mg/kg (endosulfan sulfate), 0.24 mg/kg (alpha and beta isomers of endosulfan), and 0.1 mg/kg (endosulfan ether) in

  5. Bone marrow transfusions in previously irradiated, hematologically normal syngeneic mice

    SciTech Connect

    Brecher, G.; Lawce, H.; Tjio, J.H.

    1981-03-01

    Transfusion of syngeneic marrow into normal, nonirradiated recipients results only in minimal proliferation of donor cells. However, irradiated recipients, restored to hematologic normalcy by an initial marrow transfusion, subsequently sustain proliferation which replaces approximately 10% of endogenous marrow after a single transfusion of 4 x 10/sup 7/ marrow cells of the same strain as the host. Cells from histoincompatible donors proliferate only rarely or minimally in the marrows of these irradiated, but hematologically normal recipients without reirradiation. Syngeneic male donor cells proliferate in irradiated and restored female mice, while female donor cells fail to proliferate in the marrow of syngeneic male recipients. A possible explanation is that transfused female cells respond immunologically to the abundant H-Y antigen in the male environment and are eliminated as a result.

  6. Immunohistological analysis of human bone marrow trephine biopsies using monoclonal antibodies.

    PubMed

    Falini, B; Martelli, M F; Tarallo, F; Moir, D J; Cordell, J L; Gatter, K C; Loreti, G; Stein, H; Mason, D Y

    1984-03-01

    This paper describes the use of a recently developed immuno-alkaline phosphatase method (the 'APAAP' technique) for labelling frozen sections of undecalcified bone marrow biopsies with monoclonal antibodies, including reagents reactive with T cells and their subsets, B cells, glycophorin, HLA-DR antigen, common ALL antigen, epithelial cells and megakaryocytes. Use of an immuno-alkaline phosphatase technique avoids problems due to endogenous enzyme activity encountered when staining bone marrow by immunoperoxidase procedures. Immunohistological labelling of frozen trephine biopsies is of particular value when it is impossible to aspirate marrow particles and for identifying cells which do not readily enter suspension (e.g. dendritic reticulum cells or stromal cells). Details are given of cases in which immunohistological analysis was used for the phenotyping of acute leukaemias, for the differential diagnosis of intramedullary T and B cell proliferations, and for identifying bone marrow metastases.

  7. Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis.

    PubMed

    Jafari, Abbas; Qanie, Diyako; Andersen, Thomas L; Zhang, Yuxi; Chen, Li; Postert, Benno; Parsons, Stuart; Ditzel, Nicholas; Khosla, Sundeep; Johansen, Harald Thidemann; Kjærsgaard-Andersen, Per; Delaisse, Jean-Marie; Abdallah, Basem M; Hesselson, Daniel; Solberg, Rigmor; Kassem, Moustapha

    2017-02-14

    Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.

  8. The Bone Marrow-Derived Stromal Cells: Commitment and Regulation of Adipogenesis

    PubMed Central

    Tencerova, Michaela; Kassem, Moustapha

    2016-01-01

    Bone marrow (BM) microenvironment represents an important compartment of bone that regulates bone homeostasis and the balance between bone formation and bone resorption depending on the physiological needs of the organism. Abnormalities of BM microenvironmental dynamics can lead to metabolic bone diseases. BM stromal cells (also known as skeletal or mesenchymal stem cells) [bone marrow stromal stem cell (BMSC)] are multipotent stem cells located within BM stroma and give rise to osteoblasts and adipocytes. However, cellular and molecular mechanisms of BMSC lineage commitment to adipocytic lineage and regulation of BM adipocyte formation are not fully understood. In this review, we will discuss recent findings pertaining to identification and characterization of adipocyte progenitor cells in BM and the regulation of differentiation into mature adipocytes. We have also emphasized the clinical relevance of these findings. PMID:27708616

  9. Prostaglandin E2 regulates macrophage colony stimulating factor secretion by human bone marrow stromal cells.

    PubMed

    Besse, A; Trimoreau, F; Faucher, J L; Praloran, V; Denizot, Y

    1999-07-08

    Bone marrow stromal cells regulate marrow haematopoiesis by secreting growth factors such as macrophage colony stimulating factor (M-CSF) that regulates the proliferation, differentiation and several functions of cells of the mononuclear-phagocytic lineage. By using a specific ELISA we found that their constitutive secretion of M-CSF is enhanced by tumour necrosis factor-alpha (TNF-alpha). The lipid mediator prostaglandin E2 (PGE2) markedly reduces in a time- and dose-dependent manner the constitutive and TNF-alpha-induced M-CSF synthesis by bone marrow stromal cells. In contrast, other lipid mediators such as 12-HETE, 15-HETE, leukotriene B4, leukotriene C4 and lipoxin A4 have no effect. EP2/EP4 selective agonists (11-deoxy PGE1 and 1-OH PGE1) and EP2 agonist (19-OH PGE2) inhibit M-CSF synthesis by bone marrow stromal cells while an EP1/EP3 agonist (sulprostone) has no effect. Stimulation with PGE2 induces an increase of intracellular cAMP levels in bone marrow stromal cells. cAMP elevating agents (forskolin and cholera toxin) mimic the PGE2-induced inhibition of M-CSF production. In conclusion, PGE2 is a potent regulator of M-CSF production by human bone marrow stromal cells, its effects being mediated via cAMP and PGE receptor EP2/EP4 subtypes.

  10. Regulation of heme metabolism in normal and sideroblastic bone marrow cells in culture

    SciTech Connect

    Ibraham, N.G.; Lutton, J.D.; Hoffman, R.; Levere, R.D.

    1985-05-01

    Heme metabolism was examined in developing in vitro erythroid colonies (CFUE) and in bone marrow samples taken directly from four normal donors and four patients with sideroblastic anemia. Maximum activities of delta-aminolevulinic acid synthase (ALAS), ALA dehydratase (ALAD), and /sup 14/C-ALA incorporation into heme were achieved in normal marrow CFUE after 8 days of culture, whereas heme oxygenase progressively decreased to low levels of activity during the same period. Assays on nucleated bone marrow cells taken directly from patients revealed that ALAS activity was considerably reduced in idiopathic sideroblastic anemia (IASA) and X-linked sideroblastic anemia (X-SA) bone marrow specimens, whereas the activity increased more than twofold (normal levels) when cells were assayed from 8-day CFUE. In all cases, ALAD activity appeared to be within normal levels. Measurement of heme synthesis revealed that normal levels of /sup 14/C-ALA incorporation into heme were achieved in IASA cells but were reduced in X-SA cells. In marked contrast to levels in normal cells, heme oxygenase was found to be significantly elevated (two- to fourfold) in bone marrow cells taken directly from patients with IASA and X-SA. Results from this study demonstrate that IASA and X-SA bone marrow cells have disturbances in ALAS and heme metabolism, and that erythropoiesis (CFUE) can be restored to normal levels when cells are cultured in methylcellulose.

  11. Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia.

    PubMed

    Bär, Christian; Povedano, Juan Manuel; Serrano, Rosa; Benitez-Buelga, Carlos; Popkes, Miriam; Formentini, Ivan; Bobadilla, Maria; Bosch, Fatima; Blasco, Maria A

    2016-04-07

    Aplastic anemia is a fatal bone marrow disorder characterized by peripheral pancytopenia and marrow hypoplasia. The disease can be hereditary or acquired and develops at any stage of life. A subgroup of the inherited form is caused by replicative impairment of hematopoietic stem and progenitor cells due to very short telomeres as a result of mutations in telomerase and other telomere components. Abnormal telomere shortening is also described in cases of acquired aplastic anemia, most likely secondary to increased turnover of bone marrow stem and progenitor cells. Here, we test the therapeutic efficacy of telomerase activation by using adeno-associated virus (AAV)9 gene therapy vectors carrying the telomerase Tert gene in 2 independent mouse models of aplastic anemia due to short telomeres (Trf1- and Tert-deficient mice). We find that a high dose of AAV9-Tert targets the bone marrow compartment, including hematopoietic stem cells. AAV9-Tert treatment after telomere attrition in bone marrow cells rescues aplastic anemia and mouse survival compared with mice treated with the empty vector. Improved survival is associated with a significant increase in telomere length in peripheral blood and bone marrow cells, as well as improved blood counts. These findings indicate that telomerase gene therapy represents a novel therapeutic strategy to treat aplastic anemia provoked or associated with short telomeres.

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

    PubMed Central

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

    2015-01-01

    The finding that bone marrow hosts several types of multipotent stem cell has prompted extensive research aimed at regenerating organs and building models to elucidate the mechanisms of diseases. Conventional research depends on the use of two-dimensional (2D) bone marrow systems, which imposes several obstacles. The development of 3D bone marrow systems with appropriate molecules and materials however, is now showing promising results. In this review, we discuss the advantages of 3D bone marrow systems over 2D systems and then point out various factors that can enhance the 3D systems. The intensive research on 3D bone marrow systems has revealed multiple important clinical applications including disease modeling, drug screening, regenerative medicine, etc. We also discuss some possible future directions in the 3D bone marrow research field. PMID:26283705

  13. Erythropoietin couples erythropoiesis, B-lymphopoiesis, and bone homeostasis within the bone marrow microenvironment.

    PubMed

    Singbrant, Sofie; Russell, Megan R; Jovic, Tanja; Liddicoat, Brian; Izon, David J; Purton, Louise E; Sims, Natalie A; Martin, T John; Sankaran, Vijay G; Walkley, Carl R

    2011-05-26

    Erythropoietin (Epo) has been used in the treatment of anemia resulting from numerous etiologies, including renal disease and cancer. However, its effects are controversial and the expression pattern of the Epo receptor (Epo-R) is debated. Using in vivo lineage tracing, we document that within the hematopoietic and mesenchymal lineage, expression of Epo-R is essentially restricted to erythroid lineage cells. As expected, adult mice treated with a clinically relevant dose of Epo had expanded erythropoiesis because of amplification of committed erythroid precursors. Surprisingly, we also found that Epo induced a rapid 26% loss of the trabecular bone volume and impaired B-lymphopoiesis within the bone marrow microenvironment. Despite the loss of trabecular bone, hematopoietic stem cell populations were unaffected. Inhibition of the osteoclast activity with bisphosphonate therapy blocked the Epo-induced bone loss. Intriguingly, bisphosphonate treatment also reduced the magnitude of the erythroid response to Epo. These data demonstrate a previously unrecognized in vivo regulatory network coordinating erythropoiesis, B-lymphopoiesis, and skeletal homeostasis. Importantly, these findings may be relevant to the clinical application of Epo.

  14. Autologous bone marrow injection in the management of simple bone cysts in children.

    PubMed

    Docquier, Pierre-Louis; Delloye, Christian

    2004-06-01

    The majority of simple bone cysts (SBC's) is not symptomatic and remains undiagnosed or is discovered fortuitously. A number of simple bone cysts are only diagnosed after a pathological fracture which occurs as a presenting symptom. Fractures are managed either conservatively or surgically, based on criteria such as the age of the child and the type and localisation of the fracture. The risk for fracture can be evaluated radiographically. In the absence of a fracture risk, plain radiographic follow-up is sufficient. In case of a high fracture risk, percutaneous aspiration and injection of bone marrow may be performed. The result of this treatment in 21 simple bone cysts with a high risk for fracture is reported. Slow regression of the cyst and progressive healing were obtained in 15 cases (71.4%) whereas no response was noted in 3 cases (14.3%) and recurrence in another 3 (14.3%), after a mean follow-up of 37.1 months. Guidelines are proposed for the follow-up and management of SBC.

  15. A case of isolated sacral and pelvic sarcoidosis diagnosed by bone marrow biopsy.

    PubMed

    Garwood, Amy S; Mikuls, Ted R

    2003-10-01

    Although sarcoidosis frequently involves bone, it rarely presents as isolated osseous disease. We present a case in which sarcoidosis is limited to the sacrum and pelvis, a case that underscores the potential importance of both magnetic resonance imaging (MRI) and bone marrow biopsy in establishing the diagnosis. Additionally, we report the interval resolution of bony disease by MRI following glucocorticoid treatment.

  16. Differential β3 and β1 Integrin Expression in Bone Marrow and Cortical Bone of Estrogen Deficient Rats.

    PubMed

    Voisin, Muriel; McNamara, Laoise M

    2015-09-01

    Integrin-based (β3 ) attachments to the extracellular matrix (ECM) on osteocyte cell processes have recently been proposed to play an important role in facilitating osteocyte mechanosensation. However, it is not yet known whether integrin expression is altered in the mechanoregulatory osteocytes during osteoporosis. The objective of this study was to test the hypothesis that the expression of integrin-based mechanosensory complexes (β1 and β3 integrins) is altered as a direct response to estrogen deficiency, in an estrogen deficient animal model of osteoporosis. Four weeks post-operatively, immunohistochemistry was used to detect for β1 and β3 integrin subunits in bone tissue and marrow of ovariectomized (OVX; N = 4) and SHAM (N = 4) operated animals. A tartrate resistant acid phosphatase (TRAP) control stain was performed to quantify the presence of osteoclasts in the bone marrow and bone surfaces. Image analysis was performed to quantify expression patterns in different biological compartments, that is, bone marrow, endosteum, and cortical bone. Our results showed that β1 integrins were ubiquitously expressed throughout the bone and marrow, for both OVX and SHAM groups. β3 integrin subunit expression was lower in bone cells from osteoporotic animals compared to controls, whereas β3 expression in marrow cells did not differ significantly between groups. At the endosteum no difference was observed in β3 integrin subunit expression. As expected, the number of osteoclasts was higher in the OVX group validating an imbalance in bone remodeling. We propose that a reduction in β3 integrin expression in osteocytes might impair mechanosensation by bone cells during estrogen deficiency.

  17. Bone Marrow Stromal Stem Cells in Tissue Engineering and Regenerative Medicine.

    PubMed

    Polymeri, A; Giannobile, W V; Kaigler, D

    2016-11-01

    Bone marrow stromal stem cells (BMSCs) are adult multipotent cells, which have the potential to differentiate into cell types of mesodermal origin, namely osteocytes, adipocytes, and chondrocytes. Due to their accessibility and expansion potential, BMSCs have historically held therapeutic promise in tissue engineering and regenerative medicine applications. More recently, it has been demonstrated that not only can bone marrow stromal stem cells directly participate in tissue regeneration, but they also have the capacity to migrate to distant sites of tissue injury, where they can participate in tissue repair either directly through their differentiation or indirectly through paracrine mechanisms. Additionally, they can elicit various immunomodulatory signals, which can attenuate the inflammatory and immune responses. As such, bone marrow stromal stem cells have been explored clinically for treatment of a wide variety of different conditions including bone defects, graft-vs.-host disease, cardiovascular diseases, autoimmune diseases, diabetes, neurological diseases, and liver and kidney diseases. This review provides an overview of current clinical applications of bone marrow stromal stem cells and discusses their therapeutic properties, while also addressing limitations of their use. PubMed, Ovid, and Google Scholar online databases were searched using several keywords, including "stem cells", "tissue engineering", tissue regeneration" and "clinical trials". Additionally, Clinical trials.gov was used to locate completed clinical trials using bone marrow derived stem cells.

  18. The bone marrow microenvironment as a sanctuary for minimal residual disease in CML

    PubMed Central

    Nair, Rajesh R.; Tolentino, Joel; Hazlehurst, Lori A.

    2012-01-01

    Bcr-abl kinase inhibitors have provided proof of principal that targeted therapy holds great promise for the treatment of cancer. However, despite the success of these agents in treating chronic myelogenous leukemia (CML), the majority of patients continue to present with minimal residual disease contained within the bone marrow microenvironment. These clinical observations suggest that the bone marrow microenvironment may provide survival signals that contribute to the failure to eliminate minimal residual disease. The bone marrow microenvironment is comprised of multiple sub-domains which vary in cellular composition and gradients of soluble factors and matrix composition. Experimental evidence indicates that exposure of tumor cells to either bone marrow derived soluble factors or matrixes can confer a multi-drug resistance phenotype. Together, these data indicate that targeting such pathways may be a viable approach for increasing the efficacy of chemotherapy. Moreover, we propose that personalized medicine must go beyond understanding predictive models inherent to tumors but rather build predictive models that consider diversity in response due to interactions with the tumor microenvironment. This review will focus on CML, however, understanding the contribution of the bone marrow microenvironment could contribute to rationale combination therapy in other types of leukemia, multiple myeloma and solid tumors which metastasize to the bone. PMID:20382130

  19. Adeno associated viral-mediated intraosseous labeling of bone marrow derived cells for CNS tracking.

    PubMed

    Selenica, Maj-Linda B; Reid, Patrick; Pena, Gabriela; Alvarez, Jennifer; Hunt, Jerry B; Nash, Kevin R; Morgan, Dave; Gordon, Marcia N; Lee, Daniel C

    2016-05-01

    Inflammation, including microglial activation in the CNS, is an important hallmark in many neurodegenerative diseases. Microglial stimuli not only impact the brain microenvironment by production and release of cytokines and chemokines, but also influence the activity of bone marrow derived cells and blood born macrophage populations. In many diseases including brain disorders and spinal cord injury, researchers have tried to harbor the neuroprotective and repair properties of these subpopulations. Hematopoietic bone marrow derived cells (BMDCs) are of great interest, especially during gene therapy because certain hematopoietic cell subpopulations traffic to the sites of injury and inflammation. The aim of this study was to develop a method of labeling endogenous bone marrow derived cells through intraosseous impregnation of recombinant adeno-associated virus (rAAV) or lentivirus. We utilized rAAV serotype 9 (rAAV-9) or lentivirus for gene delivery of green florescence protein (GFP) to the mouse bone marrow cells. Flow cytometry showed that both viruses were able to efficiently transduce mouse bone marrow cells in vivo. However, the rAAV9-GFP viral construct transduced BMDCs more efficiently than the lentivirus (11.2% vs. 6.8%), as indicated by cellular GFP expression. We also demonstrate that GFP labeled cells correspond to bone marrow cells of myeloid origin using CD11b as a marker. Additionally, we characterized the ability of bone marrow derived, GFP labeled cells to extravasate into the brain parenchyma upon acute and subchronic neuroinflammatory stimuli in the mouse CNS. Viral mediated over expression of chemokine (C-C motif) ligand 2 (CCL2) or intracranial injection of lipopolysaccharide (LPS) recruited GFP labeled BMDCs from the periphery into the brain parenchyma compared to vehicle treated mice. Altogether our findings demonstrate a useful method of labeling endogenous BMDCs via viral transduction and the ability to track subpopulations throughout the body

  20. Modulation of the effects of lung immune response on bone marrow by oral antigen exposure.

    PubMed

    Xavier-Elsas, P; Silva, C L C A; Pinto, L; Queto, T; Vieira, B M; Aranha, M G; De Luca, B; Masid-de-Brito, D; Luz, R A; Lopes, R S; Ferreira, R; Gaspar-Elsas, M I

    2013-01-01

    Allergic airway inflammation is attenuated by oral tolerization (oral exposure to allergen, followed by conventional sensitization and challenge with homologous antigen), which decreases airway allergen challenge-induced eosinophilic infiltration of the lungs and bone marrow eosinophilia. We examined its effects on bone marrow eosinophil and neutrophil production. Mice of wild type (BP-2, BALB/c, and C57BL/6) and mutant strains (lacking iNOS or CD95L) were given ovalbumin (OVA) or water (vehicle) orally and subsequently sensitized and challenged with OVA (OVA/OVA/OVA and H2O/OVA/OVA groups, resp.). Anti-OVA IgG and IgE, bone marrow eosinophil and neutrophil numbers, and eosinophil and neutrophil production ex vivo were evaluated. T lymphocytes from OVA/OVA/OVA or control H2O/OVA/OVA donors were transferred into naïve syngeneic recipients, which were subsequently sensitized/challenged with OVA. Alternatively, T lymphocytes were cocultured with bone marrow eosinophil precursors from histocompatible sensitized/challenged mice. OVA/OVA/OVA mice of the BP-2 and BALB/c strains showed, relative to H2O/OVA/OVA controls, significantly decreased bone marrow eosinophil counts and ex vivo eosinopoiesis/neutropoiesis. Full effectiveness in vivo required sequential oral/subcutaneous/intranasal exposures to the same allergen. Transfer of splenic T lymphocytes from OVA/OVA/OVA donors to naive recipients prevented bone marrow eosinophilia and eosinopoiesis in response to recipient sensitization/challenge and supressed eosinopoiesis upon coculture with syngeneic bone marrow precursors from sensitized/challenged donors.

