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Sample records for bone marrow diseases

  1. Bone Marrow Diseases

    Science.gov (United States)

    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 ...

  2. Bone- and bone marrow scintigraphy in Gaucher disease type 1

    Energy Technology Data Exchange (ETDEWEB)

    Mikosch, P. [Dept. of Nuclear Medicine and Endocrinology, State Hospital Klagenfurt (Austria); Dept. of Internal Medicine II, State Hospital Klagenfurt (Austria); Zitter, F. [Dept. of Internal Medicine II, State Hospital Klagenfurt (Austria); Gallowitsch, H.J.; Lind, P. [Dept. of Nuclear Medicine and Endocrinology, State Hospital Klagenfurt (Austria); Wuertz, F. [Dept. of Pathology, State Hospital Klagenfurt (Austria); Mehta, A.B.; Hughes, D.A. [Lysosomal Storage Disorder Unit, Dept. of Academic Haematology, Royal Free and Univ. Coll. Medical School, London (United Kingdom)

    2008-07-01

    Scintigraphy is a method for imaging metabolism and should be viewed as complimentary to morphological imaging. Bone and bone marrow scintigraphy can particularly contribute to the detection of focal disease in Gaucher disease. In bone crises it can discriminate within three days after pain onset between local infection and aseptic necrosis. A further advantage of bone- and bone marrow scintigraphy is the visualization of the whole skeleton within one setting. Whole body imaging for focal lesions might thus be an objective in GD, in particular in patients complaining of several painful sites. Direct imaging of bone marrow deposits in GD by MIBI scintigraphy might be of special interest in children in whom bone marrow undergoes a developmental conversion from red to yellow marrow in the ap-pendicular skeleton. MRI interpretation in young GD patients is thus difficult in order to estimate the exact amount and extent of bone marrow infiltration by Gaucher cells. 99mTc-MIBI scintigraphy with its direct visualization of lipid storage could thus add interesting additional information not shown with other methods including MRI. Although MRI is the most accepted imaging modality in assessing the skeletal status in GD, a selective use of scintigraphy for imaging bone and bone marrow may add information in the evaluation of patients with Gaucher disease.

  3. Magnetic resonance in hematological diseases. Imaging of bone marrow

    DEFF Research Database (Denmark)

    Jensen, K.E.

    1995-01-01

    Magnetic resonance imaging (MRI) is a highly sensitive alternative to plain radiography, CT, and radionuclide studies for the imaging of normal and abnormal bone marrow. The cellularity and the corresponding fat/water ratio within the bone marrow show clear changes in haematological diseases....... This enables MRI to detect differences between fatty, fibrotic, aplastic and hypercellular marrow in patients with haematological disease. MRI can evaluate the distribution of bone marrow disease because it has the potential for visualization of almost the entire bone marrow compartment. However, MRI is unable...... to establish the primary diagnosis in haematological bone marrow disease with diffuse hypercellular marrow. In case of insufficient biopsy, MRI can provide important differential diagnostic information as well as guidance for further biopsy attempts. MRI is a useful complement to morphological bone marrow...

  4. Bone marrow aspiration

    Science.gov (United States)

    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

  5. Bone marrow invasion in multiple myeloma and metastatic disease.

    Science.gov (United States)

    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.

  6. Bone marrow transplant

    Science.gov (United States)

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

  7. Role of staging bone marrow examination in children with Hodgkin disease

    NARCIS (Netherlands)

    Mahoney, DH; Schreuders, LC; Gresik, MV; McClain, KL

    1998-01-01

    Purpose. To determine the value of bone marrow trephine biopsy as part of the clinical staging for children presenting with Hodgkin disease. Patients and Methods, A retrospective study of pre-treatment bone marrow examinations was undertaken to examine the value of bone marrow staging in children wi

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

    Science.gov (United States)

    Parkman, Robertson

    1986-06-01

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

  9. Dynamic contrast-enhanced MR imaging of the water fraction of normal bone marrow and diffuse bone marrow disease

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    Katsuya, Tomoo; Inoue, Tomio; Ishizaka, Hiroshi; Aoki, Jun; Endo, Keigo [Gunma Univ., Maebashi (Japan). School of Medicine

    2000-10-01

    To clarify the contrast-enhancement pattern of the normal hematopoietic element by isolating the signal of the water fraction in vertebral bone marrow and to investigate whether this approach can be used to characterize bone marrow pathology in several diffuse bone marrow diseases. Two groups were examined: 30 normal healthy volunteers and 19 patients with primary diffuse bone marrow disease (aplastic anemia [n=8], myelodysplastic syndrome (MDS) [n=5], chronic myelogenic leukemia (CML) [n=4], polycythemia vera [n=2]). Isolation of the signal of hematopoietic tissue was done by the chemical-shift misregistration effect. Twenty consecutive T1-weighted midsagittal lumber vertebral images were obtained immediately after the intravenous administration of Gd-DTPA of 0.1 mmol/kg body weight, and the pattern of the time-intensity curve, the peak contrast-enhancement (CE) ratio, and the washout rate (%/min) of bone marrow in normal volunteers were compared with those in patients suffering from primary diffuse bone marrow disease. The pattern of the time-intensity curve of patients with aplastic anemia showed a low peak value followed by a slow washout. However, the pattern of time-intensity curves in patients with MDS, CML, and polycythemia vera was similar to that of normal volunteers. The peak CE ratio of the water fraction in normal marrow ranged from 0.45 to 1.26 (mean {+-}S.D.: 0.87{+-}0.18). Patients with aplastic anemia showed an abnormally lower peak CE ratio of the water fraction (mean {+-}S.D.: 0.34{+-}0.19, p<0.0001). On the other hand, the peak CE ratio of the water fraction in patients with MDS was significantly higher than that of normal volunteers (mean {+-}S.D. 1.35{+-}0.39, p<0.05). In contrast, the peak CE ratio of patients with CML or polycythemia vera did not differ significantly from that of normal volunteers. The mean washout rate of patients with aplastic anemia was significantly lower than that of normal volunteers (mean {+-}S.D.: 3.50{+-}2.51 %/min

  10. Bone marrow stroma in idiopathic myelofibrosis and other haematological diseases. An immunohistochemical study

    DEFF Research Database (Denmark)

    Lisse, I; Hasselbalch, H; Junker, P

    1991-01-01

    Bone marrow stroma was investigated immunohistochemically in 31 patients with haematological diseases, mainly idiopathic myelofibrosis (n = 8) and related chronic myeloproliferative disorders (n = 14). The bone marrow from patients with idiopathic myelofibrosis and some CML patients showed marked...... and capillarization, with the development of continuous sheets of basement membrane material beneath endothelial cells....

  11. Usefulness of bone marrow magnetic resonance imaging and indium-111-chloride bone marrow scintigraphy in patients with various hematological diseases

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    Kobayashi, Yutaka; Umekawa, Tsunekazu; Chikayama, Satoshi [Osaka General Hospital of West Japan Railway Compapy (Japan)] [and others

    1995-03-01

    This study investigated the ability of magnetic resonance (MR) imaging and indium-111 chloride (In-111) scintigraphy to assess bone marrow in various hematological lesions. The subjects were 7 with aplastic anemia (AA), 4 with myelodysplastic syndrome (MDS), 3 with polycythemia (PC), 3 with essential thrombocythemia (ET), 2 with multiple myeloma (MM), 2 with monoclonal gammopathy of undetermined significance (MGUS), 3 with idiopathic thrombocytopenic purpura (ITP), one with acute lymphocytic leukemia (ALL), and one with secondary anemia due to chronic inflammation (SA). Bone marrow cellularity was assessed on MR images and both uptake and tissue distribution were assessed on In-111 scintigraphy. Hypo-cellularity was seen in all AA patients, but not seen in any other patient in each group. On the other hand, hyper-cellularity was seen in 3 MDS, one PC, all 3 ET, one ALL, and one SA patients. In the group of MM, the vertebral body was seen as heterogenous signal intensity on MR images. Bone marrow was seen as iso-intensity in one MDS, 2 PC, all 2 MGUS, and all 3 ITP patients. In-111 scintigraphy showed decrease or disappearance of tracer uptake and decreased tissue distribution in all 7 AA, one MDS, one PC, and one ALL patients. Increased tracer uptake and enlarged tissue distribution were seen in one MDS, one PC, and one SA patients. One MDS, one ET, all 2 MM, all 2 MGUS, all 3 ITP patients had tracer uptake and tissue distribution that were equal to those in the normal tissues. Since MR imaging and In-111 scintigraphy provided qualitatively different information, the combination of both modalities would contribute to the understanding of bone marrow condition in hematopoietic diseases. (N.K.).

  12. Archival bone marrow samples

    DEFF Research Database (Denmark)

    Lund, Bendik; Najmi, Laeya A; Wesolowska-Andersen, Agata;

    2015-01-01

    AB Archival samples represent a significant potential for genetic studies, particularly in severe diseases with risk of lethal outcome, such as in cancer. In this pilot study, we aimed to evaluate the usability of archival bone marrow smears and biopsies for DNA extraction and purification, whole...... with samples stored for 4 to 10 years. Acceptable call rates for SNPs were detected for 7 of 42 archival samples. In conclusion, archival bone marrow samples are suitable for DNA extraction and multiple marker analysis, but WGA was less successful, especially when longer fragments were analyzed. Multiple SNP...

  13. Expression of Factors in the Hepatocyte Growth Factor (HGF) Pathway in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma

    DEFF Research Database (Denmark)

    Kristensen, Ida Bruun; Christensen, Jacob Haaber; Lyng, Maria Bibi;

    Expression of Factors in the Hepatocyte Growth Factor (HGF) Pathway in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma......Expression of Factors in the Hepatocyte Growth Factor (HGF) Pathway in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma...

  14. Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma

    DEFF Research Database (Denmark)

    Kristensen, Ida Bruun; Christensen, Jacob Haaber; Lyng, Maria Bibi

    Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma......Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma...

  15. Bone marrow accumulation in gallium scintigraphy in patients with adult still's disease

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    Kanegae, Futoshi; Tada, Yoshifumi; Ohta, Akihide; Ushiyama, Osamu; Suzuki; Noriaki; Koarada, Syuichi; Haruta, Yoshio; Yoshikai, Tomonori; Nagasawa, Kohei [Saga Medical School (Japan)

    2002-12-01

    We investigated the features and the usefulness of gallium scintigraphy in the diagnosis and the assessment of Adult Still's disease (ASD) by retrospective case review. Gallium scintigraphy have been done for 11 cases of ASD (3 males and 8 females) and 4 females were positive. Among these, 67 Ga-citrate was accumulated to the bone marrow in all 4 cases and to the major joints in 2 cases. Positive cases were rather serious and administered more immunosuppressants than negative cases. In order to characterize gallium scintigraphy findings of ASD, i.e. bone marrow accumulation, we analyzed 130 cases of collagen vascular disease. Although 101 cases (77.7%) were positive, only 7 cases (5.4%) showed the accumulation of {sup 67}Ga-citrate to the bone marrow. These include 3 cases with ASD, and 1 case with systemic lupus erythematosus, polyarteritis nodosa, Wegener's granulomatosis and Sjogren's syndrome. We also accumulated 18 patients who exhibited bone marrow accumulation of {sup 69}Ga-citrate, and found that 7 patients had collagen vascular and their related diseases. In conclusion, bone marrow accumulation in gallium scintigraphy is a specific feature of collagen vascular diseases, especially ASD, and it is suggested that cases with positive gallium scintigraphy in ASD can be serious and resistant to treatment. (author)

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

    Science.gov (United States)

    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

  17. MRI bone marrow findings in 63 patients with type I Gaucher's disease

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    Poll, L.W. [Berufsgenossenschaftliche Unfallklinik Duisburg GmbH (Germany). Abt. Radiologie; Willers, R. [Duesseldorf Univ. (Germany). Zentrum fuer Information, Kommunikation und Medientechnologie; Haeussinger, D. [Universitaetsklinikum Duesseldorf (Germany). Klinik fuer Gastroenterologie, Hepatologie und Infektiologie; Moedder, U. [Universitaetsklinikum Duesseldorf (Germany). Inst. fuer Radiologie; Dahl, S. vom [St.-Franziskus-Hospital Koeln, Akademisches Lehrkrankenhaus der Koeln Univ. (Germany). Klinik fuer Innere Medizin.

    2010-11-15

    Purpose: To determine whether MR bone marrow findings in Gaucher patients may help to identify patients at high risk of developing severe Gaucher bone complications exemplified by avascular necrosis (AVN) of the femoral head. Materials and Methods: MR images were obtained in 63 Type I Gaucher patients through a standard protocol using coronal T1 and T2-weighted sequences of the lower extremities. The location and extent of infiltrated marrow was established using a semi-quantitative MRI scoring method (Duesseldorf Gaucher score, DGS) and the morphological pattern of bone marrow involvement determined (whether homogeneous type A or non-homogeneous type B). The active marrow process with bone edema and AVN of the femoral head were also analyzed. Results: Bone marrow involvement was observed in femoral sites more than in tibial sites. A high DGS was significantly correlated with type B morphology and femoral AVN (both p < 0.0001). Splenectomized patients showed a significantly higher Duesseldorf Gaucher score and type B morphology than non-splenectomized patients (both p < 0.05). AVN was seen in 46 % of patients with type B morphology versus 3 % in type A morphology (p < 0.0001). DGS and morphology of bone marrow involvement were not significantly correlated with active marrow processes. Conclusion: Type B marrow morphology and extensive marrow packing were significantly associated with AVN of the femoral head (both p < 0.0001). These patterns are considered predictive and may be employed in a disease management context to alert physicians to the need for urgent therapeutic measures. (orig.)

  18. Upper airway obstruction and pulmonary abnormalities due to lymphoproliferative disease following bone marrow transplantation in children

    Energy Technology Data Exchange (ETDEWEB)

    Fletcher, B.D. [Department of Diagnostic Imaging, St. Jude Children`s Research Hospital, 332 N. Lauderdale St., Memphis, TN 38105 (United States)]|[Departments of Radiology and Pediatrics, University of Tennessee, Memphis, Tennessee (United States); Heslop, H.E. [Department of Hematology/Oncology, St. Jude Children`s Research Hospital, Department of Pediatrics, University of Tennessee, Memphis, Tennessee (United States); Kaste, S.C. [Department of Diagnostic Imaging, St. Jude Children`s Research Hospital, Department of Radiology, University of Tennessee, Memphis, Tennessee (United States); Bodner, S. [Department of Pathology, St. Jude Children`s Research Hospital, Department of Pathology, University of Tennessee, Memphis, Tennessee (United States)

    1998-07-01

    We report three patients who developed severe supraglottic airway obstruction due to Epstein-Barr virus lymphoproliferative disease following allogeneic bone marrow transplantation. In addition to enlarged pharyngeal lymphoid tissue seen in all three patients, two had supraglottic airway narrowing and two developed pulmonary lymphoproliferative disease. They were treated with unmanipulated T cells or EBV-specific cytotoxic T lymphocytes. Life-threatening upper airway obstruction is a radiologically detectable complication of allogeneic bone marrow transplantation in children. (orig.) With 3 figs., 1 tab., 12 refs.

  19. Autologous Bone Marrow Stem Cell Infusion (AMBI therapy for Chronic Liver Diseases

    Directory of Open Access Journals (Sweden)

    Rajkumar JS

    2007-01-01

    Full Text Available Liver Cirrhosis is the end stage of chronic liver disease which may happen due to alcoholism, viral infections due to Hepatitis B, Hepatitis C viruses and is difficult to treat. Liver transplantation is the only available definitive treatment which is marred by lack of donors, post operative complications such as rejection and high cost. Autologous bone marrow stem cells have shown a lot of promise in earlier reported animal studies and clinical trials. We have in this study administered in 22 patients with chronic liver disease, autologous bone marrow stem cell whose results are presented herewith.

  20. Cytopenia and Bone Marrow Dysplasia in a Case of Wilson's Disease.

    Science.gov (United States)

    Rau, Aarathi R; Usha, M; Mallya, Pooja; Rau, A T K

    2014-09-01

    We describe a sixteen year old with Wilson's disease on copper chelation and subsequent high dose oral zinc who developed severe anemia and neutropenia. Bone marrow aspirate done to evaluate the cause of bicytopenia revealed trilineage dysplasia. Correlating the clinical context with bone marrow and biochemical parameters, copper deficiency was suspected and he was given a trial of therapy, following which the hematological parameters improved. This case highlights hypocupremia as a reversible cause of bone marrow dysplasia in patients with Wilson's disease on chelation, where serum copper levels are not useful in the diagnosis. We also believe that monitoring of the blood counts in patients on copper chelation may provide a clue to impending copper deficiency.

  1. S-MRI score: A simple method for assessing bone marrow involvement in Gaucher disease

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    Roca, M. [Radiology (Magnetic Resonance) Instituto Aragones de Ciencias de la Salud (I-CS), Zaragoza (Spain); Mota, J. [Diagnostic Imaging Department, Medimagen, Barcelona (Spain); Alfonso, P. [Radiology (Magnetic Resonance) Instituto Aragones de Ciencias de la Salud (I-CS), Zaragoza (Spain); Pocovi, M. [Biochemistry and Cellular and Molecular Biology Department, Zaragoza University (Spain); Giraldo, P. [Haematology Department, Miguel Servet University Hospital, 50009 Zaragoza (Spain)]. E-mail: pgiraldo@salud.aragon.es

    2007-04-15

    Semi quantitative MRI is a very useful procedure for evaluating the bone marrow burden (BMB) in Gaucher disease (GD). Score systems have been applied to obtain a parameter for evaluating the severity of bone disease. Our purpose was to test a simple, reproducible and accurate score to evaluate bone marrow involvement in GD patients. MRI was performed in spine, pelvis and femora at diagnosis in 54 adult GD1 patients, 61.1% of whom were female. Three MRI patterns and punctuation in each location were defined: normal, 0; non-homogeneous infiltration subtypes reticular, 1; mottled, 2; diffuse, 3; and homogeneous infiltration, 4. This score was called Spanish-MRI (S-MRI). Two independent observers applied the S-MRI and bone marrow burden score and compared the differences using the non-parametric Mann-Whitney test. Correlation rank test was calculated. In 46 patients (85.2%), bone involvement was observed. Thirty-nine (72.3%) had their spine affected, 35 (64.8%) pelvis and 33 (61.2%) femora. Fourteen patients had bone infarcts, 14 avascular necrosis, 2 vertebral fractures and 2 bone crises. Correlation analysis between S-MRI and BMB was (r {sup 2} = .675; p = .0001). No evidence of correlation was observed between CT activity and S-MRI nor between CT activity and BMB. We have found a relationship between genotype and bone infiltration according to S-MRI site and complications. S-MRI is a simple method that provides useful information to evaluate bone infiltration and detect silent complications. Our results correlated with the BMB score but offer higher sensitivity, specificity and accuracy for classifying the extent of bone disease.

  2. Bone marrow edema syndrome

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    Korompilias, Anastasios V.; Lykissas, Marios G.; Beris, Alexandros E. [University of Ioannina, Department of Orthopaedic Surgery, School of Medicine, Ioannina (Greece); Karantanas, Apostolos H. [University of Crete School of Medicine, Department of Radiology, Heraklion (Greece)

    2009-05-15

    Bone marrow edema syndrome (BMES) refers to transient clinical conditions with unknown pathogenic mechanism, such as transient osteoporosis of the hip (TOH), regional migratory osteoporosis (RMO), and reflex sympathetic dystrophy (RSD). BMES is primarily characterized by bone marrow edema (BME) pattern. The disease mainly affects the hip, the knee, and the ankle of middle-aged males. Many hypotheses have been proposed to explain the pathogenesis of the disease. Unfortunately, the etiology of BMES remains obscure. The hallmark that separates BMES from other conditions presented with BME pattern is its self-limited nature. Laboratory tests usually do not contribute to the diagnosis. Histological examination of the lesion is unnecessary. Plain radiographs may reveal regional osseous demineralization. Magnetic resonance imaging is mainly used for the early diagnosis and monitoring the progression of the disease. Early differentiation from other aggressive conditions with long-term sequelae is essential in order to avoid unnecessary treatment. Clinical entities, such as TOH, RMO, and RSD are spontaneously resolving, and surgical treatment is not needed. On the other hand, early differential diagnosis and surgical treatment in case of osteonecrosis is of crucial importance. (orig.)

  3. MR analysis of sternal bone marrow using STIR in hematologic diseases

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    Kozawa, Eito [Saitama Medical School, Moroyama (Japan)

    1998-12-01

    The magnetic resonance (MR) signal intensity pattern of sternal bone marrow was examined in 21 normal volunteers and 10 patients with aplastic anemia (n=4), multiple myeloma (2), AML (2), gammaglobulinemia (1) and MDS (1) using a sagittal STIR sequence. Double Echo STIR images (TR/TI/TE/NEX=2000/180/20, 100/1) were obtained with a CP body array coil. Craniocaudal phase-encoding with a handmade positioning device effectively avoided overlapping artifacts due to cardiac pulsation. In the normal volunteers, age showed a significant inverse correlation with the calculated SIR (signal intensity ratio of bone marrow relative to subcutaneous fat) using STIR with short TE. The SIR in the sternal body was significantly higher than that in the manubrium (p<0.05). Knowledge of the sternal bone marrow distribution according to age is useful for evaluating hematologic diseases. The proposed method provided high spatial resolution and an excellent bone marrow signal, and may be useful for determining site for aspiration. (author)

  4. Aplastic Anemia & MDS International Foundation (AA&MDSIF): Bone Marrow Failure Disease Scientific Symposium 2014.

    Science.gov (United States)

    Visconte, Valeria; Lindsley, R Coleman; Berlyne, Deborah

    2015-01-01

    Bone marrow failure syndromes (BMFS) are characterized by a failure of the hematopoietic stem cells to produce adequate blood cells, resulting in either cytopenia (defect in one or more blood cell lineages) or pancytopenia (defect in all blood cell lineages). BMFS can be inherited or acquired. The pathogenesis of these diseases is very heterogeneous. Research efforts have been made all over the world to improve the basic knowledge of these diseases. The Aplastic Anemia and MDS International Foundation (AA&MDSIF) is an independent nonprofit organization whose mission is to help patients and family members cope with BMFS. Here, we summarize novel scientific discoveries in several BMFS that were presented at the 4th International Bone Marrow Failure Disease Scientific Symposium 2014 that AA&MDSIF sponsored on March 27-28, 2014, in Rockville, MD.

  5. Bone Marrow-Derived Cells as a Therapeutic Approach to Optic Nerve Diseases

    Directory of Open Access Journals (Sweden)

    Louise A. Mesentier-Louro

    2016-01-01

    Full Text Available Following optic nerve injury associated with acute or progressive diseases, retinal ganglion cells (RGCs of adult mammals degenerate and undergo apoptosis. These diseases have limited therapeutic options, due to the low inherent capacity of RGCs to regenerate and due to the inhibitory milieu of the central nervous system. Among the numerous treatment approaches investigated to stimulate neuronal survival and axonal extension, cell transplantation emerges as a promising option. This review focuses on cell therapies with bone marrow mononuclear cells and bone marrow-derived mesenchymal stem cells, which have shown positive therapeutic effects in animal models of optic neuropathies. Different aspects of available preclinical studies are analyzed, including cell distribution, potential doses, routes of administration, and mechanisms of action. Finally, published and ongoing clinical trials are summarized.

  6. Bone Marrow-Derived Cells as a Therapeutic Approach to Optic Nerve Diseases

    Science.gov (United States)

    Mesentier-Louro, Louise A.; Zaverucha-do-Valle, Camila; Rosado-de-Castro, Paulo H.; Silva-Junior, Almir J.; Pimentel-Coelho, Pedro M.; Mendez-Otero, Rosalia; Santiago, Marcelo F.

    2016-01-01

    Following optic nerve injury associated with acute or progressive diseases, retinal ganglion cells (RGCs) of adult mammals degenerate and undergo apoptosis. These diseases have limited therapeutic options, due to the low inherent capacity of RGCs to regenerate and due to the inhibitory milieu of the central nervous system. Among the numerous treatment approaches investigated to stimulate neuronal survival and axonal extension, cell transplantation emerges as a promising option. This review focuses on cell therapies with bone marrow mononuclear cells and bone marrow-derived mesenchymal stem cells, which have shown positive therapeutic effects in animal models of optic neuropathies. Different aspects of available preclinical studies are analyzed, including cell distribution, potential doses, routes of administration, and mechanisms of action. Finally, published and ongoing clinical trials are summarized. PMID:26649049

  7. Calcific tendinitis of the gluteus medius tendon with bone marrow edema mimicking metastatic disease

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    Yang, Ik [Department of Radiology, University of Michigan Health Systems, Ann Arbor (United States); Hayes, Curtis W. [Department of Radiology, University of Michigan Health Systems, Ann Arbor (United States); Taubman Clinic, Ann Arbor, MI (United States); Biermann, Sybil J. [Department of Orthopaedic Surgery, University of Michigan Health Systems, Ann Arbor, MI (United States)

    2002-06-01

    A case of calcific tendinitis of the gluteus medius is presented. This report describes a patient with a history of breast cancer who had the combination of amorphous calcifications in the gluteus medius tendon and the MR finding of conspicuous bone marrow edema in the adjacent greater trochanter, prompting concern for metastatic disease. We present images from radiography, bone scanning, CT, and MR imaging. The unusual combination of findings in these studies should be considered conclusive for calcific tendinitis, and should not be confused with malignancy. (orig.)

  8. Inhibition of autoimmune Chagas-like heart disease by bone marrow transplantation.

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    Maria C Guimaro

    2014-12-01

    Full Text Available Infection with the protozoan Trypanosoma cruzi manifests in mammals as Chagas heart disease. The treatment available for chagasic cardiomyopathy is unsatisfactory.To study the disease pathology and its inhibition, we employed a syngeneic chicken model refractory to T. cruzi in which chickens hatched from T. cruzi inoculated eggs retained parasite kDNA (1.4 kb minicircles. Southern blotting with EcoRI genomic DNA digests revealed main 18 and 20 kb bands by hybridization with a radiolabeled minicircle sequence. Breeding these chickens generated kDNA-mutated F1, F2, and F3 progeny. A targeted-primer TAIL-PCR (tpTAIL-PCR technique was employed to detect the kDNA integrations. Histocompatible reporter heart grafts were used to detect ongoing inflammatory cardiomyopathy in kDNA-mutated chickens. Fluorochromes were used to label bone marrow CD3+, CD28+, and CD45+ precursors of the thymus-dependent CD8α+ and CD8β+ effector cells that expressed TCRγδ, vβ1 and vβ2 receptors, which infiltrated the adult hearts and the reporter heart grafts.Genome modifications in kDNA-mutated chickens can be associated with disruption of immune tolerance to compatible heart grafts and with rejection of the adult host's heart and reporter graft, as well as tissue destruction by effector lymphocytes. Autoimmune heart rejection was largely observed in chickens with kDNA mutations in retrotransposons and in coding genes with roles in cell structure, metabolism, growth, and differentiation. Moreover, killing the sick kDNA-mutated bone marrow cells with cytostatic and anti-folate drugs and transplanting healthy marrow cells inhibited heart rejection. We report here for the first time that healthy bone marrow cells inhibited heart pathology in kDNA+ chickens and thus prevented the genetically driven clinical manifestations of the disease.

  9. Bone marrow transplantation in patients with storage diseases: a developing country experience

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    Lange Marcos C.

    2006-01-01

    Full Text Available Bone marrow transplantation (BMT is a therapeutic option for patients with genetic storage diseases. Between 1979 and 2002, eight patients, four females and four males (1 to 13 years old were submitted to this procedure in our center. Six patients had mucopolysaccharidosis (MPS I in 3; MPS III in one and MPS VI in 2, one had adrenoleukodystrophy (ALD and one had Gaucher disease. Five patients had related and three unrelated BMT donor. Three patients developed graft versus host disease (two MPS I and one MPS VI and died between 37 and 151 days after transplantation. Five patients survived 4 to 16 years after transplantation. Three patients improved (one MPS I; one MPS VI and the Gaucher disease patient, one patient had no disease progression (ALD and in one patient this procedure did not change the natural course of the disease (MPS III.

  10. UNREMITTING EARLY STAGE HODGKIN’S DISEASE: REPORT OF 7 CASES AND BONE MARROW TISSUE IMMUNOHISTOCHEMICAL MARKER STUDY

    Directory of Open Access Journals (Sweden)

    D. Tamiolakis

    2006-07-01

    Full Text Available Bone marrow is infrequently implicated in early stages of Hodgkin’s disease. We studied the immunohistochemical bone marrow tissue of 7 out of 20 cases with early stage Hodgkin’s disease of the mixed cellularity variant, diagnosed by lymph node biopsy at initial presentation, not responding to radiotherapy alone, in order to examine possible marrow attack. A statistically significant prevalence of CD45, CD45RO, and CD4 positive infiltrates, to the advantage of unremitting hosts, was found. The predominance of CD4-positive cells in the bone marrow space might be suggestive of involvement in the process and could explain the abnormal cytokine production leading to reduced T-cell immunity and inefficient antitumor response despite the existence of a vast majority of reactive infiltrating immune cells.

  11. Expression and significance of IL-18 in the bone marrow of patients with hema tological diseases

    Institute of Scientific and Technical Information of China (English)

    张斌; 饶青; 郑国光; 曹震宇; 马小彤; 李戈; 林永敏; 耿以琪; 吴克复

    2003-01-01

    Objective To investigate the levels of IL-18 in the bone marrow of both normal subjects a nd patients with hematological diseases and to determine the possible significan ce of IL-18 in pathogenesis of some hematological malignancies. Methods The IL-18 mRNA levels in the bone marrow of 140 patients with hematological dis eases and 15 normal donors were determined by the semi-quantitative reverse tra nscriptase polymerase chain reaction (RT-PCR). Immunohistochemical method was used to detect IL-18 protein in 12 patients with acute myeloid leukemia (AML). The possible regulation of IL-18 for proliferation of some leukemia cells was investigated using antisense techniques.Results IL-18 mRNA levels were obviously higher in the patients with leukemia or other malignant hematological diseases (OMHD) than in normal donors. However, no sign ificant difference was found in the level of transcription between patients with iron deficiency anemia (IDA) and normal controls. Immunohistochemical method c onfirmed the presence of IL-18 protein in 10 out of 12 AML cases with positive transcription. By 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium b romide (MTT) assay, IL-18 antisense oligodeoxynucleotides (ASON) clearly inhibi ted the growth of J6-1 and HL-60 cells (42% and 12% inhibited, respectively) i n a dose-dependant manner.Conclusions IL-18 was detected at elevated levels in the bone marrow of patients with some hematological malignancies, and might be involved in the proliferation of certai n leukemic cells in vivo through an autocrine mechanism.

  12. Magnetic resonance imaging of the bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Baur-Melnyk, Andrea (ed.) [Klinikum der Univ. Muenchen (Germany). Inst. fuer Klinische Radiologie

    2013-08-01

    The first book devoted to MRI of the bone marrow. Describes the MRI appearances of normal bone marrows and the full range of bone marrow disorders. Discusses the role of advanced MRI techniques and contrast enhancement. On account of its unrivalled imaging capabilities and sensitivity, magnetic resonance imaging (MRI) is considered the modality of choice for the investigation of physiologic and pathologic processes affecting the bone marrow. This book describes the MRI appearances of both the normal bone marrow, including variants, and the full range of bone marrow disorders. Detailed discussion is devoted to malignancies, including multiple myeloma, lymphoma, chronic myeloproliferative disorders, leukemia, and bone metastases. Among the other conditions covered are benign and malignant compression fractures, osteonecrosis, hemolytic anemia, Gaucher's disease, bone marrow edema syndrome, trauma, and infective and non-infective inflammatory disease. Further chapters address the role of MRI in assessing treatment response, the use of contrast media, and advanced MRI techniques. Magnetic Resonance Imaging of the Bone Marrow represents an ideal reference for both novice and experienced practitioners.

  13. Magnetic resonance imaging of bone marrow changes in Gaucher disease during enzyme replacement therapy: first German long-term results

    Energy Technology Data Exchange (ETDEWEB)

    Poll, L.W.; Koch, J.A.; Scherer, A.; Boerner, D.; Moedder, U. [Duesseldorf Univ. (Germany). Inst. fuer Diagnostische Radiologie; Dahl, S. vom; Niederau, C.; Haeussinger, D. [Duesseldorf Univ. (Germany). Medizinische Fakultaet; Willers, R. [Duesseldorf Univ. (Germany). Rechenzentrum

    2001-09-01

    Objective:. Since 1991, enzyme replacement therapy (ERT) has been available for patients with Gaucher disease in Germany. The aim of this study was to analyse the MR pattern of bone marrow involvement and response to ERT in Gaucher disease type I. Patients and design:. Thirty patients with Gaucher disease type I had MRI examinations prior to initiation of ERT with alglucerase/imiglucerase and during follow-up. Median MR follow-up and duration of ERT were 36 months. Coronal T1- and T2-weighted spin-echo images of the lower extremities were obtained to evaluate changes in the appearance of yellow marrow. MR images were categorized as having either a homogeneous (type A) or non-homogeneous patchy (type B) appearance of bone involvement and response to ERT was assessed by two radiologists. Results:. Overall, 19 of 30 patients (63%) showed an increased signal intensity on T1- and T2-weighted images after 36 months of ERT, consistent with partial reconversion of fatty marrow during treatment. Focal bone lesions surrounded by a low signal intensity (SI) rim did not respond to ERT, suggesting bone infarcts. Of the 11 patients with bone infarcts (low SI rim lesion), 82% had the non-homogeneous type B pattern (P=0.0021). In 86% of patients with splenectomy, bone infarcts were seen (P<0.05). Conclusions:. MRI using T1- and T2-weighted spin-echo sequences is a valuable, non-invasive method for monitoring bone marrow response in patients receiving ERT. A non- homogeneous patchy signal intensity of bone marrow involvement correlates with the presence of bone infarcts (P=0.0021). (orig.)

  14. A "bone marrow score" for predicting hematological disease in immunocompetent patients with fevers of unknown origin.

    Science.gov (United States)

    Wang, Hao-Yuan; Yang, Ching-Fen; Chiou, Tzeon-Jye; Yang, Sheng-Hsiang; Gau, Jyh-Pyng; Yu, Yuan-Bin; Liu, Chun-Yu; Liu, Jin-Hwang; Chen, Po-Min; Hsu, Hui-Chi; Fung, Chang-Phone; Tzeng, Cheng-Hwai; Hsiao, Liang-Tsai

    2014-12-01

    Delayed diagnosis of hematological malignancies in immunocompetent patients with fever of unknown origin (FUO) remains an exhausting challenge for non-hematologist physicians. This retrospective cohort study aimed to establish a scoring system, "bone marrow (BM) score", to identify FUO patients who require early bone marrow biopsy (BMB) to diagnose hematological disease. Two cohorts, comprising 85 (training) and 20 (validation) eligible immunocompetent patients, with FUOs diagnosed between January 1, 2006 and July 31, 2013, underwent BMBs and were enrolled in the study. Demographic, laboratory, imaging, diagnostic, and outcome data were collected and retrospectively analyzed. Factors associated with hematological etiologies diagnosed using BMBs in the training cohort were identified and scored according to the relative hazards. These were further validated using the validation cohort. For the training cohort, 29 of 85 (34.1%) patients had hematological etiologies diagnosed using BMB. Seven factors significantly predicted the diagnostic yield of hematological diseases in the BM and were scored, with the 6 points for leucoerythroblastic changes in peripheral blood smears, 5.5 for elevated ferritin level (>1000 ng/mL), 4 for splenomegaly, 2 for thrombocytopenia, 1.5 for each of elevated lactate dehydrogenase levels and anemia, and 1 for neutropenia. When the cut-off value of the scoring system was set to 6, its sensitivity and specificity to diagnose hematological diseases in the BM of immunocompetent FUO patients were 93% and 58%, respectively. For the validation cohort, 7 of 20 (35%) patients had hematological disease, and all had BM scores higher than the cut-off, with the sensitivity and specificity at 100% and 77%, respectively. As immunocompetent FUO patients with hematological disease have poor prognoses, the "BM score" is valuable for non-hematologist physicians to identify immunocompetent FUO patients requiring early BMB.

  15. Eradication of bone marrow minimal residual disease may prompt early treatment discontinuation in CLL.

    Science.gov (United States)

    Strati, Paolo; Keating, Michael J; O'Brien, Susan M; Burger, Jan; Ferrajoli, Alessandra; Jain, Nitin; Tambaro, Francesco Paolo; Estrov, Zeev; Jorgensen, Jeffrey; Challagundla, Pramoda; Faderl, Stefan H; Wierda, William G

    2014-06-12

    The high complete remission rate with first-line combined fludarabine, cyclophosphamide, and rituximab (FCR) begs the question of the value of minimal residual disease (MRD)-negative status as a treatment end point. We report on 237 patients with chronic lymphocytic leukemia who received first-line FCR. MRD was prospectively assessed by 4-color flow cytometry in bone marrow after course 3 and at final response assessment. After course 3 and at final response assessment, 17% and 43% of patients were MRD negative in bone marrow, respectively. A mutated immunoglobulin heavy chain variable gene and trisomy 12 were independently associated with MRD-negative status both after 3 courses of FCR and at final response assessment in multivariable analyses (MVAs). MRD-negative status was independently associated with significantly longer progression-free survival (PFS) and overall survival (OS) in MVA (P = .03 and .02, respectively). This association was confirmed also on landmark MVA at the time of MRD assessment (P = .04 and .05, respectively). MRD-negative patients had comparable PFS and OS, independent of the number of courses received or interim staging. Early MRD eradication may be a desirable goal, prompting consideration of early discontinuation of treatment. This trial was registered at www.clinicaltrials.gov as #NCT00759798.

  16. Object analysis of bone marrow MR imaging using double echo STIR sequence in hematological diseases

    Energy Technology Data Exchange (ETDEWEB)

    Mizuno, Hitomi [Saitama Medical School, Moroyama (Japan)

    1995-07-01

    The bone marrow of 84 patients with hematological disorders was investigated using short inversion time inversion recovery sequence (STIR) on an 1.5 Tesla superconducting MRI system. Double echo times of 20 and 100 msec were applied to research the signal characteristics of the lesion and carry out quantitative analysis of the receiver operating characteristic curve (ROC). The hematological diseases included 19 cases of myelodysplastic syndrome (MDS), 18 of multiple myeloma (MM), 18 of chronic myelocytic leukemia (CML), 9 of aplastic anemia (AA), 8 of acute myelocytic leukemia (AML), 3 of chronic lymphocytic leukemia (CLL), 3 of myelofibrosis, and 3 others. Using STIR with double echo times, bone marrow showed high signal intensity (SI) on short TE and low SI on long TE in MDS and CML; high SI on short and long TE in myelofibrosis and CLL; high SI on short TE and high to moderately high SI on long TE in MM; and low SI on short and long TE in AA. Quantitative analysis of 33 patients showed high sensitivity and specificity in AA (81% and 94%, respectively) and moderate sensitivity and high specificity in MM (61%, 88%). CML and MDS were similar with low sensitivities (40%, 41%) and high specificities (80%, 78%). Differential diagnosis between CML and MDS was difficult using STIR with the double echo time method. (author).

  17. Molecular Imaging of Bone Marrow Mononuclear Cell Survival and Homing in Murine Peripheral Artery Disease

    Science.gov (United States)

    van der Bogt, Koen E.A.; Hellingman, Alwine A.; Lijkwan, Maarten A.; Bos, Ernst-Jan; de Vries, Margreet R.; Fischbein, Michael P.; Quax, Paul H.; Robbins, Robert C.; Hamming, Jaap F.; Wu, Joseph C.

    2013-01-01

    Introduction Bone marrow mononuclear cell (MNC) therapy is a promising treatment for peripheral artery disease (PAD). This study aims to provide insight into cellular kinetics using molecular imaging following different transplantation methods. Methods and Results MNCs were isolated from F6 transgenic mice (FVB background) that express firefly luciferase (Fluc) and green fluorescence protein (GFP). Male FVB and C57Bl6 mice (n=50) underwent femoral artery ligation and were randomized into 4 groups receiving: (1) single intramuscular (i.m.) injection of 2×106 MNC; (2) four weekly i.m. injections of 5×105 MNC; (3) 2×106 MNCs intravenously (i.v.); and (4) PBS. Cellular kinetics, measured by in vivo bioluminescence imaging (BLI), revealed near-complete donor cell death 4 weeks after i.m. transplantation. Following i.v. transplantation, BLI monitored cells homed in on the injured area in the limb, as well as to the liver, spleen, and bone marrow. Ex vivo BLI showed presence of MNCs in the scar tissue and adductor muscle. However, no significant effects on neovascularisation were observed as monitored by Laser-Doppler-Perfusion-Imaging and histology. Conclusion This is one of the first studies to assess kinetics of transplanted MNCs in PAD using in vivo molecular imaging. MNC survival is short lived and MNCs do not significantly stimulate perfusion in this model. PMID:22239892

  18. Starvation marrow – gelatinous transformation of bone marrow

    Directory of Open Access Journals (Sweden)

    Eric Osgood

    2014-09-01

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

  19. Reconversion of bone marrow in Gaucher disease treated with enzyme therapy documented by MR

    Energy Technology Data Exchange (ETDEWEB)

    Allison, J.W.; James, C.A. [Department of Radiology, Arkansas Children`s Hospital, Little Rock, AR (United States); Arnold, G.L.; Stine, K.C.; Becton, D.L. [Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children`s Hospital, Little Rock, Arkansas (United States); Bell, J.M. [Department of Pathology, University of Arkansas for Medical Sciences, Arkansas Children`s Hospital, Little Rock, Arkansas (United States)

    1998-04-01

    Background. Skeletal complications are responsible for significant morbidity in Gaucher patients. Plain radiographs have been unreliable in assessing bone marrow infiltration and activity. A way to assess bone marrow improvement is needed during enzyme therapy. Objective. The purpose of this paper is to assess the usefulness of MR in following improvement of abnormal bone marrow in Gaucher patients on enzyme therapy. Materials and methods. Three patients aged 2, 7, and 24 years underwent serial MR scans of the lower extremities before and during treatment with Alglucerase (two patients) and Imiglucerase (one patient). T1-weighted, T2-weighted, STIR and FSE T2-weighted images were utilized. Two patients were imaged after 16 months of therapy, and one patient was imaged after 6 months of therapy. Results. All patients had improvement in marrow signal consistent with partial reconversion to fatty marrow during treatment. The findings were more marked after prolonged therapy. T1-weighted images demonstrated findings most clearly. Conclusion. MR consistently showed improvement in marrow signal in Gaucher patients on enzyme therapy. As smaller doses of enzyme therapy are the trend, MR can be utilized to determine if therapy is effecting a change in the bone marrow. (orig.) With 2 figs., 2 tabs., 7 refs.

  20. Laronidase for cardiopulmonary disease in Hurler syndrome 12 years after bone marrow transplantation.

    Science.gov (United States)

    Valayannopoulos, Vassili; de Blic, Jacques; Mahlaoui, Nizar; Stos, Bertrand; Jaubert, Francis; Bonnet, Damien; Fischer, Alain; de Lonlay, Pascale

    2010-11-01

    A patient with severe mucopolysaccharidosis type I (Hurler syndrome) underwent bone marrow transplantation twice (at the ages of 2 and 2.5 years), both times with his HLA-identical heterozygous brother as the donor. Between the ages of 10 and 14 years, despite 92% donor engraftment and 50% normal α-L-iduronidase activity, he developed progressive respiratory failure with severe pulmonary arterial hypertension, upper airway obstruction, and interstitial lung disease. Noninvasive ventilation and weekly laronidase therapy were initiated. Within 24 months, his mean pulmonary artery pressure was within the upper limit of normal and interstitial lung disease and airway obstruction improved markedly. He went from using a wheelchair to having full ambulation, he no longer required daytime ventilation, and his quality-of-life scores (Child Health Assessment Questionnaire) significantly improved.

  1. Graft-versus-Host Disease-Associated Vulvovaginal Symptoms after Bone Marrow Transplantation.

    Science.gov (United States)

    Chung, Christopher P; Sargent, Rachel E; Chung, Nadia T; Lacey, James V; Wakabayashi, Mark T

    2016-02-01

    We conducted a retrospective review to assess the prevalence of graft-versus-host disease (GVHD)-associated gynecologic conditions among bone marrow transplantation (BMT) patients at City of Hope Medical Center. We calculated the associations among the estimated risks of various gynecologic complications, including vaginal stenosis, by performing chi-square tests and t-test statistics. Between 2010 and 2014, 180 patients were referred to the gynecologic clinic after their BMT. One hundred twenty-four patients (69%) had GVHD; among these patients, 51 (41%) experienced dyspareunia and 43 (35%) had vaginal stenosis. GVHD patients were significantly more likely to have vaginal stenosis (P vulvovaginal symptoms, such as dyspareunia and pelvic pain. Patients with GVHD are at high risk for vaginal stenosis requiring the use of a vaginal dilator. However, they are at low risk for developing UI and POP.

  2. A Fatal Case of Immune Hyperhemolysis with Bone Marrow Necrosis in a Patient with Sickle Cell Disease

    Science.gov (United States)

    Singavi, Arun; Johnson, Susan T.; Field, Joshua J.

    2017-01-01

    In patients with sickle cell disease, hyperhemolysis is a rare but life-threatening complication of transfusion. In this case report, we describe a 61 year-old woman with hemoglobin sickle cell (SC) disease and history of alloimmunization who developed hyperhemolysis associated with a transfusion. She was found to have a warm and a clinically-significant cold autoantibody. Severe anemia (Hb 2.7 g/dL) with reticulocytopenia and thrombocytopenia prompted a bone marrow biopsy, which demonstrated extensive bone marrow necrosis. Despite treatment, the bone marrow failure did not improve and the patient died on hospital day 38. This case illustrates the potential risks of transfusion in a patient with sickle cell disease, especially one with previous hemolytic reactions. While uncommon, hyperhemolysis can cause death, in this case by extensive bone marrow necrosis. In patients with sickle cell disease, judicious use of red cell transfusions with phenotypically-matched units can diminish, but never completely abrogate, the risks associated with transfusion. PMID:28286630

  3. Gfi1 expressed in bone marrow stromal cells is a novel osteoblast suppressor in patients with multiple myeloma bone disease

    Science.gov (United States)

    D'Souza, Sonia; del Prete, Davide; Jin, Shunqian; Sun, Quanhong; Huston, Alissa J.; Kostov, Flavia Esteve; Sammut, Benedicte; Hong, Chang-Sook; Anderson, Judith L.; Patrene, Kenneth D.; Yu, Shibing; Velu, Chinavenmeni S.; Xiao, Guozhi; Grimes, H. Leighton; Roodman, G. David

    2011-01-01

    Protracted inhibition of osteoblast (OB) differentiation characterizes multiple myeloma (MM) bone disease and persists even when patients are in long-term remission. However, the underlying pathophysiology for this prolonged OB suppression is unknown. Therefore, we developed a mouse MM model in which the bone marrow stromal cells (BMSCs) remained unresponsive to OB differentiation signals after removal of MM cells. We found that BMSCs from both MM-bearing mice and MM patients had increased levels of the transcriptional repressor Gfi1 compared with controls and that Gfi1 was a novel transcriptional repressor of the critical OB transcription factor Runx2. Trichostatin-A blocked the effects of Gfi1, suggesting that it induces epigenetic changes in the Runx2 promoter. MM-BMSC cell-cell contact was not required for MM cells to increase Gfi1 and repress Runx2 levels in MC-4 before OBs or naive primary BMSCs, and Gfi1 induction was blocked by anti–TNF-α and anti–IL-7 antibodies. Importantly, BMSCs isolated from Gfi1−/− mice were significantly resistant to MM-induced OB suppression. Strikingly, siRNA knockdown of Gfi1 in BMSCs from MM patients significantly restored expression of Runx2 and OB differentiation markers. Thus, Gfi1 may have an important role in prolonged MM-induced OB suppression and provide a new therapeutic target for MM bone disease. PMID:22042697

  4. Blood and Bone Marrow Donation

    Science.gov (United States)

    ... waiting for a stem cell transplant. Bone marrow donation The most serious risk associated with donating bone ... you feel fully recovered. Peripheral blood stem cell donation The risks of this type of stem cell ...

  5. Autotransplantation of bone marrow-derived stem cells as a therapy for neurodegenerative diseases.

    Science.gov (United States)

    Kan, I; Melamed, E; Offen, D

    2007-01-01

    Neurodegenerative diseases are characterized by a progressive degeneration of selective neural populations. This selective hallmark pathology and the lack of effective treatment modalities make these diseases appropriate candidates for cell therapy. Bone marrow-derived mesenchymal stem cells (MSCs) are self-renewing precursors that reside in the bone marrow and may further be exploited for autologous transplantation. Autologous transplantation of MSCs entirely circumvents the problem of immune rejection, does not cause the formation of teratomas, and raises very few ethical or political concerns. More than a few studies showed that transplantation of MSCs resulted in clinical improvement. However, the exact mechanisms responsible for the beneficial outcome have yet to be defined. Possible rationalizations include cell replacement, trophic factors delivery, and immunomodulation. Cell replacement theory is based on the idea that replacement of degenerated neural cells with alternative functioning cells induces long-lasting clinical improvement. It is reasoned that the transplanted cells survive, integrate into the endogenous neural network, and lead to functional improvement. Trophic factor delivery presents a more practical short-term approach. According to this approach, MSC effectiveness may be credited to the production of neurotrophic factors that support neuronal cell survival, induce endogenous cell proliferation, and promote nerve fiber regeneration at sites of injury. The third potential mechanism of action is supported by the recent reports claiming that neuroinflammatory mechanisms play an important role in the pathogenesis of neurodegenerative disorders. Thus, inhibiting chronic inflammatory stress might explain the beneficial effects induced by MSC transplantation. Here, we assemble evidence that supports each theory and review the latest studies that have placed MSC transplantation into the spotlight of biomedical research.

  6. Intracerebroventricular transplanted bone marrow stem cells survive and migrate into the brain of rats with Parkinson’s disease

    Institute of Scientific and Technical Information of China (English)

    Ping Gu; Zhongxia Zhang; Dongsheng Cui; Yanyong Wang; Lin Ma; Yuan Geng; Mingwei Wang

    2012-01-01

    In this study, 6-hydroxydopamine was stereotaxically injected into the right substantia nigra compact and ventral tegmental area of rats to establish Parkinson’s disease models. The rats then received a transplantation of bone marrow stromal cells that were previously isolated, cultured and labeled with 5-bromo-2’-deoxyuridine in vitro. Transplantation of the bone marrow stromal cells significantly decreased apomorphine-induced rotation time and the escape latency in the Morris water maze test as compared with rats with untreated Parkinson’s disease. Immunohistochemical staining showed that, 5-bromo-2’-deoxyuridine-immunoreactive cells were present in the lateral ventricular wall and the choroid plexus 1 day after transplantation. These immunoreactive cells migrated to the surrounding areas of the lateral cerebral ventricle along the corpus callosum. The results indicated that bone marrow stromal cells could migrate to tissues surround the cerebral ventricle via the cerebrospinal fluid circulation and fuse with cells in the brain, thus altering the phenotype of cells or forming neuron-like cells or astrocytes capable of expressing neuron-specific proteins. Taken together, the present findings indicate that bone marrow stromal cells transplanted intracerebroventricularly could survive, migrate and significantly improve the rotational behavior and cognitive function of rats with experimentally induced Parkinson’s disease.

  7. Pediatric and adult MRI atlas of bone marrow. Normal appearances, variants and diffuse disease states

    Energy Technology Data Exchange (ETDEWEB)

    Ilaslan, Hakan; Sundaram, Murali [Cleveland Clinic Lerner College of Medicine, OH (United States); Cleveland Clinic Department of Radiology, OH (United States)

    2016-08-01

    This comprehensive atlas is unique in being devoted to the MRI appearances of bone marrow in the axial and appendicular skeleton of adults and children. Normal MRI findings, including common variants and degenerative changes, are first documented. MRI appearances in the entire spectrum of neoplastic and non-neoplastic infiltrative marrow disorders are then presented, with accompanying explanatory text. Among the conditions considered are multiple myeloma, the acute and chronic leukemias, diffuse metastases, diffuse lymphomas, the anemias, polycythemia vera, myelofibrosis, storage disorders, and infections. Characteristic changes to bone marrow following various forms of treatment are also displayed and discussed. The selected images reflect the use of a variety of sequences and techniques, such as fat suppression, and contrast-enhanced imaging.

  8. Hepatocyte growth factor pathway upregulation in the bone marrow microenvironment in multiple myeloma is associated with lytic bone disease

    DEFF Research Database (Denmark)

    Kristensen, Ida B; Christensen, Jacob H; Lyng, Maria Bibi;

    2013-01-01

    using bone marrow biopsies (BMBs) of patients with MM and monoclonal gammopathy of undetermined significance (MGUS), and healthy volunteers (HV). BMBs (N = 110) obtained at diagnosis were snap-frozen and used to evaluate gene expression by quantitative reverse transcription polymerase chain reaction....... LBD was evaluated using standard radiographs. Enzyme-linked immunosorbent assay (ELISA) was performed on matched bone marrow plasma and immunohistochemistry on matched formalin-fixed paraffin-embedded biopsies. Gene expression of HGF, SDC1, and MET in BMBs were significantly altered in MM versus HV...

  9. Reliability analysis of instrument design of noninvasive bone marrow disease detector

    Science.gov (United States)

    Su, Yu; Li, Ting; Sun, Yunlong

    2016-02-01

    Bone marrow is an important hematopoietic organ, and bone marrow lesions (BMLs) may cause a variety of complications with high death rate and short survival time. Early detection and follow up care are particularly important. But the current diagnosis methods rely on bone marrow biopsy/puncture, with significant limitations such as invasion, complex operation, high risk, and discontinuous. It is highly in need of a non-invasive, safe, easily operated, and continuous monitoring technology. So we proposed to design a device aimed for detecting bone marrow lesions, which was based on near infrared spectrum technology. Then we fully tested its reliabilities, including the sensitivity, specificity, signal-to-noise ratio (SNR), stability, and etc. Here, we reported this sequence of reliability test experiments, the experimental results, and the following data analysis. This instrument was shown to be very sensitive, with distinguishable concentration less than 0.002 and with good linearity, stability and high SNR. Finally, these reliability-test data supported the promising clinical diagnosis and surgery guidance of our novel instrument in detection of BMLs.

  10. Graft versus host disease in the bone marrow, liver and thymus humanized mouse model.

    Directory of Open Access Journals (Sweden)

    Matthew B Greenblatt

    Full Text Available Mice bearing a "humanized" immune system are valuable tools to experimentally manipulate human cells in vivo and facilitate disease models not normally possible in laboratory animals. Here we describe a form of GVHD that develops in NOD/SCID mice reconstituted with human fetal bone marrow, liver and thymus (NS BLT mice. The skin, lungs, gastrointestinal tract and parotid glands are affected with progressive inflammation and sclerosis. Although all mice showed involvement of at least one organ site, the incidence of overt clinical disease was approximately 35% by 22 weeks after reconstitution. The use of hosts lacking the IL2 common gamma chain (NOD/SCID/γc(-/- delayed the onset of disease, but ultimately did not affect incidence. Genetic analysis revealed that particular donor HLA class I alleles influenced the risk for the development of GVHD. At a cellular level, GVHD is associated with the infiltration of human CD4+ T cells into the skin and a shift towards Th1 cytokine production. GVHD also induced a mixed M1/M2 polarization phenotype in a dermal murine CD11b+, MHC class II+ macrophage population. The presence of xenogenic GVHD in BLT mice both presents a major obstacle in the use of humanized mice and an opportunity to conduct preclinical studies on GVHD in a humanized model.