  1. Factors affecting directional migration of bone marrow mesenchymal stem cells to the injured spinal cord.

    PubMed

    Xia, Peng; Pan, Su; Cheng, Jieping; Yang, Maoguang; Qi, Zhiping; Hou, Tingting; Yang, Xiaoyu

    2014-09-15

    Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtubule-associated protein 1B mediation of axon guidance and neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid or N-acetyl-D-erythro-sphingosine (an inhibitor and stimulator, respectively, of protein phosphatase 2A) for 24 hours. The expression of the phosphorylated form of type I microtubule-associated protein 1B in the cells was greater after exposure to okadaic acid and lower after N-acetyl-D-erythro-sphingosine. We then injected the bone marrow mesenchymal stem cells through the ear vein into rabbit models of spinal cord contusion. The migration of bone marrow mesenchymal stem cells towards the injured spinal cord was poorer in cells exposed to okadaic acid- and N-acetyl-D-erythro-sphingosine than in non-treated bone marrow mesenchymal stem cells. Finally, we blocked phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways in rabbit bone marrow mesenchymal stem cells using the inhibitors LY294002 and U0126, respectively. LY294002 resulted in an elevated expression of phosphorylated type I microtubule-associated protein 1B, whereas U0126 caused a reduction in expression. The present data indicate that PI3K and ERK1/2 in bone marrow mesenchymal stem cells modulate the phosphorylation of microtubule-associated protein 1B via a cross-signaling network, and affect the migratory efficiency of bone marrow mesenchymal stem cells towards injured spinal cord.

  2. [Protective effects of human bone marrow mesenchymal stem cells on hematopoietic organs of irradiated mice].

    PubMed

    Chen, Ling-Zhen; Yin, Song-Mei; Zhang, Xiao-Ling; Chen, Jia-Yu; Wei, Bo-Xiong; Zhan, Yu; Yu, Wei; Wu, Jin-Ming; Qu, Jia; Guo, Zi-Kuan

    2012-12-01

    The objective of this study was to explore the protective effects of human bone marrow mesenchymal stem cells (MSC) on hematopoietic organs of irradiated mice. Human bone marrow MSC were isolated, ex vivo expanded, and identified by cell biological tests. Female BALB/c mice were irradiated with (60)Co γ-ray at a single dose of 6 Gy, and received different doses of human MSC and MSC lysates or saline via tail veins. The survival of mice was record daily, and the femurs and spleens were harvested on day 9 and 16 for pathologic examination. The histological changes were observed and the cellularity was scored. The results showed that the estimated survival time of MSC- and MSC lysate-treated mice was comparable to that of controls. The hematopoiesis in the bone marrow of mice that received high-dose (5×10(6)) of MSC or MSC lysates was partially restored on day 9 and the capacity of hemopoietic tissue and cellularity scorings were significantly elevated as compared with that of controls (P < 0.05). Proliferative nudes were also obviously observed in the spleens of mice that received high-dose of MSC or MSC lysates on d 9 after irradiation. The histological structures of the spleen and bone marrow of the mice that received high-doses (5×10(6)) of MSC or MSC lysates were restored to normal, the cell proliferation displayed extraordinarily active. Further, the cellularity scores of the bone marrow were not significantly different between the high-dose MSC and MSC lysate-treated mice. It is concluded that the bone marrow MSC can promote the hematopoietic recovery of the irradiated mice, which probably is associated with the bioactive materials inherently existed in bone marrow cells.

  3. Retrospective Reconstructions of Active Bone Marrow Dose-Volume Histograms

    SciTech Connect

    Veres, Cristina; Allodji, Rodrigue S.; Llanas, Damien; Vu Bezin, Jérémi; Chavaudra, Jean; Mège, Jean Pierre; Lefkopoulos, Dimitri; Quiniou, Eric; Deutsh, Eric; Vathaire, Florent de; Diallo, Ibrahima

    2014-12-01

    Purpose: To present a method for calculating dose-volume histograms (DVH's) to the active bone marrow (ABM) of patients who had undergone radiation therapy (RT) and subsequently developed leukemia. Methods and Materials: The study focuses on 15 patients treated between 1961 and 1996. Whole-body RT planning computed tomographic (CT) data were not available. We therefore generated representative whole-body CTs similar to patient anatomy. In addition, we developed a method enabling us to obtain information on the density distribution of ABM all over the skeleton. Dose could then be calculated in a series of points distributed all over the skeleton in such a way that their local density reflected age-specific data for ABM distribution. Dose to particular regions and dose-volume histograms of the entire ABM were estimated for all patients. Results: Depending on patient age, the total number of dose calculation points generated ranged from 1,190,970 to 4,108,524. The average dose to ABM ranged from 0.3 to 16.4 Gy. Dose-volume histograms analysis showed that the median doses (D{sub 50%}) ranged from 0.06 to 12.8 Gy. We also evaluated the inhomogeneity of individual patient ABM dose distribution according to clinical situation. It was evident that the coefficient of variation of the dose for the whole ABM ranged from 1.0 to 5.7, which means that the standard deviation could be more than 5 times higher than the mean. Conclusions: For patients with available long-term follow-up data, our method provides reconstruction of dose-volume data comparable to detailed dose calculations, which have become standard in modern CT-based 3-dimensional RT planning. Our strategy of using dose-volume histograms offers new perspectives to retrospective epidemiological studies.

  4. T cell regeneration after allogenic bone marrow transplantation

    PubMed Central

    Favrot, Marie; Janossy, G.; Tidman, N.; Blacklock, Hilary; Lopez, Elisa; Bofill, Margarita; Lampert, I.; Morgenstein, G.; Powles, R.; Prentice, H. G.; Hoffbrand, A. V.

    1983-01-01

    Various T cell subsets were characterized by double immunofluorescent staining using monoclonal antibodies (MoAb) in blood, bone marrow (BM) and tissues of 29 patients after allogeneic BM transplantation (BMT). In an attempt to prevent graft versus host disease (GvHD), 15 patients received cyclosporin A (Cy A). In the remaining 14 patients the BM was pre-incubated with a MoAb, OKT3. The regeneration of T4+ subset was delayed and the level of T8+ cells was abnormally high even 1 year after engraftment. This did not have any predictive value for the appearance of complications such as GvHD or severe viral infections. The number of T8+ cells was lower in the group of patients who received Cy A than in the OKT3 group (0·7±0·2 vs 1·5±0·3×109/1 at day 90). In contrast to normal individuals, the T4/T8 ratio in both blood and regenerating BM of BMT patients was <1. A sizeable subset of circulating T cells expressed the phenotype T8+,T10+,HNK-1+,DR+. Circulating cells of this phenotype were transiently very high (up to 50%) in patients with active GvHD or suffering from severe viral infection. This subpopulation of lymphocytes was not found in the epidermal infiltrate that accompanied GvHD where the predominant phenotype was T8+,T1-,T10-,HNK-1-,DR-. We conclude therefore that after BMT the number and phenotype of circulating T cells reflects the T cell distribution seen in the regenerating BM. PMID:6352107

  5. Contribution of bone marrow-derived fibrocytes to liver fibrosis

    PubMed Central

    Xu, Jun; Cong, Min; Park, Tae Jun; Scholten, David; Brenner, David A.

    2015-01-01

    Since the discovery of fibrocytes in 1994 by Dr. Bucala and colleagues, these bone marrow (BM)-derived collagen Type I producing CD45+ cells remain the most fascinating cells of the hematopoietic system. Despite recent reports on the emerging contribution of fibrocytes to fibrosis of parenchymal and non-parenchymal organs and tissues, fibrocytes remain the most understudied pro-fibrogenic cellular population. In the past years fibrocytes were implicated in the pathogenesis of liver, skin, lung, and kidney fibrosis by giving rise to collagen type I producing cells/myofibroblasts. Hence, the role of fibrocytes in fibrosis is not well defined since different studies often contain controversial results on the number of fibrocytes recruited to the site of injury versus the number of fibrocyte-derived myofibroblasts in the same fibrotic organ. Furthermore, many studies were based on the in vitro characterization of fibrocytes formed after outgrowth of BM and/or peripheral blood cultures. Therefore, the fibrocyte function(s) still remain(s) lack of understanding, mostly due to (I) the lack of mouse models that can provide complimentary in vivo real-time and cell fate mapping studies of the dynamic differentiation of fibrocytes and their progeny into collagen type I producing cells (and/or possibly, other cell types of the hematopoietic system); (II) the complexity of hematopoietic cell differentiation pathways in response to various stimuli; (III) the high plasticity of hematopoietic cells. Here we summarize the current understanding of the role of CD45+ collagen type I+ BM-derived cells in the pathogenesis of liver injury. Based on data obtained from various organs undergoing fibrogenesis or other type of chronic injury, here we also discuss the most recent evidence supporting the critical role of fibrocytes in the mediation of pro-fibrogenic and/or pro-inflammatory responses. PMID:25713803

  6. Increased incidence of murine graft-versus-host disease after allogeneic bone marrow transplantation by previous infusion of syngeneic bone marrow cells

    SciTech Connect

    Waer, M.; Ang, K.K.; van der Schueren, E.; Vandeputte, M.

    1984-10-01

    Different groups of BALB/c mice received supralethal total-body irradiation (TBI; 8.5 Gy, day 0). When 30 x 10(6) allogeneic (C57B1) bone marrow (BM) cells were infused with or without 10 x 10(6) syngeneic (BALB/c) bM cells on day 1, many animals (60%) died from graft-versus-host disease (GVHD). Typing of peripheral blood leukocytes for donor antigens showed that, respectively, 22/22 and 17/21 of the mice in both groups became chimeric. When syngeneic bone marrow was given on day 1 and allogeneic bone marrow on day 2 after TBI, a similar number of animals (21/23) became chimeric, but GVHD occurred more frequently in this group (25/26 mice, P less than 0.01). When the syngeneic bone marrow cells were replaced by spleen cells, or when the transplantation of allogeneic bone marrow was delayed till days 3 or 6 after TBI, almost all mice rejected the allogeneic BM graft and became long-term survivors. BALB/c mice receiving 30 x 10(6) C57B1 BM cells after 17 daily fractions of 0.2 Gy of total lymphoid irradiation (TLI), showed a high incidence of chimerism (15/17) and in none of the latter animals was GVHD observed. Despite the high incidence of GVHD in the mice receiving allogeneic BM after TBI and syngeneic BM transplantation, as compared with mice prepared with TLI which do not develop GVHD, suppressor cells were as easily induced after TBI and syngeneic BM transplantation as after TLI.

  7. The need for T₂ correction on MRS-based vertebral bone marrow fat quantification: implications for bone marrow fat fraction age dependence.

    PubMed

    Dieckmeyer, Michael; Ruschke, Stefan; Cordes, Christian; Yap, Samuel P; Kooijman, Hendrik; Hauner, Hans; Rummeny, Ernst J; Bauer, Jan S; Baum, Thomas; Karampinos, Dimitrios C

    2015-04-01

    Vertebral bone marrow fat quantification using single-voxel MRS is confounded by overlapping water-fat peaks and the difference in T2 relaxation time between water and fat components. The purposes of the present study were: (i) to determine the proton density fat fraction (PDFF) of vertebral bone marrow using single-voxel multi-TE MRS, addressing these confounding effects; and (ii) to investigate the implications of these corrections with respect to the age dependence of the PDFF. Single-voxel MRS was performed in the L5 vertebral body of 86 subjects (54 women and 32 men). To reliably extract the water peak from the overlying fat peaks, the mean bone marrow fat spectrum was characterized based on the area of measurable fat peaks and an a priori knowledge of the chemical triglyceride structure. MRS measurements were performed at multiple TEs. The T2 -weighted fat fraction was calculated at each TE. In addition, a T2 correction was performed to obtain the PDFF and the T2 value of water (T2w ) was calculated. The implications of the T2 correction were investigated by studying the age dependence of the T2 -weighted fat fractions and the PDFF. Compared with the PDFF, all T2 -weighted fat fractions significantly overestimated the fat fraction. Compared with the age dependence of the PDFF, the age dependence of the T2 -weighted fat fraction showed an increased slope and intercept as TE increased for women and a strongly increased intercept as TE increased for men. For women, a negative association between the T2 value of bone marrow water and PDFF was found. Single-voxel MRS-based vertebral bone marrow fat quantification should be based on a multi-TE MRS measurement to minimize confounding effects on PDFF determination, and also to allow the simultaneous calculation of T2w , which might be considered as an additional parameter sensitive to the composition of the water compartment.

  8. A hostel for the hostile: the bone marrow niche in hematologic neoplasms

    PubMed Central

    Krause, Daniela S.; Scadden, David T.

    2015-01-01

    Our understanding of the biology of the normal hematopoietic stem cell niche has increased steadily due to improved murine models and sophisticated imaging tools. Less well understood, but of growing interest, is the interaction between cells in the bone marrow during the initiation, maintenance and treatment of hematologic neoplasms. This review summarizes the emerging concepts of the normal and leukemic hematopoietic bone marrow niche. Furthermore, it reviews current models of how the microenvironment of the bone marrow may contribute to or be modified by leukemogenesis. Finally, it provides the rationale for a “two-pronged” approach, directly targeting cancer cells themselves while also targeting the bone microenvironment to make it inhospitable to malignant cells and, ultimately, eradicating cancer stem-like cells. PMID:26521296

  9. Alfacalcidol increases cancellous bone in low turnover, fatty marrow sites in aged, orchidectomized rats.

    PubMed

    Tian, X Y; Chen, H Y; Setterberg, R B; Li, M; Jee, W S S

    2009-01-01

    The objectives of this study were to determine the responses of cancellous bone in the distal tibial metaphysis (DTM), a low turnover, fatty (yellow) marrow site, to sham-aged, orchidectomy (ORX) and alfacalcidol treatment in sham-aged and ORX rats. Eighteen-month-old male sham and ORX rats were treated with 0.1 and 0.2 microg/kg alfacalcidol 5 days/wk p.o. for 12 weeks, double fluorescent labeled, and the DTM were processed for bone histomorphometry analyses. The current study found the DTM in sham-aged male rats were resistant to age-related and ORX-induced cancellous bone loss and alfacalcidol-induced bone gain, findings that differ from that in the proximal tibial metaphysis (PTM) and lumbar vertebral body (LVB), two high turnover, red marrow bone sites. However, alfacalcidol treatment increased DTM bone mass in ORX rats where bone turnover was elevated by androgen deficiency. These results in concert with the previously positive findings in red marrow bone sites following alfacalcidol treatment suggest that alfacalcidol is more effective in increasing cancellous bone mass in the skeletal sites with higher bone turnover.

  10. Role of T cells in sex differences in syngeneic bone marrow transfers

    SciTech Connect

    Raveche, E.S.; Santoro, T.; Brecher, G.; Tjio, J.H.

    1985-11-01

    Transferred marrow cells will proliferate in normal mice not exposed to irradiation or any other type of stem cell depletion when five consecutive transfers of 40 million cells are given. Approximately 25% of the mitotic cells are of male donor origin observed cytogenetically in all of the female recipient spleens and marrow analyzed from two weeks to one and one-half years after transfusions. Male donor stem cells are accepted and form a stable component of the self-renewing stem cell pool. In contrast, only 5% female cells are found in male recipients. This sex difference in engraftment is not hormonal since castration of recipients does not alter the percentage of donor cells. Rigorous T depletion of female donor bone marrow, however, increases the percentage of donor engraftment to the level observed when male marrow, either whole or T depleted, is transferred to female recipients. The success of T-depleted female stem cells to seed male recipients is observed in both C57BL/6 and CBA/J. In addition, recipient nude BALB/c males, which lack a thymus, fail to accept whole bone marrow from BALB/c females. However, male bone marrow cells seed BALB/c nude females. These studies demonstrate that the poor engraftment of female cells in transfused male recipients is abrogated by the removal of T cells from the donor female marrow.

  11. Bone Marrow Adipocytes Facilitate Fatty Acid Oxidation Activating AMPK and a Transcriptional Network Supporting Survival of Acute Monocytic Leukemia Cells.

    PubMed

    Tabe, Yoko; Yamamoto, Shinichi; Saitoh, Kaori; Sekihara, Kazumasa; Monma, Norikazu; Ikeo, Kazuho; Mogushi, Kaoru; Shikami, Masato; Ruvolo, Vivian; Ishizawa, Jo; Hail, Numsen; Kazuno, Saiko; Igarashi, Mamoru; Matsushita, Hiromichi; Yamanaka, Yasunari; Arai, Hajime; Nagaoka, Isao; Miida, Takashi; Hayashizaki, Yoshihide; Konopleva, Marina; Andreeff, Michael

    2017-03-15

    Leukemia cells in the bone marrow must meet the biochemical demands of increased cell proliferation and also survive by continually adapting to fluctuations in nutrient and oxygen availability. Thus, targeting metabolic abnormalities in leukemia cells located in the bone marrow is a novel therapeutic approach. In this study, we investigated the metabolic role of bone marrow adipocytes in supporting the growth of leukemic blasts. Prevention of nutrient starvation-induced apoptosis of leukemic cells by bone marrow adipocytes, as well as the metabolic and molecular mechanisms involved in this process, was investigated using various analytic techniques. In acute monocytic leukemia (AMoL) cells, the prevention of spontaneous apoptosis by bone marrow adipocytes was associated with an increase in fatty acid β-oxidation (FAO) along with the upregulation of PPARγ, FABP4, CD36, and BCL2 genes. In AMoL cells, bone marrow adipocyte coculture increased adiponectin receptor gene expression and its downstream target stress response kinase AMPK, p38 MAPK with autophagy activation, and upregulated antiapoptotic chaperone HSPs. Inhibition of FAO disrupted metabolic homeostasis, increased reactive oxygen species production, and induced the integrated stress response mediator ATF4 and apoptosis in AMoL cells cocultured with bone marrow adipocytes. Our results suggest that bone marrow adipocytes support AMoL cell survival by regulating their metabolic energy balance and that the disruption of FAO in bone marrow adipocytes may be an alternative, novel therapeutic strategy for AMoL therapy. Cancer Res; 77(6); 1453-64. ©2017 AACR.

  12. The role of bone marrow-derived cells in bone fracture repair in a green fluorescent protein chimeric mouse model

    SciTech Connect

    Taguchi, Kazuhiro . E-mail: s3061@nms.ac.jp; Ogawa, Rei; Migita, Makoto; Hanawa, Hideki; Ito, Hiromoto; Orimo, Hideo

    2005-05-27

    We investigated the role of bone marrow cells in bone fracture repair using green fluorescent protein (GFP) chimeric model mice. First, the chimeric model mice were created: bone marrow cells from GFP-transgenic C57BL/6 mice were injected into the tail veins of recipient wild-type C57BL/6 mice that had been irradiated with a lethal dose of 10 Gy from a cesium source. Next, bone fracture models were created from these mice: closed transverse fractures of the left femur were produced using a specially designed device. One, three, and five weeks later, fracture lesions were extirpated for histological and immunohistochemical analyses. In the specimens collected 3 and 5 weeks after operation, we confirmed calluses showing intramembranous ossification peripheral to the fracture site. The calluses consisted of GFP- and osteocalcin-positive cells at the same site, although the femur consisted of only osteocalcin-positive cells. We suggest that bone marrow cells migrated outside of the bone marrow and differentiated into osteoblasts to make up the calluses.

  13. Selective retention of bone marrow-derived cells to enhance spinal fusion.

    PubMed

    Muschler, George F; Matsukura, Yoichi; Nitto, Hironori; Boehm, Cynthia A; Valdevit, Antonio D; Kambic, Helen E; Davros, William J; Easley, Kirk A; Powell, Kimerly A

    2005-03-01

    Connective tissue progenitors can be concentrated rapidly from fresh bone marrow aspirates using some porous matrices as a surface for cell attachment and selective retention, and for creating a cellular graft that is enriched with respect to the number of progenitor cells. We evaluated the potential value of this method using demineralized cortical bone powder as the matrix. Matrix alone, matrix plus marrow, and matrix enriched with marrow cells were compared in an established canine spinal fusion model. Fusions were compared based on union score, fusion mass, fusion volume, and by mechanical testing. Enriched matrix grafts delivered a mean of 2.3 times more cells and approximately 5.6 times more progenitors than matrix mixed with bone marrow. The union score with enriched matrix was superior to matrix alone and matrix plus marrow. Fusion volume and fusion area also were greater with the enriched matrix. These data suggest that the strategy of selective retention provides a rapid, simple, and effective method for concentration and delivery of marrow-derived cells and connective tissue progenitors that may improve the outcome of bone grafting procedures in various clinical settings.

  14. Allospecific rejection of MHC class I-deficient bone marrow by CD8 T cells

    PubMed Central

    Haspot, Fabienne; Li, Hao Wei; Lucas, Carrie L.; Fehr, Thomas; Beyaz, Semir; Sykes, Megan

    2014-01-01

    Avoidance of long-term immunosuppression is a desired goal in organ transplantation. Mixed chimerism offers a promising approach to tolerance induction, and we have aimed to develop low-toxicity, non-immunodepleting approaches to achieve this outcome. In a mouse model achieving fully MHC-mismatched allogeneic bone marrow engraftment with minimal conditioning (3 Gy total body irradiation followed by anti-CD154 and T cell-depleted allogeneic bone marrow cells), CD4 T cells in the recipient are required to promote tolerance of pre-existing alloreactive recipient CD8 T cells and thereby permit chimerism induction. We now demonstrate that mice devoid of CD4 T cells and NK cells reject MHC class-I deficient and class I/class II-deficient marrow in a CD8 T cell-dependent manner. This rejection is specific for donor alloantigens, since recipient hematopoiesis is not affected by donor marrow rejection and MHC class-I deficient bone marrow that is syngeneic to the recipient is not rejected. Recipient CD8 T cells are activated and develop cytotoxicity against MHC class I-deficient donor cells in association with rejection. These data implicate a novel CD8 T cell-dependent bone marrow rejection pathway, wherein recipient CD8 T cells indirectly activated by donor alloantigens promote direct killing, in a TCR-independent manner, of class I-deficient donor cells. PMID:24304495

  15. Cadmium stimulates osteoclast-like multinucleated cell formation in mouse bone marrow cell cultures

    SciTech Connect

    Miyahara, Tatsuro; Takata, Masakazu; Miyata, Masaki; Nagai, Miyuki; Sugure, Akemi; Kozuka, Hiroshi; Kuze, Shougo )

    1991-08-01

    Most of cadmium (Cd)-treated animals have been reported to show osteoporosis-like changes in bones. This suggests that Cd may promote bone loss by a direct action on bone. It was found that Cd stimulated prostaglandin E{sub 2}(PGE{sub 2}) production in the osteoblast-like cell, MC3T3-E1. Therefore, Cd stimulates bone resorption by increasing PGE{sub 2} production. Recently, several bone marrow cell culture systems have been developed for examining the formation of osteoclast-like multinucleated cells in vitro. As osteoblasts produce PGE{sub 2} by Cd-induced cyclooxygenase and may play an important role in osteoclast formation, the present study was undertaken to clarify the possibility that Cd might stimulate osteoclast formation in a mouse bone marrow culture system.

  16. Comparison of autogenic and allogenic bone marrow derived mesenchymal stem cells for repair of segmental bone defects in rabbits.

    PubMed

    Udehiya, Rahul Kumar; Amarpal; Aithal, H P; Kinjavdekar, P; Pawde, A M; Singh, Rajendra; Taru Sharma, G

    2013-06-01

    Autogenic and allogenic bone marrow derived mesenchymal stem cells (BM-MSCs) were compared for repair of bone gap defect in rabbits. BM-MSCs were isolated from bone marrow aspirates and cultured in vitro for allogenic and autogenic transplantation. A 5mm segmental defect was created in mid-diaphysis of the radius bone. The defect was filled with hydroxyapatite alone, hydroxyapatite with autogeneic BM-MSCs and hydroxyapatite with allogenic BM-MSCs in groups A, B and C, respectively. On an average 3.45×10(6) cells were implanted at each defect site. Complete bridging of bone gap with newly formed bone was faster in both treatment groups as compared to control group. Histologically, increased osteogenesis, early and better reorganization of cancellous bone and more bone marrow formation were discernible in treatment groups as compared to control group. It was concluded that in vitro culture expanded allogenic and autogenic BM-MSCs induce similar, but faster and better healing as compared to control.

  17. Murine bone marrow IgA responses to orally administered sheep erythrocytes.

    PubMed

    Alley, C D; Kiyono, H; McGhee, J R

    1986-06-15

    Specific immunization protocols have been established for the induction of murine bone marrow IgA responses to the T cell-dependent (TD) antigen sheep red blood cells (SRBC). Systemic immunization, either i.p. or i.v., followed by a second injection, induced splenic IgM and IgG responses and a bone marrow IgM response. No significant IgA responses were observed in either lymphoid tissue compartment. Oral immunization with SRBC by gastric intubation for 2 days, followed 1 wk later by an i.p. injection of SRBC resulted in a splenic IgA plaque-forming cell (PFC) response, but did not elicit a bone marrow IgA response. Repeated daily gastric intubation of SRBC to C3H/HeN and C3H/HeJ mice led to the previously reported pattern of systemic unresponsiveness in C3H/HeN mice and good anamnestic type IgM, IgG, and IgA splenic anti-SRBC PFC responses in the C3H/HeJ strain upon parenteral challenge. Oral administration of SRBC for 14 days to C3H/HeN mice, followed by systemic SRBC challenge, resulted in diminished splenic PFC responses of all isotypes, whereas gastric intubation of SRBC for 28 days led to complete systemic unresponsiveness to antigen in C3H/HeN mice. Interestingly, the repeated oral administration of SRBC resulted in significant bone marrow IgA PFC responses upon i.p. challenge in both C3H/HeN and C3H/HeJ mouse strains. The bone marrow IgA responses were clearly dependent upon chronic oral exposure to SRBC, because gastric intubation with SRBC for 2 consecutive days/wk for 10 wk also induced bone marrow and splenic IgA anti-SRBC PFC responses in C3H/HeN mice. These results suggest that memory B cells reside in the bone marrow of orally immunized mice and can yield anamnestic-type responses to challenge with the inducing antigen. The memory cells may arise in the Peyer's patches of the gut and migrate to the bone marrow. The possibility that the bone marrow is a component of the common mucosal immune system in mammals is suggested by this study.

  18. Characterization of a 5-fluorouracil-enriched osteoprogenitor population of the murine bone marrow.

    PubMed

    Falla, N; Van Vlasselaer; Bierkens, J; Borremans, B; Schoeters, G; Van Gorp, U

    1993-12-15

    In the presence of beta-glycerophosphate and vitamin C, cultures of normal mouse bone marrow cells form three-dimensional structures that stain positive with the Von Kossa technique and express alkaline phosphatase (ALP), collagen type I, and osteocalcin. Little is known about the characteristics and frequency of the cells that contribute to this phenomenon. Most likely, mature osteoblastic cells do not contribute to the nodule formation because no osteocalcin expressing cells are detected in the flushed marrow by in situ hybridization. Limiting dilution analysis shows that, in normal bone marrow, 1 of 2.2 x 10(5) cells has the potency to form a bone nodule and to express ALP, collagen, and osteocalcin in a temporal fashion. Upon in vivo treatment with 5-fluorouracil (5-FU), this frequency increases 12-fold, eg, 1 in 1.75 x 10(4) cells shows osteogenic activity. In comparison, fibroblast colony forming cells occur at a frequency of 1 of 2.5 x 10(4) or 1 of 5 x 10(3) plated cells in normal or 5-FU-treated marrow, respectively. Using density centrifugation, the majority of the osteoprogenitor cells in 5-FU marrow are found in the low-density (1.066 to 1.067 g/mL) fractions. In addition, these cells bind to nylon wool but not to plastic and aggregate in the presence of wheat germ agglutinin and soybean agglutinin. Scanning and transmission electron microscopy shows that the bone nodules in 5-FU marrow cultures are composed of fibroblastoid cells embedded in a mineralized collagen matrix. In conclusion, our results show that a quiescent cell population in the murine bone marrow with fibroblastoid characteristics contributes to the formation of bone-like nodules in vitro.

  19. Granule cargo release from bone marrow-derived cells sustains cardiac hypertrophy.

    PubMed

    Yang, Fanmuyi; Dong, Anping; Ahamed, Jasimuddin; Sunkara, Manjula; Smyth, Susan S

    2014-11-15

    Bone marrow-derived inflammatory cells, including platelets, may contribute to the progression of pressure overload-induced left ventricular hypertrophy (LVH). However, the underlying mechanisms for this are still unclear. One potential mechanism is through release of granule cargo. Unc13-d(Jinx) (Jinx) mice, which lack Munc13-4, a limiting factor in vesicular priming and fusion, have granule secretion defects in a variety of hematopoietic cells, including platelets. In the current study, we investigated the role of granule secretion in the development of LVH and cardiac remodeling using chimeric mice specifically lacking Munc13-4 in marrow-derived cells. Pressure overload was elicited by transverse aortic constriction (TAC). Chimeric mice were created by bone marrow transplantation. Echocardiography, histology staining, immunohistochemistry, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and mass spectrometry were used to study LVH progression and inflammatory responses. Wild-type (WT) mice that were transplanted with WT bone marrow (WT→WT) and WT mice that received Jinx bone marrow (Jinx→WT) developed LVH and a classic fetal reprogramming response early (7 days) after TAC. However, at late times (5 wk), mice lacking Munc13-4 in bone marrow-derived cells (Jinx→WT) failed to sustain the cardiac hypertrophy observed in WT chimeric mice. No difference in cardiac fibrosis was observed at early or late time points. Reinjection of WT platelets or platelet releasate partially restored cardiac hypertrophy in Jinx chimeric mice. These results suggest that sustained LVH in the setting of pressure overload depends on one or more factors secreted from bone marrow-derived cells, possibly from platelets. Inhibiting granule cargo release may represent a novel target for preventing sustained LVH.

  20. Stereological study of human bone marrow adipocytes. A comparison of four methods for estimating size distributions.

    PubMed

    Reverter, J C; Feliu, E; Climent, C; Rozman, M; Berga, L; Rozman, C

    1993-12-01

    Several methods are available for estimating size distributions of spherical objects in tissue sections. In this article a comparative study of four stereological techniques applied to human bone marrow adipocytes was carried out. In the first part, four stereological methods (Giger-Riedwyl, Saltykov, Wicksell, and Cruz-Orive) were used for the evaluation of adipocyte size in a set of 50 human bone marrow specimens (20 normal controls, 10 aplastic, 10 hyperplastic and 10 dysplastic bone marrows). In the second part, a computer simulation model was employed for generating both control and test populations. The latter were analyzed by means of the four stereological methods and compared to the control. When applied to bone marrow specimens, no statistically significant differences were seen among the four methods. Results were very close between the Giger-Riedwyl and Saltykov methods, and between the Wicksell and Cruz-Orive methods. In the simulation model, Saltykov's method was the most accurate stereological technique for the studied conditions. Additional advantages of this method are that the assumption of Gaussian distribution is not required, and that a higher relative weight is assigned to the largest classes, in which accurate definition is easier in the microphotographs. However, since the differences among the four methods are very small, they may all be considered as valid for the stereological study of human bone marrow adipocytes.

  1. Immunoglobulin levels in dogs after total-body irradiation and bone marrow transplantation

    SciTech Connect

    Vriesendorp, H.M.; Halliwell, R.E.; Johnson, P.M.; Fey, T.A.; McDonough, C.M.

    1985-06-01

    The influence of total-body irradiation (TBI) and autologous or allogeneic bone marrow transplantation on serum immunoglobulin subclasses was determined in a dog model. Only IgG1 levels decreased after low-dose (+/- 4.5 Gy) TBI, but levels of all immunoglobulin classes fell after high-dose TBI (8.5 GyX1 or 2X6.0 Gy). After autologous bone marrow transplantation IgM levels were the first and IgE levels were the last to return to normal. After successful allogeneic bone marrow transplantation prolonged low IgM and IgE levels were found but IgA levels increased rapidly to over 150% of pretreatment values. A comparison of dogs with or without clinical signs or graft-versus-host disease (GVHD), revealed no differences in IgM levels. Dogs with GVHD had higher IgA but lower IgE levels. Dogs that rejected their allogeneic bone marrow cells showed significant early rises in IgE and IgA levels in comparison with dogs with GVHD. These results differ from the observations made on Ig levels in human bone marrow transplant patients. No significant differences in phytohemagglutinin stimulation tests were found between dogs with or without GVHD or dogs receiving an autologous transplant for the first four months after TBI and transplantation. An early primary or secondary involvement of humoral immunity in GVHD and graft rejection in dogs is postulated.

  2. Characterization, Quantification, and Determination of the Toxicity of Iron Oxide Nanoparticles to the Bone Marrow Cells

    PubMed Central

    Paik, Sae-Yeol-Rim; Kim, Jong-Seok; Shin, Sung Jae; Ko, Sanghoon

    2015-01-01

    Iron oxide nanoparticles (IONPs) have been used to develop iron supplements for improving the bioavailability of iron in patients with iron deficiency, which is one of the most serious nutritional deficiencies in the world. Accurate information about the characteristics, concentration, and cytotoxicity of IONPs to the developmental and reproductive cells enables safe use of IONPs in the supplement industry. The objective of this study was to analyze the physicochemical properties and cytotoxicity of IONPs in bone marrow cells. We prepared three different types of iron samples (surface-modified iron oxide nanoparticles (SMNPs), IONPs, and iron citrate) and analyzed their physicochemical properties such as particle size distribution, zeta potential, and morphology. In addition, we examined the cytotoxicity of the IONPs in various kinds of bone marrow cells. We analyzed particle size distribution, zeta potential, iron levels, and subcellular localization of the iron samples in bone marrow cells. Our results showed that the iron samples were not cytotoxic to the bone marrow cells and did not affect the expression of cell surface markers and lipopolysaccharide (LPS)-induced the secretion of cytokines by murine bone marrow-derived dendritic cells (BMDCs). Our results may be used to investigate the interactions between nanoparticles and cells and tissues and the developmental toxicity of nanoparticles. PMID:26389886

  3. Combined Bone Marrow and Kidney Transplantation for the Induction of Specific Tolerance

    PubMed Central

    Chen, Yi-Bin; Kawai, Tatsuo; Spitzer, Thomas R.

    2016-01-01

    The induction of specific tolerance, in order to avoid the detrimental effects of lifelong systemic immunosuppressive therapy after organ transplantation, has been considered the “Holy Grail” of transplantation. Experimentally, tolerance has been achieved through clonal deletion, through costimulatory blockade, through the induction or infusion of regulatory T-cells, and through the establishment of hematopoietic chimerism following donor bone marrow transplantation. The focus of this review is how tolerance has been achieved following combined bone marrow and kidney transplantation. Preclinical models of combined bone marrow and kidney transplantation have shown that tolerance can be achieved through either transient or sustained hematopoietic chimerism. Combined transplants for patients with multiple myeloma have shown that organ tolerance and prolonged disease remissions can be accomplished with such an approach. Similarly, multiple clinical strategies for achieving tolerance in patients without an underlying malignancy have been described, in the context of either transient or durable mixed chimerism or sustained full donor hematopoiesis. To expand the chimerism approach to deceased donor transplants, a delayed tolerance approach, which will involve organ transplantation with conventional immunosuppression followed months later by bone marrow transplantation, has been successful in a primate model. As combined bone marrow and organ transplantation become safer and increasingly successful, the achievement of specific tolerance may become more widely applicable. PMID:27239198

  4. Expression of Cadherin-17 Promotes Metastasis in a Highly Bone Marrow Metastatic Murine Breast Cancer Model

    PubMed Central

    Kurabayashi, Atsushi; Furihata, Mutsuo

    2017-01-01

    We previously established 4T1E/M3 highly bone marrow metastatic mouse breast cancer cells through in vivo selection of 4T1 cells. But while the incidence of bone marrow metastasis of 4T1E/M3 cells was high (~80%) when injected intravenously to mice, it was rather low (~20%) when injected subcutaneously. Therefore, using 4T1E/M3 cells, we carried out further in vitro and in vivo selection steps to establish FP10SC2 cells, which show a very high incidence of metastasis to lungs (100%) and spines (85%) after subcutaneous injection into mice. qRT-PCR and western bolt analysis revealed that cadherin-17 gene and protein expression were higher in FP10SC2 cells than in parental 4T1E/M3 cells. In addition, immunostaining revealed the presence of cadherin-17 at sites of bone marrow and lung metastasis after subcutaneous injection of FP10SC2 cells into mice. Suppressing cadherin-17 expression in FP10SC2 cells using RNAi dramatically decreased the cells' anchorage-independent growth and migration in vitro and their metastasis to lung and bone marrow in vivo. These findings suggest that cadherin-17 plays a crucial role in mediating breast cancer metastasis to bone marrow. PMID:28197418

  5. Regression of Adjuvant-Induced Arthritis in Rats Following Bone Marrow Transplantation

    NASA Astrophysics Data System (ADS)

    van Bekkum, Dirk W.; Bohre, Els P. M.; Houben, Paul F. J.; Knaan-Shanzer, Shoshan

    1989-12-01

    Total body irradiation followed by bone marrow transplantation was found to be an effective treatment for adjuvant arthritis induced in rats. This treatment is most effective when applied shortly after the clinical manifestation of arthritis--i.e., 4-7 weeks after administration of Mycobacterium tuberculosis. Transplantation of bone marrow at a later stage results in a limited recovery, in that the inflammatory reaction regresses but the newly formed excessive bone is not eliminated. Local irradiation of the affected joints had no effect on the disease. It could also be excluded that the recovery of arthritis following marrow transplantation is due to lack of available antigen. Transplantation of syngeneic bone marrow is as effective as that of allogeneic bone marrow from a rat strain that is not susceptible to induction of adjuvant arthritis. The beneficial effect of this treatment cannot be ascribed to the immunosuppressive effect of total body irradiation, since treatment with the highly immunosuppressive drug Cyclosporin A resulted in a regression of the joint swelling but relapse occurred shortly after discontinuation of the treatment.