  11. Potential of bone marrow mesenchymal stem cells in management of Alzheimer's disease in female rats.

    Science.gov (United States)

    Salem, Ahmed M; Ahmed, Hanaa H; Atta, Hazem M; Ghazy, Mohamed A; Aglan, Hadeer A

    2014-12-01

    Alzheimer's disease (AD) has been called the disease of the century with significant clinical and socioeconomic impacts. Pharmacological treatment has limited efficacy and only provides symptomatic relief without long-term cure. Accordingly, there is an urgent need to develop novel and effective medications for AD. Stem cell-based therapy is a promising approach to handling neurodegenerative diseases. Therefore, the current study aimed to explore the possible therapeutic role of single intravenous injection of bone marrow derived mesenchymal stem cells (BM-MSCs) after 4 months in management of AD in the experimental model. The work also extended to compare the therapeutic potential of BM-MSCs with 2 conventional therapies of AD; rivastigmine and cerebrolysin administered daily. BM-MSCs were able to home at the injured brains and produced significant increases in the number of positive cells for choline acetyltransferase (ChAT) and survivin expression, as well as selective AD indicator-1 (seladin-1) and nestin gene expression. Histopathological examination indicated that BM-MSCs could remove beta-amyloid plaques from hippocampus. Significant improvement in these biomarkers was similar to or better sometimes than the reference drugs, clearly showing the potential therapeutic role of BM-MSCs against AD through their anti-apoptotic, neurogenic and immunomodulatory properties.

  12. Transplantation of mononuclear cells from bone marrow in a rat model of Huntington’s disease

    Directory of Open Access Journals (Sweden)

    Serrano T

    2016-12-01

    Full Text Available Teresa Serrano,1 Paula Pierozan,2 Esteban Alberti,1 Lisette Blanco,1 Karelys de la Cuétara Bernal,1 María E González,1 Nancy Pavón,1 Lourdes Lorigados,1 María A Robinson-Agramonte,1 Jorge A Bergado1 1International Center for Neurological Restoration (CIREN, La Habana, Cuba; 2Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil Abstract: This article investigates the possible effects of transplantation of mononuclear bone marrow cells (mBMCs to ameliorate or prevent the behavioral impairments and the cellular damage observed in a quinolinic acid (QA model of Huntington’s disease. mBMCs were isolated using a standard procedure and implanted within the QA-lesioned striatum. Behavior was explored using motor (beam test and memory (object recognition and Morris water maze tests. Morphology was evaluated using conventional histology (cresyl violet, bisbenzimide (to evaluate cell vitality, and immunohystochemistry to identify neurons or glia. mBMC-transplanted animals showed improvements in motor coordination (beam test. Regarding memory, object recognition was significantly improved in transplanted animals, while spatial memory (Morris water maze test was not severely affected by QA and, therefore, the results after transplantation were significant only in the probe-trial retention test. In samples taken from the animals that participated in the behavioral tests, a preserved morphology of striatal neurons and a reduced glial reaction indicated a possible neuroprotective effect of the transplanted mBMCs. A parallel study confirmed that the transplanted mBMCs have a long survival period (1 year follow-up. The results presented confirm the possibility that mBMC transplantation may be a viable therapeutic option for Huntington’s disease. Keywords: mononuclear bone marrow cells, Huntington’s disease, quinolinic acid, transplant, Fluoro-Jade C

  13. The risk of renal disease is increased in lambda myeloma with bone marrow amyloid deposits

    Science.gov (United States)

    Kozlowski, Piotr; Montgomery, Scott; Befekadu, Rahel; Hahn-Strömberg, Victoria

    2017-01-01

    Background Light chain amyloidosis (AL) is a rare deposition disease and is present in 10–15% of patients with myeloma (MM). In contrast to symptomatic AL in MM, presence of bone marrow (BM) amyloid deposits (AD) in MM is not connected to kidney damage. Renal AD but not BM-AD occur mostly in MM with lambda paraprotein (lambda MM). Methods We investigated amyloid presence in BM clots taken at diagnosis in 84 patients with symptomatic MM and compared disease characteristics in MM with kappa paraprotein (kappa MM)/lambda MM with and without BM-AD. Results Lambda MM with BM-AD was compared with kappa MM without BM-AD, kappa MM with BM-AD, and lambda MM without BM-AD: lambda MM with BM-AD patients had a significantly higher mean creatinine level (4.23 mg/dL vs 1.69, 1.14, and 1.28 mg/dL, respectively) and a higher proportion presented with severe kidney failure (6/11 [55%] vs 6/32 [19%], 1/22 [5%], and 3/19 [16%], respectively). Proteinuria was more common in lambda MM with BM-AD patients compared with kappa MM without BM-AD patients (8/11 [73%] vs 5/32 [16%], respectively). Conclusion Kidney damage was more common in lambda MM with BM-AD indicating presence of renal AD. PMID:28293126

  14. Bone marrow transplantation. [Mice, gamma radiation

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    Storb, R.; Santos, G.W.

    1979-03-01

    Bone marrow transplantation has been increasingly used to treat patients with severe combined immunodeficiency diseases, severe aplastic anemia, and malignant hematologic diseases, especially leukemia. At the Workshop a number of problems were discussed, e.g., conditioning regimens aimed at overcoming the problem of marrow graft rejection and reducing the incidence of recurrent leukemia, prevention of graft-versus-host disease (GVHD), possible mechanisms involved in stable graft-host tolerance, graft-versus-leukemia effect in mice, and finally, the possible use of autologous marrow transplantation.

  15. Exploring the role of FDG-PET in the assessment of bone marrow involvement in lymphoma patients as interpreted by qualitative and semiquantitative disease metabolic activity parameter

    Directory of Open Access Journals (Sweden)

    P G Kand

    2010-01-01

    Full Text Available Bone marrow biopsy (BMB is currently the standard method to evaluate marrow involvement in malignant lymphomas. However, there exist a number of pitfalls in this technique that can have important implications for initial staging, prognostification, and treatment of the disease. The present study was undertaken to investigate the utility of FDG-PET imaging in the detection of bone marrow involvement in untreated lymphoma patients. Forty untreated patients (36 males and 12 females with either Hodgkin′s disease (HD (n = 17 or non-Hodgkin′s lymphoma (NHL (n = 31 underwent whole body FDG-PET study for disease evaluation. Bone marrow uptake of FDG was graded as absence or presence of disease activity at marrow sites by qualitative assessment. Semiquantitative analysis involved deriving disease metabolic index (DMI using the following formula: DMI = SUV max of suitable circular ROI over PSIS or trochanteric region/ SUVmax of similar ROI over adjoining background. Findings of BMB and FDG-PET were compared for final analysis. Eleven out of 17 HD patients (12 males and 5 females demonstrated concordance between FDG PET findings and BMB reports. Remaining 6 cases showed discordance of FDG-PET demonstrating presence of marrow involvement at marrow sites and uninvolved marrow on BMB. Twenty six of the 31 NHL cases (24 males and 7 females demonstrated concordance between FDG PET findings and BMB reports. Remaining 5 cases showed discordance of FDG-PET demonstrating presence of marrow involvement at marrow sites and uninvolved marrow on BMB. All the BMB positive patients (2 of HD and 5 of NHL demonstrated disease activity in bone marrow on FDG-PET study. All patients with absence of disease activity at marrow sites on FDG-PET scan (9 of HD and 21 of NHL had histology proven uninvolved marrow. The quantitative assessment by DMI showed a mean of >2.5 in HD and NHL patients at the PSIS region and the trochanteric region bilaterally in cases of bone marrow

  16. Repeated Administration of Bone Marrow-Derived Cells Prevents Disease Progression in Experimental Silicosis

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    Miquéias Lopes-Pacheco

    2013-12-01

    Full Text Available Background/Aims: Bone marrow-derived cells (BMDCs reduced mechanical and histologic changes in the lung in a murine model of silicosis, but these beneficial effects did not persist in the course of lung injury. We hypothesized that repeated administration of BMDCs may decrease lung inflammation and remodeling thus preventing disease progression. Methods: One hundred and two C57BL/6 mice were randomly divided into SIL (silica, 20 mg intratracheally [IT] and control (C groups (saline, IT. C and SIL groups were further randomized to receive BMDCs (2×106 cells or saline IT 15 and 30 days after the start of the protocol. Results: By day 60, BMDCs had decreased the fractional area of granuloma and the number of polymorphonuclear cells, macrophages (total and M1 phenotype, apoptotic cells, the level of transforming growth factor (TGF-β‚ and types I and III collagen fiber content in the granuloma. In the alveolar septa, BMDCs reduced the amount of collagen and elastic fibers, TGF-β, and the number of M1 and apoptotic cells. Furthermore, interleukin (IL-1β, IL-1R1, caspase-3 mRNA levels decreased and the level of IL-1RN mRNA increased. Lung mechanics improved after BMDC therapy. The presence of male donor cells in lung tissue was not observed using detection of Y chromosome DNA. Conclusion: repeated administration of BMDCs reduced inflammation, fibrogenesis, and elastogenesis, thus improving lung mechanics through the release of paracrine factors.

  17. Treatment of Moyamoya disease by multipoint skull drilling for indirect revascularization combined with mobilization of autologous bone marrow stem cells.

    Science.gov (United States)

    Wu, R; Su, N; Zhang, Z; Jia, F

    2015-07-06

    This study discusses the clinical efficacy of multipoint skull drilling for indirect revascularization combined with mobilization of autologous bone marrow stem cells and use of simvastatin in the treatment of moyamoya disease. Seventy-eight patients [control group (group A), 39 patients; experimental group (group B), 39 patients] with moyamoya disease were selected. Group A underwent indirect revascularization, and group B, in addition to indirect revascularization, received alternate subcutaneous injections from day 7 post-surgery. The number and differentiation of the mobilized bone marrow stem cells were detected by the proportion of hematopoietic progenitor cell (HPCs) in mononuclear cells (MNCs) in the peripheral blood. There was no statistical difference in the BI (80.2 ± 13.7) and NIHSS (6.7 ± 2.3) scores between the groups before treatment (P > 0.05). The CSS score of group B was 13.5 ± 0.6 and there was a statistical significance compared to group A (18.2 ± 0.8) (P 0.05) and the proportions of CD34+ CDl33+ cells in MNCs in peripheral blood in groups A and B at 30 days after surgery were significantly higher than those before surgery (P moyamoya disease by multipoint skull drilling for indirect revascularization combined with mobilization of autologous bone marrow stem cells and simvastatin is a safe and effective method as it can promote recovery of neurological functions and improve patients' daily living abilities and quality of life.

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

    Science.gov (United States)

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

    2014-07-01

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

  19. Acute renal graft-versus-host disease in a murine model of allogeneic bone marrow transplantation.

    Science.gov (United States)

    Schmid, Peter M; Bouazzaoui, Abdellatif; Schmid, Karin; Birner, Christoph; Schach, Christian; Maier, Lars S; Holler, Ernst; Endemann, Dierk H

    2017-03-23

    Acute kidney injury (AKI) is a very common complication after allogeneic bone marrow transplantation (BMT) and associated with poor prognosis. Generally kidneys are assumed to be no direct target of Graft-versus-Host Disease (GvHD), and renal impairment is often attributed to several other factors occurring in the early phase after BMT. Our study aimed to prove the existence of renal GvHD in a fully MHC-mismatched model of BALB/c mice conditioned and transplanted according to two different intensity protocols. Syngeneically transplanted and untreated animals served as controls. 4 weeks after transplantation, allogeneic animals developed acute GvHD that was more pronounced in the high-intensity protocol (HIP) group than in the low-intensity protocol (LIP) group. Urea and creatinine as classic serum markers of renal function could not verify renal impairment 4 weeks after BMT. Creatinine levels were even reduced as a result of catabolic metabolism and loss of muscle mass due to acute GvHD. Proteinuria, albuminuria, and urinary N-acetyl-beta-Dglucosaminidase (NAG) levels were measured as additional renal markers before and after transplantation. Albuminuria and NAG were only significantly increased after allogeneic transplantation, correlating with disease severity between HIP and LIP animals. Histological investigations of the kidneys showed renal infiltration of T-cells and macrophages with endarteriitis, interstitial nephritis, tubulitis, and glomerulitis. T-cells consisted of CD4+, CD8+, and FoxP3+ cells. Renal expression analysis of allogeneic animals showed increases in indoleamine-2,3 dioxygenase (IDO), different cytokines (TNFα, IFN-γ, IL-1α, IL2, IL-6, and IL-10), and adhesion molecules (ICAM-1 and VCAM-1), resembling findings from other tissues in acute GvHD. In summary, our study supports the entity of renal GvHD with histological features suggestive of cell-mediated renal injury. Albuminuria and urinary NAG levels may serve as early markers of renal

  20. Ex vivo exposure of bone marrow from chronic kidney disease donor rats to pravastatin limits renal damage in recipient rats with chronic kidney disease

    NARCIS (Netherlands)

    Koppen, A. van; Papazova, D.A.; Oosterhuis, N.R.; Gremmels, H.; Giles, R.H.; Fledderus, J.O.; Joles, J.A.; Verhaar, M.C.

    2015-01-01

    Introduction: Healthy bone marrow cell (BMC) infusion improves renal function and limits renal injury in a model of chronic kidney disease (CKD) in rats. However, BMCs derived from rats with CKD fail to retain beneficial effects, demonstrating limited therapeutic efficacy. Statins have been reported

  1. Ex vivo exposure of bone marrow from chronic kidney disease donor rats to pravastatin limits renal damage in recipient rats with chronic kidney disease

    NARCIS (Netherlands)

    van Koppen, Arianne; Papazova, Diana A.; Oosterhuis, Nynke R.; Gremmels, Hendrik; Giles, Rachel H.; Fledderus, Joost O.; Joles, Jaap A.; Verhaar, Marianne C.

    2015-01-01

    INTRODUCTION: Healthy bone marrow cell (BMC) infusion improves renal function and limits renal injury in a model of chronic kidney disease (CKD) in rats. However, BMCs derived from rats with CKD fail to retain beneficial effects, demonstrating limited therapeutic efficacy. Statins have been reported

  2. Fat/water separation in MRI. Detection of bone marrow reactions in patients with degenerative disc disease

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    Assheuer, J.; Lenz, G.; Lenz, W.; Gottschlich, K.W.; Schulitz, K.P.

    1987-07-01

    We examined 410 patients with lumbar disc degeneration. In 23% fat suppressing IR sequences and phase contrast techniques displayed marrow reactions in subchondral bone adjacent to the affected discs. Only in some cases conventional MRI sequences were able to depict these marrow reactions. CT, plain X-ray and scintigraphy did not show marrow changes. Bacterial infection was excluded. Histological analysis showed substitution of haematopoietic marrow by fatty tissue, necrobiosis and increase in mucoid extracellular fluid.

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

    Science.gov (United States)

    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.

  4. Intra-bone marrow-bone marrow transplantation slows disease progression and prolongs survival in G93A mutant SOD1 transgenic mice, an animal model mouse for amyotrophic lateral sclerosis.

    Science.gov (United States)

    Ohnishi, Shizuo; Ito, Hidefumi; Suzuki, Yasuhiro; Adachi, Yasushi; Wate, Reika; Zhang, Jianhua; Nakano, Satoshi; Kusaka, Hirofumi; Ikehara, Susumu

    2009-11-03

    It has been reported that bone marrow transplantation (BMT) has clinical effects on not only hematopoietic diseases and autoimmune diseases but also solid malignant tumors and metabolic diseases. We have found that intra-bone marrow-bone marrow transplantation (IBM-BMT) is superior to conventional intravenous BMT, since IBM-BMT enables rapid recovery of donor hematopoiesis and reduces the extent of graft-versus-host disease (GVHD). In this experiment, we examined the effects of IBM-BMT on symptomatic G93A mutant SOD1 transgenic mice (mSOD1 Tg mice), a model mouse line for amyotrophic lateral sclerosis (ALS). Symptomatic mSOD1 Tg mice (12 weeks old) were irradiated with 6Gyx2 at a 4-hour interval, one day before IBM-BMT. The mice were transplanted with bone marrow cells (BMCs) from 12-wk-old eGFP-transgenic C57BL/6 mice (eGFP Tg mice) or BMCs from 12-wk-old mSOD1 Tg mice. The ALS model mice transplanted with BMCs from eGFP Tg mice showed longer survival and slower disease progression than those transplanted with BMCs from mSOD1 Tg mice or untreated mSOD1 Tg mice. There was a significantly high number of eGFP(+) cells in the anterior horn of the spinal cord of the mSOD1 Tg mice transplanted with BMCs of eGFP Tg mice, some of which expressed Iba-1, a marker of microglia, although they did not differentiate into neural cells. These results suggest that the replacement with normal hematopoietic cells improved the neural cell environment, thereby slowing the progression of the disease.

  5. Transplanted bone marrow mesenchymal stem cells improve memory in rat models of Alzheimer's disease.

    Science.gov (United States)

    Babaei, Parvin; Soltani Tehrani, Bahram; Alizadeh, Arsalan

    2012-01-01

    The present study aims to evaluate the effect of bone marrow mesenchymal stem cells (MSCs) grafts on cognition deficit in chemically and age-induced Alzheimer's models of rats. In the first experiments aged animals (30 months) were tested in Morris water maze (MWM) and divided into two groups: impaired memory and unimpaired memory. Impaired groups were divided into two groups and cannulated bilaterally at the CA1 of the hippocampus for delivery of mesenchymal stem cells (500 × 10(3)/μL) and PBS (phosphate buffer saline). In the second experiment, Ibotenic acid (Ibo) was injected bilaterally into the nucleus basalis magnocellularis (NBM) of young rats (3 months) and animals were tested in MWM. Then, animals with memory impairment received the following treatments: MSCs (500 × 10(3)/μL) and PBS. Two months after the treatments, cognitive recovery was assessed by MWM in relearning paradigm in both experiments. Results showed that MSCs treatment significantly increased learning ability and memory in both age- and Ibo-induced memory impairment. Adult bone marrow mesenchymal stem cells show promise in treating cognitive decline associated with aging and NBM lesions.

  6. Transplanted Bone Marrow Mesenchymal Stem Cells Improve Memory in Rat Models of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Parvin Babaei

    2012-01-01

    Full Text Available The present study aims to evaluate the effect of bone marrow mesenchymal stem cells (MSCs grafts on cognition deficit in chemically and age-induced Alzheimer's models of rats. In the first experiments aged animals (30 months were tested in Morris water maze (MWM and divided into two groups: impaired memory and unimpaired memory. Impaired groups were divided into two groups and cannulated bilaterally at the CA1 of the hippocampus for delivery of mesenchymal stem cells (500×103/ and PBS (phosphate buffer saline. In the second experiment, Ibotenic acid (Ibo was injected bilaterally into the nucleus basalis magnocellularis (NBM of young rats (3 months and animals were tested in MWM. Then, animals with memory impairment received the following treatments: MSCs (500×103/ and PBS. Two months after the treatments, cognitive recovery was assessed by MWM in relearning paradigm in both experiments. Results showed that MSCs treatment significantly increased learning ability and memory in both age- and Ibo-induced memory impairment. Adult bone marrow mesenchymal stem cells show promise in treating cognitive decline associated with aging and NBM lesions.

  7. Bone marrow examination in pancytopenia.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    ... page please turn Javascript on. Feature: Bone Marrow Transplants “Another Possibility at Life” Past Issues / Summer 2011 ... for 16,000 of them, a bone marrow transplant is the best treatment option, notes Susan F. ...

  9. Bone marrow depletion with haemorrhagic diathesis in calves in Germany: characterization of the disease and preliminary investigations on its aetiology.

    Science.gov (United States)

    Kappe, Eva C; Halami, Mohammad Yahya; Schade, Benjamin; Alex, Michaela; Hoffmann, Doris; Gangl, Armin; Meyer, Karsten; Dekant, Wolfgang; Schwarz, Bernd-Andreas; Johne, Reimar; Buitkamp, Johannes; Böttcher, Jens; Müller, Hermann

    2010-01-01

    Since 2007 a new fatal haemorrhagic diathesis in calves has been observed in all areas of Germany. Analysis of 56 cases submitted for necropsy allowed its characterization. Calves fell ill within the first month of life independent of breed and sex. Only single or a few animals per herd were affected. Petechial and ecchymotic haemorrhages in many organs and tissues, particularly in skin, subcutis and gastrointestinal tract, were major findings in all animals. Microscopically a severe depletion of bone marrow cells was always observed. Lymphocytic depletion (43%) and inflammatory lesions (46%) were less frequently observed. Blood analysis of five animals indicated an aplastic pancytopenia. The resulting thrombocytopenia is regarded as major pathomechanism of this Haemorrhagic Disease Syndrome (HDS). Pedigree analysis gave no indication of hereditary disease. Tests for specific toxins such as S-(1,2-Dichlorovinyl)-L-cysteine (DCVC), furazolidone, or mycotoxins resulting in bone marrow depletion were negative. Bacterial infections, Bovine Viral Diarrhoea Virus, and Bluetongue Virus were ruled out as cause of the disease. HDS shares similarities with a circoviral infection in chickens (chicken infectious anaemia). A broad-spectrum PCR allowed detection of circoviral DNA in 5 of 25 HDS cases and in 1 of 8 non-HDS cases submitted for necropsy. Sequencing of the whole viral genome revealed a high similarity (up to 99%) with Porcine Circovirus type 2b. Single bone marrow cells stained weakly positive for PCV2 antigen by immunohistochemistry in 1 of 8 tested HDS animals. This is the first report of circovirus detection in cattle in Germany. The exact cause of HDS still remains unknown. A multifactorial aetiology involving infection, poisoning, immunopathy, or a genetic predisposition is conceivable. Additional research is necessary to clarify the pathogenesis and the potential role of PCV2 in HDS.

  10. Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Andre Castro Lyra; Bernd Genser; Ricardo Ribeiro dos Santos; Luiz Guilherme Costa Lyra; Milena Botelho Pereira Soares; Luiz Flavio Maia da Silva; Marcos Fraga Fortes; André Goyanna Pinheiro Silva; Augusto César de Andrade Mota; Sheilla A Oliveira; Eduardo Lorens Braga; Wilson Andrade de Carvalho

    2007-01-01

    AIM:To evaluate the safety and feasibility of bone marrow cell(BMC)transplantation in patients with chronic liver disease on the waiting list for liver transplantation.METHODS:Ten patients(eight males)with chronic liver disease were enrolled to receive infusion of autologous bone marrow-derived cells.Seven patients were classified as Child-Pugh B and three as Child-Pugh C.Baseline assessment included complete clinical and laboratory evaluation and abdominal MRI.Approximately 50 mL of bone marrow aspirate was prepared by centrifugation in a ficoll-hypaque gradient.At least of 100 millions of mononuclear-enriched BMCs were infused into the hepatic artery using the routine technique for arterial chemoembolization for liver tumors.Patients were followed up for adverse events up to 4 mo.RESULTS:The median age of the patients was 52 years(range 24-70 years).All patients were discharged 48 h after BMC infusion.Two patients complained of mild pain at the bone marrow needle puncture site.No other complications or specific side effects related to the procedure were observed.Bilirubin levels were lower at 1(2.19 ± 0.9)and 4 mo(2.10 ± 1.0)after cell transplantation that baseline levels(2.78 ± 1.2).Albumin levels 4 mo after BMC infusion(3.73 ± 0.5)were higher than baseline levels(3.47 ± 0.5).International normalized ratio(INR)decreased from 1.48(SD = 0.23)to 1.43(SD = 0.23)one month after cell transplantation.CONCLUSION:BMC infusion into hepatic artery of patients with advanced chronic liver disease is safe and feasible.In addition,a decrease in mean serum bilirubin and INR levels and an increase in albumin levels are observed.Our data warrant further studies in order to evaluate the effect of BMC transplantation in patients with advanced chronic liver disease.

  11. Prospective study of bone marrow in haematological disorders

    Directory of Open Access Journals (Sweden)

    Bhagya Lakshmi Atla

    2015-08-01

    Conclusion: The present study showed the usefulness of bone marrow aspiration and trephine biopsy in evaluation of the bone marrow in routine haematological disorders and also for understanding disease progression, for diagnosis and therapeutic evaluation. These are also helpful in planning further investigation and management. [Int J Res Med Sci 2015; 3(8.000: 1917-1921

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

    Science.gov (United States)

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

    2016-01-01

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

  13. Bone Marrow Matters

    Science.gov (United States)

    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…

  14. [Prolonged acute pancreatitis after bone marrow transplantation].

    Science.gov (United States)

    De Singly, B; Simon, M; Bennani, J; Wittnebel, S; Zagadanski, A-M; Pacault, V; Gornet, J-M; Allez, M; Lémann, M

    2008-04-01

    Acute pancreatitis is not infrequent after allogenic marrow transplantation. Several causes can predispose to pancreatitis, including Graft-Versus-Host Disease (GVHD), a condition which is probably underestimated. In the literature, few description of pancreatic GVHD can be found. Pancreatic GVHD diagnosis can be difficult if pancreatic involvement occurs without other typical manifestations of GVHD. We report the case of a woman, 54 years old, suffering from prolonged, painful pancreatitis two months after allogenic bone marrow transplantation for acute myeloid leucemia. Pancreatic GVHD diagnosis was performed after five weeks on duodenal biopsies despite the absence of diarrheoa. The patient dramatically improved within few days on corticosteroids.

  15. Staphylococcal enterotoxin A regulates bone marrow granulocyte trafficking during pulmonary inflammatory disease in mice

    Energy Technology Data Exchange (ETDEWEB)

    Takeshita, W.M.; Gushiken, V.O.; Ferreira-Duarte, A.P.; Pinheiro-Torres, A.S.; Roncalho-Buck, I.A. [Department of Biology and Physiology, Faculty of Medicine of Jundiai (FMJ), Jundiai, SP (Brazil); Squebola-Cola, D.M.; Mello, G.C.; Anhê, G.F.; Antunes, E. [Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP (Brazil); DeSouza, I.A., E-mail: ivanidesouza@uol.com.br [Department of Biology and Physiology, Faculty of Medicine of Jundiai (FMJ), Jundiai, SP (Brazil)

    2015-09-15

    Pulmonary neutrophil infiltration produced by Staphylococcal enterotoxin A (SEA) airway exposure is accompanied by marked granulocyte accumulation in bone marrow (BM). Therefore, the aim of this study was to investigate the mechanisms of BM cell accumulation, and trafficking to circulating blood and lung tissue after SEA airway exposure. Male BALB/C mice were intranasally exposed to SEA (1 μg), and at 4, 12 and 24 h thereafter, BM, circulating blood, bronchoalveolar lavage (BAL) fluid and lung tissue were collected. Adhesion of BM granulocytes and flow cytometry for MAC-1, LFA1-α and VLA-4 and cytokine and/or chemokine levels were assayed after SEA-airway exposure. Prior exposure to SEA promoted a marked PMN influx to BAL and lung tissue, which was accompanied by increased counts of immature and/or mature neutrophils and eosinophils in BM, along with blood neutrophilia. Airway exposure to SEA enhanced BM neutrophil MAC-1 expression, and adhesion to VCAM-1 and/or ICAM-1-coated plates. Elevated levels of GM-CSF, G-CSF, INF-γ, TNF-α, KC/CXCL-1 and SDF-1α were detected in BM after SEA exposure. SEA exposure increased production of eosinopoietic cytokines (eotaxin and IL-5) and BM eosinophil VLA-4 expression, but it failed to affect eosinophil adhesion to VCAM-1 and ICAM-1. In conclusion, BM neutrophil accumulation after SEA exposure takes place by integrated action of cytokines and/or chemokines, enhancing the adhesive responses of BM neutrophils and its trafficking to lung tissues, leading to acute lung injury. BM eosinophil accumulation in SEA-induced acute lung injury may occur via increased eosinopoietic cytokines and VLA-4 expression. - Highlights: • Airway exposure to SEA causes acute lung inflammation. • SEA induces accumulation of bone marrow (BM) in immature and mature neutrophils. • SEA increases BM granulocyte or BM PMN adhesion to ICAM-1 and VCAM-1, and MAC-1 expression. • SEA induces BM elevations of CXCL-1, INF-γ, TNF-α, GM-CSF, G-CSF and

  16. A novel and feasible way to cultivate and purify endothelial progenitor cells from bone marrow of children with congenital heart diseases

    Institute of Scientific and Technical Information of China (English)

    WU Yong-tao; LI Jing-xing; LIU Shuo; XIN Yi; WANG Zi-jian; GAO Jin; JI Bing-yang; FAN Xiang-ming; ZHOU Qi-wen

    2012-01-01

    Background Endothelial progenitor cells (EPCs) are used in vascular tissue engineering and clinic therapy.Some investigators get EPCs from the peripheral blood for clinic treatment,but the number of EPCs is seldom enough.We have developed the cultivation and purification of EPCs from the bone marrow of children with congenital heart disease,to provide enough seed cells for a small calibre vascular tissue engineering study.Methods The 0.5-ml of bone marrow was separated from the sternum bone,and 5-ml of peripheral blood was collected from children with congenital heart diseases who had undergone open thoracic surgery.CD34+ and CD34+/VEGFR+cells in the bone marrow and peripheral blood were quantified by flow cytometry.CD34+NEGFR+ cells were defined as EPCs.Mononuclear cells in the bone marrow were isolated by Ficoll(R) density gradient centrifugation and cultured by the EndoCult Liquid Medium KitTM.Colony forming endothelial cells was detected.Immunohistochemistry staining for Dil-ac-LDL and FITC-UEA-1 confirmed the endothelial lineage of these cells.Results CD34+ and CD34+NEGFR+ cells in peripheral blood were (0.07±0.05)% and (0.05±0.02)%,respectively.The number of CD34+ and CD34+NEGFR+ cells in bone marrow were significantly higher than in blood,(4.41±1.47)% and (0.98±0.65)%,respectively (P <0.0001).Many colony forming units formed in the culture.These cells also expressed high levels of Dil-ac-LDL and FITC-UEA-1.Conclusion This is a novel and feasible approach that can cultivate and purify EPCs from the bone marrow of children with congenital heart disease,and provide seed cells for small calibre vascular tissue engineering.