  6. Monoclonal antibodies in the detection of bone marrow metastases in small cell lung cancer.

    PubMed

    Skov, B G; Hirsch, F R; Bobrow, L

    1992-04-01

    Using conventional examination (CE) of H&E stained slides from bone marrow aspirates, metastases can be detected in approximately 25% of patients with small cell lung cancer. We investigated a panel of monoclonal antibodies using immunohistochemistry in the diagnosis of bone marrow infiltration from SCLC and compared the results with CE. Seven monoclonal antibodies raised against epithelial antigens (CAM 5.2, MOV 15, NCCST 433, PE 35, LCA1/L38, HMFG 1 AND HMFG 2) were applied on bone marrow sections from three groups of patients (pts): (1) 19 pts in whom SCLC-metastases were detected by CE, (2) 44 pts with SCLC in whom metastases could not be detected by CE, and (3) 20 pts with non-malignant bone marrow diseases. All the antibodies except LCA1/L38 were positive in 60-90% of the slides with infiltrating tumour cells in group 1. No positive tumour cells were detected in group 2. A few plasma cells and megakaryocytes were slightly positive for MOV 15 and NCCST 433, but no other positive cells were detected in group 3. In conclusion, the monoclonal antibodies used in this study may be useful for diagnostic purposes when a suspicious looking infiltration is detected by CE. However, these antibodies could not detect metastatic tumour cells in the bone marrow sections from patients in whom CE did not reveal any tumour cells.

  7. Tracking Intracavernously Injected Adipose-Derived Stem Cells to Bone Marrow

    PubMed Central

    Lin, Guiting; Qiu, Xuefeng; Fandel, Thomas; Banie, Lia; Wang, Guifang; Lue, Tom F.; Lin, Ching-Shwun

    2012-01-01

    Intracavernous (IC) injection of stem cells (SCs) has been shown to improve erectile function in various erectile dysfunction (ED) animal models. However, the tissue distribution of the injected cells remains unknown. In this study we tracked IC injected adipose-derived stem cells (ADSCs) in various tissues. Rat paratesticular fat was processed for ADSC isolation and culture. The animals were then subject to cavernous nerve (CN) crush injury or sham operation, followed by IC injection of one million autologous or allogeneic ADSCs that were labeled with 5-ethynyl-2-deoxyuridine (EdU). Another group of rats received IC injection of EdU-labeled allogeneic penile smooth muscle cells (PSMCs). At 2 and 7 days post-injection, penises and femoral bone marrow were processed for histological analyses. Whole femoral bone marrows were also analyzed for EdU-positive cells by flow cytometry. The results show that ADSCs exited the penis within days of IC injection and migrated preferentially to bone marrow. Allogenicity did not affect ADSC's bone marrow appearance either at 2 or 7 days, while CN injury reduced the number of ADSCs in bone marrow significantly at 7 but not 2 days. The significance of these results in relation to SC therapy for ED is discussed. PMID:21796145

  8. Encapsulated Whole Bone Marrow Cells Improve Survival in Wistar Rats after 90% Partial Hepatectomy

    PubMed Central

    Uribe-Cruz, Carolina; Kieling, Carlos Oscar; López, Mónica Luján; Osvaldt, Alessandro; Ochs de Muñoz, Gustavo; da Silveira, Themis Reverbel; Giugliani, Roberto; Matte, Ursula

    2016-01-01

    Background and Aims. The use of bone marrow cells has been suggested as an alternative treatment for acute liver failure. In this study, we investigate the effect of encapsulated whole bone marrow cells in a liver failure model. Methods. Encapsulated cells or empty capsules were implanted in rats submitted to 90% partial hepatectomy. The survival rate was assessed. Another group was euthanized at 6, 12, 24, 48, and 72 hours after hepatectomy to study expression of cytokines and growth factors. Results. Whole bone marrow group showed a higher than 10 days survival rate compared to empty capsules group. Gene expression related to early phase of liver regeneration at 6 hours after hepatectomy was decreased in encapsulated cells group, whereas genes related to regeneration were increased at 12, 24, and 48 hours. Whole bone marrow group showed lower regeneration rate at 72 hours and higher expression and activity of caspase 3. In contrast, lysosomal-β-glucuronidase activity was elevated in empty capsules group. Conclusions. The results show that encapsulated whole bone marrow cells reduce the expression of genes involved in liver regeneration and increase those responsible for ending hepatocyte division. In addition, these cells favor apoptotic cell death and decrease necrosis, thus increasing survival. PMID:26649048

  9. Imaging Sensitivity of Quiescent Cancer Cells to Metabolic Perturbations in Bone Marrow Spheroids

    PubMed Central

    Cavnar, Stephen P.; Xiao, Annie; Gibbons, Anne E.; Rickelmann, Andrew D.; Neely, Taylor; Luker, Kathryn E.; Takayama, Shuichi; Luker, Gary D.

    2016-01-01

    Malignant cells from breast cancer and other common cancers such as prostate and melanoma may persist in bone marrow as quiescent, non-dividing cells that remain viable for years or even decades before resuming proliferation to cause recurrent disease. This phenomenon, referred to clinically as tumor dormancy, poses tremendous challenges to curing patients with breast cancer. Quiescent tumor cells resist chemotherapy drugs that predominantly target proliferating cells, limiting success of neo-adjuvant and adjuvant therapies. We recently developed a 3D spheroid model of quiescent breast cancer cells in bone marrow for mechanistic and drug testing studies. We combined this model with optical imaging methods for label-free detection of cells preferentially utilizing glycolysis versus oxidative metabolism to investigate the metabolic state of co-culture spheroids with different bone marrow stromal and breast cancer cells. Through imaging and biochemical assays, we identified different metabolic states of bone marrow stromal cells that control metabolic status and flexibilities of co-cultured breast cancer cells. We tested metabolic stresses and targeted inhibition of specific metabolic pathways to identify approaches to preferentially eliminate quiescent breast cancer cells from bone marrow environments. These studies establish an integrated imaging approach to analyze metabolism in complex tissue environments to identify new metabolically-targeted cancer therapies. PMID:27478871

  10. Sinusoidal ephrin receptor EPHB4 controls hematopoietic progenitor cell mobilization from bone marrow

    PubMed Central

    Kwak, Hyeongil; Salvucci, Ombretta; Weigert, Roberto; Martinez-Torrecuadrada, Jorge L.; Henkemeyer, Mark; Poulos, Michael G.; Butler, Jason M.

    2016-01-01

    Hematopoietic stem and progenitor cells (HSPCs) reside in the bone marrow. Stress signals from cancer and other conditions promote HSPC mobilization into circulation and subsequent homing to tissue microenvironments. HSPC infiltration into tissue microenvironments can influence disease progression; notably, in cancer, HSPCs encourage tumor growth. Here we have uncovered a mutually exclusive distribution of EPHB4 receptors in bone marrow sinusoids and ephrin B2 ligands in hematopoietic cells. We determined that signaling interactions between EPHB4 and ephrin B2 control HSPC mobilization from the bone marrow. In mice, blockade of the EPHB4/ephrin B2 signaling pathway reduced mobilization of HSPCs and other myeloid cells to the circulation. EPHB4/ephrin B2 blockade also reduced HSPC infiltration into tumors as well as tumor progression in murine models of melanoma and mammary cancer. These results identify EPHB4/ephrin B2 signaling as critical to HSPC mobilization from bone marrow and provide a potential strategy for reducing cancer progression by targeting the bone marrow. PMID:27820703

  11. Intensive care outcomes in bone marrow transplant recipients: a population-based cohort analysis

    PubMed Central

    Scales, Damon C; Thiruchelvam, Deva; Kiss, Alexander; Sibbald, William J; Redelmeier, Donald A

    2008-01-01

    Introduction Intensive care unit (ICU) admission for bone marrow transplant recipients immediately following transplantation is an ominous event, yet the survival of these patients with subsequent ICU admissions is unknown. Our objective was to determine the long-term outcome of bone marrow transplant recipients admitted to an ICU during subsequent hospitalizations. Methods We conducted a population-based cohort analysis of all adult bone marrow transplant recipients who received subsequent ICU care in Ontario, Canada from 1 January 1992 to 31 March 2002. The primary endpoint was mortality at 1 year. Results A total of 2,653 patients received bone marrow transplantation; 504 of which received ICU care during a subsequent hospitalization. Patients receiving any major procedure during their ICU stay had higher 1-year mortality than those patients who received no ICU procedure (87% versus 44%, P < 0.0001). Death rates at 1 year were highest for those receiving mechanical ventilation (87%), pulmonary artery catheterization (91%), or hemodialysis (94%). In combination, the strongest independent predictors of death at 1 year were mechanical ventilation (odds ratio, 7.4; 95% confidence interval, 4.8 to 11.4) and hemodialysis (odds ratio, 8.7; 95% confidence interval, 2.1 to 36.7), yet no combination of procedures uniformly predicted 100% mortality. Conclusion The prognosis of bone marrow transplant recipients receiving ICU care during subsequent hospitalizations is very poor but should not be considered futile. PMID:18547422

  12. Thyroid dysfunction among long-term survivors of bone marrow transplantation

    SciTech Connect

    Sklar, C.A.; Kim, T.H.; Ramsay, N.K.

    1982-11-01

    Thyroid function studies were followed serially in 27 long-term survivors (median 33 months) of bone marrow transplantation. There were 15 men and 12 women (median age 13 1/12 years, range 11/12 to 22 6/12 years). Aplastic anemia (14 patients) and acute nonlymphocytic leukemia (eight patients) were the major reasons for bone marrow transplantation. Pretransplant conditioning consisted of single-dose irradiation combined with high-dose, short-term chemotherapy in 23 patients, while four patients received a bone marrow transplantation without any radiation therapy. Thyroid dysfunction occurred in 10 of 23 (43 percent) irradiated patients; compensated hypothyroidism (elevated thyroid-stimulating hormone levels only) developed in eight subjects, and two patients had primary thyroid failure (elevated thyroid-stimulating hormone levels and low T4 index). The abnormal thyroid studies were detected a median of 13 months after bone marrow transplantation. The four subjects who underwent transplantation without radiation therapy have remained euthyroid (median follow-up two years). The only variable that appeared to correlate with the subsequent development of impaired thyroid function was the type of graft-versus-host disease prophylaxis employed; the irradiated subjects treated with methotrexate alone had a higher incidence of thyroid dysfunction compared to those treated with methotrexate combined with antithymocyte globulin and prednisone (eight of 12 versus two of 11, p less than 0.05). The high incidence and subtle nature of impaired thyroid function following single-dose irradiation for bone marrow transplantation are discussed.

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

    PubMed

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

    2015-01-01

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

  14. Visual bone marrow mesenchymal stem cell transplantation in the repair of spinal cord injury

    PubMed Central

    Zhang, Rui-ping; Xu, Cheng; Liu, Yin; Li, Jian-ding; Xie, Jun

    2015-01-01

    An important factor in improving functional recovery from spinal cord injury using stem cells is maximizing the number of transplanted cells at the lesion site. Here, we established a contusion model of spinal cord injury by dropping a weight onto the spinal cord at T7-8. Superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells were transplanted into the injured spinal cord via the subarachnoid space. An outer magnetic field was used to successfully guide the labeled cells to the lesion site. Prussian blue staining showed that more bone marrow mesenchymal stem cells reached the lesion site in these rats than in those without magnetic guidance or superparamagnetic iron oxide labeling, and immunofluorescence revealed a greater number of complete axons at the lesion site. Moreover, the Basso, Beattie and Bresnahan (BBB) locomotor rating scale scores were the highest in rats with superparamagnetic labeling and magnetic guidance. Our data confirm that superparamagnetic iron oxide nanoparticles effectively label bone marrow mesenchymal stem cells and impart sufficient magnetism to respond to the external magnetic field guides. More importantly, superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells can be dynamically and non-invasively tracked in vivo using magnetic resonance imaging. Superparamagnetic iron oxide labeling of bone marrow mesenchymal stem cells coupled with magnetic guidance offers a promising avenue for the clinical treatment of spinal cord injury. PMID:25878588

  15. Immune humanization of immunodeficient mice using diagnostic bone marrow aspirates from carcinoma patients.

    PubMed

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

    2014-01-01

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

  16. The cellular changes during osteogenesis in bone and bone marrow composite autografts.

    PubMed Central

    Thorogood, P V; Gray, J C

    1975-01-01

    Osteogenesis in and around autografts has been studied in the hope of identifying the osteoblast precursor. Fresh autografts of cortical bone with its constituent bone marrow were implanted into intramuscular sites in rats. The grafts were removed at intervals over a four week period and examined by light and electron microscopy. A chronological sequence of degenerative, reparative and differentiative events was found and described. The relative contributions of the host and graft components to post-grafting osteogenesis are discussed and the problem of the origin of the osteoblast cells is examined, taking into account present views about the interrelationships between skeletal connective tissue cells and their precursors. It is concluded that, in the investigation described, the presence of host granulation tissue was necessary for osteogenesis and it is postulated that osteoblast progenitor cells can arise from this granulation tissue, their differentiation along the osteogenic line being stimulated in some way by the presence of the graft bone. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 PMID:1102503

  17. Neonatal bone marrow transplantation prevents bone pathology in a mouse model of mucopolysaccharidosis type I

    PubMed Central

    Pievani, Alice; Azario, Isabella; Antolini, Laura; Shimada, Tsutomu; Patel, Pravin; Remoli, Cristina; Rambaldi, Benedetta; Valsecchi, Maria Grazia; Riminucci, Mara; Biondi, Andrea; Tomatsu, Shunji

    2015-01-01

    Neonatal bone marrow transplantation (BMT) could offer a novel therapeutic opportunity for genetic disorders by providing sustainable levels of the missing protein at birth, thus preventing tissue damage. We tested this concept in mucopolysaccharidosis type I (MPS IH; Hurler syndrome), a lysosomal storage disorder caused by deficiency of α-l-iduronidase. MPS IH is characterized by a broad spectrum of clinical manifestations, including severe progressive skeletal abnormalities. Although BMT increases the life span of patients with MPS IH, musculoskeletal manifestations are only minimally responsive if the timing of BMT delays, suggesting already irreversible bone damage. In this study, we tested the hypothesis that transplanting normal BM into newborn MPS I mice soon after birth can prevent skeletal dysplasia. We observed that neonatal BMT was effective at restoring α-l-iduronidase activity and clearing elevated glycosaminoglycans in blood and multiple organs. At 37 weeks of age, we observed an almost complete normalization of all bone tissue parameters, using radiographic, microcomputed tomography, biochemical, and histological analyses. Overall, the magnitude of improvements correlated with the extent of hematopoietic engraftment. We conclude that BMT at a very early stage in life markedly reduces signs and symptoms of MPS I before they appear. PMID:25298037

  18. Quantitative and Qualitative Analysis of Bone Marrow CD8(+) T Cells from Different Bones Uncovers a Major Contribution of the Bone Marrow in the Vertebrae.

    PubMed

    Geerman, Sulima; Hickson, Sarah; Brasser, Giso; Pascutti, Maria Fernanda; Nolte, Martijn A

    2015-01-01

    Bone marrow (BM) plays an important role in the long-term maintenance of memory T cells. Yet, BM is found in numerous bones throughout the body, which are not equal in structure, as they differ in their ratio of cortical and trabecular bone. This implies that BM cells within different bones are subjected to different microenvironments, possibly leading to differences in their frequencies and function. To address this, we examined BM from murine tibia, femur, pelvis, sternum, radius, humerus, calvarium, and the vertebrae and analyzed the presence of effector memory (TEM), central memory (TCM), and naïve (TNV) CD8(+) T cells. During steady-state conditions, the frequency of the total CD8(+) T cell population was comparable between all bones. Interestingly, most CD8(+) T cells were located in the vertebrae, as it contained the highest amount of BM cells. Furthermore, the frequencies of TEM, TCM, and TNV cells were similar between all bones, with a majority of TNV cells. Additionally, CD8(+) T cells collected from different bones similarly expressed the key survival receptors IL-7Rα and IL-15Rβ. We also examined BM for memory CD8(+) T cells with a tissue-resident memory phenotype and observed that approximately half of all TEM cells expressed the retention marker CD69. Remarkably, in the memory phase of acute infection with the lymphocytic choriomeningitis virus (LCMV), we found a massive compositional change in the BM CD8(+) T cell population, as the TEM cells became the dominant subset at the cost of TNV cells. Analysis of Ki-67 expression established that these TEM cells were in a quiescent state. Finally, we detected higher frequencies of LCMV-specific CD8(+) T cells in BM compared to spleen and found that BM in its entirety contained fivefold more LCMV-specific CD8(+) T cells. In conclusion, although infection with LCMV caused a dramatic change in the BM CD8(+) T cell population, this did not result in noticeable differences between BM collected from different

  19. Bone marrow derived stem cells in trauma and orthopaedics: a review of the current trend.

    PubMed

    Singh, Jagwant; Onimowo, Jemina O; Khan, Wasim S

    2015-01-01

    Bone tissue engineering is a promising therapeutic option to enhance tissue regeneration and repair. The development of bone tissue engineering is directly related to changes in materials technology. While the inclusion of material requirements is standard in the design process of engineered bone substitutes, it is critical to incorporate clinical requirements in order to engineer a clinically relevant device. This review focuses on the potentials of bone marrow derived mesenchymal stem cells (BM-MSCs) in trauma and orthopaedics and presents the need for bone tissue-engineered alternatives.

  20. Role of Nanog in the maintenance of marrow stromal stem cells during post natal bone regeneration

    SciTech Connect

    Bais, Manish V.; Shabin, Zabrina M.; Young, Megan; Einhorn, Thomas A.; Kotton, Darrell N.; Gerstnefeld, Louis C.

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Nanog is related to marrow stromal stem cell maintenance. Black-Right-Pointing-Pointer Increasing Nanog expression is seen during post natal surgical bone repair. Black-Right-Pointing-Pointer Nanog knockdown decreases post surgical bone regeneration. -- Abstract: Post natal bone repair elicits a regenerative mechanism that restores the injured tissue to its pre-injury cellular composition and structure and is believed to recapitulate the embryological processes of bone formation. Prior studies showed that Nanog, a central epigenetic regulator associated with the maintenance of embryonic stem cells (ESC) was transiently expressed during fracture healing, Bais et al. . In this study, we show that murine bone marrow stromal cells (MSCs) before they are induced to undergo osteogenic differentiation express {approx}50 Multiplication-Sign the background levels of Nanog seen in murine embryonic fibroblasts (MEFs) and the W20-17 murine marrow stromal cell line stably expresses Nanog at {approx}80 Multiplication-Sign the MEF levels. Nanog expression in this cell line was inhibited by BMP7 treatment and Nanog lentivrial shRNA knockdown induced the expression of the terminal osteogenic gene osteocalcin. Lentivrial shRNA knockdown or lentiviral overexpression of Nanog in bone MSCs had inverse effects on proliferation, with knockdown decreasing and overexpression increasing MSC cell proliferation. Surgical marrow ablation of mouse tibia by medullary reaming led to a {approx}3-fold increase in Nanog that preceded osteogenic differentiation during intramembranous bone formation. Lentiviral shRNA knockdown of Nanog after surgical ablation led to an initial overexpression of osteogenic gene expression with no initial effect on bone formation but during subsequent remodeling of the newly formed bone a {approx}50% decrease was seen in the expression of terminal osteogenic gene expression and a {approx}50% loss in trabecular bone mass. This

  1. Mobilization of bone marrow mesenchymal stem cells in vivo augments bone healing in a mouse model of segmental bone defect.

    PubMed

    Kumar, Sanjay; Ponnazhagan, Selvarangan

    2012-04-01

    Although the number of mesenchymal stem cells (MSC) in the bone marrow is sufficient to maintain skeletal homeostasis, in osteopenic pathology, aggravated osteoclast activity or insufficient osteoblast numbers ensue, affecting normal bone remodeling. Most of the currently available therapies are anti-resorptive with limited osteogenic potential. Since mobilization of stem/progenitors from the BM is a prerequisite for their participation in tissue repair, amplification of endogenous stem cells may provide an alternative approach in these conditions. The present study determined the potential of MSC mobilization in vivo, using combinations of different growth factors with the CXCR4 antagonist, AMD3100, in a mouse model of segmental bone defect. Results indicated that among several factors tested IGF1 had maximum proliferative ability of MSC in vitro. Results of the in vivo studies indicated that the combination of IGF1 and AMD3100 provided significant augmentation of bone growth as determined by DXA, micro-CT and histomorphometry in mice bearing segmental fractures. Further, characterization of MSC isolated from mice treated with IGF1 and AMD3100 indicated Akt/PI3K, MEK1/2-Erk1/2 and smad2/3 as key signaling pathways mediating this effect. These data indicate the potential of in vivo stem cell mobilization as a novel alternative for bone healing.

  2. Tributyltin alters the bone marrow microenvironment and suppresses B cell development.

    PubMed

    Baker, Amelia H; Wu, Ting Hua; Bolt, Alicia M; Gerstenfeld, Louis C; Mann, Koren K; Schlezinger, Jennifer J

    2017-04-07

    Organotins are industrial chemicals and agricultural pesticides, and they contaminate both outdoor and indoor environments. Organotins are detectable in human sera at biologically active concentrations and are immuno-and neuro-toxicants. Triphenyltin, tributyltin (TBT) and dibutyltin activate peroxisome proliferator-activated receptor γ (PPARγ) in bone marrow multipotent mesenchymal stromal cells (BM-MSC) and promote adipogenesis. TBT also has been shown to suppress osteogenesis; osteoblasts not only support bone homeostasis but also support B lymphopoiesis. In addition, developing B cells are highly sensitive to exogenous insults. Thus, we hypothesized that bone marrow B cells may be negatively affected by TBT exposure both directly, through activation of apoptosis, and indirectly, through alterations of the bone marrow microenvironment. TBT activated apoptosis in developing B cells at environmentally relevant concentrations (as low as 80 nM) in vitro, via a mechanism that is distinct from that induced by high dose (μM) TBT and that requires p53. TBT suppressed the proliferation of hematopoietic cells in an ex vivo bone marrow model. Concurrent treatment of stromal cells and B cells or pretreatment of stromal cells with TBT induced adipogenesis in the stromal cells and reduced the progression of B cells from the early pro B (Hardy fraction B) to the pre B stage (Hardy fraction D). In vivo, TBT induced adipogenesis in bone marrow, reduced "aging-sensitive" AA4+CD19+ B cells in bone marrow, and reduced splenic B cell numbers. Immunosenescence and osteoporosis are adverse health effects of aging, we postulate that TBT exposure may mimic, and possibly intensify, these pathologies.

  3. Pathophysiology and Management of Inherited Bone Marrow Failure Syndromes

    PubMed Central

    Shimamura, Akiko; Alter, Blanche P.

    2012-01-01

    The inherited marrow failure syndromes are a diverse set of genetic disorders characterized by hematopoietic aplasia and cancer predisposition. The clinical phenotypes are highly variable and much broader than previously recognized. The medical management of the inherited marrow failure syndromes differs from that of acquired aplastic anemia or malignancies arising in the general population. Diagnostic workup, molecular pathogenesis, and clinical treatment are reviewed. PMID:20417588

  4. Cytogenetic effects of pesticides. II. Induction of micronuclei in mouse bone marrow by the insecticide gardona.

    PubMed

    Amer, S M; Fahmy, M A

    1983-01-01

    The induction of micronuclei in mouse bone marrow by the organophosphorus insecticide gardona (also known as tetrachlorvinphos) was tested. 3 routes of administration were used for the pure insecticide: intraperitoneal, oral and dermal. The different routes of treatment with gardona caused toxicity of marrow indicated as significant increases in the percentage of polychromatic erythrocytes over that of the control. Intraperitoneal and oral treatments induced a statistically significant percentage of micronucleated PE.

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

    PubMed

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

    2015-07-01

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

  6. Nocardiosis after bone marrow transplantation: a retrospective study.

    PubMed

    van Burik, J A; Hackman, R C; Nadeem, S Q; Hiemenz, J W; White, M H; Flowers, M E; Bowden, R A

    1997-06-01

    To evaluate the spectrum of nocardiosis after marrow transplantation, we reviewed the medical records of 27 patients with nocardiosis who were treated at three centers, and we reviewed the findings of three cases reported in the literature. Nocardial involvement was defined as invasive nocardiosis (n = 25), colonization (n = 4), or contamination (n = 1). The median time to the diagnosis of nocardiosis after marrow transplantation was 210 days. Nocardia asteroides complex accounted for 96% of isolates. All 25 invasive infections occurred in allogeneic marrow recipients. Ten (40%) of 25 patients with invasive nocardiosis were receiving double-strength oral trimethoprimsulfamethoxazole twice weekly as prophylaxis for Pneumocystis carinii pneumonia. Treatment regimens for nocardiosis included sulfonamides; synergistic agents were also often added. The overall survival rate at 6 years was 34%; survival from the infection itself was 84%. Two of four nocardiosis-related deaths also involved other pathogens. The incidence of nocardiosis among allogeneic marrow recipients averaged 0.3% over 25 years. We conclude that nocardiosis is a rare infection that occurs later after marrow transplantation than other infections and that is marginally associated with increased mortality among long-term survivors of allogeneic marrow transplantation.

  7. An alternative model of vascularized bone marrow transplant: partial femur transplantation.

    PubMed

    Chen, Jian-Wu; Chen, Chen; Su, Ying-Jun; Yan, Lun; Wang, Shi-Ping; Guo, Shu-Zhong

    2014-12-01

    The vascularized whole femur transplantation model is one of the commonly used vascularized bone marrow transplant models. It involves technical complexity and morbidities. To optimize this model, we took 2/3 femur as the carrier of bone marrow cells, and developed a vascularized partial femur model. Four experimental groups were carried out, namely, the syngeneic partial femur transplantation, allogeneic partial femur transplantation with or without cyclosporine A, and allogeneic whole femur transplantation with cyclosporine A. The results showed that the partial femur model was technically simpler and shortened the operative and ischemia time compared to the whole femur model. Gross and histologic appearance confirmed the viability of femur, and its bone marrow inside the bone could also maintain normal morphologically at 60-day posttransplant. Besides, donor multilineage chimerism could be continuously detected in immunosuppressed allogeneic partial femur recipients at 1-, 2-, 3-, 4-, and 8-week posttransplant, and it showed no significant differences when compared with whole femur transplantation. Meanwhile, long-term engraftment of donor-origin cells was also confirmed in recipients' bone marrow, lymph nodes, and spleen, but not in thymus. Therefore, the vascularized partial femur can serve as a continuous resource of bone morrow cells and may provide a useful tool for the study of immune tolerance in vascularized composite allotransplantation.

  8. Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging and diabetes.

    PubMed

    Krings, A; Rahman, S; Huang, S; Lu, Y; Czernik, P J; Lecka-Czernik, B

    2012-02-01

    Fat occupies a significant portion of bone cavity however its function is largely unknown. Marrow fat expands during aging and in conditions which affect energy metabolism, indicating that fat in bone is under similar regulatory mechanisms as other fat depots. On the other hand, its location may determine specific functions in the maintenance of the environment for bone remodeling and hematopoiesis. We have demonstrated that marrow fat has a distinctive phenotype, which resembles both, white and brown adipose tissue (WAT and BAT, respectively). Marrow adipocytes express gene markers of brown adipocytes at levels characteristic for the BAT, including transcription factor Prdm16, and regulators of thermogenesis such as deiodinase 2 (Dio2) and PGC1α. The levels of expression of BAT-specific gene markers are decreased in bone of 24 mo old C57BL/6 and in diabetic yellow agouti A(vy)/a mice implicating functional changes of marrow fat occurring with aging and diabetes. Administration of antidiabetic TZD rosiglitazone, which sensitizes cells to insulin and increases adipocyte metabolic functions, significantly increased both, BAT (UCP1, PGC1α, Dio2, β3AR, Prdm16, and FoxC2) and WAT (adiponectin and leptin) gene expression in marrow of normoglycemic C57BL/6 mice, but failed to increase the expression of BAT, but not WAT, gene markers in diabetic mice. In conclusion, the metabolic phenotype of marrow fat combines both BAT and WAT characteristics. Decrease in BAT-like characteristics with aging and diabetes may contribute to the negative changes in the marrow environment supporting bone remodeling and hematopoiesis.

  9. Bone marrow fibrosis in myelodysplastic syndromes: a prospective evaluation including mutational analysis

    PubMed Central

    Ramos, Fernando; Robledo, Cristina; Izquierdo-García, Francisco Miguel; Suárez-Vilela, Dimas; Benito, Rocío; Fuertes, Marta; Insunza, Andrés; Barragán, Eva; del Rey, Mónica; de Morales, José María García-Ruiz; Tormo, Mar; Salido, Eduardo; Zamora, Lurdes; Pedro, Carmen; Sánchez-del-Real, Javier; Díez-Campelo, María; del Cañizo, Consuelo; Sanz, Guillermo F.; Hernández-Rivas, Jesús María

    2016-01-01

    The biological and molecular events that underlie bone marrow fibrosis in patients with myelodysplastic syndromes are poorly understood, and its prognostic role in the era of the Revised International Prognostic Scoring System (IPSS-R) is not yet fully determined. We have evaluated the clinical and biological events that underlie bone marrow fibrotic changes, as well as its prognostic role, in a well-characterized prospective patient cohort (n=77) of primary MDS patients. The degree of marrow fibrosis was linked to parameters of erythropoietic failure, marrow cellularity, p53 protein accumulation, WT1 gene expression, and serum levels of CXCL9 and CXCL10, but not to other covariates including the IPSS-R score. The presence of bone marrow fibrosis grade 2 or higher was associated with the presence of mutations in cohesin complex genes (31.5% vs. 5.4%, p=0.006). By contrast, mutations in CALR, JAK2, PDGFRA, PDGFRB, and TP53 were very rare. Survival analysis showed that marrow fibrosis grade 2 or higher was a relevant significant predictor for of overall survival, and independent of age, performance status, and IPSS-R score in multivariate analysis. PMID:27127180

  10. Human osteoblasts derived from mesenchymal stem cells express adipogenic markers upon coculture with bone marrow adipocytes.

    PubMed

    Clabaut, Aline; Delplace, Séverine; Chauveau, Christophe; Hardouin, Pierre; Broux, Odile

    2010-07-01

    In osteoporosis, bone loss is accompanied by greater adiposity in the marrow. Given the cellular proximity within the bone marrow, we wondered whether adipocytes might have a paracrine impact on osteoblast differentiation. To test this hypothesis, we cocultured adipocytes with osteoblasts derived from mesenchymal stem cells (MSCs) in the absence of direct cell contact and then analyzed gene expression changes in the osteoblastic population by using real-time reverse transcription polymerase chain reaction. We found that, upon coculture, MSC-derived osteoblasts showed appearance of adipogenic (lipoprotein lipase, leptin) and decrease of osteogenic (osteocalcin) mRNA markers. Our results indicate that in vitro, MSC-derived adipocytes are capable of inducing MSC-derived osteoblasts to differentiate to an adipocyte phenotype. These new data suggest that (i) transdifferentiation of committed osteoblasts into adipocytes may contribute to the increase in marrow fat content at the expense of bone-forming cells and (ii) this switch might be initiated by the adipocytes themselves.

  11. Three-Dimensional Arrangement of Human Bone Marrow Microvessels Revealed by Immunohistology in Undecalcified Sections

    PubMed Central

    Wilhelmi, Verena; Seiler, Anja; Lampp, Katrin; Neff, Andreas; Guthe, Michael; Lobachev, Oleg

    2016-01-01

    The arrangement of microvessels in human bone marrow is so far unknown. We combined monoclonal antibodies against CD34 and against CD141 to visualise all microvessel endothelia in 21 serial sections of about 1 cm2 size derived from a human iliac crest. The specimen was not decalcified and embedded in Technovit® 9100. In different regions of interest, the microvasculature was reconstructed in three dimensions using automatic methods. The three-dimensional models were subject to a rigid semiautomatic and manual quality control. In iliac crest bone marrow, the adipose tissue harbours irregularly distributed haematopoietic areas. These are fed by networks of large sinuses, which are loosely connected to networks of small capillaries prevailing in areas of pure adipose tissue. Our findings are compatible with the hypothesis that capillaries and sinuses in human iliac crest bone marrow are partially arranged in parallel. PMID:27997569

  12. Tubulointerstitial Nephritis and Uveitis Syndrome with non caseating granuloma in bone marrow biopsy.

    PubMed

    Fraga, Maria; Nunes da Silva, Maria João; Lucas, Margarida; Victorino, Rui M

    2014-01-01

    The Tubulointerstitial Nephritis and Uveitis syndrome is a very rare condition, probably under-diagnosed in clinical practice. It is characterized by the combination of an interstitial nephritis and uveitis, and is an exclusion diagnosis. Tissue non caseating granuloma can be rarely present, with only 6 cases reported on bone marrow. We present a case of a 55 year old female with a 3-month history of asthenia and weight loss. Blood tests showed anemia and renal insufficiency. Renal biopsy revealed interstitial nephritis and the bone marrow biopsy showed caseating granuloma. One month later anterior uveitis of the left eye appeared. An extensive exclusion of all possible causes allowed a diagnosis of Tubulointerstitial Nephritis and Uveitis syndrome with caseating granuloma in bone marrow. As ocular and renal manifestations may not occur simultaneously, Tubulointerstitial Nephritis and Uveitis Syndrome should be systematically considered in cases of interstitial nephritis and/or uveitis, and tissue granulomas can be part of this rare syndrome.

  13. KSC CENTER DIRECTOR ACCEPTS PLAQUE FOR RECORD-SETTING BONE MARROW DONOR REGISTRATION DRIVE

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Kennedy Space Center's Bone Marrow Donor Registration Drive Chairman Dr. George A. Martin and Center Director Jay Honeycutt (left to right) accept a plaque from the Leukemia Society of America's Associate Executive Director Martin Bernstine and the American Red Cross' Southeast Regional Director Jeff Koenreich. Representatives from the American Red Cross and the Leukemia Society of America came to KSC to honor those involved in the record-setting Bone Marrow Donor Registration Drive held here earlier this year. Over 900 potential donors were added to the National Bone Marrow Registry as a result of the KSC drive. The drive established a new record for the most people registered in a single day for the American Red Cross in the three state region of which Florida is a part.

  14. Pure red-cell aplasia of long duration after major ABO-incompatible bone marrow transplantation.

    PubMed

    Volin, L; Ruutu, T

    1990-01-01

    We describe a patient with an exceptionally long-lasting red-cell aplasia of 330 days following ABO-incompatible bone marrow transplantation (BMT). Before BMT, the anti-B titre was high, 1:1,024, and it was only temporarily reduced by extensive plasma exchange. The anti-B titre remained above the level of 1:64 for 270 days, and host-derived isoagglutinin could still be detected 3 years after BMT. In vitro bone marrow cultures during the red-cell aplasia showed greatly reduced numbers or total absence of CFU-E, while the number of BFU-E colonies was only moderately subnormal. Six years after BMT, bone marrow and peripheral-blood cell counts are normal.

  15. Resveratrol Increases the Bone Marrow Hematopoietic Stem and Progenitor Cell Capacity

    PubMed Central

    Rimmelé, Pauline; Lofek-Czubek, Sébastien; Ghaffari, Saghi

    2014-01-01

    Resveratrol is a plant-derived polyphenol that has shown protective effects against many disorders including, several types of cancers and other age-associated diseases as well as blood disorders in cultured cells and/or animal models. However, whether resveratrol has any impact specifically on normal blood stem cells remains unknown. Here we show that a three-week treatment of resveratrol increases the frequency and total numbers of normal bone marrow hematopoietic stem cells (HSC) without any impact on their competitive repopulation capacity. In addition, we show that resveratrol enhances the bone marrow multipotent progenitor capacity in vivo. These results have therapeutic value for disorders of hematopoietic stem and progenitor cells (HSPC) as well as for bone marrow transplantation settings. PMID:25163926

  16. Evaluation of iron status: zinc protoporphyrin vis-a-vis bone marrow iron stores.

    PubMed

    Das, Sheila; Philip, Kandathil Joseph

    2008-01-01

    Zinc protoporphyrin (ZPP) in the red cells is an indicator of iron status in the bone marrow (BM) and can be easily measured by Protofluor-Z Hematofluorometer from Helena Laboratories. It is well known that bone marrow iron is a gold standard for the diagnosis of iron deficiency anemia (IDA) even in the pre-latent phase. Hence, it was considered pertinent to evaluate the diagnostic utility of ZPP in comparison with bone marrow iron stores. 107 random BM were selected over a period of 2(1/2) years; in each case, RBC indices where recorded along with ZPP and Perls' Prussian blue reaction for BM iron stores. The specificity and sensitivity were found to be 77.8% and sensitivity 69.8%, respectively. However, the sensitivity increased up to 96.2% when Hb, RBC indices and ZPP were considered for the diagnosis of IDA.

  17. A Rare Case of Disseminated Tuberculosis of the Bone Marrow in Systemic Lupus Erythematosus: Case Report.

    PubMed

    Chen, Dongying; Yang, Zheng; Yang, Ying; Zhan, Zhongping; Yang, Xiuyan

    2016-05-01

    Patients with systemic lupus erythematosus (SLE) are susceptible to tuberculosis (TB), especially in endemic areas such as China. The variable and nonspecific clinical features of disseminated TB often leads to an erroneous or misdiagnosis. When a patient presents with TB of the bone marrow, the clinical condition is more perplexing and the prognosis is typically poor. Till now, there is no case report after apatinib came in the market.Here, we report a case of TB of the bone marrow accompanied with SLE. The patient exhibited remarkable features, including widespread lesions in the lungs, spinal vertebrae, sacrum, and ilium that were found to be consistent with TB of the bone marrow after histopathological examination.This case highlights the importance of clinical suspicion for TB during the follow-up of SLE patients, especially in endemic areas. An aggressive diagnostic biopsy should be performed in suspected TB patients as early as possible.

  18. A novel view of the adult bone marrow stem cell hierarchy and stem cell trafficking

    PubMed Central

    Ratajczak, M Z

    2015-01-01

    This review presents a novel view and working hypothesis about the hierarchy within the adult bone marrow stem cell compartment and the still-intriguing question of whether adult bone marrow contains primitive stem cells from early embryonic development, such as cells derived from the epiblast, migrating primordial germ cells or yolk sac-derived hemangioblasts. It also presents a novel view of the mechanisms that govern stem cell mobilization and homing, with special emphasis on the role of the complement cascade as a trigger for egress of hematopoietic stem cells from bone marrow into blood as well as the emerging role of novel homing factors and priming mechanisms that support stromal-derived factor 1-mediated homing of hematopoietic stem/progenitor cells after transplantation. PMID:25486871

  19. Australian Dental Research Fund Trebitsch Scholarship. Efficacy of antifungal prophylaxis in bone marrow transplantation.