  17. Bone marrow edema in sports: General concepts

    Energy Technology Data Exchange (ETDEWEB)

    Vanhoenacker, F.M. [AZ Sint-Maarten Duffel-Mechelen, Department of Radiology, Rooienberg 25, B-2570 Duffel (Belgium) and University Hospital Antwerp, Department of Radiology, Wilrijkstraat 10, B-2650 Edegem (Belgium)]. E-mail: filip.vanhoenacker@telenet.be; Snoeckx, A. [AZ Sint-Maarten Duffel-Mechelen, Department of Radiology, Rooienberg 25, B-2570 Duffel (Belgium); University Hospital Antwerp, Department of Radiology, Wilrijkstraat 10, B-2650 Edegem (Belgium)

    2007-04-15

    This paper will discuss the value of medical imaging in the detection and follow-up of bone marrow edema (BME), resulting from acute and chronic trauma in sports. MR imaging is the only imaging technique that allows direct evaluation of bone marrow edema in sports medicine. The use of fat suppressed T2-weighted or STIR images is particularly appropriate to detect bone marrow edema. The extent of bone marrow edema reflects the biomechanics of trauma. Compressive forces between two bony structures will result in extensive areas of bone marrow edema, whereas distraction forces provoke more subtle areas of bone marrow edema at the insertion of supporting structures of joints. In most clinical situations, a combination of compression and distraction forces is present, causing a complex pattern of bone marrow edema. A meticulous pattern approach of the distribution of these bone marrow changes around a joint can reveal in most instances the underlying mechanism of trauma. This may be helpful to analyze which joint supporting structures may be at risk. In the acute setting, plain radiography and CT scan may have an additional role in the detection of small avulsion fractures occurring at the site of minor areas of bone marrow edema. The clinical significance and natural history of bone marrow edema is still a matter of debate.

  18. Minimal residual disease in bone marrow and peripheral blood of patients with metastatic breast cancer.

    Science.gov (United States)

    Bischoff, Joachim; Rosenberg, Robert; Dahm, Michael; Janni, Wolfgang; Gutschow, Klaus

    2003-01-01

    The presence of occult micrometastases in bone marrow (BM) of patients with early breast cancer increases the risk of relapse. Detection of circulation tumor cells in peripheral blood (PB) may also influence the patient's prognosis. Few data are available on the correlation between tumor cell dissemination in BM and PB in solid epithelial tumors. Twenty-milliliter blood samples were collected from PB of 42 patients with advanced breast cancer and centrifuged using the density gradient OncoQuick (OncoQuick Greiner BioOne, Frickenhausen, Germany). The BM aspirates available from 11 of the 42 patients were centrifuged using density centrifugation Ficoll. Tumor cell detection was performed by microscopy after cytospin preparation and immunocytochemical staining with the monoclonal antibody A45-B/B3. Cytokeratin-positive cells were detected in 23 patients (55%) in the PB and in three patients (27%) in the BM. A cohort with bone lesions as the only metastatic side showed a correlation as follows: 7 of the 11 patients (64%) had negative findings in BM and PB, whereas cytokeratin-positive cells in PB were present in 3 of these 11 patients (27%). The presence of visceral metastases was associated with the detection of cytokeratin-positive cells in the PB in 20 of the 31 patients (65%) in this subgroup. The density gradient OncoQuick in combination with immunocytochemical staining allows the detection of cytokeratin-positive cells in PB of patients with advanced breast cancer. The immunocytochemical detection of cytokeratin-positive cells in PB seems to be associated with the site of metastatic manifestation.

  19. The impact of bone marrow micrometastases on metastatic disease-free survival in patients with colorectal carcinoma.

    LENUS (Irish Health Repository)

    O'Connor, O J

    2012-02-03

    AIMS: The biological relevance of bone marrow micrometastases (BMM) in colorectal cancer remains unknown. Here, we investigate their nature by examining the impact of the presence of BMM on metastatic disease-free survival in a cohort of patients with this disease. METHODS: Sixty-three consecutive patients undergoing surgery for colorectal cancer of any stage were studied after approval of the study protocol by the local ethics committee and with full individual informed consent. All had bilateral iliac crest bone marrow aspirates prior to operation. Aspirates were then examined for the presence of aberrant cytokeratin-18-positive cells by a blinded observer using both flow cytometric and APAAP immunohistochemical techniques. RESULTS: Mean follow-up after surgery was 4.6 years (range 1.9-6.9) for those without hepatic metastases at diagnosis. Seven of 34 patients with Dukes\\' stage A or B developed metastatic disease after a mean interval of 4.7 years (range 3.8-6.8). However, only 2 of these patients demonstrated BMM at the time of surgery. Nine of 15 patients with Dukes\\' C carcinoma at the time of surgery subsequently developed metastases after a mean interval of 4.4 years (range 1.9-6.9). Again, only two of these patients had BMM detectable initially. In only three of the 14 patients known to have metastases at the time of operation (i.e. Dukes\\'\\'D\\' disease) were BMM found. CONCLUSION: The presence of BMM as detected by this methodology was not predictive of tumour recurrence or metastasis. This study does not support the consideration of adjuvant therapy based on the presence of BMM at a single pre-operative time point in patients with colorectal cancer.

  20. Karyotype of cryopreserved bone marrow cells

    Directory of Open Access Journals (Sweden)

    M.L.L.F. Chauffaille

    2003-07-01

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

  1. Elevated interferon-gamma in CNS inflammatory disease: a potential complication for bone marrow reconstitution in MS

    DEFF Research Database (Denmark)

    Hassan-Zahraee, M; Tran, E H; Bourbonnière, L;

    2000-01-01

    Bone marrow transplantation (BMT) is increasingly used to treat Multiple Sclerosis (MS) a CNS inflammatory disease with elevated CNS and systemic IFNgamma levels. We wished to determine the effect of IFNgamma on BM graft survival in a transgenic mouse model for chronic MS. BM transplantation...... into transgenic mice which express elevated levels of IFNgamma in the CNS was unsuccessful. By contrast, there was 100% survival of even fully allogeneic, T-depleted transplants to transgenics that over express TNFalpha in the CNS, using the same MBP promoter. IFNgamma was detectable in spleen of irradiated mice...... but levels were higher in IFNgamma transgenics. BM transplantation into IFNgamma-deficient recipients also had a high failure rate. Transplants of BM from mice lacking expression of IFNgamma-receptor failed, whereas IFNgamma-deficient grafts survived, suggesting that IFNgamma response status of the graft can...

  2. Multiparameter MRI assessment of normal-appearing and diseased vertebral bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Biffar, Andreas; Dietrich, Olaf [LMU University Hospitals Munich-Grosshadern, Josef Lissner Laboratory for Biomedical Imaging, Institute of Clinical Radiology, Munich (Germany); Baur-Melnyk, Andrea; Schmidt, Gerwin P. [LMU University Hospitals Munich-Grosshadern, Institute of Clinical Radiology, Munich 81377 (Germany); Reiser, Maximilian F. [LMU University Hospitals Munich-Grosshadern, Josef Lissner Laboratory for Biomedical Imaging, Institute of Clinical Radiology, Munich (Germany); LMU University Hospitals Munich-Grosshadern, Institute of Clinical Radiology, Munich 81377 (Germany)

    2010-11-15

    To evaluate spin-lattice (T1) and spin-spin (T2) relaxation times as well as apparent diffusion coefficients (ADCs) of the fat and water components in the vertebral bone marrow (vBM) of patients with benign and malignant lesions. Forty-four patients were examined at 1.5 T: there were 24 osteoporotic vertebral fractures (15 women, 9 men; median age: 73, 48-86 years) and 20 malignant vertebral infiltrations (9 women, 11 men; median age: 60, 25-87). Relaxation times were determined separately for the water and the fat component using a saturation-recovery technique for T1 and measurements with variable echo times for T2. ADCs were determined with a diffusion-weighted (DW) echo-planar imaging (EPI) and a single-shot turbo-spin-echo (ssTSE) sequence. T1 of the water component and ADCs were significantly increased in the lesions compared with normal-appearing vBM (malignant: 1,252 vs. 828 ms, osteoporotic: 1,315 vs. 872 ms). ADCs determined with the DW-ssTSE were significantly increased compared with the DW-EPI. ADCs determined with the DW-ssTSE differed significantly between osteoporotic and malignant lesions (1.74vs1.35 x 10{sup -3}mm{sup 2}/s). All parameters exhibit significant differences between normal-appearing vBM and the lesions. However, only the ADCs determined with the DW-ssTSE differed significantly between osteoporotic fractures and malignant lesions, potentially allowing for a differential diagnosis of these two entities. (orig.)

  3. Kinetics of lymphocyte reconstitution after allogeneic bone marrow transplantation: markers of graft-versus-host disease.

    Science.gov (United States)

    Zinöcker, Severin; Sviland, Lisbet; Dressel, Ralf; Rolstad, Bent

    2011-07-01

    GVHD causes extensive morbidity and mortality in patients who receive alloHCT. Predictive and reliable markers for GVHD are currently lacking but required to improve the safety and accessibility of alloHCT. We present an experimental rat model of myeloablative total body irradiation and fully mismatched major and minor histoincompatible, T cell-depleted BMT, followed by delayed infusion of donor lymphocytes. This treatment, in contrast to marrow transplantation alone, resulted in severe aGVHD and 100% lethality within 2-6 weeks. We investigated the reconstitution kinetics and phenotypes of donor leukocyte subpopulations as well as the histopathology of selected organs that may correlate with GVHD, with the goal to find potential disease-related markers. We observed histological changes mainly confined to the skin, with degenerative changes in the basal layer. LNs and spleen showed deranged architecture with markedly increased accumulation of lymphocytes, whereas the gut, liver, and lungs appeared normal. Of the lymphocyte markers tested, donor-derived CD62L(+) T cells were markedly decreased in animals suffering from GVHD. Furthermore, we observed peripheral depletion of CD4(+)CD25(hi)FoxP3(+) T(reg), which was in contrast to controls. The relative frequency of these lymphocyte subpopulations in blood may therefore serve as accessible cellular markers of aGVHD. We propose that the animal model presented is instructive for the identification of clinically relevant markers of GVHD, which could improve disease diagnosis and management in alloHCT.

  4. Impact of cytomegalovirus and grafts versus host disease on the dynamics of CD57+CD28-CD8+ T cells after bone marrow transplant

    Directory of Open Access Journals (Sweden)

    Ana Verena Almeida Mendes

    2008-01-01

    Full Text Available OBJECTIVES: The present study aimed to evaluate the dynamics of CD28 and CD57 expression in CD8+ T lymphocytes during cytomegalovirus viremia in bone marrow transplant recipients. METHODS: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients. To evaluate the expression of CD57 and CD28 on CD8+ T lymphocytes, flow cytometry analysis was performed on blood samples for four months after bone marrow transplant, together with cytomegalovirus antigenemia assays. RESULTS: Compared to cytomegalovirus-seronegative healthy subjects, seropositive healthy subjects demonstrated a higher percentage of CD57+ and a lower percentage of CD28+ cells (p<0.05. A linear regression model demonstrated a continuous decrease in CD28+ expression and a continuous increase in CD57+ expression after bone marrow transplant. The occurrence of cytomegalovirus antigenemia was associated with a steep drop in the percentage of CD28+ cells (5.94%, p<0.01 and an increase in CD57+ lymphocytes (5.60%, p<0.01. This cytomegalovirus-dependent effect was for the most part concentrated in the allogeneic bone marrow transplant patients. The development of acute graft versus host disease, which occurred at an earlier time than antigenemia (day 26 vs. day 56 post- bone marrow transplant, also had an impact on the CD57+ subset, triggering an increase of 4.9% in CD57+ lymphocytes (p<0.05. CONCLUSION: We found continuous relative changes in the CD28+ and CD57+ subsets during the first 120 days post- bone marrow transplant, as part of immune system reconstitution and maturation. A clear correlation was observed between the expansion of the CD57+CD28-CD8+ T lymphocyte subpopulation and the occurrence of graft versus host disease and cytomegalovirus viremia.

  5. Effects of recombinant human erythropoietin on the haemopoietic bone marrow monitored by magnetic resonance spectroscopy in patients with end-stage renal disease

    DEFF Research Database (Denmark)

    Jensen, K E; Stenver, D; Jensen, M;

    1990-01-01

    Volume selective magnetic resonance (MR) proton spectroscopy was used to investigate changes in the haemopoietic bone marrow in patients with end-stage renal disease undergoing treatment with recombinant human erythropoietin (rHuEPO). Significant changes could be detected in the spectra 14 days...

  6. Tetanus after allogeneic bone-marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Kendra, J.R.; Halil, O.; Barrett, A.J.; Selwyn, S. (Westminster Medical School, London (UK))

    1982-11-13

    A brief report is presented of a case of tetanus after allogeneic bone-marrow transplantation complicated by radiation-induced pneumonitis. A 30-year-old army sergeant received a bone-marrow transplant from his brother for the treatment of a granulocytic sarcoma after local radiotherapy to the tumour. Six years earlier he had sustained an open, compound fracture of the left tibia and fibula while on army exercise. At the time a pin and plate had been inserted and booster anti-tetanus administered. Bone-marrow transplantation was performed after total body irradiation. Cyclosporin A was given against graft-versus-host disease. Fifty four days after transplantation tetanus was diagnosed and death followed 14 days later. Necropsy disclosed radiation-induced pneumonitis, but no organisms were cultured from the lungs or the old fracture site. It is suggested that spores were incorporated into the wound site before surgery and that oxygenation around the plate became compromised after transplantation, permitting germination of dormant spores, immunosuppression allowing development of the disease.

  7. [Bone disease in Gaucher's disease].

    Science.gov (United States)

    Roca Espiau, Mercedes

    2011-09-01

    The exposition aims, is to review the pathophysiological mechanisms of bone marrow involvement and the patterns of marrow infiltration by Gaucher cells. We have reviewed the different methods of assessment of bone marrow infiltration and its temporal development. Qualitative methods include simple radiography, magnetic resonance imaging (MRI), computed tomography (CT) and radioisotope. The simple radiography is the basic element, but its sensitivity is limited and only allows for assessing changes and trabecular bone remodeling MRI allows us to appreciate the bone marrow infiltration, detection of complications and response to therapy. Radioisotopes can contribute to the differential diagnosis of osteomyelitis and bone crises. Among the quantitative methods are the QCSI (quantitative chemical shift imaging) and the dual-energy X-ray absorptiometry (DEXA), as well as new quantitative techniques of CT, MRI and ultrasound densitometry. The QCSI performed an assessment of fat content of bone marrow in the spine. DEXA quantifies bone density by measuring the attenuation coefficient. The semiquantitative methods have various "scores" to establish criteria for generalized bone disease endpoints of disease progression and response to therapy.

  8. Bone marrow oedema on MR imaging indicates ARCO stage 3 disease in patients with AVN of the femoral head

    Energy Technology Data Exchange (ETDEWEB)

    Meier, Reinhard; Schaeffeler, Christoph; Waldt, Simone; Rummeny, Ernst J.; Woertler, Klaus [Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Diagnostic and Interventional Radiology, Munich (Germany); Kraus, Tobias M. [Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Orthopaedics, Munich (Germany); Berufsgenossenschaftliche Unfallklinik Tuebingen, Department of Trauma and Orthopaedics, Tuebingen (Germany); Torka, Sebastian [Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Orthopaedics, Munich (Germany); Berufsgenossenschaftliche Unfallklinik Murnau, Department of Trauma and Orthopaedics, Murnau (Germany); Schlitter, Anna Melissa; Specht, Katja [Klinikum rechts der Isar, Technische Universitaet Muenchen, Institute of Pathology, Munich (Germany); Haller, Bernhard [Klinikum rechts der Isar, Technische Universitaet Muenchen, Institute of Medical Statistics and Epidemiology, Munich (Germany); Rechl, Hans [Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Orthopaedics, Munich (Germany)

    2014-09-15

    To test the hypothesis that bone marrow oedema (BME) observed on MRI in patients with avascular necrosis (AVN) of the femoral head represents an indicator of subchondral fracture. Thirty-seven symptomatic hips of 27 consecutive patients (53 % women, mean age 49.2) with AVN of the femoral head and associated BME on magnetic resonance (MR) imaging were included. MR findings were correlated with computed tomography (CT) of the hip and confirmed by histopathological examination of the resected femoral head. Imaging studies were analysed by two radiologists with use of the ARCO classification. On MR imaging a fracture line could be identified in 19/37 (51 %) cases, which were classified as ARCO stage 3 (n = 15) and stage 4 (n = 4). The remaining 18/37 (49 %) cases were classified as ARCO stage 2. However, in all 37/37 (100 %) cases a subchondral fracture was identified on CT, indicating ARCO stage 3/4 disease. The extent of subchondral fractures and the femoral head collapse was graded higher on CT as compared to MRI (P < 0.05). Histopathological analysis confirmed bone necrosis and subchondral fractures. In patients with AVN, BME of the femoral head represents a secondary sign of subchondral fracture and thus indicates ARCO stage 3 disease. circle BME on MRI in AVN of femoral head indicates a subchondral fracture. (orig.)

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

    Science.gov (United States)

    Colnot, C; 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.

  10. Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Laurent Spahr

    Full Text Available OBJECTIVE: Impaired liver regeneration is associated with a poor outcome in patients with decompensated alcoholic liver disease (ALD. We assessed whether autologous bone marrow mononuclear cell transplantation (BMMCT improved liver function in decompensated ALD. DESIGN: 58 patients (mean age 54 yrs; mean MELD score 19, all with cirrhosis, 81% with alcoholic steatohepatitis at baseline liver biopsy were randomized early after hospital admission to standard medical therapy (SMT alone (n = 30, including steroids in patients with a Maddrey's score ≥32, or combined with G-CSF injections and autologous BMMCT into the hepatic artery (n = 28. Bone marrow cells were harvested, isolated and reinfused the same day. The primary endpoint was a ≥3 points decrease in the MELD score at 3 months, corresponding to a clinically relevant improvement in liver function. Liver biopsy was repeated at week 4 to assess changes in Ki67+/CK7+ hepatic progenitor cells (HPC compartment. RESULTS: Both study groups were comparable at baseline. After 3 months, 2 and 4 patients died in the BMMCT and SMT groups, respectively. Adverse events were equally distributed between groups. Moderate alcohol relapse occurred in 31% of patients. The MELD score improved in parallel in both groups during follow-up with 18 patients (64% from the BMMCT group and 18 patients (53% from the SMT group reaching the primary endpoint (p = 0.43 (OR 1.6, CI 0.49-5.4 in an intention to treat analysis. Comparing liver biopsy at 4 weeks to baseline, steatosis improved (p<0.001, and proliferating HPC tended to decrease in both groups (-35 and -33%, respectively. CONCLUSION: Autologous BMMCT, compared to SMT is a safe procedure but did not result in an expanded HPC compartment or improved liver function. These data suggest either insufficient regenerative stimulation after BMMCT or resistance to liver regenerative drive in patients with decompensated alcoholic cirrhosis. TRIAL REGISTRATION

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

    Science.gov (United States)

    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.

  12. Primary bone marrow lymphoma: an uncommon extranodal presentation of aggressive non-hodgkin lymphomas.

    NARCIS (Netherlands)

    Martinez, A.; Ponzoni, M.; Agostinelli, C.; Hebeda, K.M.; Matutes, E.; Peccatori, J.; Campidelli, C.; Espinet, B.; Perea, G.; Acevedo, A.; Mehrjardi, A.Z.; Martinez-Bernal, M.; Gelemur, M.; Zucca, E.; Pileri, S.; Campo, E.; Lopez-Guillermo, A.; Rozman, M.

    2012-01-01

    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

  13. Radionuclide imaging of bone marrow disorders

    NARCIS (Netherlands)

    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-label

  14. Evaluation of bone marrow infiltration in non-neuropathic Gaucher disease patients with use of whole-body MRI. A retrospective data analysis

    Energy Technology Data Exchange (ETDEWEB)

    Laudemann, K.; Moos, L.; Lollert, A.; Wagner, D.; Staatz, G. [University Medical Center of the Johannes Gutenberg University, Mainz (Germany). Section of Pediatric Radiology; Mengel, K.E.; Reinke, J.; Brixius-Huth, M. [University Medical Center of the Johannes Gutenberg University, Mainz (Germany). Clinic for Metabolic Diseases; Dueber, C. [University Medical Center of the Johannes Gutenberg University, Mainz (Germany). Dept. of Diagnostic and Interventional Radiology

    2015-12-15

    To evaluate whole-body magnetic resonance imaging (WB-MRI) for the assessment of bone marrow infiltration in patients with confirmed Gaucher disease type 1 under long-term enzyme replacement therapy (ERT). This retrospective data analysis included 38 patients in two subgroups. Group A: 10 females, 9 males, 15-29 years, mean age 22 years and Group B: 11 females, 8 males, 29-77 years, mean age 49 years, all treated with alglucerase or imiglucerase for at least 12.5 years. Whole-body MRI was carried out in all patients using a standard MRI protocol. Two radiologists assessed all MR images retrospectively with the use of three different MRI score systems: The bone marrow burden (BMB) score, the Duesseldorf-Gaucher score (DGS) and the vertebra disc ratio (VDR). As a clinical component, severity score index type 1 (GD-DS3) was determined. In both groups the MR scores showed low to moderate pathologic levels but no statistically significant difference was found between both groups. The median scores in group A/group B were 7.00/9.00 for the BMB score (p=0.07), 4.00/3.00 for the DGS score (p=0.062) and 1.54/1.62 for the VDR score (p=0.267). The GD-DS3 score was statistically significantly different between both groups (1.6/3.9, p=0.000) and osseous Gaucher disease complications were only found in group B. Bone marrow involvement and typical clinical manifestations are reduced to a minimum, when ERT starts immediately after the confirmed diagnosis of Gaucher disease type 1. The applied MR scores are useful markers to control bone marrow infiltration under enzyme replacement therapy in older patients. Pathologic MR scores in young patients may reflect postponed fat conversion of the juvenile bone marrow. This issue has to be examined in further studies.

  15. Follicular lymphoma (in situ) pattern in the bone marrow: does it indicate an early stage in disease evolution?

    Science.gov (United States)

    Alobeid, Bachir; Mears, John Gregory; Bhagat, Govind

    2015-01-01

    Key Clinical Message Bone marrow involvement by an isolated interstitial lymphoid aggregate exhibiting the pattern and phenotype described for follicular lymphoma in situ (FLIS) has not been reported before. The detection of clinically silent FL in this case highlights the necessity of complete staging workup when such lesions are encountered in biopsies. PMID:26185645

  16. HLA-DP and bone marrow transplantation: DP-incompatibility and severe acute graft versus host disease

    DEFF Research Database (Denmark)

    Ødum, Niels; Platz, P; Jakobsen, B K;

    1987-01-01

    Thirteen recipients of HLA-haploidentical, DR compatible bone marrow (BM) and the corresponding BM donors were HLA-DP typed using primed lymphocyte typing (PLT). Severe acute GVHD (greater than or equal to grade 2) developed within 3 months after BM-transplantation in all of eight recipients of DP...... a role as transplantation antigens....

  17. Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation.

    Directory of Open Access Journals (Sweden)

    Sydney X Lu

    Full Text Available Allogeneic bone marrow transplantation (allo-BMT is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT activity are limited by graft-versus-host-disease (GVHD. Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1 is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT in mouse models. In vivo, Ceacam1(-/- T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi, CD62L(lo. Additionally, Ceacam1(-/- CD8 T cells had greater expression of the gut-trafficking integrin α(4β(7, though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/- recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/- mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+ lymphoma model was improved in animals receiving Ceacam1(-/- vs. control T cells.We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the

  18. Bone marrow oedema associated with benign and malignant bone tumours

    Energy Technology Data Exchange (ETDEWEB)

    James, S.L.J. [Department of Radiology, Royal Orthopaedic Hospital, Birmingham, B31 2AP (United Kingdom)], E-mail: steven.james@roh.nhs.uk; Panicek, D.M. [Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Davies, A.M. [Department of Radiology, Royal Orthopaedic Hospital, Birmingham, B31 2AP (United Kingdom)

    2008-07-15

    Bone marrow oedema is associated with a wide variety of pathological processes including both benign and malignant bone tumours. This imaging finding in relation to intraosseous tumours can aid in providing a more focused differential diagnosis. In this review, we will discuss the MR imaging of bone marrow oedema surrounding intraosseous neoplasms. The different pulse sequences used in differentiating underlying tumour from surrounding oedema are discussed along with the role of dynamic contrast enhanced MRI. Benign lesions commonly associated with bone marrow oedema include osteoid osteoma, osteoblastoma, chondroblastoma and Langerhan's cell histiocytosis. Metastases and malignant primary bone tumours such as osteosarcoma, Ewing's sarcoma and chondrosarcoma may also be surrounded by bone marrow oedema. The imaging findings of these conditions are reviewed and illustrated. Finally, the importance of bone marrow oedema in assessment of post chemotherapeutic response is addressed.

  19. Updates in the pathophysiological mechanisms of Parkinson’s disease: Emerging role of bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Hanaa; H; Ahmed; Ahmed; M; Salem; Hazem; M; Atta; Emad; F; Eskandar; Abdel; Razik; H; Farrag; Mohamed; A; Ghazy; Neveen; A; Salem; Hadeer; A; Aglan

    2016-01-01

    AIM: To explore the approaches exerted by mesenchymal stem cells(MSCs) to improve Parkinson’s disease(PD) pathophysiology.METHODS: MSCs were harvested from bone marrowof femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group(1) was control, Groups(2) and(3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group(2) was left untreated, while Group(3) was treated with single intravenous dose of bone marrow derived MSCs(BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1(TGF-β1), monocyte chemoattractant protein-1(MCP-1) and brain derived neurotrophic factor(BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase(TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done.RESULTS: BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1(489.7 ± 13.0 vs 691.2 ± 8.0, P 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs. CONCLUSION: The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.

  20. Bone marrow contribution to eosinophilic inflammation

    Directory of Open Access Journals (Sweden)

    Denburg Judah A

    1997-01-01

    Full Text Available Allergen-induced bone marrow responses are observable in human allergic asthmatics, involving specific increases in eosinophil-basophil progenitors (Eo/B-CFU, measured either by hemopoietic assays or by flow cytometric analyses of CD34-positive, IL-3Ralpha-positive, and/or IL-5-responsive cell populations. The results are consistent with the upregulation of an IL-5-sensitive population of progenitors in allergen-induced late phase asthmatic responses. Studies in vitro on the phenotype of developing eosinophils and basophils suggest that the early acquisition of IL-5Ralpha, as well as the capacity to produce cytokines such as GM-CSF and IL-5, are features of the differentiation process. These observations are consistent with findings in animal models, indicating that allergen-induced increases in bone marrow progenitor formation depend on hemopoietic factor(s released post-allergen. The possibility that there is constitutive marrow upregulation of eosinophilopoiesis in allergic airways disease is also an area for future investigation.

  1. Analysis of fatty acid composition in human bone marrow aspirates.

    Science.gov (United States)

    Deshimaru, Ryota; Ishitani, Ken; Makita, Kazuya; Horiguchi, Fumi; Nozawa, Shiro

    2005-09-01

    In the present study, the fatty acid composition of bone marrow aspirates and serum phospholipids in nine patients with hematologic diseases was investigated, and the effect of fatty acids on osteoblast differentiation in ST2 cells was examined. The concentrations of oleic acid and palmitic acid were significantly higher in bone marrow aspirates than in serum phospholipids, but the concentrations of other fatty acids did not differ. The rate of alkaline phosphatase positive ST2 cells induced by BMP2 was significantly increased by oleic acid, but was unaffected by the presence or absence of palmitic acid. We conclude that the fatty acid composition of bone marrow aspirates differs from that of serum phospholipids. This difference may affect osteoblast differentiation in the bone marrow microenvironment.

  2. Mesenchymal bone marrow cell therapy in a mouse model of chagas disease. Where do the cells go?

    Directory of Open Access Journals (Sweden)

    Jasmin

    Full Text Available BACKGROUND: Chagas disease, resulting from infection with the parasite Trypanosoma cruzi (T. cruzi, is a major cause of cardiomyopathy in Latin America. Drug therapy for acute and chronic disease is limited. Stem cell therapy with bone marrow mesenchymal cells (MSCs has emerged as a novel therapeutic option for cell death-related heart diseases, but efficacy of MSC has not been tested in Chagas disease. METHODS AND RESULTS: We now report the use of cell-tracking strategies with nanoparticle labeled MSC to investigate migration of transplanted MSC in a murine model of Chagas disease, and correlate MSC biodistribution with glucose metabolism and morphology of heart in chagasic mice by small animal positron emission tomography (microPET. Mice were infected intraperitoneally with trypomastigotes of the Brazil strain of T. cruzi and treated by tail vein injection with MSC one month after infection. MSCs were labeled with near infrared fluorescent nanoparticles and tracked by an in vivo imaging system (IVIS. Our IVIS results two days after transplant revealed that a small, but significant, number of cells migrated to chagasic hearts when compared with control animals, whereas the vast majority of labeled MSC migrated to liver, lungs and spleen. Additionally, the microPET technique demonstrated that therapy with MSC reduced right ventricular dilation, a phenotype of the chagasic mouse model. CONCLUSIONS: We conclude that the beneficial effects of MSC therapy in chagasic mice arise from an indirect action of the cells in the heart rather than a direct action due to incorporation of large numbers of transplanted MSC into working myocardium.

  3. Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

    Science.gov (United States)

    Garcia-Gomez, Antonio; Las Rivas, Javier De; Ocio, Enrique M.; Díaz-Rodríguez, Elena; Montero, Juan C.; Martín, Montserrat; Blanco, Juan F.; Sanchez-Guijo, Fermín M.; Pandiella, Atanasio; San Miguel, Jesús F.; Garayoa, Mercedes

    2014-01-01

    Despite evidence about the implication of the bone marrow (BM) stromal microenvironment in multiple myeloma (MM) cell growth and survival, little is known about the effects of myelomatous cells on BM stromal cells. Mesenchymal stromal cells (MSCs) from healthy donors (dMSCs) or myeloma patients (pMSCs) were co-cultured with the myeloma cell line MM.1S, and the transcriptomic profile of MSCs induced by this interaction was analyzed. Deregulated genes after co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and osteoblast inhibition. Additional genes induced by co-culture were exclusively deregulated in pMSCs and predominantly associated to RNA processing, the ubiquitine-proteasome pathway, cell cycle regulation, cellular stress and non-canonical Wnt signaling. The upregulated expression of five genes after co-culture (CXCL1, CXCL5 and CXCL6 in d/pMSCs, and Neuregulin 3 and Norrie disease protein exclusively in pMSCs) was confirmed, and functional in vitro assays revealed putative roles in MM pathophysiology. The transcriptomic profile of pMSCs co-cultured with myeloma cells may better reflect that of MSCs in the BM of myeloma patients, and provides new molecular insights to the contribution of these cells to MM pathophysiology and to myeloma bone disease. PMID:25268740

  4. Therapy Effect: Impact on Bone Marrow Morphology.

    Science.gov (United States)

    Li, K David; Salama, Mohamed E

    2016-03-01

    This article highlights the most common morphologic features identified in the bone marrow after chemotherapy for hematologic malignancies, growth-stimulating agents, and specific targeted therapies. The key is to be aware of these changes while reviewing post-therapeutic bone marrow biopsies and to not mistake reactive patterns for neoplastic processes. In addition, given the development and prevalent use of targeted therapy, such as tyrosine kinase inhibitors and immune modulators, knowledge of drug-specific morphologic changes is required for proper bone marrow interpretation and diagnosis.

  5. The effect of intrathecal delivery of bone marrow stromal cells on hippocampal neurons in rat model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Mina Eftekharzadeh

    2015-05-01

    Full Text Available Objective(s: Intracerebral injection of bone marrow stromal cells (BMSCs is being investigated as a therapeutic tool to prevent Alzheimer's disease (AD. Our aim was to investigate the effects of BMSCs by intrathecal injection in AD rat model. Materials and Methods: BMSCs were obtained from the bone marrow of Wistar rat and transplanted into AD rat model via intrathecal injection. The rat model had received an injection of β amyloid into the hippocampus for histological and immunohistochemical studies. Results: Histological examination of the brains in transplanted rats compared to controls demonstrated the migration of BrdU-labeled BMSCs from the site of delivery, confirmed the differentiation of BMSCs transplanted cells into the cholinergic neurons, and increased number of healthy and decreased number of dark neurons. Conclusion: Our results showed that BMSCs intratechal administration could be a promising method for treatment ofAlzheimer’s disease in rat model.

  6. Bone marrow involvement in Gaucher disease at MRI: what long-term evolution can we expect under enzyme replacement therapy?

    Energy Technology Data Exchange (ETDEWEB)

    Fedida, Benjamin; Touraine, Sebastien; Laredo, Jean-Denis [Hopital Lariboisiere, AP-HP, Department of Musculoskeletal Imaging, Paris (France); Stirnemann, Jerome [Universite Paris-Diderot Hopital Bichat, AP-HP, Department of Biostatistics and Medical Data Processing, INSERM UMR 738, Paris (France); Geneva University Hospital, Division of General Internal Medicine, Faculty of Medicine, Geneva (Switzerland); Belmatoug, Nadia [Hopital Beaujon, AP-HP, Referral Center for Lysosomal Diseases (RCLD), Clichy (France); Hopital Beaujon, AP-HP, Department of Internal Medicine, Clichy (France); Petrover, David [Hopital Lariboisiere, AP-HP, Department of Musculoskeletal Imaging, Paris (France); Hopital Beaujon, AP-HP, Referral Center for Lysosomal Diseases (RCLD), Clichy (France)

    2015-10-15

    To study the long-term evolution of the bone marrow burden (BMB) score at MRI in patients with Gaucher disease (GD) under enzyme replacement therapy (ERT). Forty patients treated for GD were retrospectively studied in a referral centre. BMB scores were assessed on spine and femur MR examinations performed between January 2003 and June 2014. The long-term evolution of the BMB scores was analyzed using a linear mixed model. A total of 121 MRI examinations were performed during the study period with a mean follow-up of 7.1 years ± 5.6, an average rate of 3.1 MR examinations ± 1.7 per patient and an interval of 2.3 years ± 1.1 between examinations. Patients had received ERT during 12 years on average ± 6.7. The trend of BMB scores with time decreased significantly by 15 % (P = 0.008) during the total study period and 39 % (P = 0.01) during the first 5 years of treatment. No changes in BMB scores were observed after five years of treatment. In Gaucher patients, the trend of MRI BMB scores with time decreased significantly under ERT the first 5 years of treatment before a long-term stabilization. (orig.)

  7. Intravenous transplantation of bone marrow-derived mononuclear cells prevents memory impairment in transgenic mouse models of Alzheimer's disease.

    Science.gov (United States)

    Kanamaru, Takuya; Kamimura, Naomi; Yokota, Takashi; Nishimaki, Kiyomi; Iuchi, Katsuya; Lee, Hyunjin; Takami, Shinya; Akashiba, Hiroki; Shitaka, Yoshitsugu; Ueda, Masayuki; Katsura, Ken-Ichiro; Kimura, Kazumi; Ohta, Shigeo

    2015-04-24

    Stem cell transplantation therapy is currently in clinical trials for the treatment of ischemic stroke, and several beneficial aspects have been reported. Similarly, in Alzheimer's disease (AD), stem cell therapy is expected to provide an efficient therapeutic approach. Indeed, the intracerebral transplantation of stem cells reduced amyloid-β (Aβ) deposition and rescued memory deficits in AD model mice. Here, we show that intravenous transplantation of bone marrow-derived mononuclear cells (BMMCs) improves cognitive function in two different AD mouse models, DAL and APP mice, and prevents neurodegeneration. GFP-positive BMMCs were isolated from tibiae and femurs of 4-week-old mice and then transplanted intravenously into DAL and APP mice. Transplantation of BMMCs suppressed neuronal loss and restored memory impairment of DAL mice to almost the same level as in wild-type mice. Transplantation of BMMCs to APP mice reduced Aβ deposition in the brain. APP mice treated with BMMCs performed significantly better on behavioral tests than vehicle-injected mice. Moreover, the effects were observed even with transplantation after the onset of cognitive impairment in DAL mice. Together, our results indicate that intravenous transplantation of BMMCs has preventive effects against the cognitive decline in AD model mice and suggest a potential therapeutic effect of BMMC transplantation therapy.

  8. Effect of bone marrow mesenchymal stem cells on the proliferation of bone marrow CD34~+ cells in vitro

    Institute of Scientific and Technical Information of China (English)

    王荣

    2013-01-01

    Objective To investigate the effect on the marrow CD34+ cells by bone marrow mesenchymal stem cells(BMMSC),VarioMACS was used to sort bone marrow CD34+ cells,and then the purity of CD34+ cell was tested by FCM. Marrow mononuclear cells from abortion fetal bone marrow were isolated,and BMMSC were

  9. Etiological Profile of Plasmacytosis on Bone Marrow Aspirates

    Directory of Open Access Journals (Sweden)

    Monika Gupta

    2016-03-01

    Full Text Available Objective: In recent years, during routine examination of bone marrow aspirates, an increased plasma cell per­centage has been noted in a good number of cases which included both neoplastic and non-neoplastic diseases. An attempt has been made to observe the spectra of condi­tions with plasmacytosis in bone marrow. Methods: The present study was conducted in the de­partment of pathology over a period of one year. A total of 114 bone marrow aspirates that showed increased plas­ma cells (>3.5% constitute the study material. A detailed relevant clinical examination followed by complete blood count, peripheral smear examination and bone marrow aspiration was done in all cases. Results: There was slight female predominance with male to female ratio of 1:1.1. The majority of patients were in 4th decade. The plasma cell concentration ranged from 5% to 36%. As far as the etiology is concerned, 96 cases (84.2% were non-neoplastic and 18 cases (15.7% had neoplastic etiology. Conclusion: Bone marrow plasmacytosis can present as diagnostic dilemma and some time can be challenging to differentiate reactive from neoplastic condition as there is an overlap both in counts and morphology. Each case with plasmacytosis especially in the overlap range requires complete clinical evaluation, individualized investigations and more specific tests like immunoelectrophoresis and bone marrow biopsy with immunohistochemistry to arrive at a final diagnosis for patient management.

  10. Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders

    Science.gov (United States)

    2017-03-21

    Chronic Kidney Disease; Acute Myeloid Leukemia (AML); Acute Lymphoblastic Leukemia (ALL); Chronic Myelogenous Leukemia (CML); Chronic Lymphocytic Leukemia (CLL); Non-Hodgkin's Lymphoma (NHL); Hodgkin Disease; Multiple Myeloma; Myelodysplastic Syndrome (MDS); Aplastic Anemia; AL Amyloidosis; Diamond Blackfan Anemia; Myelofibrosis; Myeloproliferative Disease; Sickle Cell Anemia; Autoimmune Diseases; Thalassemia

  11. Bone marrow lesions: A systematic diagnostic approach

    Directory of Open Access Journals (Sweden)

    Filippo Del Grande

    2014-01-01

    Full Text Available 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.

  12. Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases

    Science.gov (United States)

    2017-03-16

    Severe Combined Immunodeficiency (SCID); Immunodeficiency With Predominant T-cell Defect, Unspecified; Severe Chronic Neutropenia; Chronic Granulomatous Disease (CGD); Hyper IgE Syndromes; Hyper IgM Deficiencies; Wiskott-Aldrich Syndrome; Mendelian Susceptibility to Mycobacterial Disease; Common Variable Immune Deficiency (CVID)

  13. Gaucher disease diagnosed after bone marrow trephine biopsy — a report of two cases

    Directory of Open Access Journals (Sweden)

    Bożena Sokołowska

    2011-07-01

    Full Text Available The hematologist is at the forefront of specialists to whom patients with Gaucher disease presentbecause of cytopenia and hepatosplenomegaly. Usually, patients with such symptoms have undergone trephinebiopsy. We present the cases of two patients in whom Gaucher disease was suspected because of the discovery ofGaucher cells in trephine biopsy, and subsequently confirmed via enzymatic and molecular investigations.

  14. Intramyocardial Bone Marrow Cell Injection : Clinical and Functional Effects in Ischemic Heart Disease

    NARCIS (Netherlands)

    Ramshorst, Jan van

    2014-01-01

    Coronary artery disease is a major cause of mortality and morbidity in the western world. Despite successive revascularization procedures, a large number of patients ends up with end-stage coronary artery disease, not amenable for conventional revascularization. These patients often have stress-indu

  15. Gaucher disease diagnosed after bone marrow trephine biopsy — a report of two cases

    Directory of Open Access Journals (Sweden)

    Anna Dmoszyńska

    2011-07-01

    Full Text Available The hematologist is at the forefront of specialists to whom patients with Gaucher disease present because of cytopenia and hepatosplenomegaly. Usually, patients with such symptoms have undergone trephine biopsy. We present the cases of two patients in whom Gaucher disease was suspected because of the discovery of Gaucher cells in trephine biopsy, and subsequently confirmed via enzymatic and molecular investigations. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 352–356

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

    Science.gov (United States)

    2014-11-30

    M, Battiwalla M, Baxter-Lowe LA, Bitan M, Fernandez-Viña M, Gandhi M, Jakubowski AA, Maiers M, Marino SR, Marsh SG, Oudshoorn M, Palmer J, Prasad...1487-1496, 2012 Oct 18. (Response to Letter to the Editor) Peripheral-blood versus bone marrow stem cells. N Engl J Med 368(3):288, 2013 Jan 17. New

  17. MC1288, a vitamin D analog, prevents acute graft-versus-host disease in rat bone marrow transplantation.

    Science.gov (United States)

    Pakkala, I; Taskinen, E; Pakkala, S; Räisänen-Sokolowski, A

    2001-04-01

    The major obstacle to successful bone marrow transplantation (BMT) is graft-versus-host disease (GVHD). Vitamin D analogs have shown their efficacy in solid organ transplantation. The purpose of this study was to investigate the suitability of a novel vitamin D analog, MC1288, in the prevention of acute GVHD in a rat BMT model. Allogeneic BMT were performed from Lewis to BN rats (n = 18). The animals were divided into four groups: an untreated control group, MC1288, cyclosporin A (CsA), and MC1288 + CsA-treated groups. Rats were harvested for histology and immunohistochemistry on day 20 after BMT. Histological changes for GVHD in liver, skin, and spleen were scored. Positivity in immunostaining was quantified as the number of positive cells/high power field. Treatment with MC1288 decreased clinical signs of GVHD compared with untreated or CsA-treated rats. Histological manifestations of GVHD, expressed as mean total increment, were significantly lower (1.4 +/- 0.5) in MC1288 than in untreated (5.0 +/- 1.6) or CsA (3.5 +/- 1.0) groups. Combining MC1288 and CsA further improved histology (1.1 +/- 0.6). The expression of CD4, CD8, MHC class II, interleukin-2 receptor, nitric oxide 2, and NKR-P1A (NK cells) positivity was significantly decreased in the liver and skin of BMT rats by MC1288. MC1288 was effective in preventing clinical and histological signs and symptoms of GVHD. This novel vitamin D analog could be used as an immunomodulating agent in BMT.

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

    Science.gov (United States)

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

    Science.gov (United States)

    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. Scanning electron microscopy of erythropoietin-stimulated bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Leblond, P.F. (Hospital of St. Sacrement, Quebec); Chamberlain, J.K.; Weed, R.I.

    1975-01-01

    This work describes and illustrates the scanning electron microscopic modifications observed in the femoral bone marrow of normal mice 72 hours after a single injection of partly purified sheep erythropoietin and of mice afflicted with a chronic congenital hemolytic anemia analogous to the disease Hereditary Spherocytosis in man. In acordance with previous transmission electron microscopic studies, the observations are consistent with an effect of erythropoietin both on the frequency of cell migration across the normally intact marrow sinus endothelium and on the morphology of sinus adventitial cells. It is suggested that these ultrastructural modifications may be responsible for the greater patency of the marrow-blood barrier under erythropoietin stimulation.

  1. Hemolytic uremic syndrome after bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Arai, Ayako; Sakamaki, Hisashi; Tanikawa, Shu [Tokyo Metropolitan Komagome Hospital (Japan)] [and others

    1998-06-01

    One hundred and thirteen patients who underwent autologous or allogeneic bone marrow transplantation (BMT) were investigated for the subsequent development of hemolytic uremic syndrome (HUS). HUS developed in seven patients (four males and three females, five acute lymphocytic leukemia (ALL), one acute myelogenous leukemia, one non-Hodgkin`s lymphoma) between 36-196 days after BMT. Four patients were recipients of autologous BMT and three were those of allogeneic BMT. Six patients were preconditioned with the regimens including fractionated total body irradiation (TBI). ALL and preconditioning regimen with TBI were suspected to be the risk factors for the development of HUS. Cyclosporin A (CSP) administration was discontinued in three patients who had been given CSP for graft-versus-host disease prophylaxis. Predonisolone was given to the three patients and plasma exchange was performed in one patient. Both hemolytic anemia and thrombocytopenia were resolved in virtually all patients, while creatinine elevation has persisted along with hypertension in one patient. (author)

  2. Bone marrow cells and myocardial regeneration.

    Science.gov (United States)

    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.

  3. Bone marrow edema syndrome in postpartal women: treatment with iloprost.

    Science.gov (United States)

    Aigner, Nicholas; Meizer, Roland; Meraner, Dominik; Becker, Stephan; Meizer, Elizabeth; Landsiedl, Franz

    2009-04-01

    Bone marrow edema syndrome of the femoral head in pregnant women is a rare disease resulting in disabling coxalgia, beginning in the last 3 months of pregnancy and persisting for several months after parturition. The parenteral administration of the vasoactive drug iloprost constitutes a new approach to the treatment of painful bone marrow edema syndrome of the hip of pregnant women. Six postpartal women (8 hips) with bone marrow edema syndrome of the femoral head were treated with iloprost followed by 3 weeks of partial weight-bearing. Relief from pain, restoration of functional capacity, and normalization of the MRI signal pattern were rapidly achieved, thus avoiding the need for surgical intervention. As the substance is contraindicated in pregnancy, therapy may begin only some days after parturition, with a short discontinuation in breastfeeding.

  4. Rationale and Design for the Intramyocardial Injection of Autologous Bone Marrow Mononuclear Cells for Patients with Chronic Ischemic Heart Disease and Left Ventricular Dysfunction Trial (FOCUS)

    Science.gov (United States)

    Willerson, James T.; Perin, Emerson C.; Ellis, Stephen G.; Pepine, Carl J.; Henry, Timothy D.; Zhao, David X.M.; Lai, Dejian; Penn, Marc S.; Byrne, Barry J.; Silva, G; Gee, Adrian; Traverse, Jay H.; Hatzopoulos, Antonis K.; Forder, John R.; Martin, Daniel; Kronenberg, Marvin; Taylor, Doris A.; Cogle, Christopher R.; Baraniuk, Sarah; Westbrook, Lynette; Sayre, Shelly L.; Vojvodic, Rachel W.; Gordon, David J.; Skarlatos, Sonia I.; Moyé, Lemuel A.; Simari, Robert D.

    2010-01-01

    Background The increasing worldwide prevalence of coronary artery disease (CAD) continues to challenge the medical community. Management options include medical and revascularization therapy. Despite advances in these methods, CAD is a leading cause of recurrent ischemia and heart failure, posing significant morbidity and mortality risks along with increasing health costs in a large patient population worldwide. Trial Design The Cardiovascular Cell Therapy Research Network (CCTRN) was established by the National Institutes of Health to investigate the role of cell therapy in the treatment of chronic cardiovascular disease. FOCUS is a CCTRN-designed randomized Phase II, placebo-controlled clinical trial that will assess the effect of autologous bone marrow mononuclear cells delivered transendocardially to patients with left ventricular (LV) dysfunction and symptomatic heart failure or angina. All patients need to have limiting ischemia by reversible ischemia on SPECT assessment. Results After thoughtful consideration of both statistical and clinical principles, we will recruit 87 patients (58 cell treated and 29 placebo) to receive either bone marrow–derived stem cells or placebo. Myocardial perfusion, LV contractile performance, and maximal oxygen consumption are the primary outcome measures. Conclusions The designed clinical trial will provide a sound assessment of the effect of autologous bone marrow mononuclear cells in improving blood flow and contractile function of the heart. The target population is patients with CAD and LV dysfunction with limiting angina or symptomatic heat failure. Patient safety is a central concern of the CCTRN, and patients will be followed for at least 5 years. PMID:20691824

  5. Shifting bone marrow edema of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Moosikasuwan, Josh B.; Schultz, Elizabeth [Department of Radiology, North Shore University Hospital, 300 Community Drive, NY 11030, Manhasset (United States); Miller, Theodore T. [Department of Radiology, North Shore University Hospital, 300 Community Drive, NY 11030, Manhasset (United States); Department of Radiology, North Shore University Hospital, 825 Northern Boulevard, NY 11021, Great Neck (United States); Math, Kevin [Department of Radiology, Beth Israel Medical Center, First Avenue at 16th Street, NY 10003, New York (United States)

    2004-07-01

    The purpose of our study is to describe shifting bone marrow edema in the knee as the MR imaging feature of intra-articular regional migratory osteoporosis of the knee. Five men, aged 45-73 years, were referred by orthopedic surgeons for MR imaging evaluation of knee pain, which had been present for 2 weeks to 6 months. One patient had a prior history of blunt trauma. None had risk factors for osteonecrosis. Four patients had two MR examinations and the patient with prior blunt trauma had four. Plain radiographs were obtained in all patients. In all cases, a large area of marrow edema initially involved a femoral condyle, with migration of the bone marrow edema to the other femoral condyle, tibia, and/or patella occurring over a 2- to 4-month period. Adjacent soft tissue edema was present in all five patients, while none had a joint effusion. Radiographs of two patients showed generalized osteopenia. In the absence of acute trauma or clinical suspicion of infection, a large area of bone marrow edema without a zone of demarcation may represent intra-articular regional migratory osteoporosis. Demonstration of shifting bone marrow edema on follow-up examinations suggests this diagnosis. (orig.)

  6. APOE3, but not APOE4, bone marrow transplantation mitigates behavioral and pathological changes in a mouse model of Alzheimer disease.

    Science.gov (United States)

    Yang, Yue; Cudaback, Eiron; Jorstad, Nikolas L; Hemingway, Jake F; Hagan, Catherine E; Melief, Erica J; Li, Xianwu; Yoo, Tom; Khademi, Shawn B; Montine, Kathleen S; Montine, Thomas J; Keene, C Dirk

    2013-09-01

    Apolipoprotein E4 (APOE4) genotype is the strongest genetic risk factor for late-onset Alzheimer disease and confers a proinflammatory, neurotoxic phenotype to microglia. Here, we tested the hypothesis that bone marrow cell APOE genotype modulates pathological progression in experimental Alzheimer disease. We performed bone marrow transplants (BMT) from green fluorescent protein-expressing human APOE3/3 or APOE4/4 donor mice into lethally irradiated 5-month-old APPswe/PS1ΔE9 mice. Eight months later, APOE4/4 BMT-recipient APPswe/PS1ΔE9 mice had significantly impaired spatial working memory and increased detergent-soluble and plaque Aβ compared with APOE3/3 BMT-recipient APPswe/PS1ΔE9 mice. BMT-derived microglia engraftment was significantly reduced in APOE4/4 recipients, who also had correspondingly less cerebral apoE. Gene expression analysis in cerebral cortex of APOE3/3 BMT recipients showed reduced expression of tumor necrosis factor-α and macrophage migration inhibitory factor (both neurotoxic cytokines) and elevated immunomodulatory IL-10 expression in APOE3/3 recipients compared with those that received APOE4/4 bone marrow. This was not due to detectable APOE-specific differences in expression of microglial major histocompatibility complex class II, C-C chemokine receptor (CCR) type 1, CCR2, CX3C chemokine receptor 1 (CX3CR1), or C5a anaphylatoxin chemotactic receptor (C5aR). Together, these findings suggest that BMT-derived APOE3-expressing cells are superior to those that express APOE4 in their ability to mitigate the behavioral and neuropathological changes in experimental Alzheimer disease.

  7. Diffusion and perfusion imaging of bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Biffar, Andreas; Dietrich, Olaf [Josef Lissner Laboratory for Biomedical Imaging, Department of Clinical Radiology, LMU University Hospitals, Grosshadern-Munich (Germany); Sourbron, Steven [Josef Lissner Laboratory for Biomedical Imaging, Department of Clinical Radiology, LMU University Hospitals, Grosshadern-Munich (Germany); Division of Medical Physics, University of Leeds, Leeds (United Kingdom); Duerr, Hans-Roland [Department of Orthopedic Surgery, LMU University Hospitals, Grosshadern-Munich (Germany); Reiser, Maximilian F. [Josef Lissner Laboratory for Biomedical Imaging, Department of Clinical Radiology, LMU University Hospitals, Grosshadern-Munich (Germany); Department of Clinical Radiology, LMU University Hospitals, Grosshadern-Munich (Germany); Baur-Melnyk, Andrea, E-mail: andrea.baur@med.uni-muenchen.de [Department of Clinical Radiology, LMU University Hospitals, Grosshadern-Munich (Germany)

    2010-12-15

    In diffusion-weighted magnetic resonance imaging (DWI), the observed MRI signal intensity is attenuated by the self-diffusion of water molecules. DWI provides information about the microscopic structure and organization of a biological tissue, since the extent and orientation of molecular motion is influenced by these tissue properties. The most common method to measure perfusion in the body using MRI is T1-weighted dynamic contrast enhancement (DCE-MRI). The analysis of DCE-MRI data allows determining the perfusion and permeability of a biological tissue. DWI as well as DCE-MRI are established techniques in MRI of the brain, while significantly fewer studies have been published in body imaging. In recent years, both techniques have been applied successfully in healthy bone marrow as well as for the characterization of bone marrow alterations or lesions; e.g., DWI has been used in particular for the differentiation of benign and malignant vertebral compression fractures. In this review article, firstly a short introduction to diffusion-weighted and dynamic contrast-enhanced MRI is given. Non-quantitative and quantitative approaches for the analysis of DWI and semiquantitative and quantitative approaches for the analysis of DCE-MRI are introduced. Afterwards a detailed overview of the results of both techniques in healthy bone marrow and their applications for the diagnosis of various bone-marrow pathologies, like osteoporosis, bone tumors, and vertebral compression fractures are described.

  8. IMPACT OF IMMUNOGENETIC POLYMORPHISMS ON IMMUNE RESPONSE AND CLINICAL FEATURES IN BONE MARROW FAILURE SYNDROMES

    OpenAIRE

    2008-01-01

    Hematopietic stem cells (HSC) are responsible for the production of mature blood cells in bone marrow; peripheral pancytopenia may result from several different conditions, including hematological or extra-hematological diseases (mostly cancers) affecting the marrow function as well as primary failure of hematopoiesis. Although the clinical presentation may appear homogeneous, primary bone marrow failure syndromes are a heterogeneous group of diseases with specific pathogenic mechanisms, whic...