    PubMed

    Quirk, P C; Osborne, P J; Walsh, L J

    1995-08-01

    Oral candidal infection is a common problem in bone marrow transplantation. This prospective study compared the effectiveness of antifungal prophylaxis with topical antifungals (nystatin and amphotericin B suspensions) versus oral fluconazole in 196 patients undergoing bone marrow transplantation. Oral candidosis occurred frequently in the group receiving topical antifungals (61/113, 54%), but was rare in the group receiving fluconazole (6/83, 7%). The difference in efficacy between the two groups was highly significant (p < 0.00001). There was no difference in the incidence of suspected systemic fungal infection between the two groups. While nausea was a problem with antifungal suspensions, no significant adverse reactions to fluconazole occurred. Because of greater efficacy in preventing oral candidosis and better patient tolerance, oral fluconazole is preferred to antifungal suspensions for prophylactic use in patients undergoing bone marrow transplantation.

  20. Induction of chromosomal aberrations in bone marrow cells of asbestotic rats

    SciTech Connect

    Fatma, N.; Khan, S.G.; Aslam, M.; Rahman, Q. )

    1992-04-01

    In the present study, cytogenetic effects of Indian chrysotile asbestos in rat bone marrow cells after 290 days of intratracheal inoculation, when it develops massive pulmonary fibrosis, were investigated. The pulmonary fibrosis was confirmed by both histopathological studies and increased collagen content in the lung of the treated animals. In the asbestotic rats a significant increase in chromosomal aberrations was recorded and a decrease in mitotic index of bone marrow cells. The types of chromosomal aberrations in these cells were chromatid gaps and breaks. The results indicate the significant cytogenetic changes in the bone marrow cells of asbestotic rats and also suggest that these changes directly or indirectly may be one of the biological events involved in eliciting the asbestos-mediated toxic responses.

  1. Bone marrow long label-retaining cells reside in the sinusoidal hypoxic niche

    SciTech Connect

    Kubota, Yoshiaki; Takubo, Keiyo; Suda, Toshio

    2008-02-08

    In response to changing signals, quiescent hematopoietic stem cells (HSCs) can be induced to an activated cycling state and provide multi-lineage hematopoietic cells to the whole body via blood vessels. However, the precise localization of quiescent HSCs in bone marrow microenvironment is not fully characterized. Here, we performed whole-mount immunostaining of bone marrow and found that BrdU label-retaining cells (LRCs) definitively reside in the sinusoidal hypoxic zone distant from the 'vascular niche'. Although LRCs expressed very low level of a well-known HSC marker, c-kit in normal circumstances, myeloablation by 5-FU treatment caused LRCs to abundantly express c-kit and proliferate actively. These results demonstrate that bone marrow LRCs reside in the sinusoidal hypoxic niche, and function as a regenerative cell pool of HSCs.

  2. Cytokeratin-positive cells in bone marrow of breast cancer patients and noncancer donors

    PubMed Central

    Krag, David N.; Kusminsky, Roberto; Manna, Edward; Weaver, Donald; Harlow, Seth P.; Covelli, Michael; Stanley, Mary A.; McCahill, Laurence; Ittleman, Frank; Leavitt, Bruce; Krag, Martin; Amarante, Patricia

    2009-01-01

    Detection of disseminated tumor cells in the bone marrow may provide important prognostic information in breast cancer patients. With few exceptions the number of stained cells scored as cancer is very low; there may be only one cell per slide. This makes definitive interpretation of cancer in marrow challenging. False-positive staining of marrow cells with cytokeratin (CK) antibody is relatively common and makes interpretation more difficult. In this report we focus on false-positive staining of marrow specimens from breast cancer patients and noncancer controls and demonstrate that the frequency of false positive events is common. Bone marrow was collected from 23 cancer-free donors and 60 breast cancer patients. Samples were processed by Ficoll density gradient centrifugation and slides were prepared for immunocytochemical staining with CK and irrelevant (IR) antibody. Slides were evaluated manually and positive cells were categorized as tumor cells (TCs), hematopoetic cells (HCs), or questionable cells (QCs). False-positive staining events were commonly observed in noncancer cases stained with CK or IR antibodies and in breast cancer cases stained with IR antibody. There was little difference in the number of breast cancer marrow specimens scored as tumor cells regardless of whether the antibody used was CK or IR. It is important to devise improved criteria and methods for accurate detection and interpretation of disseminated tumor cells in the marrow of breast cancer patients. PMID:19417625

  3. Twenty years of unrelated donor bone marrow transplantation for pediatric acute leukemia facilitated by the National Marrow Donor Program.

    PubMed

    MacMillan, Margaret L; Davies, Stella M; Nelson, Gene O; Chitphakdithai, Pintip; Confer, Dennis L; King, Roberta J; Kernan, Nancy A

    2008-09-01

    The National Marrow Donor Program (NMDP) has facilitated unrelated donor hematopoietic cell transplants for more than 20 years. In this time period, there have been many changes in clinical practice, including improvements in HLA typing and supportive care, and changes in the source of stem cells. Availability of banked unrelated donor cord blood (incorporated into the NMDP registry in 2000) as a source of stem cells has become an important option for children with leukemia, offering the advantages of immediate availability for children with high-risk disease, the need for a lesser degree of HLA match, and expanding access for those with infrequent HLA haplotypes. Overall survival (OS) in children with acute leukemia transplanted with unrelated donor bone marrow (BM) is markedly better in more recent years, largely attributable to less treatment-related mortality (TRM). Within this cohort, 2-year survival was markedly better for patients with acute lymphoblastic leukemia (ALL) in first complete response (CR1) (74%) versus second complete response (CR2) (62%) or more advanced disease (33%). Similar findings are observed with patients with AML, suggesting earlier referral to bone marrow transplant (BMT) is optimal for survival. Notably, this improvement over time was not observed in unmodified peripheral blood stem cell (PBSC) recipients, suggesting unmodified PBSC may not be the optimal stem cell source for children.

  4. Induction of tolerance to cardiac allografts in lethally irradiated rats reconstituted with syngeneic bone marrow

    SciTech Connect

    Hartnett, L.C.

    1983-01-01

    Generally, organ grafts from one individual animal to another are rejected in one-two weeks. However, if the recipients are given Total Body Irradiation (TBI) just prior to grafting, followed by reconstitution of hemopoietic function with syngeneic (recipient-type) bone marrow cells, then vascularized organ grafts are permanently accepted. Initially after irradiation, it is possible to induce tolerance to many strain combinations in rats. This thesis examines the system of TBI as applied to the induction of tolerance in LEW recipients of WF cardiac allografts. These two rat strains are mismatched across the entire major histocompatibility complex. When the LEW recipient are given 860 rads, a WF cardiac allograft and LEW bone marrow on the same day, 60% of the grafts are accepted. Methods employed to improve the rate of graft acceptance include: treating either donor or recipient with small amounts of methotrexate, or waiting until two days after irradiation to repopulate with bone marrow. It seems from these investigations of some of the early events in the induction of tolerance to allografts following TBI and syngeneic marrow reconstitution that an immature cell population in the bone marrow interacts with a radioresistant cell population in the spleen to produce tolerance to completely MHC-mismatched allografts.

  5. [Occult involvement of bone marrow in Hodgkin's disease: detection with magnetic resonance].

    PubMed

    Sanz, L; Cervantes, F; Mercader, J M; Rozman, M; Rozman, C; Montserrat, E

    1996-06-22

    Although bone marrow biopsy is considered the best procedure to detect bone marrow involvement by Hodgkin's disease (HD), in recent years several studies have emphasized the value of magnetic resonance imaging (MRI). We present the case of a patient with HD apparently localized in a laterocervical lymph node, who also referred disestasiae at a region corresponding to D10 metamera. Bone marrow biopsy, vertebral TC and 67-Ga scintigraphy were all normal. However, a node of 1 cm in diameter was detected by MRI in the tenth dorsal vertebra. Because of the topographic coincidence between the patient's symptomatology and the MRI findings, the HD was considered to be in advanced stage and CMOPP/ABV chemotherapy was administered, this resulting in a rapid improvement of symptoms and disappearance of the MRI abnormalities. Since in the present case, the MRI determined a change in disease stage and treatment, the role of MRI as a complementary exploration of bone marrow biopsy to detect marrow involvement by HD is reviewed.

  6. Transcoronary sinus delivery of autologous bone marrow and angiogenesis in pig models with myocardial injury

    SciTech Connect

    Vicario, J.; Piva, J.; Pierini, A.; Ortega, H.H.; Canal, A.; Gerardo, L.; Pfeiffer, H.; Campos, C.; Fendrich, I.; Novero, R.; Monti, A

    2002-06-01

    Purpose: The aim of the investigation is to study myocardial injury on pig model with two objectives: (1) feasibility of stimulating angiogenesis with fresh autologous bone marrow; (2) administration of the same fresh autologous bone marrow via coronary sinus with transitory occlusion. Methods: A controlled study was done in animal model with three phases, in a study group of 12 pigs (bone marrow administration) as well as in control group of 4 pigs (saline administration). Phase 1--production of coronary stenosis and myocardial injury; Phase 2--two weeks later, administration of bone marrow through coronary sinus with 10 min occlusion in the study group and saline solution in the control group. Phase 3--two weeks later, histological staining with hematoxylin-eosin and inmunohistochemical staining with monoclonal antibody for smooth muscle {alpha}-actin were conducted on both study and control groups. Results: The percentage of angionenesis observed in the study group was 91% and 0% in control group. Counting of positive actin in affected and control areas showed statistically significant differences in relation to both groups: study group (1.37 vs. 0.79) and control group (0.47 vs. 0.51). The percentage of mononuclear immature cells observed in the myocardium in the study group was 25% and in the control group was 0%. There was no increment in the coronary collateral circulation when comparing coronary angiography. Conclusions: Autologous bone marrow in animal model with experimental myocardial injury enhances angiogenesis, as well as vessels with smooth muscles. The transitory occlusion of the coronary sinus might be an effective way to administer cells as those from the bone marrow.

  7. Potential therapeutic application of intravenous autologous bone marrow infusion in patients with alcoholic liver cirrhosis.

    PubMed

    Saito, Takafumi; Okumoto, Kazuo; Haga, Hiroaki; Nishise, Yuko; Ishii, Rika; Sato, Chikako; Watanabe, Hisayoshi; Okada, Akio; Ikeda, Motoki; Togashi, Hitoshi; Ishikawa, Tsuyoshi; Terai, Shuji; Sakaida, Isao; Kawata, Sumio

    2011-09-01

    The present study was conducted to evaluate the application and efficacy of autologous bone marrow infusion (ABMi) for improvement of liver function in patients with alcoholic liver cirrhosis (ALC). Five subjects and 5 control patients with ALC who had abstained from alcohol intake for 24 weeks before the study were enrolled. Autologous bone marrow cells were washed and injected intravenously, and the changes in serum liver function parameters, and the level of the type IV collagen 7S domain as a marker of fibrosis, were monitored for 24 weeks. The distribution of activated bone marrow was assessed by indium-111-chloride bone marrow scintigraphy. The number of cells infused was 8.0±7.3×10(9) (mean±standard error). The serum levels of albumin and total protein and the prothrombin time were significantly higher during the follow-up period after ABMi than during the observation period in treated patients, whereas no such changes were observed in the controls. In the patients who received ABMi, the Child-Pugh score decreased in all 3 who were classified as class B; the serum levels of type IV collagen 7S domain improved in 4 of the 5 patients; and bone marrow scintigraphy demonstrated an increase of indium-111-chloride uptake in 3 of the 4 patients tested. ABMi for patients with ALC helps improve liver function parameters in comparison with observation during abstinence and ameliorates the degree of fibrosis in terms of serum markers and bone marrow activation in most cases.

  8. Cigarette smoke inhibits recruitment of bone-marrow-derived stem cells to the uterus.

    PubMed

    Zhou, Yuping; Gan, Ye; Taylor, Hugh S

    2011-02-01

    Cigarette smoking leads to female infertility and a decreased incidence of endometriosis. Bone marrow derived stem cells are recruited to uterine endometrium and endometriosis. The effect of cigarette smoking on stem cell recruitment to any organ is uncharacterized. We hypothesized that bone marrow-derived mesenchymal stem cell recruitment to the uterus and differentiation would be diminished by cigarette smoke. We used human mesenchymal stem cells (hMSC) in vitro and a mouse model of cigarette smoke exposure. After myeloablation female C57BL/6J received bone marrow cells from males. Mice were exposed to room air or smoke from unfiltered cigarettes. Immunofluorescence and Y-FISH was performed on uterine sections. In vitro hMSCs were treated with 8-Br-cAMP to induce endometrial cell differentiation with or without cigarette smoke extract (CSE) and decidualization assessed morphologically and by prolactin expression. After 4 weeks the total number of Y-chromosome cells in the uterus was reduced by 68% in the smoke exposed mice. Both leukocytes and bone marrow derived endometrial cells were reduced by 60% and 73%, respectively. Differentiation of bone marrow derived cell to endometrial epithelial cells was reduced by 84%. hMSC treated with CSE failed to show cytological characteristics of decidualization. mRNA levels of the decidualization marker prolactin were decreased by 90% in CSE treated cells. Smoking inhibits both recruitment of bone marrow derived stem cells to uterus and stem cell differentiation. Inhibition of stem cells recruitment may be a general mechanism by which smoking leads to long term organ damage through inability to repair or regenerate multiple tissues.

  9. CD87-positive tumor cells in bone marrow aspirates identified by confocal laser scanning fluorescence microscopy.

    PubMed

    Noack, F; Helmecke, D; Rosenberg, R; Thorban, S; Nekarda, H; Fink, U; Lewald, J; Stich, M; Schutze, K; Harbeck, N; Magdolen, V; Graeff, H; Schmitt, M

    1999-10-01

    Dissemination of single tumor cells to the bone marrow is a common event in cancer. The clinical significance of cytokeratin-positive cells detected in the bone marrow of cancer patients is still a matter of debate. In gastric cancer, overexpression of the receptor (uPAR or CD87) for the serine protease urokinase-type plasminogen activator (uPA) in disseminated cancer cells indicates shorter survival of cancer patients. A new immunofluorescence approach, applying confocal laser scanning microscopy, is introduced to locate CD87 antigen in cytokeratin-positive tumor cells and to quantify the CD87 antigen by consecutive scanning. At first, cytokeratin 8/18/19-positive carcinoma cells are identified at excitation wavelength 488 nm using monoclonal antibody A45B/B3 to the cytokeratins and goat anti-mouse IgG labeled with the fluorochrome Alexa488. Next, CD87 in tumor cells is identified by chicken antibody HU277 to the uPA-receptor and goat anti-chicken IgY labeled with fluorochrome Alexa568 (excitation wavelength 568 nm) and the fluorescence signal quantified on a single cell basis using fluorescently labeled latex beads as the fluorescence reference. From 16 patients with gastric or esophageal carcinoma, bone marrow aspirates were obtained, stained for cytokeratins and CD87 and then subjected to laser scanning fluorescence microscopy. Three of six gastric cancer patients had tumor cells present in the bone marrow of which 2 stained for CD87. Three of ten esophageal carcinoma patients had tumor cells in the bone marrow, all three samples stained for CD87. CD87-positive tumor cells were also dissected from stained bone marrow aspirates by laser microdissection microscope to allow analysis of single cells at the gene level.

  10. Myelopotentiating effect of curcumin in tumor-bearing host: Role of bone marrow resident macrophages

    SciTech Connect

    Vishvakarma, Naveen Kumar; Kumar, Anjani; Kumar, Ajay; Kant, Shiva; Bharti, Alok Chandra; Singh, Sukh Mahendra

    2012-08-15

    The present investigation was undertaken to study if curcumin, which is recognized for its potential as an antineoplastic and immunopotentiating agent, can also influence the process of myelopoiesis in a tumor-bearing host. Administration of curcumin to tumor-bearing host augmented count of bone marrow cell (BMC) accompanied by an up-regulated BMC survival and a declined induction of apoptosis. Curcumin administration modulated expression of cell survival regulatory molecules: Bcl2, p53, caspase-activated DNase (CAD) and p53-upregulated modulator of apoptosis (PUMA) along with enhanced expression of genes of receptors for M-CSF and GM-CSF in BMC. The BMC harvested from curcumin-administered hosts showed an up-regulated colony forming ability with predominant differentiation into bone marrow-derived macrophages (BMDM), responsive for activation to tumoricidal state. The number of F4/80 positive bone marrow resident macrophages (BMM), showing an augmented expression of M-CSF, was also augmented in the bone marrow of curcumin-administered host. In vitro reconstitution experiments indicated that only BMM of curcumin-administered hosts, but not in vitro curcumin-exposed BMM, augmented BMC survival. It suggests that curcumin-dependent modulation of BMM is of indirect nature. Such prosurvival action of curcumin is associated with altered T{sub H1}/T{sub H2} cytokine balance in serum. Augmented level of serum-borne IFN-γ was found to mediate modulation of BMM to produce enhanced amount of monokines (IL-1, IL-6, TNF-α), which are suggested to augment the BMC survival. Taken together the present investigation indicates that curcumin can potentiate myelopoiesis in a tumor-bearing host, which may have implications in its therapeutic utility. Highlights: ► Curcumin augments myelopoiesis in tumor-bearing host. ► Bone marrow resident macrophages mediate curcumin-dependent augmented myelopoiesis. ► Serum borne cytokine are implicated in modulation of bone marrow resident

  11. Bone marrow-derived cells are differentially involved in pathological and physiological retinal angiogenesis in mice

    SciTech Connect

    Zou, He; Otani, Atsushi; Oishi, Akio; Yodoi, Yuko; Kameda, Takanori; Kojima, Hiroshi; Yoshimura, Nagahisa

    2010-01-08

    Purpose: Bone marrow-derived cells have been shown to play roles in angiogenesis. Although these cells have been shown to promote angiogenesis, it is not yet clear whether these cells affect all types of angiogenesis. This study investigated the involvement of bone marrow-derived cells in pathological and physiological angiogenesis in the murine retina. Materials and methods: The oxygen-induced retinopathy (OIR) model was used as a retinal angiogenesis model in newborn mice. To block the influence of bone marrow-derived cells, the mice were irradiated with a 4-Gy dose of radiation from a {sup 137}Cs source. Irradiation was performed in four different conditions with radio dense 2-cm thick lead disks; (1) H group, the head were covered with these discs to protect the eyes from radiation; (2) A group, all of the body was covered with these discs; (3) N group, mice were completely unshielded; (4) C group, mice were put in the irradiator but were not irradiated. On P17, the retinal areas showing pathological and physiological retinal angiogenesis were measured and compared to the retinas of nonirradiated mice. Results: Although irradiation induced leukocyte depletion, it did not affect the number of other cell types or body weight. Retinal nonperfusion areas were significantly larger in irradiated mice than in control mice (P < 0.05), indicating that physiological angiogenesis was impaired. However, the formation of tuft-like angiogenesis processes was more prominent in the irradiated mice (P < 0.05), indicating that pathological angiogenesis was intact. Conclusions: Bone marrow-derived cells seem to be differentially involved in the formation of physiological and pathological retinal vessels. Pathological angiogenesis in the murine retina does not require functional bone marrow-derived cells, but these cells are important for the formation of physiological vessels. Our results add a new insight into the pathology of retinal angiogenesis and bolster the hypothesis that

  12. [Renal transplantation without maintenance immunosuppression. Identical twins and kidney transplantation following a successful bone marrow graft].

    PubMed

    Hadi, Riad Abdel; Thomé, Gustavo Gomes; Ribeiro, Adriana Reginato; Manfro, Roberto Ceratti

    2015-01-01

    Renal transplantation without maintenance immunosuppression has been sporadically reported in the literature. The cases include non-adherent patients who discontinued their immunosuppressive medications, transplantation between identical twins, kidney transplantation after a successful bone marrow graft from the same donor and simultaneous bone marrow and kidney transplantation for the treatment of multiple myeloma with associated renal failure. There are also ongoing clinical trials designed to induce donor specific transplant tolerance with infusion of hematopoietic cells from the same kidney donor. Here we describe two cases of renal transplantation without immunosuppression as examples of situations described above.

  13. Effect of dexamethasone on moesin gene expression in rabbit bone marrow stromal cells.

    PubMed

    Cornet, F; Broux, O; Anselme, K; Hardouin, P; Jeanfils, J

    2004-10-01

    The influence of dexamethasone on rabbit bone marrow stromal cells differentiation was studied by screening the action of dexamethasone on gene expression. Using differential display, we observed some differential amplifications. The use of five of thirteen different primers combination allowed to identify one or more differential bands. One of them was identified as moesin gene. Real-time PCR confirmed a significant reduction of moesin gene expression following dexamethasone treatment. The decrease of expression for this protein, involved in cytoskeletal organization, could explain the effects of dexamethasone treatment on bone marrow stromal cells differentiation.

  14. Bone Marrow Stromal Cells Generate Muscle Cells and Repair Muscle Degeneration

    NASA Astrophysics Data System (ADS)

    Dezawa, Mari; Ishikawa, Hiroto; Itokazu, Yutaka; Yoshihara, Tomoyuki; Hoshino, Mikio; Takeda, Shin-ichi; Ide, Chizuka; Nabeshima, Yo-ichi

    2005-07-01

    Bone marrow stromal cells (MSCs) have great potential as therapeutic agents. We report a method for inducing skeletal muscle lineage cells from human and rat general adherent MSCs with an efficiency of 89%. Induced cells differentiated into muscle fibers upon transplantation into degenerated muscles of rats and mdx-nude mice. The induced population contained Pax7-positive cells that contributed to subsequent regeneration of muscle upon repetitive damage without additional transplantation of cells. These MSCs represent a more ready supply of myogenic cells than do the rare myogenic stem cells normally found in muscle and bone marrow.

  15. A simple technique for red blood cell removal in major ABO-incompatible bone marrow transplantation.

    PubMed

    Mayer, G; Wernet, D; Northoff, H; Schneider, W

    1994-01-01

    A simple technique for red blood cell (RBC) removal in major ABO-incompatible bone marrow transplantation is reported requiring two centrifugation steps, special blood bags and a mechanical device to separate the buffy coat from RBCs within the bag. In 42 transplantations an average of 84% of nucleated cells was recovered with an average contamination of 7.5 ml packed RBCs. The preparations were well tolerated in all patients whose isoagglutinin titers had not been reduced. Bone marrow engraftment was not significantly different from control groups.

  16. Ultrastructural apoptotic lesions induced in bone marrow after neptunium-237 contamination.

    PubMed

    Pusset, D; Boulahdour, H; Fromm, M; Poncy, J L; Kantelip, B; Griffond, B; Baud, M; Galle, P

    2003-01-01

    This study describes the ultrastructure of lesions induced by neptunium-237 (237Np), a by-product of uranium in nuclear reactors, in the bone marrow. A group of rats were given a single injection of 237Np-nitrate solution in order to observe the acute toxicity effects of this actinide. Electron microscopy was used to describe the different lesions. Observations included the swelling of the cell membrane, nuclear membrane lyses, abnormal chromatin condensation or nucleus convolution. These ultrastructural alterations of the nucleus and the cellular membrane appeared shortly after treatment. This study demonstrates the toxic effects of neptunium and its implication in the induction of apoptosis in bone marrow.

  17. A double blind trial with cartilage and bone marrow extract in degenerative gonarthrosis.

    PubMed

    Adler, E; Wolf, E; Taustein, I

    1987-01-01

    A double-blind trial with cartilage and bone-marrow extract (Rumalon A) and placebo (Rumalon B) was carried out on 106 patients with degenerative bilateral gonarthrosis. Favorable results were obtained in 64% of the patients treated with Rumalon A and in only 29% of the placebo group. This difference is statistically significant (p < 0.05). The slight influence of placebo can be related to the psychosomatic effect of injections and/or coincident spontaneous improvement of the gonarthrosis. Cartilage and bone marrow extract increases the therapeutic possibilities in degenerative joint disease. It is easy to administer and practically without side effects.

  18. A patient with progressive multiple myeloma treated successfully with arsenic trioxide after allogeneic bone marrow transplantation.

    PubMed

    Gesundheit, B; Shapira, M Y; Ackerstein, A; Resnik, I B; Bitan, M; Or, R

    2007-01-01

    Multiple myeloma (MM) is an incurable progressive disease. Many therapeutic options are available to delay progression, including autologous and allogeneic bone marrow transplantation. At advanced stages, MM is often refractory to treatment. We report a heavily pretreated patient with graft-versus-host disease after bone marrow transplantations, treated at a terminal stage with a modified protocol for arsenic trioxide (ATO). This patient with poor clinical status tolerated the treatment very well. He had a remarkable clinical response and achieved complete remission. The mechanisms of ATO are presented and the potential role of ATO for MM is discussed.

  19. Cyclosporin A in the treatment of CLL associated PRCA and bone marrow hypoplasia.

    PubMed

    Tura, S; Finelli, C; Bandini, G; Cavo, M; Gobbi, M

    1988-01-01

    Three patients (1 PRCA-T-CLL, 1 PRCA-B-CLL, 1 B-CLL aplasia) were treated with cyclosporin A (CS-A). Patient no 1 had relapsed during steroid therapy and the remaining two patients had been resistant to conventional immunosuppression. CS-A produced in all cases a prompt remission (within 1-4 weeks) of bone marrow failure. Mild reversible renal toxicity was the only side-effect noted. CS-A might be tried in every case of CLL-associated bone marrow failure.

  20. [Origin of Hematopoietic Stem Cells in Bone Marrow--Endothelial to Hematopoietic Transition (EHT)?].

    PubMed

    Wang, Fen; Yuan, Yan; Chen, Tong

    2015-06-01

    In contrast to primitive hematopoiesis, during embryonic definitive hematopoiesis, it has been demonstrated that multilineage hematopoietic stem/progenitor cells (HSPCs) arise from hemogenic endothelium, and the endothelial to hematopoietic transition (EHT) exists within the yolk sac, placenta, AGM, mouse head vascular and extraembryonic vessels. However, whether hemogenic endothelial cells contribute to blood cell development at other sites of definitive hematopoiesis, including fetal liver and bone marrow, remains largely unknown. Recently, more and more researches showed that hematopoiesis within bone marrow had a close relationship with vascular endothelium development, too. This review summarizes the mechanism of EHT during embryo development, and discuss whether EHT exists in adult hematopoiesis.

  1. Rhus javanica Gall Extract Inhibits the Differentiation of Bone Marrow-Derived Osteoclasts and Ovariectomy-Induced Bone Loss

    PubMed Central

    Kim, Tae-Ho; Park, Eui Kyun; Huh, Man-Il; Kim, Hong Kyun; Kim, Shin-Yoon; Lee, Sang-Han

    2016-01-01

    Inhibition of osteoclast differentiation and bone resorption is a therapeutic strategy for the management of postmenopausal bone loss. This study investigated the effects of Rhus javanica (R. javanica) extracts on bone marrow cultures to develop agents from natural sources that may prevent osteoclastogenesis. Extracts of R. javanica (eGr) cocoons spun by Rhus javanica (Bell.) Baker inhibited the osteoclast differentiation and bone resorption. The effects of aqueous extract (aeGr) or 100% ethanolic extract (eeGr) on ovariectomy- (OVX-) induced bone loss were investigated by various biochemical assays. Furthermore, microcomputed tomography (µCT) was performed to study bone remodeling. Oral administration of eGr (30 mg or 100 mg/kg/day for 6 weeks) augmented the inhibition of femoral bone mineral density (BMD), bone mineral content (BMC), and other factors involved in bone remodeling when compared to OVX controls. Additionally, eGr slightly decreased bone turnover markers that were increased by OVX. Therefore, it may be suggested that the protective effects of eGr could have originated from the suppression of OVX-induced increase in bone turnover. Collectively, the findings of this study indicate that eGr has potential to activate bone remodeling by inhibiting osteoclast differentiation and bone loss. PMID:27313644

  2. Expression of resistance to Friend virus-stimulated erythropoiesis in bone marrow chimeras containing Fv-2rr and Fv-2ss bone marrow

    SciTech Connect

    Silver, J.; Teich, N.

    1981-07-01

    Bone marrow chimeras were formed containing mixtures of DBA/2 (Fv-2ss, Hbbdd) and B10.D2 (Fv-2rr, Hbbss) bone marrow. When these mice were infected with the polycythemia-inducing strain of Friend virus, erythropoiesis was stimulated, but the proportion of B10.D2 hemoglobin fell rapidly and newly synthesized hemoglobin was essentially all of the DBA/2 type. The treatment of infected polycythemic chimeras with phenylhydrazine lowered the hematocrit and restored the synthesis of B10.D2 hemoglobin. These results imply that B10.D2 erythroid precursors are intrinsically resistant to Friend virus-stimulated erythropoiesis. The experiments also suggest that virus-stimulated erythropoiesis is not mediated by a factor or cell-cell interactions, unless such factors or interactions do not act across strain barriers.

  3. Osterix-cre labeled progenitor cells contribute to the formation and maintenance of the bone marrow stroma.

    PubMed

    Liu, Yaling; Strecker, Sara; Wang, Liping; Kronenberg, Mark S; Wang, Wen; Rowe, David W; Maye, Peter

    2013-01-01

    We have carried out fate mapping studies using Osterix-EGFPCre and Osterix-CreERt animal models and found Cre reporter expression in many different cell types that make up the bone marrow stroma. Constitutive fate mapping resulted in the labeling of different cellular components located throughout the bone marrow, whereas temporal fate mapping at E14.5 resulted in the labeling of cells within a region of the bone marrow. The identity of cell types marked by constitutive and temporal fate mapping included osteoblasts, adipocytes, vascular smooth muscle, perineural, and stromal cells. Prolonged tracing of embryonic precursors labeled at E14.5dpc revealed the continued existence of their progeny up to 10 months of age, suggesting that fate mapped, labeled embryonic precursors gave rise to long lived bone marrow progenitor cells. To provide further evidence for the marking of bone marrow progenitors, bone marrow cultures derived from Osterix-EGFPCre/Ai9 mice showed that stromal cells retained Cre reporter expression and yielded a FACS sorted population that was able to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro and into osteoblasts, adipocytes, and perivascular stromal cells after transplantation. Collectively, our studies reveal the developmental process by which Osterix-Cre labeled embryonic progenitors give rise to adult bone marrow progenitors which establish and maintain the bone marrow stroma.

  4. Bone marrow mesenchymal stem cells repair spinal cord ischemia/reperfusion injury by promoting axonal growth and anti-autophagy.

    PubMed

    Yin, Fei; Meng, Chunyang; Lu, Rifeng; Li, Lei; Zhang, Ying; Chen, Hao; Qin, Yonggang; Guo, Li

    2014-09-15

    Bone marrow mesenchymal stem cells can differentiate into neurons and astrocytes after transplantation in the spinal cord of rats with ischemia/reperfusion injury. Although bone marrow mesenchymal stem cells are known to protect against spinal cord ischemia/reperfusion injury through anti-apoptotic effects, the precise mechanisms remain unclear. In the present study, bone marrow mesenchymal stem cells were cultured and proliferated, then transplanted into rats with ischemia/reperfusion injury via retro-orbital injection. Immunohistochemistry and immunofluorescence with subsequent quantification revealed that the expression of the axonal regeneration marker, growth associated protein-43, and the neuronal marker, microtubule-associated protein 2, significantly increased in rats with bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Furthermore, the expression of the autophagy marker, microtubule-associated protein light chain 3B, and Beclin 1, was significantly reduced in rats with the bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Western blot analysis showed that the expression of growth associated protein-43 and neurofilament-H increased but light chain 3B and Beclin 1 decreased in rats with the bone marrow mesenchymal stem cell transplantation. Our results therefore suggest that bone marrow mesenchymal stem cell transplantation promotes neurite growth and regeneration and prevents autophagy. These responses may likely be mechanisms underlying the protective effect of bone marrow mesenchymal stem cells against spinal cord ischemia/reperfusion injury.

  5. A critical damping approach for assessing the role of marrow fat on the mechanical strength of trabecular bone.

    PubMed

    Braidotti, P; Stagni, L

    2007-01-01

    Several clinical findings revealed that post-menopausal osteoporosis and age-related osteopenia are accompanied by trabecular bone marrow fat (BMF) increase. To help understand this phenomenon, a vibrating string model is proposed, based on the hypothesis that, when bone marrow properties change, the trabecular bone structure remodels itself to preserve its critical damping state. It is found that an inverse relationship holds between trabecular average length and marrow damping coefficient. Such a result leads us to hypothesize the following bone-weakening mechanism. Since fat-rich bone marrow is a worse damper, a BMF increment causes an increase of trabecular average length, which is accomplished by the absorption of horizontal trabeculae (structurally less important than vertical trabeculae). The resulting bone patterns are in excellent agreement with clinical observations of osteoporotic bone. A definitive confirmation of the proposed mechanism will support a therapeutical approach to widespread osteopenic diseases aimed at avoiding, or limiting, BMF increase.

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

    NASA Astrophysics Data System (ADS)

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

    2013-05-01

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

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

    PubMed

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

    2013-05-21

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

  8. Embryonic Hematopoietic Progenitor Cells Reside in Muscle before Bone Marrow Hematopoiesis.

    PubMed

    Tanaka, Yuka; Inoue-Yokoo, Tomoko; Kulkeaw, Kasem; Yanagi-Mizuochi, Chiyo; Shirasawa, Senji; Nakanishi, Yoichi; Sugiyama, Daisuke

    2015-01-01

    In mice, hematopoietic cells home to bone marrow from fetal liver prenatally. To elucidate mechanisms underlying homing, we performed immunohistochemistry with the hematopoietic cell marker c-Kit, and observed c-Kit(+) cells localized inside muscle surrounding bone after 14.5 days post coitum. Flow cytometric analysis showed that CD45(+) c-Kit(+) hematopoietic cells were more abundant in muscle than in bone marrow between 14.5 and 17.5 days post coitum, peaking at 16.5 days post coitum. CD45(+) c-Kit(+) cells in muscle at 16.5 days post coitum exhibited higher expression of Gata2, among several hematopoietic genes, than did fetal liver or bone marrow cells. Colony formation assays revealed that muscle hematopoietic cells possess hematopoietic progenitor activity. Furthermore, exo utero transplantation revealed that fetal liver hematopoietic progenitor cells home to muscle and then to BM. Our findings demonstrate that hematopoietic progenitor cell homing occurs earlier than previously reported and that hematopoietic progenitor cells reside in muscle tissue before bone marrow hematopoiesis occurs during mouse embryogenesis.

  9. EFFECT OF USE OF BONE-MARROW CENTRIFUGATE ON MUSCLE INJURY TREATMENT: EXPERIMENTAL STUDY ON RABBITS

    PubMed Central

    Vieira, Daniel Ferreira Fernandes; Guarniero, Roberto; Vaz, Carlos Eduardo Sanches; de Santana, Paulo José

    2015-01-01

    Objective: The objective of this study was to evaluate the effect of bone-marrow centrifugate on the healing of muscle injuries in rabbits. Methods: This experimental study involved use of fifteen adult male New Zealand White rabbits. Each animal received a transverse lesion in the middle of the right tibialis anterior muscle, to which an absorbable collagen sponge, soaked in a centrifugate of bone marrow aspirate from the ipsilateral iliac bone, was added. The left hind limb was used as a control and underwent the same injury, but in this case only the absorbable collagen sponge. Thirty days later, the animals were sacrificed to study the muscle healing. These muscle areas were subjected to histological analysis with histomorphometry, with the aim of measuring the number of muscle cells per square micrometer undergoing regeneration and the proportion of resultant fibrosis. Results: The centrifugation method used in this study resulted in an average concentration of nucleated cells greater than the number of these cells in original aspirates, without causing significant cell destruction. Addition of the bone marrow centrifugate did not result in any significant increase in the number of muscle cells undergoing regeneration, in relation to the control group. There was also no significant difference in the proportion of resultant fibrosis, compared with the control group. Conclusion: Administration of the bone marrow centrifugate used in this study did not favor healing of muscle injuries in rabbits. PMID:27047832

  10. High dietary intake of retinol leads to bone marrow hypoxia and diaphyseal endosteal mineralization in rats.

    PubMed

    Lind, Thomas; Lind, P Monica; Jacobson, Annica; Hu, Lijuan; Sundqvist, Anders; Risteli, Juha; Yebra-Rodriguez, Africa; Larsson, Sune; Rodriguez-Navarro, Alejandro; Andersson, Göran; Melhus, Håkan

    2011-03-01

    Vitamin A (retinol) is the only molecule known to induce spontaneous fractures in laboratory animals and we have identified retinol as a risk factor for fracture in humans. Since subsequent observational studies in humans and old animal data both show that high retinol intake appears to only have small effects on bone mineral density (BMD) we undertook a mechanistic study of how excess retinol reduces bone diameter while leaving BMD essentially unaffected. We fed growing rats high doses of retinol for only 1 week. Bone analysis involved antibody-based methods, histology, pQCT, biomechanics and bone compartment-specific PCR together with Fourier Transform Infrared Spectroscopy of bone mineral. Excess dietary retinol induced weakening of bones with little apparent effect on BMD. Periosteal osteoclasts increased but unexpectedly endosteal osteoclasts disappeared and there was a reduction of osteoclastic serum markers. There was also a lack of capillary erythrocytes, endothelial cells and serum retinol transport protein in the endosteal/marrow compartment. A further indication of reduced endosteal/marrow blood flow was the increased expression of hypoxia-associated genes. Also, in contrast to the inhibitory effects in vitro, the marrow of retinol-treated rats showed increased expression of osteogenic genes. Finally, we show that hypervitaminotic bones have a higher degree of mineralization, which is in line with biomechanical data of preserved stiffness in spite of thinner bones. Together these novel findings suggest that a rapid primary effect of excess retinol on bone tissue is the impairment of endosteal/marrow blood flow leading to hypoxia and pathological endosteal mineralization.

  11. Increase of Compact Bone Thickness in Rat Tibia after Implanting MgO into the Bone Marrow Cavity

    PubMed Central

    Nygren, Håkan; Chaudhry, Mobina; Gustafsson, Stefan; Kjeller, Göran; Malmberg, Per; Johansson, Kjell-Erik

    2014-01-01

    The effect of implanting MgO paste into the bone marrow of rat tibia, was studied by light microscopy, time of flight-secondary ion mass spectrometry (ToF-SIMS), and environmental scanning electron microscopy (ESEM), and energy dispersive X-ray (EDX) analysis. After three weeks of implantation, the thickness of compact bone increased by 25% compared to sham-operated controls, while no effect was seen on the trabecular bone. In order to further elucidate the mechanism of the Mg-induced increase in bone mass, EDX and ToF-SIMS analysis of the bone samples was made at two weeks. At this time-point, no detectable difference in the thickness of the compact bone in Mg-treated and non-treated animals was observed. The Mg-content of the bone marrow and bone tissue of the Mg-exposed animals did not differ from that of sham-operated controls, implying that there are no traces of the implanted MgO when the mass of compact bone increases, between two and three weeks after surgery. The ratio of Mg/Ca content was higher in the bone of Mg-treated animals, indicating an altered structure of the bone mineral, which was confirmed by the ToF-SIMS analysis, showing increased levels of MgCO3, phosphate ions and CaF in the bone of MgO-exposed animals. Possible cellular activities behind the effect of MgO on compact bone thickness are discussed. PMID:25215425

  12. Electron absorbed fractions and dose conversion factors for marrow and bone by skeletal regions

    SciTech Connect

    Eckerman, K.F.; Stabin, M.G.