  9. Gaucher disease: MR evaluation of bone marrow features during treatment with enzyme replacement; Morbus Gaucher: Analyse der Knochenmarkveraenderungen in der MRT waehrend Enzymersatztherapie

    Energy Technology Data Exchange (ETDEWEB)

    Poll, L.W.; Koch, J.A.; Boerner, D.; Cohnen, M.; Jung, G.; Scherer, A.; Moedder, U. [Duesseldorf Univ. (DF). Inst. fuer Diagnostische Radiologie; Dahl, S. vom; Haeussinger, D. [Duesseldorf Univ. (Germany). Klinik fuer Gastroenterologie, Hepatologie und Infektiologie; Willers, R. [Rechenzentrum, Heinrich-Heine-Univ. Duesseldorf (Germany); Niederau, C. [Innere Abt., St. Josef-Hospital Oberhausen, Akademisches Lehrkrankenhaus der Univ. Essen (Germany)

    2001-10-01

    Purpose: Enzyme replacement therapy (ERT) arrests and reverses the hematological and visceral symptoms of adult Gaucher disease, the most frequent lysosomal storage disorder. There are only a few studies available evaluating bone disease during ERT. The aim of this study was to investigate the features of bone marrow (bm) by magnetic resonance imaging (MRI) in these patients during ERT. Materials and Methods: MRI was performed prospectively in thirty adult type I Gaucher patients before and during ERT with a mean follow-up of 3 years. Spin-echo sequences (T{sub 1}/T{sub 2}) of the lower extremities were obtained and the reconversion (response) or lack of reconversion (non-response) to fatty marrow during treatment was analyzed. The morphological features of bm involvement, a homogeneous or non-homogeneous distribution of bm changes and focal bone lesions surrounded by a rim of reduced signal intensity (SI), were analyzed. Results: Infiltration of bm by Gaucher cells is characterized by a reduction of Sl on both T{sub 1}- and T{sub 2}-weighted sequences. Bone marrow responses were seen in 19 patients (63%) during treatment. Focal bone lesions, surrounded by a rim of reduced Sl, did not respond to ERT and correlated with a non-homogenous distribution of bone involvement and splenectomy. (orig.) [German] Ziel: Unter Enzymersatztherapie (enzyme replacement therapy = ERT) zeigen Patienten mit adulter Form des Morbus Gaucher, der haeufigsten lysosomalen Speicherkrankheit, eine deutliche Besserung der haematologischen und visceralen Symptome. Bislang liegen nur wenige Untersuchungen zur Analyse der Knochenveraenderungen waehrend der ERT vor. Ziel war es, die Knochenmarkveraenderungen bei Gaucher-Patienten waehrend der Enzymersatztherapie mit Alglucerase/Imiglucerase in der Magnetresonanztomographie (MRT) zu evaluieren. Material und Methoden: In einer prospektiven Untersuchung wurden 30 adulte Patienten mit gesichertem Morbus Gaucher vor und waehrend der ERT in der MRT

  10. Bone Marrow-Derived Macrophages (BMM)

    DEFF Research Database (Denmark)

    Weischenfeldt, Joachim; Porse, Bo

    2008-01-01

    of committed myeloid progenitors into cells of the macrophage/monocyte lineage. Mice lacking functional M-CSF are deficient in macrophages and osteoclasts and suffer from osteopetrosis. In this protocol, bone marrow cells are grown in culture dishes in the presence of M-CSF, which is secreted by L929 cells...

  11. Allogeneic and Autologous Bone-Marrow Transplantation

    OpenAIRE

    Deeg, H. Joachim

    1988-01-01

    The author of this paper presents an overview of the current status of bone marrow transplantation, including indications, pre-transplant considerations, the transplant procedure, acute and delayed transplant-related problems, results currently attainable, and a short discussion of possible future developments.

  12. Pain and Anxiety During Bone Marrow Biopsy

    NARCIS (Netherlands)

    Tanasale, Betty; Kits, Jenne; Kluin, Philip M.; Trip, Albert; Kluin-Nelemans, Hanneke C.

    2013-01-01

    A bone marrow biopsy is considered to be painful, often causing anxiety. We observed large differences between patients and wondered which factors cause pain and anxiety. In a prospective study, 202 patients were analyzed. Experienced hematologists and fellows in training (17% of biopsies) performed

  13. Bone marrow scan evaluation of arthropathy in sickle cell disorders

    Energy Technology Data Exchange (ETDEWEB)

    Alavi, A.; Schumacher, H.R.; Dorwart, B.; Kuhl, D.E.

    1976-04-01

    Twelve patients with sickle cell hemoglobinopathies and arthropathy were studied, using technetium Tc 99m sulfur colloid bone marrow scans. Eight of 12 had decreased marrow radionuclide activity adjacent to painful joints, suggesting obliteration of vessels supplying bone marrow. Four patients without marrow defects on scanning had causes other than infarction for their joint symptoms, viz, small fractures, postinfectious synovitis, degenerative arthritis, and osteochondromas. Roentgenograms never showed bony abnormalities in five patients with marrow infarctions, and, in three others, showed defects several months later than did the marrow scans. Bone marrow scans offer a sensitive and early diagnostic aid in sickle cell hemoglobinopathies with arthropathy.

  14. Esophageal Cancer with Bone Marrow Hyperplasia Mimicking Bone Metastasis: Report of a Case

    Directory of Open Access Journals (Sweden)

    Hiromi Yasuda

    2016-11-01

    Full Text Available A 63-year-old man visited the clinic with numbness in the right hand. Magnetic resonance imaging demonstrated multiple low-intensity lesions in the cervical vertebrae and sacrum, which was suspicious of cervical bone metastasis. Fluorodeoxyglucose positron emission tomography/computed tomography revealed areas of increased fluorodeoxyglucose uptake in the thoracic esophagus, sternum and sacrum. A flat, elevated esophageal cancer was identified by upper gastrointestinal endoscopy, and the macroscopic appearance indicated early-stage disease. From the cervical, thoracic and abdominal computed tomography images, there were no metastatic lesions except for the bone lesions. To confirm whether the bone lesions were metastatic, we performed bone biopsy. The histopathological diagnosis was bone marrow hyperplasia. It was crucial for treatment planning to establish whether the lesions were distant metastases. Here, we report a case of esophageal cancer with bone marrow hyperplasia mimicking bone metastasis.

  15. Biomarkers of bone and mineral metabolism following bone marrow transplantation.

    Science.gov (United States)

    Baek, Ki Hyun; Kang, Moo Il

    2009-01-01

    The loss of bone mass often occurs after patients undergo bone marrow transplantation (BMT). The rapid impairment of bone formation and the increase in bone resorption, as mirrored by the biochemical markers of bone turnover, might play a role in this bone loss, and especially during the immediate post-BMT period. The possible direct causes for this paradoxical uncoupling are exposure to immunosuppressants, hypogonadism, the changes of cytokines, the changes of the bone growth factors, and the damage to the osteoprogenitor cells because of myeloablative therapy. In this chapter, we discuss the general aspects of post-BMT bone loss with a peculiar focus on the remodeling imbalance of bone and its relation to the use of immunosuppressants and the changes of sex hormones, growth factors, and cytokines.

  16. Immunomodulation and neuroprotection with mesenchymal bone marrow stem cells (MSCs): a proposed treatment for multiple sclerosis and other neuroimmunological/neurodegenerative diseases.

    Science.gov (United States)

    Karussis, Dimitrios; Kassis, Ibrahim; Kurkalli, Basan Gowda S; Slavin, Shimon

    2008-02-15

    Bone marrow (BM) derived mesenchymal stem cells (MSCs) (non-hematopoietic, stromal cells) can differentiate under certain circumstances into cells from various neuronal and glial type lineages; they also exert immunomodulatory effects. For potential clinical applications, BM-MSCs offer significant practical advantages over other types of stem cells, since they can be obtained from the adult BM (the patient himself being the donor) and can be easily cultured and expanded posing in parallel a very low risk for development of malignancies. We have shown that BM-MSCs cultured with a cocktail of growth factors (containing FGF and BDNF) differentiate into neuronal/glial lineage cells with a predominance of cells expressing astrocytes' markers. BM-MSCs were effective in suppression of chronic EAE in mice and induced neuroprotection, preserving most of the axons in the CNS of successfully-treated animals. Histopathological studies revealed that MSCs could efficiently migrate into the CNS inflamed tissue (both when administered intravenously and intraventricularly) and differentiated into cells expressing neural-glial lineage markers. Our preclinical results indicate that bone marrow can provide a source of stem cells with a potential for migration into inflamed CNS tissue and differentiation into cells expressing neuronal and glial cell markers. Such an approach may provide a feasible and practical way for in situ immunomodulation, neuroprotection and possibly remyelination/regeneration in diseases like multiple sclerosis. We therefore developed a explorative protocol for the evaluation of this therapeutic approach in a small group of patients with MS and other neurodegenerative diseases.

  17. Bone marrow: its contribution to heme catabolism.

    Science.gov (United States)

    Mähönen, Y; Anttinen, M; Vuopio, P; Tenhunen, R

    1976-01-01

    Heme oxygenase (HO) and biliverdin reductase (BR), the two NADPH-dependent enzymes involved in the degradation of hemoglobin and its derivatives, were measured in bone marrow aspirates from 5 hematologically normal persons, 4 patients with chronic leucemia (CL), 11 patients with acute leucemia (AL), 8 patients with refractory sideroblastic anemia (RA), 7 patients with iron-deficiency anemia (IA), 5 patients with hemolytic anemia (HA), and 7 patients with secondary anemia (SA) to determine the enzymatic capacity of the bone marrow in different hematologic disorders for heme catabolism. HO activity in the bone marrow of normal persons was 0.42 +/- 0.28 (SD) nmoles bilirubin/10 mg protein/min; in CL, 2.15 +/- 1.34; in AL, 0.39 +/- 0.25; in RA, 0.58 +/- 0.37; in IA, 0.41 +/- 0.28; in HA, 2.56 +/- 1.40; and in SA, 1.72 +/- 1.06. BR activity, respectively, was in normal persons 8.7 +/- 2.4 (SD) nmoles bilirubin/10 mg protein/min; in CL, 13.6 +/- 9.1; in AL, 3.8 +/- 3.1 in RA, 5.1 +/- 2.7; in IA, 5.5 +/- 3.7; in HA, 17.0 +/- 7.2; and in SA, 10.5 +/- 4.2. On the basis of these findings it seems evident that both oxygenase and biliverdin reductase activities of the bone marrow are capable of adaptive regulation. The physiologic role of bone marrow in heme catabolism seems to be of significant importance.

  18. Effects of Ligustrazine on Expression of Bone Marrow Heparan Sulfates in Syngeneic Bone Marrow Transplantation Mice

    Institute of Scientific and Technical Information of China (English)

    任天华; 刘文励; 孙汉英; 戴琪琳; 孙岚

    2003-01-01

    To explore the effects of ligustrazine on bone marrow heparan sulfates (HS) expression in bone marrow transplantation (BMT) mice, the syngeneic BMT mice were orally given 2 mg ligustrazine twice a day. On the 7th, 10th, 14th, 18th day after BMT, peripheral blood cells and bone marrow nuclear cells (BMNC) were counted, and the expression levels of HS in bone marrow and on the stromal cell surfaces were detected by immunohistochemistry and flow cytometry assay respectively. In ligustrazine-treated group, the white blood cells (WBC) and BMNC on the 7th, 10th, 14th, 18th day and platelets (PLT) on the 7th, 10th day were all significantly more than those in control group (P<0.05). The bone marrow HS expression levels in ligustrazine-treated group were higher than those in control group (P<0. 05) on the 7th, 10th, 14th, 18th day. However, the HS expression levels on the stromal cell surfaces showed no significant difference between the two groups on the 18th day (P>0. 05). It was concluded that ligustrazine could up-regulate HS expression in bone marrow, which might be one of the mechanisms contributing to ligustrazine promoting hematopoietic reconstitution after BMT.

  19. Bone Marrow Pathology Predicts Mortality in Chronic Hemodialysis Patients

    Directory of Open Access Journals (Sweden)

    Cheng-Hao Weng

    2015-01-01

    Full Text Available Introduction. A bone marrow biopsy is a useful procedure for the diagnosis and staging of various hematologic and systemic diseases. The objective of this study was to investigate whether the findings of bone marrow studies can predict mortality in chronic hemodialysis patients. Methods. Seventy-eight end-stage renal disease patients on maintenance hemodialysis underwent bone marrow biopsies between 2000 and 2011, with the most common indication being unexplained anemia followed by unexplained leukocytosis and leukopenia. Results. The survivors had a higher incidence of abnormal megakaryocyte distribution P=0.001, band and segmented cells P=0.021, and lymphoid cells P=0.029 than the nonsurvivors. The overall mortality rate was 38.5% (30/78, and the most common cause of mortality was sepsis (83.3% followed by respiratory failure (10%. In multivariate Cox regression analysis, both decreased (OR 3.714, 95% CI 1.671–8.253, P=0.001 and absent (OR 9.751, 95% CI 2.030–45.115, P=0.004 megakaryocyte distribution (normal megakaryocyte distribution as the reference group, as well as myeloid/erythroid ratio (OR 1.054, CI 1.012–1.098, P=0.011, were predictive of mortality. Conclusion. The results of a bone marrow biopsy can be used to assess the pathology, and, in addition, myeloid/erythroid ratio and abnormal megakaryocyte distribution can predict mortality in chronic hemodialysis patients.

  20. Perfusion Method for Intra-bone Marrow Collection and Stem Cell Transplantation: A Critical Review.

    Science.gov (United States)

    Korrapati, Narasimhulu; Nanganuru, Harikrishna Yadav

    2014-03-19

    A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Bone marrow is the soft, fatty tissue inside our bones. Bone marrow transplantation (BMT) is a powerful strategy for the treatment of leukemia, aplastic anemia, congenital immunodeficiency and autoimmune diseases. In humans, bone marrow cells (BMCs) have usually been collected by multiple bone marrow aspirations from the iliac crest. We have established a new "perfusion" method for collecting BMCs with minimal contamination with the peripheral blood using the long bones of cynomolgus monkeys. This method has proven to be a simple and safe method for harvesting BMCs and reduces the risk of acute graft versus host disease in allogeneic BMT. Intra-bone marrow-BMT (IBM-BMT) provides distinct advantages because it recruits donor-derived hematopoietic stem cells and mesenchymal stem cells. IBM-BMT has been shown to currently be the best strategy for allogeneic BMT. Here we review the perfusion method (for harvesting BMCs) and IBM-BMT (for their transplantation) and show that this combination will become a powerful new clinical strategy for allogeneic BMT.

  1. Bone marrow micrometastasis detected by flow cytometry is associated bone, bone marrow, lung macrometastasis in breast cancer

    Directory of Open Access Journals (Sweden)

    Mustafa Salih Akin

    2014-04-01

    Material and Methods: Bone marrow samples were obtained from 52 breast cancer patients and 16 control patients via aspiration from the iliac spine at the time of first diagnosis after the surgery. Epithelial cells were identified with anti-cytokeratin monoclonal antibody, and double-staining with propidium iodide and CD45using flow cytometry. Results: In all, 2 (12.5% of the 16 control patients and 11 (21% of the 52 breast cancer patients had cytokeratin-18 positive cells in their bone marrow. A relationship between the presence of occult metastatic cells in bone marrow, and the presence/absence of lymph node metastases, tumor size, stage, menopausal status, hormone receptor status, histological grade, c-erb-B2 expression, tumor subtype, lymphovascular invasion, Ductal carcinoma in situ (DCIS component, and gender was not observed. Significant positive relationships were observed between bone marrow micrometastasis, and age, and bone, bone marrow, lung, and liver metastases. Conclusion: Bone marrow micrometastasis was associated with age, bone, bone marrow, lung, and liver metastases at the time of diagnosis.. [Cukurova Med J 2014; 39(2.000: 305-314

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

    Science.gov (United States)

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

    2016-03-01

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

  3. Bone Marrow Transplantation in Thalassemia (Part 2

    Directory of Open Access Journals (Sweden)

    Maryam Zakerinia

    2009-06-01

    Full Text Available During the last two decades conventional therapy has improvedthe prognosis of thalassemia. However, despite such improvementit still remains a progressive disease with treatment-relatedcomplications such as hepatitis, liver fibrosis, and cardiac disease.Bone marrow transplantation (BMT can prevent or delayprogression of the aforementioned complications. The importanceof clinical research in the field of BMT was recognizedwith the award of the 1990 Nobel Prize in Physiology andMedicine to E. Donnall Thomas, one of the pioneers of BMT inhumans. George Mathe' was a pioneer in the early developmentof clinical BMT. Mathe' and co-workers were the first to describegraft-versus-host-disease and its treatment, and the graftversus-leukemia effect in human. The first BMT for β-thalassemia major was performed successfully by Thomas andcolleagues in Seattle, in 1981. In the same year another patientwith β-thalassemia major underwent BMT in Pesaro, Italy, byLucarelli and others Since then, several hundred transplantationshave been performed worldwide, mostly in Italy. From 1991through 2007 BMT have been performed on 497 (Tehran=342,Shiraz=155 blood transfusion dependent patients with thalassemiamajor in Iran, with disease-free survival of 71-77% respectively.Because of high graft failure and high rates of graftversus-host-disease rates, BMT from alternative donors shouldbe restricted to patients who have poor life expectancies becausethey cannot receive adequate conventional treatment or becauseof alloimmunization to minor blood antigens. Beginning in theearly 1980s, it was shown that umbilical cord blood containedhigh levels of hematopoietic progenitor cells.

  4. Archival bone marrow samples: suitable for multiple biomarker analysis.

    Science.gov (United States)

    Lund, Bendik; Najmi, Laeya A; Wesolowska-Andersen, Agata; Landsem, Veslemøy M; Rasmussen, Kirsten K; Borst, Louise; Gupta, Ramneek; Schmiegelow, Kjeld; Klungland, Helge

    2015-01-01

    AB Archival samples represent a significant potential for genetic studies, particularly in severe diseases with risk of lethal outcome, such as in cancer. In this pilot study, we aimed to evaluate the usability of archival bone marrow smears and biopsies for DNA extraction and purification, whole genome amplification (WGA), multiple marker analysis including 10 short tandem repeats, and finally a comprehensive genotyping of 33,683 single nucleotide polymorphisms (SNPs) with multiplexed targeted next-generation sequencing. A total of 73 samples from 21 bone marrow smears and 13 bone marrow biopsies from 18 Danish and Norwegian childhood acute lymphoblastic leukemia patients were included and compared with corresponding blood samples. Samples were grouped according to the age of sample and whether WGA was performed or not. We found that measurements of DNA concentration after DNA extraction was dependent on detection method and that spectrophotometry overestimated DNA amount compared with fluorometry. In the short tandem repeat analysis, detection rate dropped slightly with longer fragments. After WGA, this drop was more pronounced. Samples stored for 0 to 3 years showed better results compared with samples stored for 4 to 10 years. Acceptable call rates for SNPs were detected for 7 of 42 archival samples. In conclusion, archival bone marrow samples are suitable for DNA extraction and multiple marker analysis, but WGA was less successful, especially when longer fragments were analyzed. Multiple SNP analysis seems feasible, but the method has to be further optimized.

  5. Neuronal-like differentiation of bone marrow-derived mesenchymal stem cells induced by striatal extracts from a rat model of Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Xiaoling Qin; Wang Han; Zhigang Yu

    2012-01-01

    A rat model of Parkinson's disease was established by 6-hydroxydopamine injection into the medial forebrain bundle. Bone marrow-derived mesenchymal stem cells (BMSCs) were isolated from the femur and tibia, and were co-cultured with 10% and 60% lesioned or intact striatal extracts. The results showed that when exposed to lesioned striatal extracts, BMSCs developed bipolar or multi-polar morphologies, and there was an increase in the percentage of cells that expressed glial fibrillary acidic protein (GFAP), nestin and neuron-specific enolase (NSE). Moreover, the percentage of NSE-positive cells increased with increasing concentrations of lesioned striatal extracts. However, intact striatal extracts only increased the percentage of GFAP-positive cells. The findings suggest that striatal extracts from Parkinson's disease rats induce BMSCs to differentiate into neuronal-like cells in vitro.

  6. Pulmonary fungal infections after bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Allan, B.T.; Patton, D.; Ramsey, N.K.C.; Day, D.L.

    1988-02-01

    Of 319 pediatric patients treated with bone marrow transplantation (BMT) during a 10-year period, 27 developed pulmonary fungal infections (PFI). Only 2 patients (7%) survived. Twenty-three patients (85%) had been treated with systemic anti-fungal therapy immediately before or at the time of diagnosis. Nineteen patients (70%) were neutropenic, and 4 of the 8 patients who were not neutropenic were being treated with systemic steroids for graft vs. host disease (GVHD). Seven patients (26%) died within 7 days of diagnosis. The diagnosis was made ante-mortem in 9 patients (33%). Radiographic abnormalities were variable. At the onset of chest X-ray (CXR) change, the pulmonary infiltrates were unilateral in 14 patients (52%) and, at diagnosis, bilateral in 18 (66%). At diagnosis the infiltrates were interstitial in 3 patients (11%), alveolar in 20 (74%) and mixed in 4 (15%). Six patients (22%) developed cavitary lesions. The infecting agents were Aspergillus in 21 patients (78%), Candida in 7 (26%), Mucormycosis in 3 (11%), and Fusarium in 1 (4%). Five patients (19%) had mixed fungal infections and 7 (26%) had concurrent cytomegalovirus (CMV) pulmonary infections. Although the radiographic changes are often nonspecific in PFI, alveolar or nodular infiltrates in neutropenic patients or in those being treated for GVHD should strongly suggest a fungal etiology.

  7. Improved method for assessing iron stores in the bone marrow

    NARCIS (Netherlands)

    Phiri, K.S.; Calis, J.C.J.; Kachala, D.; Borgstein, E.; Waluza, J.; Bates, I.; Brabin, B.; Boele van Hensbroek, M.

    2009-01-01

    BACKGROUND: Bone marrow iron microscopy has been the "gold standard" method of assessing iron deficiency. However, the commonly used method of grading marrow iron remains highly subjective. AIM: To improve the bone marrow grading method by developing a detailed protocol that assesses iron in fragmen

  8. Gene expression profiling suggests a pathological role of human bone marrow-derived mesenchymal stem cells in aging-related skeletal diseases.

    Science.gov (United States)

    Jiang, Shih Sheng; Chen, Chung-Hsing; Tseng, Kuo-Yun; Tsai, Fang-Yu; Wang, Ming Jen; Chang, I-Shou; Lin, Jiunn-Liang; Lin, Shankung

    2011-07-01

    Aging is associated with bone loss and degenerative joint diseases, in which the aging of bone marrow-derived mesenchymal stem cell (bmMSC)[1] may play an important role. In this study, we analyzed the gene expression profiles of bmMSC from 14 donors between 36 and 74 years old, and obtained age-associated genes (in the background of osteoarthritis) and osteoarthritis-associated genes (in the background of old age). Pathway analysis of these genes suggests that alterations in glycobiology might play an important role in the aging of human bmMSC. On the other hand, antigen presentation and signaling of immune cells were the top pathways enriched by osteoarthritis-associated genes, suggesting that alteration in immunology of bmMSC might be involved in the pathogenesis of osteoarthritis. Most intriguingly, we found significant age-associated differential expression of HEXA, HEXB, CTSK, SULF1, ADAMTS5, SPP1, COL8A2, GPNMB, TNFAIP6, and RPL29; those genes have been implicated in the bone loss and the pathology of osteoporosis and osteoarthritis in aging. Collectively, our results suggest a pathological role of bmMSC in aging-related skeletal diseases, and suggest the possibility that alteration in the immunology of bmMSC might also play an important role in the etiology of adult-onset osteoarthritis.

  9. Bone Marrow Failure Secondary to Cytokinesis Failure

    Science.gov (United States)

    2015-12-01

    have assessed the role of FA pathway in mitosis and confirmed that murine FA-deficient hematopoietic stem cells exhibit p53- mediated growth defects...results suggest that bone marrow failure in FA may be caused, in part, by p53- mediated cellular defects and underscore the importance of... mediated apoptosis of HSCs due to cytokinesis failure. The major goal of the project was to assess whether the p53- mediated apoptosis due to

  10. Acceleration of Immune Reconstitution after Bone Marrow Transplantation in Mice by Bone Marrow Stromal

    Institute of Scientific and Technical Information of China (English)

    秦凤华; 蒋激扬; 李爱玲; 金永柱; 郝洁; 谢蜀生

    2003-01-01

    To observe potential effect of the engineered bone marrow stromal cell line QXMSC1 secreting IL-6 (QXMSCIL-6) on accelerating immnune reconstitution in syngeneic bone marrow transplantation in mice, QXMSC1 was transfected with the eukaryocytic expression vector pcDNAIL-6, which contained hIL-6 cDNA by liposome-mediated gene transfecting technique. G418-resistance clone was selected by limiting dilution. The highest secreting clone was selected by ELISA assay and used in animal experiments. The recipient mice (BALB/c) were lethally irradiated and cotransplanted syngeneic bone marrow (107/mice) and the QXMSCIIL-6 (5×105/mice). Lymphocyte proliferation induced by ConA and LPS, helper T lymphocyte precursor (HTLp), cytotoxic T lymphocyte precursor (CTLp), plaque-forming cell (PFC), delayed type hypersensitivity (DTH) were examined 30, 60 days in post transplantation respectively. The results showed that lymphocytes proliferation to ConA and LPS, HTLp, CTLp increased, DTH and PFC were improved by cografted stromal cells QXMSCIIL-6 on 30, 60 days after BMT. These results demonstrated that the bone marrow stromal cell line QXMSC1 IL-6 transfected with IL-6 (QXMSC11L-6) accelerated immnune reconstitution in syngeneic bone marrow transplantation.

  11. Ex vivo expansion of Primate CD34+ Cells isolated from Bone Marrow and Human Bone Marrow Mononuclear Cells using a Novel Scaffold

    Directory of Open Access Journals (Sweden)

    Devaprasad D

    2009-01-01

    Full Text Available Bone marrow derived CD34+ cells have been in clinical application in patients with haematological malignancies. One of the major problems with this treatment is the non-availability of matched donors or the necessity of multiple transfusions depending upon the pathology. Recently evidences have been accumulating to prove the safety and efficacy of autologous CD34+ cells in diseases such as myocardial dysfunction, peripheral vascular diseases and neurological certain conditions. However there are only a few reports in the literature on ex vivo expansion of the bone marrow derived CD34+ cells. We have in two different studies proven that isolated CD34+ cells from baboon bone marrow and non-isolated BMMNCs from human bone marrow could be expanded with increase in percentage of CD34+ cells using a novel scaffold.

  12. Bone marrow transplantation at the University of Nebraska Medical Center.

    Science.gov (United States)

    Bierman, P J; Armitage, J O

    1993-08-01

    The bone marrow transplant program at UNMC is currently one of the most active programs in the country. The benefits to patients who are cured of disease by transplantation cannot be measured. The large volume of clinical and basic science research related to transplantation has enhanced the academic stature of UNMC. The combination of patient care, education, clinical research, and basic science research provides an excellent model for the operation of an academic medical institution.

  13. Hepatocyte growth factor modulates interleukin-6 production in bone marrow derived macrophages: implications for inflammatory mediated diseases.

    Directory of Open Access Journals (Sweden)

    Gina M Coudriet

    Full Text Available The generation of the pro-inflammatory cytokines IL-6, TNF-α, and IL-1β fuel the acute phase response (APR. To maintain body homeostasis, the increase of inflammatory proteins is resolved by acute phase proteins via presently unknown mechanisms. Hepatocyte growth factor (HGF is transcribed in response to IL-6. Since IL-6 production promotes the generation of HGF and induces the APR, we posited that accumulating HGF might be a likely candidate for quelling excess inflammation under non-pathological conditions. We sought to assess the role of HGF and how it influences the regulation of inflammation utilizing a well-defined model of inflammatory activation, lipopolysaccharide (LPS-stimulation of bone marrow derived macrophages (BMM. BMM were isolated from C57BL6 mice and were stimulated with LPS in the presence or absence of HGF. When HGF was present, there was a decrease in production of the pro-inflammatory cytokine IL-6, along with an increase in the anti-inflammatory cytokine IL-10. Altered cytokine production correlated with an increase in phosphorylated GSK3β, increased retention of the phosphorylated NFκB p65 subunit in the cytoplasm, and an enhanced interaction between CBP and phospho-CREB. These changes were a direct result of signaling through the HGF receptor, MET, as effects were reversed in the presence of a selective inhibitor of MET (SU11274 or when using BMM from macrophage-specific conditional MET knockout mice. Combined, these data provide compelling evidence that under normal circumstances, HGF acts to suppress the inflammatory response.

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

    Directory of Open Access Journals (Sweden)

    Sabine Wislet-Gendebien

    2012-01-01

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

  15. Bone marrow processing for transplantation using Cobe Spectra cell separator.

    Science.gov (United States)

    Veljković, Dobrila; Nonković, Olivera Šerbić; Radonjić, Zorica; Kuzmanović, Miloš; Zečević, Zeljko

    2013-06-01

    Concentration of bone marrow aspirates is an important prerequisite prior to infusion of ABO incompatible allogeneic marrow and prior to cryopreservation and storage of autologous marrow. In this paper we present our experience in processing 15 harvested bone marrow for ABO incompatible allogeneic and autologous bone marrow (BM) transplantation using Cobe Spectra® cell separator. BM processing resulted in the median recovery of 91.5% CD34+ cells, erythrocyte depletion of 91% and volume reduction of 81%. BM processing using cell separator is safe and effective technique providing high rate of erythrocyte depletion and volume reduction, and acceptable recovery of the CD34+ cells.

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

    Science.gov (United States)

    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.

  17. Increasing utilization of bone marrow transplantation. II. Results of the 1985-1987 survey.

    Science.gov (United States)

    Bortin, M M; Rimm, A A

    1989-09-01

    The International Bone Marrow Transplant REgistry conducts periodic surveys to determine activity in the field of allogeneic and syngeneic bone marrow transplantation. Data were reported to the IBMTR by 258 institutions in 41 countries regarding their patients who received bone marrow transplants during the period 1985-1987. To the best of our knowledge, the data represent essentially all bone marrow transplants (exclusive of autologous transplants) performed in the past 3 years. A total of 10,887 patients received bone marrow transplants; 73% were for leukemia, 11% for other malignant diseases, 9% for severe aplastic anemia and related disorders, 3% for immune deficiency diseases, 2% for thalassemia major, and 2% for genetic, metabolic, and several other rare diseases. 161 (62%) of the 258 institutions performed fewer than one transplant per month. More than 50% of the patients were transplanted in 37 institutions. 46% of the world's bone marrow transplants were performed in North America, 42% in Western Europe, 5% in Asia, 3% in Australia and New Zealand, 2% in the Mideast and Africa, 1% in South and Central America, and 1% in Eastern Europe and the USSR. The data reflect continued growth in utilization of allogeneic and syngeneic bone marrow transplantation and quantify the annual increases in the number of patients receiving transplants.

  18. Drug-induced chimerism and prevention of graft-versus-host disease in lethally irradiated mice transplanted with rat bone marrow. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Pierpaoli, W.; Maestroni, G.J.M.

    1978-12-01

    L-5-hydroxytryptophan, haloperidol, and phentolamine were administered subcutaneously to groups of mice. Some groups were inoculated i.p. or i.v. with bone marrow cells. The mice were given a dose of 900 rad of whole-body gamma radiation. Observations were made on survival rate, reconstitution with rat hematopoietic tissue, and capacity to reject or accept skin grafts. Results indicate that the combination of drug-induced tolerance and a newly established preconditioning regimen that eliminated postradiation damage and mortality results in reduction in incidence or delay in onset of GVHD, successful bone marrow grafting, and induction of persistent rat chimerism. (HLW)

  19. Bone marrow blood vessels: normal and neoplastic niche

    Directory of Open Access Journals (Sweden)

    Saeid Shahrabi

    2016-11-01

    Full Text Available 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.

  20. Bone Marrow Stem Cell as a Potential Treatment for Diabetes

    Directory of Open Access Journals (Sweden)

    Ming Li

    2013-01-01

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

  1. Transplantation? Peripheral Stem Cell/Bone Marrow/Cord Blood

    Directory of Open Access Journals (Sweden)

    Itır Sirinoglu Demiriz

    2012-01-01

    Full Text Available The introduction of peripheral stem cell (PSC and cord blood (CB as an alternative to bone marrow (BM recently has caused important changes on hematopoietic stem cell transplantation (HSCT practice. According to the CIBMTR data, there has been a significant decrease in the use of bone marrow and increase in the use of PSC and CB as the stem cell source for HSCT performed during 1997–2006 period for patients under the age of 20. On the other hand, the stem cell source in 70% of the HSCT procedures performed for patients over the age of 20 was PSC and the second most preferred stem cell source was bone marrow. CB usage is very limited for the adult population. Primary disease, stage, age, time and urgency of transplantation, HLA match between the patient and the donor, stem cell quantity, and the experience of the transplantation center are some of the associated factors for the selection of the appropriate stem cell source. Unfortunately, there is no prospective randomized study aimed to facilitate the selection of the correct source between CB, PSC, and BM. In this paper, we would like to emphasize the data on stem cell selection in light of the current knowledge for patient populations according to their age and primary disease.

  2. Bone marrow biopsy findings in brucellosis patients with hematologic abnormalities

    Institute of Scientific and Technical Information of China (English)

    Cengiz Demir; Mustafa Kasim Karahocagil; Ramazan Esen; Murat Atmaca; Hayriye G(o)nüllü; Hayrettin Akdeniz

    2012-01-01

    Background Brucellosis can mimic various multisytem diseases,showing wide clinical polymorphism that frequently leads to misdiagnosis and treatment delay,further increasing the complication rates.In this study,we aimed to examine bone marrow biopsy findings in brucellosis cases presenting with hematologic abnormalities.Methods Forty-eight brucellosis cases were prospectively investigated.Complaints and physical examination findings of patients were recorded.Patients' complete blood count,routine biochemical tests,erythrocyte sedimentation rate,C-reactive protein and serological screenings were performed.Bone marrow biopsy and aspiration was performed in patients with cytopenia,for bone marrow examination and brucella culture,in accordance with the standard procedures from spina iliaca posterior superior region of pelvic bone.Results Of the 48 patients,35 (73%) were female and 13 (27%) were male.Mean age was (34.8±15.4) years (age range:15-70 years).Anemia,leukopenia,thrombocytopenia and pancytopenia were found in 39 (81%),28 (58%),22 (46%) and 10 patients (21%),respectively.In the examination of bone marrow,hypercellularity was found In 35 (73%) patients.Increased megacariocytic,erythroid and granulocytic series were found in 28 (58%),15 (31%) and 5 (10%) patients,respectively.In addition,hemophagocytosis was observed in 15 (31%) patients,granuloma observed in 12 (25%) and increased eosinophil and plasma cells observed in 9 (19%) patients.Conclusion According to the results of our series,hemophagocytosis,microgranuloma formation and hypersplenism may be responsible for hematologic complications of brucellosis.

  3. Testing stem cell therapy in a rat model of inflammatory bowel disease: role of bone marrow stem cells and stem cell factor in mucosal regeneration.

    Directory of Open Access Journals (Sweden)

    Bo Qu

    Full Text Available BACKGROUND: The gastrointestinal (GI mucosal cells turnover regularly under physiological conditions, which may be stimulated in various pathological situations including inflammation. Local epithelial stem cells appear to play a major role in such mucosal renewal or pathological regeneration. Less is clear about the involvement of multipotent stem cells from blood in GI repair. We attempted to explore a role of bone marrow mesenchymal stromal cells (BMMSCs and soluble stem cell factor (SCF in GI mucosa regeneration in a rat model of inflammatory bowel diseases (IBD. METHODS: BMMSCs labelled with the fluorescent dye PKH26 from donor rats were transfused into rats suffering indomethacin-induced GI injury. Experimental effects by BMMSCs transplant and SCF were determined by morphometry of intestinal mucosa, double labeling of PKH26 positive BMMSCs with endogenous proliferative and intestinal cell markers, and western blot and PCR analyses of the above molecular markers in the recipient rats relative to controls. RESULTS: PKH26 positive BMMSCs were found in the recipient mucosa, partially colocalizing with the proliferating cell nuclear antigen (PCNA, Lgr5, Musashi-1 and ephrin-B3. mRNA and protein levels of PCNA, Lgr5, Musashi-1 and ephrin-B3 were elevated in the intestine in BMMSCs-treated rats, most prominent in the BMMSCs-SCF co-treatment group. The mucosal layer and the crypt layer of the small intestine were thicker in BMMSCs-treated rats, more evident in the BMMSCs-SCF co-treatment group. CONCLUSION: BMMSCs and SCF participate in but may play a synergistic role in mucosal cell regeneration following experimentally induced intestinal injury. Bone marrow stem cell therapy and SCF administration may be of therapeutic value in IBD.

  4. Graft versus host disease in a rat small bowel transplant model after T-cell depleted donor specific bone marrow infusion

    Directory of Open Access Journals (Sweden)

    Bakonyi Neto Alexandre

    2003-01-01

    Full Text Available Low cytoreductive regimen of irradiation associated to unmodified bone marrow infusion (UBM does not prevent the occurrence of graft versus host disease (GVHD after transplant. PURPOSE: In this study we evaluated the potential advantages of a long-term immunossupression and T-cell depleted bone marrow infusion (TCDBMI in preventing the occurrence of GVHD after small bowel transplantation (SBTx. METHODS: Heterotopic SBTX was performed with Lewis rats as recipients and DA as donors and distributed into 5 groups according to the irradiation, duration of immunossupression and the use of UBM or TCDBMI: G1 (n=6, without irradiation and G2 (n=9, G3 (n=4, G4 (n=5 and G5 (n=6 was given 250 rd of irradiation. Groups 1,2,4 and G3 and 5 were infused with 100 x 10(6 UBM and TCDBM respectively. Animals in G1, 2, 3 were immunossupressed with 1mg/ FK506/Kg/IM for 5 days and G4 and G5 for 15 days. Anti CD3 monoclonal antibodies and immunomagnetic beads were used for T-cell depletion.Animals were examined for rejection, GVHD, chimerism characterization and ileal and skin biopsies. RESULTS: Minimal to mild rejection was observed in all groups; however, GVHD were present only in irradiated groups. Long-term immunossupression changed the severity of GVHD in G4 and G5. Rejection was the cause of death in G1 while GVHD in G2, 3, 4 and 5, not avoided by the use of TCDBMI. Total chimerism and T-cell chimerism was statistically higher in irradiated groups when compared to G1. CONCLUSION: Extended immunossupression associated to low dose of irradiation decrease the severity of GVHD, not avoided by the use of TCDBMI.

  5. Bone marrow-derived versus parenchymal sources of inducible nitric oxide synthase in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Zehntner, Simone P; Bourbonniere, Lyne; Hassan-Zahraee, Mina;

    2004-01-01

    . These discrepancies may reflect balance between immunoregulatory and neurocytopathologic roles for NO. We investigated selective effects of bone marrow-derived versus CNS parenchymal sources of iNOS in EAE in chimeric mice. Chimeras that selectively expressed or ablated iNOS in leukocytes both showed significant...... delay in disease onset, with no difference in disease severity. We conclude that bone marrow-derived and CNS parenchymal sources of iNOS-derived NO both play a regulatory role in EAE....

  6. Autologous bone marrow transplantation by photodynamic therapy

    Science.gov (United States)

    Gulliya, Kirpal S.

    1992-06-01

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

  7. Bone marrow-derived dendritic cells.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  9. Regenerate augmentation with bone marrow concentrate after traumatic bone loss.

    Science.gov (United States)

    Gessmann, Jan; Köller, Manfred; Godry, Holger; Schildhauer, Thomas Armin; Seybold, Dominik

    2012-01-01

    Distraction osteogenesis after post-traumatic segmental bone loss of the tibia is a complex and time-consuming procedure that is often complicated due to prolonged consolidation or complete insufficiency of the regenerate. The aim of this feasibility study was to investigate the potential of bone marrow aspiration concentrate (BMAC) for percutaneous regenerate augmentation to accelerate bony consolidation of the regenerate. Eight patients (age 22-64) with an average posttraumatic bone defect of 82.4 mm and concomitant risk factors (nicotine abuse, soft-tissue defects, obesity and/or circulatory disorders) were treated with a modified Ilizarov external frame using an intramedullary cable transportation system. At the end of the distraction phase, each patient was treated with a percutaneously injection of autologous BMAC into the centre of the regenerate. The concentration factor was analysed using flow cytometry. The mean follow up after frame removal was 10 (4-15) months. With a mean healing index (HI) of 36.9 d/cm, bony consolidation of the regenerate was achieved in all eight cases. The mean concentration factor of the bone marrow aspirate was 4.6 (SD 1.23). No further operations concerning the regenerate were needed and no adverse effects were observed with the BMAC procedure. This procedure can be used for augmentation of the regenerate in cases of segmental bone transport. Further studies with a larger number of patients and control groups are needed to evaluate a possible higher success rate and accelerating effects on regenerate healing.

  10. Bone Diseases

    Science.gov (United States)

    Your bones help you move, give you shape and support your body. They are living tissues that rebuild constantly ... childhood and your teens, your body adds new bone faster than it removes old bone. After about ...

  11. Monitoring of residual disease and guided donor leucocyte infusion after allogeneic bone marrow transplantation by chimaerism analysis with short tandem repeats

    NARCIS (Netherlands)

    de Weger, RA; Tilanus, MGJ; Scheidel, KC; van den Tweel, JG; Verdonck, LF

    2000-01-01

    In this study, we analysed the chimaeric status of peripheral blood leucocytes (PBLs) in recipients of allogeneic bone marrow transplantation (BMT) with the use of short tandem repeat (STR) microsatellite markers for monitoring the efficacy of BMT and donor leucocyte infusions (DLIs). A set of four

  12. Magnetic resonance imaging of the bone marrow following treatment with recombinant human erythropoietin in patients with end-stage renal disease

    DEFF Research Database (Denmark)

    Jensen, K E; Stenver, D; Jensen, M;

    1990-01-01

    We used magnetic resonance imaging (MRI) to study vertebral bone marrow in hemodialysis patients during treatment with recombinant human erythropoietin (rHuEPO). We found changes in T1 relaxation times and image contrast within 14 days after starting treatment, before any response was seen in the...

  13. Bone marrow acid phosphatase by radioimmunoassay. [/sup 125/I; prostatic carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Belville, W.D.; Cox, H.D.; Mahan, D.E.; Olmert, J.P.; Mittemeyer, B.T.; Bruce, A.W.

    1978-06-01

    A double-antibody radioimmunoassay was developed and utilized to measure prostatic acid phosphatase in bone marrow aspirates. One hundred-eighteen patients with carcinoma of the prostate in various clinical stages, and fifty with benign prostatic hyperplasia were studied. In patients with carcinoma, levels of prostatic acid phosphatase in bone marrow aspirates were found to correlate well with increasing clinical stage of the disease. Determination of bone marrow prostatic acid phosphatase by radioimmunoassay may be a valuable adjunct to clinicopathologic staging of prostatic carcinoma.

  14. Selective resistance of bone marrow-derived hemopoietic progenitor cells to gliotoxin

    Energy Technology Data Exchange (ETDEWEB)

    Muellbacher, A.; Hume, D.; Braithwaite, A.W.; Waring, P.; Eichner, R.D.

    1987-06-01

    The fungal metabolite gliotoxin at low concentrations prevents mitogen stimulation of mature lymphocytes as a result of gliotoxin-induced genomic DNA degradation. Bone marrow, on the other hand, contains a subpopulation of cells resistant to gliotoxin at similar concentrations. This population includes the hemopoietic progenitor cells that grow in vitro in response to appropriate colony-stimulating factors and cells that form colonies in the spleens of lethally irradiated recipients. Gliotoxin treatment of lymph node cell-enriched bone marrow significantly delayed the onset of graft-versus-host disease in fully allogeneic bone marrow chimeras.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Wiwanitkit, Viroj

    2011-10-01

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

  17. Correlation of lung abnormalities on high-resolution CT with clinical graft-versus-host disease after allogeneic versus autologous bone marrow transplantation in children

    Energy Technology Data Exchange (ETDEWEB)

    Merlini, Laura; Borzani, Irene Maria Olivia; Anooshiravani, Mehrak; Hanquinet, Sylviane [University of Geneva Children' s Hospital, Paediatric Radiology Unit, Geneva (Switzerland); Rochat, Isabelle [University of Geneva Children' s Hospital, Paediatric Pneumology Unit, Geneva (Switzerland); Ozsahin, Ayse Hulya [University of Geneva Children' s Hospital, Paediatric Oncology Unit, Geneva (Switzerland)

    2008-11-15

    Late-onset noninfectious pulmonary complications (LONIPCs) are life-threatening complications of bone marrow transplantation (BMT). Several pathological patterns are described in the literature with different prognoses, and with different relationships to graft-versus-host disease (GVHD). The role of high-resolution CT (HRCT) is not yet well established. To illustrate different patterns of LONIPCs on HRCT in allogeneic versus autologous BMT in order to investigate the correlation with chronic GVHD (cGVHD). A total of 67 HRCT scans were performed in 24 patients with noninfectious pulmonary disease at least 3 months after BMT (16 allogeneic, 8 autologous). Abnormality patterns and extension on HRCT images were correlated with the clinical outcome and with the severity of cGVHD. Of 24 patients, 9 showed LONIPCs (1 autologous, 8 allogeneic). There was a significant association between abnormalities on HRCT and severe cGVHD (P = 0.038), with no specific pattern. Prognosis seemed to be related to the severity of cGVHD and not to the extent of abnormalities on HRCT. The significant association between abnormalities on HRCT and severe GVHD suggests that LONIPCs can be a pulmonary manifestation of the disease. HRCT is a useful tool when combined with clinical data. (orig.)

  18. Osteonecrosis of the femoral head after bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Mi; Jun, Jeong Su; Park, Chang Suk; Kim, Yong Sik; Kwon, Soon Yong; Kim, Yoo Jin; Kim, Chun Choo [The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2003-07-01

    To retrospectively review findings of osteonecrosis of the femoral head after bone marrow transplantation. We reviewed the clinical and MR findings of osteonecrosis of the femoral head in 23 of 1112 patients who underwent marrow transplantation during a five-year follow-up period lasting from 1996 to 2000. Mean age at the time of diagnosis was 31 (range, 20-47) years, and the mean time from transplant to diagnosis was 17 months. All patients developed variable graft-versus-host disease and seventeen were treated with high-dose prednisolone and/or cysclosporin for severe acute or extensive chronic graft versus host disease. Osteonecrosis was diagnosed by magnetic resonance (MR) imaging, which allowed early detection of disease assessment of its stage. At the time of diagnosis, 15 hips were at stage I, 28 at stage II, two at stage III, and none at stage IV, according to the international ARCO classification system. Osteonecrosis of femoral diaphyses, the lower lumbar spine, or pelvic bones in the MR field was also found to have occurred in 11 patients. Initial treatment was conservative: 21 hips underwent surgery [core decompression (n=10), vascularized fibular bone graft (n=5), and joint replacement (n=6)]. In patients receiving high-dose steroids for the treatment of graft-versus-host disease, MR screening might help detect osteonecrosis at an early stage.

  19. Aerobic nitroreduction of dehydrochloramphenicol by bone marrow.

    Science.gov (United States)

    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.

  20. Bone marrow stromal cell : mediated neuroprotection for spinal cord repair

    NARCIS (Netherlands)

    Ritfeld, Gaby Jane

    2014-01-01

    Currently, there is no treatment available that restores anatomy and function after spinal cord injury. This thesis explores transplantation of bone marrow-derived mesenchymal stem cells (bone marrow stromal cells; BMSCs) as a therapeutic approach for spinal cord repair. BMSCs secrete neurotrophic f

  1. Neuroamines — regulators of local processes at bone marrow autotransplantation

    Directory of Open Access Journals (Sweden)

    Vorobyova O.V.

    2015-12-01

    Full Text Available Purpose: to determine the content of neuroamines (histamine, serotonin, catecholamines in bioamine structures of bone marrow after autotransplantation. Material and methods. Animals were injected into the tail vein of bone marrow suspension obtained from the femur of the same mouse. It was taken from the femoral bone marrow of 1 ml and placed in 2 ml of physiological saline and thoroughly stirred. 1 ml of bone marrow suspension was injected into the tail vein. Cryostat sections were treated with luminescent-histochemical methods. Results. After bone marrow autotransplantation marked changes were observed in the neurotransmitters of the bone marrow — an increasing number of granular luminescent cells decrease in the amount of granules in them, and a decrease in the number of mast cells because of their degranulation. A weak luminescence was determined in nuclei in neutrophils. Perhaps this proves the activation of the immune response. Conclusion. The bone marrow autotransplantation leads to a redistribution of the structures of the bone marrow of histamine, catecholamines and serotonin, which changes the direction of cytodifferentiation, the content of neuroamines in granular luminescent cells and mast cells (cells of autonomic regulation.

  2. In vivo cell kinetics of the bone marrow transplantation using dual colored transgenic rat system

    Science.gov (United States)

    Kai, Kotaro; Teraoka, Satoshi; Adachi, Yasushi; Ikehara, Susumu; Murakami, Takashi; Kobayashi, Eiji

    2008-02-01

    Because bone marrow is an adequate site for bone marrow stem cells, intra-bone marrow - bone marrow transplantation (IBM-BMT) is an efficient strategy for bone marrow transplantation (BMT). However, the fate of the transplanted cells remains unclear. Herein, we established a dual-colored transgenic rat system utilizing green fluorescent protein (GFP) and a luciferase (luc) marker. We then utilized this system to investigate the in vivo kinetics of transplanted bone marrow cells (BMCs) after authentic intravenous (IV)-BMT or IBM-BMT. The in vivo fate of the transplanted cells was tracked using an in vivo luminescent imaging technique; alterations in peripheral blood chimerism were also followed using flow cytometry. IBM-BMT and IV-BMT were performed using syngeneic and allogeneic rat combinations. While no difference in the proliferation pattern was observed between the two treatment groups at 7 days after BMT, different distribution patterns were clearly observed during the early phase. In the IBM-BMT-treated rats, the transplanted BMCs were engrafted immediately at the site of the injected bone marrow and expanded more rapidly than in the IV-BMT-treated rats during this phase. Graft-versus-host disease was also visualized. Our bio-imaging system using dual-colored transgenic rats is a powerful tool for performing quantitative and morphological assessments in vivo.

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

    Science.gov (United States)

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

    1994-01-01

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

  4. Bone marrow edema of the knee joint; Differenzialdiagnosen des Knochenmarkoedems am Kniegelenk

    Energy Technology Data Exchange (ETDEWEB)

    Breitenseher, M.J. [Waldviertelklinikum Horn (Austria). Institut fuer Radiologie; Universitaetsklinik fuer Radiodiagnostik Wien (Austria). Abteilung Osteologie; Kramer, J. [Institut fuer CT- und MRT-Diagnostik, Linz (Austria); Mayerhoefer, M.E. [Universitaetsklinik fuer Radiodiagnostik Wien (Austria). Abteilung Osteologie; Aigner, N. [Orthopaedisches Krankenhaus Speising, Erste Orthopaedische Abteilung, Wien (Austria); Hofmann, S. [LKH Stolzalpe (Austria). Orthopaedische Abteilung

    2006-01-01

    Bone marrow edema of the knee joint is a frequent clinical picture in MR diagnostics. It can be accompanied by symptoms and pain in the joint. Diseases that are associated with bone marrow edema can be classified into different groups. Group 1 includes vascular ischemic bone marrow edema with osteonecrosis (synonyms: SONK or Ahlbaeck's disease), osteochondrosis dissecans, and bone marrow edema syndrome. Group 2 comprises traumatic or mechanical bone marrow edema. Group 3 encompasses reactive bone marrow edemas such as those occurring in gonarthrosis, postoperative bone marrow edemas, and reactive edemas in tumors or tumorlike diseases. Evidence for bone marrow edema is effectively provided by MRI, but purely morphological MR information is often unspecific so that anamnestic and clinical details are necessary in most cases for definitive disease classification. (orig.) [German] Das Knochenmarkoedem des Kniegelenks ist ein haeufiges Erscheinungsbild in der MR-Diagnostik. Es kann mit Symptomen und Schmerzen des Gelenks einhergehen. Erkrankungen, die mit einem Knochenmarkoedem vergesellschaftet sind, koennen in verschiedene Gruppen eingeteilt werden. Zur 1. Gruppe gehoeren das vaskulaer-ischaemische Knochenmarkoedem mit Osteonekrose (Synonyme SONK oder Morbus Ahlbaeck), die Osteochondrosis dissecans und das Knochenmarkoedemsyndrom, zur 2. Gruppe das traumatologische oder mechanische Knochenmarkoedem. In der 3. Gruppe werden reaktive Knochenmarkoedeme zusammengefasst wie bei Gonarthrose, postoperative Knochenmarkoedeme und reaktive Oedeme bei Tumor oder tumoraehnlichen Erkrankungen. Der Nachweis eines Knochenmarkoedems gelingt mit der MRT sehr sensitiv, die rein morphologische MR-Information ist jedoch oft unspezifisch, sodass anamnestische und klinische Informationen fuer die sichere Zuordnung einer Erkrankung in den meisten Faellen notwendig sind. (orig.)

  5. Evaluation of bone-marrow scanning with technetium-99m sulfur colloid in pediatric oncology.

    Science.gov (United States)

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

    1979-05-01

    Eighty-six technetium-99m sulfur colloid (Tc-SC) bone-marrow scans in 56 pediatric oncology patients were reviewed. The distribution of the sulfur colloid was similar to that in adult bone marrow in normal children older than 10 yr, and involved progressively more marrow of the extremities in normal children under 10 years of age. After irradiation or chemotherapy there was an extension of the Tc-SC to peripheral marrow sites. There was also diminished uptake of the tracer in sites corresponding to irradiated areas. In most patients there was recovery of these defects by 6 mo after completion of therapy. Tumor replacement of the marrow was reflected in the scans, and the extent of the scan defect paralleled the course of the disease. In four patients, despite normal bone scans and radiographs, marrow-scan abnormalities due to tumor replacement were present and confirmed by needle aspiration and/or biopsy. In two other patients, the marrow-scan abnormality preceded radiographic and histologic evidence of tumor metastasis. Two patients who responded clinically showed persistent defects; biopsy in one revealed fibrosis. Technetium-99m sulfur colloid bone-marrow scanning appears to be a sensitive monitor of marrow alteration caused by metastases, irradiation damage, or tissue fibrosis in children receiving treatment for cancer.

  6. CCR2 regulates the uptake of bone marrow-derived fibroblasts in renal fibrosis.

    Directory of Open Access Journals (Sweden)

    Yunfeng Xia

    Full Text Available Recent studies have shown that bone marrow-derived fibroblasts contribute significantly to the pathogenesis of renal fibrosis. However, the molecular mechanisms underlying the recruitment of bone marrow-derived fibroblasts into the kidney are incompletely understood. Bone marrow-derived fibroblasts express the chemokine receptor--CCR2. In this study, we tested the hypothesis that CCR2 participates in the recruitment of fibroblasts into the kidney during the development of renal fibrosis. Bone marrow-derived collagen-expressing GFP⁺ fibroblasts were detected in the obstructed kidneys of chimeric mice transplanted with donor bone marrow from collagen α1(I-GFP reporter mice. These bone marrow-derived fibroblasts expressed PDGFR-β and CCR2. CCR2 knockout mice accumulated significantly fewer bone marrow-derived fibroblast precursors expressing the hematopoietic marker-CD45 and the mesenchymal markers-PDGFR-β or procollagen I in the obstructed kidneys compared with wild-type mice. Furthermore, CCR2 knockout mice displayed fewer bone marrow-derived myofibroblasts and expressed less α-SMA or FSP-1 in the obstructed kidneys compared with wild-type mice. Consistent with these findings, genetic deletion of CCR2 inhibited total collagen deposition and suppressed expression of collagen I and fibronectin. Moreover, genetic deletion of CCR2 inhibits MCP-1 and CXCL16 gene expression associated with a reduction of inflammatory cytokine expression and macrophage infiltration, suggesting a linear interaction between two chemokines/ligand receptors in tubular epithelial cells. Taken together, our results demonstrate that CCR2 signaling plays an important role in the pathogenesis of renal fibrosis through regulation of bone marrow-derived fibroblasts. These data suggest that inhibition of CCR2 signaling could constitute a novel therapeutic approach for fibrotic kidney disease.