    2000-02-01

    The possible inductions of bone cancer and leukemia are the two health effects of primary concern in the irradiation of the skeleton. The relevant target tissues to consider in the dosimetric evaluation have been the cells on or near endosteal surfaces of bone, from which osteosarcomas are thought to arise, and hematopoietic bone marrow, which is associated with leukemia. The complex geometry of the soft tissue-bone intermixture makes calculations of absorbed doses to these target regions a difficult problem. In the case of photon or neutron radiations, charged particle equilibrium may not exist in the vicinity of a soft tissue-bone mineral interface. In this paper, absorbed fraction data are developed for calculations of the dose in the target tissues from electron emitters deposited within the volume or on the surfaces of trabecular bone. The skeletal average absorbed fractions presented are consistent with usage of this quantity in the contemporary dosimetric formulations of the International Commission on Radiological Protection (ICRP). Implementation of the new bone and marrow model is then developed within the context of the calculational schema of the Medical Internal Radiation Dose (MIRD) Committee. Model parameters relevant to the calculation of dose conversion factors (S values) for different regions of the skeleton of individuals of various age are described, and an example calculation is performed for a monoclonal antibody which localizes in the marrow. The utility of these calculations for radiation dose calculations in nuclear medicine is discussed.

  13. T2-based temperature monitoring in trabecular bone marrow for MRgHIFU

    NASA Astrophysics Data System (ADS)

    Ozhinsky, Eugene; Han, Misung; Krug, Roland; Rieke, Viola

    2017-03-01

    Current clinical protocols for HIFU treatment of painful bone metastases rely on measurement of temperature change of adjacent muscle to estimate the temperature of the bone. In this study, we investigated if T2-based temperature mapping could be used to determine the temperature within ex vivo trabecular bone during HIFU ablation. We have shown that T2-based ablation monitoring in the red marrow in trabecular bone is feasible. The linear relationship between T2 change and temperature could be used to quantify the temperature during heating of up to 60°C.

  14. A bone marrow toxicity model for 223Ra alpha-emitter radiopharmaceutical therapy

    NASA Astrophysics Data System (ADS)

    Hobbs, Robert F.; Song, Hong; Watchman, Christopher J.; Bolch, Wesley E.; Aksnes, Anne-Kirsti; Ramdahl, Thomas; Flux, Glenn D.; Sgouros, George

    2012-05-01

    Ra-223, an α-particle emitting bone-seeking radionuclide, has recently been used in clinical trials for osseous metastases of prostate cancer. We investigated the relationship between absorbed fraction-based red marrow dosimetry and cell level-dosimetry using a model that accounts for the expected localization of this agent relative to marrow cavity architecture. We show that cell level-based dosimetry is essential to understanding potential marrow toxicity. The GEANT4 software package was used to create simple spheres representing marrow cavities. Ra-223 was positioned on the trabecular bone surface or in the endosteal layer and simulated for decay, along with the descendants. The interior of the sphere was divided into cell-size voxels and the energy was collected in each voxel and interpreted as dose cell histograms. The average absorbed dose values and absorbed fractions were also calculated in order to compare those results with previously published values. The absorbed dose was predominantly deposited near the trabecular surface. The dose cell histogram results were used to plot the percentage of cells that received a potentially toxic absorbed dose (2 or 4 Gy) as a function of the average absorbed dose over the marrow cavity. The results show (1) a heterogeneous distribution of cellular absorbed dose, strongly dependent on the position of the cell within the marrow cavity; and (2) that increasing the average marrow cavity absorbed dose, or equivalently, increasing the administered activity resulted in only a small increase in potential marrow toxicity (i.e. the number of cells receiving more than 4 or 2 Gy), for a range of average marrow cavity absorbed doses from 1 to 20 Gy. The results from the trabecular model differ markedly from a standard absorbed fraction method while presenting comparable average dose values. These suggest that increasing the amount of radioactivity may not substantially increase the risk of toxicity, a result unavailable to the

  15. Radiation sensitivity and cycling status of mouse bone marrow prothymocytes and day 8 colony forming units spleen (CFUs)

    SciTech Connect

    Boersma, W.J.

    1983-11-01

    Mouse bone marrow prothymocytes as determined in an in vivo thymus regeneration assay have an in vitro gamma radiation sensitivity which is different from that of spleen colony forming cells (CFUs). Determination of Do according to in vivo irradiation revealed similar but insignificant differences. Prothymocytes in normal bone marrow maintain a low but slightly different proliferative state as compared to CFUs, according to determinations using the /sup 3/H-TdR suicide technique. In regenerating bone marrow prothymocytes were found to be sensitive to an inhibitory effect of in vitro incubation with cold thymidine. CFUs and normal bone marrow prothymocytes were not affected by cold thymidine. Taking into account the cold thymidine effect it can be concluded that prothymocytes and CFUs in regenerating bone marrow are fully in cycle. These results are best explained when prothymocytes and CFUs are considered to be different cells.

  16. Outcomes of Demineralized Bone Matrix Enriched with Concentrated Bone Marrow Aspirate in Lumbar Fusion

    PubMed Central

    Eckardt, Mark A.; Hamamoto, Jason T.; Plotkin, Benjamin; Daubs, Michael D.; Wang, Jeffrey C.

    2016-01-01

    Background Multiple studies have demonstrated that a significant amount of variability exists in various demineralized bone matrix (DBM) formulations, which casts doubts on its reliability in consistently promoting fusion. Bone marrow aspirate (BMA) is a cellular based graft that contains mesenchymal stem cells (MSCs) and growth factors can confer osteogenic and osteoinductive potential to DBM. The goal of this study was to describe the outcome of DBM enriched with concentrated BMA in patients undergoing combined lumbar interbody and posterolateral fusion. Methods Eighty patients with a minimum of 12 months of follow-up were evaluated. Fusion and rates of complication were evaluated. Functional outcomes were assessed based on the modified Odom’s criteria. Multiple logistic regression analysis was used to examine the effects of independent variables on fusion outcome. Results The overall rate of solid fusion (i.e patients with both solid posterolateral and interbody fusion) was 81.3% (65/80). Specifically, the radiographic evidence of solid posterolateral and interbody fusions were 81.3% (65/80) and 92.5% (74/80), respectively. Seven (8.75%) patients developed hardware-related complications, 2 (2.5%) patients developed a postoperative infection and 2 (2.5%) patients developed clinical pseudarthrosis. Charlson comorbidity index (CCI) scores of 3 and 4 were associated with non-solid unions (CCI-3, p = 0.048; CCI-4, p = 0.03). Excellent or good outcomes were achieved in 58 (72.5%) patients. Conclusions Patients undergoing lumbar fusion using an enriched bone graft containing concentrated BMA added to DBM can achieve successful fusion with relatively low complications and good functional outcomes. Despite these findings, more studies with higher level of evidence are needed to better understand the efficacy of this promising graft option. PMID:27909656

  17. Biological conduits combining bone marrow mesenchymal stem cells and extracellular matrix to treat long-segment sciatic nerve defects.

    PubMed

    Wang, Yang; Li, Zheng-Wei; Luo, Min; Li, Ya-Jun; Zhang, Ke-Qiang

    2015-06-01

    The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some respects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group, followed by the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve fibers, and a completely degraded and resorbed conduit, in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group. These results indicate that bridging 10-mm sciatic nerve defects with a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is beneficial for the regeneration and functional reconstruction of sciatic nerve. Better regeneration was

  18. Retroviral-mediated transfer of the human glucocerebrosidase gene into cultured Gaucher bone marrow.

    PubMed Central

    Nolta, J A; Yu, X J; Bahner, I; Kohn, D B

    1992-01-01

    Gaucher disease, a lysosomal glycolipid storage disorder, results from the genetic deficiency of an acidic glucosidase, glucocerebrosidase (GC). The beneficial effects of allogeneic bone marrow transplantation (BMT) for Gaucher disease suggest that GC gene transduction and the transplantation of autologous hematopoietic stem cells (gene therapy) may similarly alleviate symptoms. We have constructed a retroviral vector, L-GC, produced by a clone of the amphotropic packaging cell line PA317, which transduces the normal human GC cDNA with high efficiency. Whole-marrow mononuclear cells and CD34-enriched cells from a 4-yr-old female with type 3 Gaucher disease were transduced by the L-GC vector and studied in long-term bone marrow culture (LTBMC). Prestimulation of marrow with IL-3 and IL-6, followed by co-cultivation with vector-producing fibroblasts, produced gene transfer into 40-45% of the hematopoietic progenitor cells. The levels of GC expression in progeny cells (primarily mature myelomonocytic) produced by the LTBMC were quantitatively analyzed by Northern blot, Western blot, and glucocerebrosidase enzyme assay. Normal levels of GC RNA, immunoreactive protein, and enzymatic activity were detected throughout the duration of culture. These studies demonstrate that retroviral vectors can efficiently transfer the GC gene into long-lived hematopoietic progenitor cells from the bone marrow of patients with Gaucher disease and express physiologically relevant levels of GC enzyme activity. Images PMID:1379609

  19. Osteoclast activity modulates B-cell development in the bone marrow.

    PubMed

    Mansour, Anna; Anginot, Adrienne; Mancini, Stéphane J C; Schiff, Claudine; Carle, Georges F; Wakkach, Abdelilah; Blin-Wakkach, Claudine

    2011-07-01

    B-cell development is dependent on the interactions between B-cell precursors and bone marrow stromal cells, but the role of osteoclasts (OCLs) in this process remains unknown. B lymphocytopenia is a characteristic of osteopetrosis, suggesting a modulation of B lymphopoiesis by OCL activity. To address this question, we first rescued OCL function in osteopetrotic oc/oc mice by dendritic cell transfer, leading to a restoration of both bone phenotype and B-cell development. To further explore the link between OCL activity and B lymphopoiesis, we induced osteopetrosis in normal mice by injections of zoledronic acid (ZA), an inhibitor of bone resorption. B-cell number decreased specifically in the bone marrow of ZA-treated mice. ZA did not directly affect B-cell differentiation, proliferation and apoptosis, but induced a decrease in the expression of CXCL12 and IL-7 by stromal cells, associated with reduced osteoblastic engagement. Equivalent low osteoblastic engagement in oc/oc mice confirmed that it resulted from the reduced OCL activity rather than from a direct effect of ZA on osteoblasts. These dramatic alterations of the bone microenvironment were disadvantageous for B lymphopoiesis, leading to retention of B-cell progenitors outside of their bone marrow niches in the ZA-induced osteopetrotic model. Altogether, our data revealed that OCLs modulate B-cell development in the bone marrow by controlling the bone microenvironment and the fate of osteoblasts. They provide novel basis for the regulation of the retention of B cells in their niche by OCL activity.

  20. Primary bone marrow lymphoma: an uncommon extranodal presentation of aggressive non-hodgkin lymphomas.

    PubMed

    Martinez, Antonio; Ponzoni, Maurilio; Agostinelli, Claudio; Hebeda, Konnie M; Matutes, Estella; Peccatori, Jacopo; Campidelli, Cristina; Espinet, Blanca; Perea, Granada; Acevedo, Agustin; Mehrjardi, Ali Zare; Martinez-Bernal, Monica; Gelemur, Marta; Zucca, Emanuele; Pileri, Stefano; Campo, Elias; López-Guillermo, Armando; Rozman, Maria

    2012-02-01

    Bone marrow involvement by lymphoma is considered a systemic dissemination of the disease arising elsewhere, although some tumors may arise primarily in the bone marrow microenvironment. Primary bone marrow lymphoma (PBML) is a rare entity whose real boundaries and clinicobiological significance are not well defined. Criteria to diagnose PBML encompass isolated bone marrow infiltration, with no evidence of nodal or extranodal involvement, including the bone, and the exclusion of leukemia/lymphomas that are considered to primarily involve the bone marrow. Twenty-one out of 40 lymphomas retrospectively reviewed by the International Extranodal Lymphoma Study Group from 12 institutions in 7 different countries over a 25-year period fulfilled the inclusion criteria. These cases comprised 4 follicular lymphomas (FLs), 15 diffuse large B-cell lymphomas (DLBCLs), and 2 peripheral T-cell lymphomas, not otherwise specified. The FL cases showed paratrabecular infiltration, BCL2 protein and CD10 expression, and BCL2 gene rearrangement. DLBCL showed nodular infiltration in 6 cases and was diffuse in 9 cases; it also showed positivity for BCL2 protein (9/10) and IRF4 (6/8). Median age was 65 years with male predominance. All but 3 FL patients were symptomatic. Most cases presented with cytopenias and high lactate dehydrogenase. Four patients (3 FL cases and 1 DLBCL case) had leukemic involvement. Most DLBCL patients received CHOP-like or R-CHOP-like regimens. The outcome was unfavorable, with a median overall survival of 1.8 years. In conclusion, PBML is a very uncommon lymphoma with particular clinical features and heterogenous histology. Its recognition is important to establish accurate diagnosis and adequate therapy.

  1. Bone marrow regeneration promoted by biophysically sorted osteoprogenitors from mesenchymal stromal cells.

    PubMed

    Poon, Zhiyong; Lee, Wong Cheng; Guan, Guofeng; Nyan, Lin Myint; Lim, Chwee Teck; Han, Jongyoon; Van Vliet, Krystyn J

    2015-01-01

    Human tissue repair deficiencies can be supplemented through strategies to isolate, expand in vitro, and reimplant regenerative cells that supplant damaged cells or stimulate endogenous repair mechanisms. Bone marrow-derived mesenchymal stromal cells (MSCs), a subset of which is described as mesenchymal stem cells, are leading candidates for cell-mediated bone repair and wound healing, with hundreds of ongoing clinical trials worldwide. An outstanding key challenge for successful clinical translation of MSCs is the capacity to produce large quantities of cells in vitro with uniform and relevant therapeutic properties. By leveraging biophysical traits of MSC subpopulations and label-free microfluidic cell sorting, we hypothesized and experimentally verified that MSCs of large diameter within expanded MSC cultures were osteoprogenitors that exhibited significantly greater efficacy over other MSC subpopulations in bone marrow repair. Systemic administration of osteoprogenitor MSCs significantly improved survival rates (>80%) as compared with other MSC subpopulations (0%) for preclinical murine bone marrow injury models. Osteoprogenitor MSCs also exerted potent therapeutic effects as "cell factories" that secreted high levels of regenerative factors such as interleukin-6 (IL-6), interleukin-8 (IL-8), vascular endothelial growth factor A, bone morphogenetic protein 2, epidermal growth factor, fibroblast growth factor 1, and angiopoietin-1; this resulted in increased cell proliferation, vessel formation, and reduced apoptosis in bone marrow. This MSC subpopulation mediated rescue of damaged marrow tissue via restoration of the hematopoiesis-supporting stroma, as well as subsequent hematopoiesis. Together, the capabilities described herein for label-freeisolation of regenerative osteoprogenitor MSCs can markedly improve the efficacy of MSC-based therapies.

  2. Bone marrow dosimetry via microCT imaging and stem cell spatial mapping

    NASA Astrophysics Data System (ADS)

    Kielar, Kayla N.

    In order to make predictions of radiation dose in patients undergoing targeted radionuclide therapy of cancer, an accurate model of skeletal tissues is necessary. Concerning these tissues, the dose-limiting factor in these therapies is the toxicity of the hematopoietically active bone marrow. In addition to acute effects, one must be concerned as well with long-term stochastic effects such as radiation-induced leukemia. Particular cells of interest for both toxicity and cancer risk are the hematopoietic stem cells (HSC), found within the active marrow regions of the skeleton. At present, cellular-level dosimetry models are complex, and thus we cannot model individual stem cells in an anatomic model of the patient. As a result, one reverts to looking at larger tissue regions where these cell populations may reside. To provide a more accurate marrow dose assessment, the skeletal dosimetry model must also be patient-specific. That is, it should be designed to match as closely as possible to the patient undergoing treatment. Absorbed dose estimates then can be tailored based on the skeletal size and trabecular microstructure of an individual for an accurate prediction of marrow toxicity. Thus, not only is it important to accurately model the target tissues of interest in a normal patient, it is important to do so for differing levels of marrow health. A skeletal dosimetry model for the adult female was provided for better predictions of marrow toxicity in patients undergoing radionuclide therapy. This work is the first fully established gender specific model for these applications, and supersedes previous models in scalability of the skeleton and radiation transport methods. Furthermore, the applicability of using bone marrow biopsies was deemed sufficient in prediction of bone marrow health, specifically for the hematopoietic stem cell population. The location and concentration of the HSC in bone marrow was found to follow a spatial gradient from the bone trabeculae

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  4. CT imaging of bone and bone marrow infiltration in malignant melanoma--Challenges and limitations for clinical staging in comparison to 18FDG-PET/CT.

    PubMed

    Bier, Georg; Hoffmann, Vera; Kloth, Christopher; Othman, Ahmed E; Eigentler, Thomas; Garbe, Claus; La Fougère, Christian; Pfannenberg, Christina; Nikolaou, Konstantin; Klumpp, Bernhard

    2016-04-01

    Rationale of this study was the evaluation of the diagnostic value of computed tomography (CT) in the detection of bone marrow infiltration in comparison to PET/CT. Fifty patients (age 61 ± 15.12 years) with metastatic malignant melanoma underwent 18F-FDG-PET/CT, including contrast-enhanced CT. 2 readers evaluated the CT images in consensus for bone and bone marrow lesions focusing on lesion location, type and size. PET/CT was used as reference standard to estimate sensitivity, specificity, negative and positive predictive value. Moreover, the bone marrow density was estimated in the long bones and the sacral bone. Serum hamoglobin, thrombocyte level and S100 protein were correlated with the presence or absence of bone and bone marrow lesions. According to PET/CT as standard of reference, of 594 bone and medullary lesions 495 were considered malignant. Of these 77.8% were medullary, 20.4% lytic, 1% sclerotic and 0.8% mixed lytic/sclerotic. Contrast-enhanced CT yielded a lesion-based sensitivity of 36.8% and a specificity of 87.9% (PPV 93.8%; NPV 21.8%). Patient-based sensitivity and specificity were 78.8% and 82.4%, respectively. Of the missed lesions, most were medullary (95.8%). A disseminated bone marrow involvement (defined as >10 bone marrow lesions or diffuse infiltration of a whole body segment) was described in 11 cases, in 6 cases the disseminated involvement was underestimated or missed on CT. In cases with disseminated bone marrow involvement the bone marrow density was significantly higher in the humerus (p=0.04), but not in the femur or sacral bone (p=0.06). Multivariate analysis revealed no isolated effect of bone metastases on S100 serum and hemoglobin level, but both were significantly altered in patients with disseminated bone marrow involvement (p<0.05). In conclusion, the diagnostic value of computed tomography for the detection of bone marrow metastases in patients with melanoma, is limited. Especially in cases with disseminated bone marrow

  5. Effects of T cell depletion in radiation bone marrow chimeras. III. Characterization of allogeneic bone marrow cell populations that increase allogeneic chimerism independently of graft-vs-host disease in mixed marrow recipients

    SciTech Connect

    Sykes, M.; Chester, C.H.; Sundt, T.M.; Romick, M.L.; Hoyles, K.A.; Sachs, D.H. )

    1989-12-01

    The opposing problems of graft-vs-host disease vs failure of alloengraftment severely limit the success of allogeneic bone marrow transplantation as a therapeutic modality. We have recently used a murine bone marrow transplantation model involving reconstitution of lethally irradiated mice with mixtures of al