  7. Regenerate augmentation with bone marrow concentrate after traumatic bone loss

    Directory of Open Access Journals (Sweden)

    Jan Gessmann

    2012-03-01

    Full Text Available Distraction osteogenesis after post-traumatic segmental bone loss of the tibia is a complex and time-consuming procedure that is often complicated due to prolonged consolidation or complete insufficiency of the regenerate. The aim of this feasibility study was to investigate the potential of bone marrow aspiration concentrate (BMAC for percutaneous regenerate augmentation to accelerate bony consolidation of the regenerate. Eight patients (age 22-64 with an average posttraumatic bone defect of 82.4 mm and concomitant risk factors (nicotine abuse, soft-tissue defects, obesity and/or circulatory disorders were treated with a modified Ilizarov external frame using an intramedullary cable transportation system. At the end of the distraction phase, each patient was treated with a percutaneously injection of autologous BMAC into the centre of the regenerate. The concentration factor was analysed using flow cytometry. The mean follow up after frame removal was 10 (4-15 months. With a mean healing index (HI of 36.9 d/cm, bony consolidation of the regenerate was achieved in all eight cases. The mean concentration factor of the bone marrow aspirate was 4.6 (SD 1.23. No further operations concerning the regenerate were needed and no adverse effects were observed with the BMAC procedure. This procedure can be used for augmentation of the regenerate in cases of segmental bone transport. Further studies with a larger number of patients and control groups are needed to evaluate a possible higher success rate and accelerating effects on regenerate healing.

  8. Glutamine supplementation in bone marrow transplantation.

    Science.gov (United States)

    Ziegler, Thomas R

    2002-01-01

    An increasing number of clinical investigations have focused on supplementation of specialized enteral and parenteral nutrition with the amino acid glutamine. This interest derives from strong evidence in animal models and emerging clinical data on the efficacy of glutamine administration following chemotherapy, trauma, sepsis and other catabolic conditions. Glutamine has protein-anabolic effects in stressed patients and, among many key metabolic functions, is used as a major fuel/substrate by cells of the gastrointestinal epithelium and the immune system. These effects may be particularly advantageous in patients undergoing bone marrow transplantation (BMT), who exhibit post-transplant body protein wasting, gut mucosal injury and immunodeficiency. Studies to date indicate that enteral and parenteral glutamine supplementation is well tolerated and potentially efficacious after high-dose chemotherapy or BMT for cancer treatment. Although not all studies demonstrate benefits, sufficient positive data have been published to suggest that this nutrient should be considered as adjunctive metabolic support of some individuals undergoing marrow transplant. However, BMT is a rapidly evolving clinical procedure with regard to the conditioning and supportive protocols utilized. Thus, additional randomized, double-blind, controlled clinical trials are indicated to define the efficacy of glutamine with current BMT regimens.

  9. Effects of lateral ventricular transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene on cognition in a rat model of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Ping Zhang; Gangyong Zhao; Xianjiang Kang; Likai Su

    2012-01-01

    In the present study, transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene into the lateral ventricle of a rat model of Alzheimer's disease, resulted in significant attenuation of nerve cell damage in the hippocampal CA1 region. Furthermore, brain-derived neurotrophic factor and tyrosine kinase B mRNA and protein levels were significantly increased, and learning and memory were significantly improved. Results indicate that transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene can significantly improve cognitive function in a rat model of Alzheimer's disease, possibly by increasing the levels of brain-derived neurotrophic factor and tyrosine kinase B in the hippocampus.

  10. New approaches to graft engineering for haploidentical bone marrow transplantation.

    Science.gov (United States)

    Handgretinger, Rupert

    2012-12-01

    Haploidentical transplantation opens the possibility to offer this treatment to a large number of patients with an otherwise incurable disease, such as some hematologic or oncologic malignancies, inborn or acquired bone marrow failure syndromes, hemoglobinopathies, immunodeficiencies, or other genetic diseases. Initial attempts at haploidentical transplantation using unmanipulated bone marrow were associated with a high transplant-related mortality. However, recent insights into the biology of haploidentical transplantation, the availability of effective in vivo large-scale graft-manipulation technology, and improved supportive care strategies have led to and are still leading to significantly better outcomes compared to previous decades. Methods for the in vitro depletion of T lymphocytes from mobilized peripheral blood stem cells (PBSC) to prevent graft-versus-host disease (GvHD) have facilitated the wider use and acceptance of haploidentical transplantation in children and adult patients. Besides in vitro T-cell depletion techniques, other methods, such as the isolation of alloreactive natural killer (NK) cells, virus-specific T lymphocytes, and other effector or regulatory cells are nowadays available to rapidly rebuild the immune system after haploidentical transplantation for the prevention of severe infections or relapses of the underlying diseases.

  11. A method for generation of bone marrow-derived macrophages from cryopreserved mouse bone marrow cells.

    Directory of Open Access Journals (Sweden)

    Fernanda M Marim

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

  12. No narcosis for bone marrow harvest in autologous bone marrow transplantation.

    Science.gov (United States)

    de Vries, E G; Vriesendorp, R; Meinesz, A F; Mulder, N H; Postmus, P E; Sleijfer, D T

    1984-11-01

    A prospective study with mild general analgesia and sedation together with local anesthesia during bone marrow harvest was performed. Thirty-one patients underwent 33 bone marrow collections. Pretreatment consisted of 100 mg meperidine i.m. and 20 mg diazepam i.m. 1 h before start of procedure. Eight patients got additional meperidine and diazepam during the procedure, all patients got lidocaine 1% locally. A mean volume of 1.321 was obtained with 42.5 punctures. Twenty-two patients had no complications, 4 vomited, 4 had easily correctable hypotension of short duration, one got oxygen for cyanosis of short duration. Acceptance was good in 23 patients, in 6 reasonably well, in two bad. Only one patient experienced pain problems, due to suction. Anxiety was no major problem due to good information before the procedure and mild sedation. This form of anesthesia for bone marrow collection is a safe procedure, it is generally well accepted by the patient and it can be performed on an out-patient basis.

  13. The adipocyte component of bone marrow in heterotopic bone induced by demineralized incisor grafts The adipocyte component of bone marrow in heterotopic bone induced by demineralized incisor grafts

    Directory of Open Access Journals (Sweden)

    Krzysztof H. Włodarski

    2012-10-01

    Full Text Available The relative proportion of adipocytes to hematopoietic elements in the marrow of heterotopically
    induced bone evaluated 4–42 weeks post implantation of demineralized murine incisors was estimated by histological
    analysis of hematoxylin-eosin stained tissue sections. Using computerized image analysis of microphotographs,
    the proportion of nuclear cells vs. adipocytes was ascertained. The percentage of adipocytes in marrow
    increases over time. Such an effect, the replacement of myelopoietic marrow by adipogenic (yellow marrow
    and the resorption of induced bone, is observed in human osteoporosis. A decline in the non-adipogenic cell
    compartments of bone marrow accompanying induced bone begins in the fourth week of induction, gradually
    progresses until the 26th week, and does not change after that. The luminosity, a parameter used in image analysis
    and proportional to the number of nuclear cells, was 124 ± 3 in hematopoietic femoral bone marrow, and
    that of bone marrow of the induced bone was of a similar value (117 ± 8 in the fourth week. An evident decline
    in luminosity of bone marrow filling the foci of heterotopic bone was observed in samples taken at nine weeks
    (82 ± 20. This process progressed until the 26th week, reaching a luminosity of 70 ± 21. At the 42nd week, the
    luminosity remained at the same level (71 ± 27. This indicates that the replacement of hematopoietic bone
    marrow of heterotopically induced bone by unilocular adipocytes begins relatively early (the fourth week and is
    persistent.The relative proportion of adipocytes to hematopoietic elements in the marrow of heterotopically
    induced bone evaluated 4–42 weeks post implantation of demineralized murine incisors was estimated by histological
    analysis of hematoxylin-eosin stained tissue sections. Using computerized image analysis of microphotographs,
    the proportion of nuclear cells vs

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

    Science.gov (United States)

    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. Improvement of myocardial perfusion reserve detected by cardiovascular magnetic resonance after direct endomyocardial implantation of autologous bone marrow cells in patients with severe coronary artery disease

    Directory of Open Access Journals (Sweden)

    Lau Chu-Pak

    2010-01-01

    Full Text Available Abstract Background Recent studies suggested that bone marrow (BM cell implantation in patients with severe chronic coronary artery disease (CAD resulted in modest improvement in symptoms and cardiac function. This study sought to investigate the functional changes that occur within the chronic human ischaemic myocardium after direct endomyocardial BM cells implantation by cardiovascular magnetic resonance (CMR. Methods and Results We compared the interval changes of left ventricular ejection fraction (LVEF, myocardial perfusion reserve and the extent of myocardial scar by using late gadolinium enhancement CMR in 12 patients with severe CAD. CMR was performed at baseline and at 6 months after catheter-based direct endomyocardial autologous BM cell (n = 12 injection to viable ischaemic myocardium as guided by electromechanical mapping. In patients randomized to receive BM cell injection, there was significant decrease in percentage area of peri-infarct regions (-23.6%, P = 0.04 and increase in global LVEF (+9.0%, P = 0.02, the percentage of regional wall thickening (+13.1%, P= 0.04 and MPR (+0.25%, P = 0.03 over the target area at 6-months compared with baseline. Conclusions Direct endomyocardial implantation of autologous BM cells significantly improved global LVEF, regional wall thickening and myocardial perfusion reserve, and reduced percentage area of peri-infarct regions in patients with severe CAD.

  16. Iron overload following bone marrow transplantation in children: MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Kornreich, L.; Horev, G.; Grunebaum, M. [Department of Imaging, Schneider Children`s Medical Center of Israel, Beilinson Medical Campus, 49202 Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University (Israel); Yaniv, I.; Stein, J.; Zaizov, R. [Department of Pediatric Hematology-Oncology, Schneider Children`s Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University (Israel)

    1997-11-01

    Objective. The purpose of this study was to determine the incidence of post-transfusional iron overload in children after bone marrow transplantation by reviewing their magnetic resonance imaging (MR) findings. Materials and methods. We reviewed the abdominal MR studies of 13 children after autologous bone marrow transplantation. Nine of the children had also undergone MR prior to transplantation. Iron deposition in the liver, spleen and bone marrow was graded semi-quantitatively on both T1- and T2-weighted images. Serum ferritin levels and number of blood units given after bone marrow transplantation were recorded. Results. None of the pre-transplantation MR studies revealed iron overload. After bone marrow transplantation, three children showed normal liver and spleen. Iron overload in the liver was noted in ten patients (77 %), six of whom also showed iron overload in the spleen (46 %) and five in the bone marrow (38.5 %). The degree of hepatic iron overload was correlated significantly and splenic iron overload was correlated weakly with the number of blood transfusions (P = 0.01 and P > 0.01, respectively), but neither was correlated with the serum ferritin level. Conclusion. Iron overload commonly accompanies bone marrow transplantation. The observed pattern of iron deposition, in which the spleen was uninvolved in 40 % of patients demonstrating iron overload, is not typical of post-transfusional hemochromatosis. (orig.) With 1 fig., 2 tabs., 15 refs.

  17. Bone marrow response in treated patients with Gaucher disease: evaluation by T1-weighted magnetic resonance images and correlation with reduction in liver and spleen volume

    Energy Technology Data Exchange (ETDEWEB)

    Terk, M.R. [University of Southern California, Los Angeles, CA (United States). Dept. of Radiology; LAC/USC Imaging Science Center, Los Angeles, CA (United States); Dardashti, S. [University of Southern California, Los Angeles, CA (United States). Dept. of Radiology; Liebman, H.A. [University of Southern California, Los Angeles, CA (United States). Dept. of Medicine

    2000-10-01

    Purpose. To determine whether T1-weighted magnetic resonance (MR) images can demonstrate response in the marrow of patients with type 1 Gaucher disease treated with enzyme replacement therapy (ERT) and to determine whether a relationship exists between liver and spleen volume reductions and visible marrow changes.Patients. Forty-two patients with type 1 Gaucher disease were evaluated on at least two occasions. Thirty-two patients received ERT. Of these patients, 15 had a baseline examination prior to the initiation of ERT. The remaining 10 patients did not receive ERT.Design. T1-weighted and gradient recalled echo (GRE) coronal images of the femurs and hips were obtained. Concurrently, liver and spleen volumes were determined using contiguous breath-hold axial gradient-echo images. T1-weighted images of the hips and femurs were evaluated to determine change or lack of change in the yellow marrow.Results. Of the 32 patients receiving ERT, 14 (44%) demonstrated increased signal on T1-weighted images suggesting an increase in the amount of yellow marrow. If only the 15 patients with a baseline examination were considered, the response rate to ERT was 67%. Using Student's t-test a highly significant correlation (P<0.005) was found between marrow response and reduction in liver and spleen volume.Conclusions. Marrow changes in patients receiving ERT can be detected by T1-weighted images. This response correlated with reductions in visceral volumes (P<0.0005). (orig.)

  18. The effects of bone marrow aspirate, bone graft, and collagen composites on fixation of titanium implants

    DEFF Research Database (Denmark)

    Babiker, Hassan; Ding, Ming; Sandri, Monica

    2012-01-01

    contamination, and non union as well as the potential risk of disease transmission. Hydroxyapatite and collagen composites (HA/Collagen) have the potential in mimicking and replacing skeletal bones. This study attempted to determine the effects of newly developed HA/Collagen-composites with and without bone...... marrow aspirate (BMA) on enhancement of bone implant fixation. Method: Titanium alloy implants were inserted into bilateral femoral condyles of eight skeletally mature sheep, four implants per sheep. The implant had a circumferential gap of 2 mm. The gap was filled with: HA/Collagen; HA/Collagen...... and histomorphometry between autograft and allograft groups. The implants in both the HA/Collagen and HA/Collagen-BMA groups were mostly surrounded by fibrous tissue. Thus, mechanical testing of these samples was impossible. The histomorphometry results showed significantly more new bone and bone ongrowth...

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  20. MR imaging in adults with Gaucher disease type I: evulation of marrow involvement and disease activity

    Energy Technology Data Exchange (ETDEWEB)

    Hermann, G. (Dept. of Radiology, Mount Sinai Medical Center, City Univ. of New York, NY (United States)); Shaprio, R.S. (Dept. of Radiology, Mount Sinai Medical Center, City Univ. of New York, NY (United States)); Abdelwahab, I.F. (Dept. of Radiology, Mount Sinai Medical Center, City Univ. of New York, NY (United States)); Grabowski, G. (Dept. of Pediatrics, Mount Sinai Medical Center, City Univ. of New York, NY (United States))

    1993-05-01

    An investigation was conducted to determine the usefulness of magnetic resonance imaging (MRI) in the evaluation of bone marrow involvement in patients with Gaucher disease type I. T1- and T2-weighted images were obtained of the lower extremities of 29 adult patients. Patients were classified into one of three groups based on marrow signal patterns on T1- and T2-weighted images as well as change in signal intensity from T1- to T2-weighted images. An increase in signal intensity from T1- to T2-weighted images was the criterion for an 'active process' within the bone marrow. Classification of the 29 patients produced the following results: Group A: Normal, 4 patients; group B: Marrow infiltration, 16 patients; group C: Marrow infiltration plus active marrow process, 9 patients. Correlation with clinical findings revealed that all nine patients with evidence of an active marrow process on MRI (group C) had acute bone pain. Conversely, only one of the remaining 20 patients (groups A and B) had bone pain. There was no correlation between disease activity and findings on conventional radiographs. We conclude the MRI provides an excellent noninvasive assessment of the extent and activity of marrow involvement in type I Gaucher disease. (orig.)

  1. Sequential expression of adhesion and costimulatory molecules in graft-versus-host disease target organs after murine bone marrow transplantation across minor histocompatibility antigen barriers.

    Science.gov (United States)

    Eyrich, Matthias; Burger, Gudrun; Marquardt, Katja; Budach, Wilfried; Schilbach, Karin; Niethammer, Dietrich; Schlegel, Paul G

    2005-05-01

    Graft-versus-host disease (GVHD) is a potentially fatal complication after allogeneic bone marrow transplantation. However, few data exist thus far on the molecular signals governing leukocyte trafficking during the disease. We therefore investigated the sequential pattern of distinct adhesion, costimulatory, and apoptosis-related molecules in GVHD organs (ileum, colon, skin, and liver) after transplantation across minor histocompatibility barriers (B10.D2 --> BALB/c, both H-2d). To distinguish changes induced by the conditioning regimen from effects achieved by allogeneic cell transfer, syngeneic transplant recipients (BALB/c --> BALB/c) and irradiated nontransplanted mice were added as controls. Irradiation upregulated the expression of vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-l, and B7-2 in ileum, as well as VCAM-1 and B7-2 in colon, on day 3 in all animals. Whereas in syngeneic mice these effects were reversed from day 9 on, allogeneic recipients showed further upregulation of VCAM-1, ICAM-1, B7-1, and B7-2 in these organs on day 22, when GVHD became clinically evident. Infiltration of CD4+ and CD8+ donor T cells was noted on day 9 in skin and liver and on day 22 in ileum and colon. Surprisingly, the expression of several other adhesion molecules, such as ICAM-2, platelet-endothelial cell adhesion molecule 1, E-selectin, and mucosal addressin cell adhesion molecule 1, did not change. Proapoptotic and antiapoptotic markers were balanced in GVHD organs with the exception of spleen, in which a preferential expression of the proapoptotic Bax could be noted. Our results indicate that irradiation-induced upregulation of VCAM-1, ICAM-1, and B7-2 provides early costimulatory signals to incoming donor T cells in the intestine, followed by a cascade of proinflammatory signals in other organs once the alloresponse is established.

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

    Science.gov (United States)

    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

  3. Cardiac differentiation and electrophysiology characteristics of bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    LIU Bo-wu; AI Shi-yi; L(U) An-lin; HOU Jing; HUANG Wei; LI Yao; HOU Zhao-lei; HOU Hong; DA Jing; YANG Na

    2012-01-01

    Objective To review the progress of cardiac differentiation and electrophysiological characteristics of bone marrow mesenchymal stem cells.Data sources The databases of PubMed,Springer Link,Science Direct and CNKI were retrieved for papers published from January 2000 to January 2012 with the key words of “bone marrow mesenchymal stem cells,cardiac or heart,electrophysiology or electrophysiological characteristics”.Study selection The articles concerned cardiac differentiation and electrophysiological characteristics of bone marrow mesenchymal stem cells were collected.After excluding papers that study purposes are not coincident with this review or contents duplicated,56 papers were internalized at last.Results For the treatment of myocardial infarction and myocardiac disease,the therapeutic effects of transplantation of bone marrow mesenchymal stem cells which have the ability to develop into functional myocardial cells by lots of methods have been proved by many researches.But the arrhythmogenic effect on ventricles affer transplantation of bone marrow mesenchymal stem cells derived myocardial cells is still controversial in animal models.Certainly,the low differentiation efficiency and heterogeneous development of electricial function could be the most important risk for proarrhythmia.Conclusion Many studies of cardiac differentiation of bone marrow mesenchymal stem cells have paid attention to improve the cardiac differentiation rate,and the electrophysiology characteristics of the differentiated cells should be concerned for the risk for proarrhythmia as well.

  4. Precursor T-cell acute lymphoblastic leukemia presenting with bone marrow necrosis: a case report

    Directory of Open Access Journals (Sweden)

    Khoshnaw Najmaddin SH

    2012-10-01

    Full Text Available Abstract Introduction Bone marrow necrosis is a clinicopathological condition diagnosed most often at postmortem examination, but it is also seen during the course of malignancy and is not always associated with a poor prognosis. The morphological features of bone marrow necrosis are disruption of the normal marrow architecture and necrosis of myeloid tissue and medullary stroma. Non-malignant conditions associated with bone marrow necrosis are sickle cell anemia, infections, drugs (sulfasalazine, interferon α, all-trans retinoic acid, granulocyte colony-stimulating factor and fludarabine, disseminated intravascular coagulation, antiphospholipid antibody syndrome and acute graft versus host diseases. The malignant causes are leukemia, lymphoma and metastatic carcinomas. Herein we report the case of a patient with precursor T-cell acute lymphoblastic leukemia and bone marrow necrosis at initial presentation. Case presentation A 10-year-old Kurdish boy was presented with generalized bone pain and fever of 1 month’s duration which was associated with sweating, easy fatigability, nose bleeding, breathlessness and severe weight loss. On examination, we observed pallor, tachypnea, tachycardia, low blood pressure, fever, petechial hemorrhage, ecchymoses, tortuous dilated veins over the chest and upper part of abdomen, multiple small cervical lymph node enlargements, mildly enlarged spleen, palpable liver and gross abdominal distention. Blood analysis revealed pancytopenia and elevated lactate dehydrogenase and erythrocyte sedimentation rate. Imaging results showed mediastinal widening on a planar chest X-ray and diffuse focal infiltration of the axial bone marrow on magnetic resonance imaging of the lumbosacral vertebrae. Bone marrow aspiration and biopsy examination showed extensive bone marrow necrosis. Immunophenotyping analysis of the bone marrow biopsy confirmed T-cell acute lymphoblastic leukemia, as CD3 and terminal deoxynucleotidyl

  5. Bone marrow hypoplasia in a cat treated with griseofulvin.

    Science.gov (United States)

    Rottman, J B; English, R V; Breitschwerdt, E B; Duncan, D E

    1991-02-01

    Three weeks after initiation of griseofulvin treatment for dermatophytosis (40 mg/kg of body weight, q 12 h), an 8-yr-old domestic shorthair cat developed depression, vomiting, and pyrexia. Abnormalities found during physical examination included bilateral mydriasis, visual impairment, grade-II/V systolic murmur and multiple areas of alopecia. The cat was pancytopenic; serum biochemical abnormalities included hyperbilirubinemia, hyperglycemia, hyponatremia, and hypokalemia, and urinalysis revealed proteinuria, glycosuria, and bilirubinuria. Examination of a bone marrow aspirate revealed profound hypoplasia of all precursors. Griseofulvin toxicosis was diagnosed on the basis of the temporal relationship of drug administration with onset of clinical, hematologic, and biochemical abnormalities and failure to identify an infective or neoplastic cause for the bone marrow hypoplasia. The condition was refractory to treatment and the cat was euthanatized. Pathologic changes in the bone marrow were consistent with severe hypoplasia of all bone marrow precursors.

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

    OpenAIRE

    Park, SS; Moisseiev, E; Bauer, G.; Anderson, JD; Grant, MB; Zam, A; Zawadzki, RJ; Werner., JS; Nolta, JA

    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 ret...

  7. Immune Cell Isolation from Mouse Femur Bone Marrow

    OpenAIRE

    Liu, Xiaoyu; Quan, Ning

    2015-01-01

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

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

    Science.gov (United States)

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

    Directory of Open Access Journals (Sweden)

    Liao Cui

    Full Text Available 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 m

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

    Science.gov (United States)

    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

  11. Early stage transplantation of bone marrow cells markedly ameliorates copper metabolism and restores liver function in a mouse model of Wilson disease

    Directory of Open Access Journals (Sweden)

    Wang Chuhuai

    2011-06-01

    Full Text Available Abstract Background Recent studies have demonstrated that normal bone marrow (BM cells transplantation can correct liver injury in a mouse model of Wilson disease (WD. However, it still remains unknown when BM cells transplantation should be administered. The aim of this study was to investigate the potential impact of normal BM cells transplantation at different stages of WD to correct liver injury in toxic milk (tx mice. Methods Recipient tx mice were sublethally irradiated (5 Gy prior to transplantation. The congenic wild-type (DL BM cells labeled with CM-DiI were transplanted via caudal vein injection into tx mice at the early (2 months of age or late stage (5 months of age of WD. The same volume of saline or tx BM cells were injected as controls. The DL donor cell population, copper concentration, serum ceruloplasmin oxidase activity and aspartate aminotransferase (AST levels in the various groups were evaluated at 1, 4, 8 and 12 weeks post-transplant, respectively. Results The DL BM cells population was observed from 1 to 12 weeks and peaked by the 4th week in the recipient liver after transplantation. DL BM cells transplantation during the early stage significantly corrected copper accumulation, AST across the observed time points and serum ceruloplasmin oxidase activity through 8 to 12 weeks in tx mice compared with those treated with saline or tx BM cells (all P P P > 0.05. Conclusions Early stage transplantation of normal BM cells is better than late stage transplantation in correcting liver function and copper metabolism in a mouse model of WD.

  12. Detection of minimal residual disease in patients with multiple myeloma using clonotype-specific PCR primers designed from DNA extracted from archival bone marrow slides.

    Science.gov (United States)

    Takamatsu, Hiroyuki; Ogawa, Yoshiyasu; Kobayashi, Noriko; Obata, Kazue; Narisawa, Tadashi; Nakayama, Kouji; Munemoto, Saori; Aoki, Go; Ohata, Kinya; Kumano, Yoshihisa; Ozaki, Jun; Murata, Ryoichi; Kondo, Yukio; Terasaki, Yasushi; Kurokawa, Toshiro; Miyamoto, Toshihiro; Shimizu, Naomi; Fukushima, Toshihiro; Yoshida, Akira; Ueda, Takanori; Yoshida, Takashi; Nakao, Shinji

    2013-10-01

    Polymerase chain reaction (PCR)-negative molecular complete remission (mCR) can be induced by stem cell transplantation in some patients with multiple myeloma (MM) and is associated with long-term progression-free survival (PFS). The detection of molecular minimal residual disease (MRD), however, requires fresh or frozen materials for designing clone-specific primers, which are not always readily available. In this study, we used DNA extracted from archival bone marrow (BM) slides for PCR to detect MRD in 50 patients with MM who received various induction therapies and autologous peripheral blood stem cell transplantation (ASCT). Clonotype-specific immunoglobulin (Ig) H PCR primers were prepared for 32 of 50 cases (64%) using BM slides, and for 9 of 14 cases (64%) using fresh BM cells. DNA in peripheral blood stem cell autografts of the 22 patients who achieved at least a partial response after ASCT was subjected to PCR to amplify clonotype-specific rearranged IgH gene sequences. The median PFS of the eight patients with MRD-positive autografts was 18 months, whereas that of 14 patients with MRD-negative autografts was not reached at a median follow-up of 27 months (p = 0.012). Post-ASCT PFS of the four patients who achieved mCR was 100% at a median follow-up of 47 months. These results indicate that archival BM slides can serve as a source of DNA for preparing clonotype-specific primers for MRD monitoring in patients with MM whose cryopreserved myeloma cells are not available for DNA preparation. Our results also suggest that patients with MM who received MRD-negative autografts and achieved mCR have a long PFS.

  13. Diffuse Hypermetabolism at Bone Marrow in F-18 FDG PET/CT: Correlation with Bone Marrow Biopsy and Complete Blood Cell Counts

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Yun Hee; Lim, Seok Tae; Jeong, Young Jin; Kim, Dong Wook; Jeong, Hwan Jeong; Sohn, Myung Hee [Chonbuk National University Medical School, Jeonju (Korea, Republic of)

    2009-02-15

    Increased FDG uptake in the bone marrow has been reported in patients taking erythropoietin or granulocyte-colony stimulating factor (G-CSF). The aim of this study is to investigate the correlation between F-18 FDG uptake in the bone marrow and bone marrow finding, hematological parameters. Twenty patients who had diffuse FDG uptake at the bone marrow and received hematological examinations, bone marrow biopsy within 10 days before or after PET/CT were enrolled in this study. Among them, 11 patients were excluded; 4 patients received G-CSF or erythropoietin before PET/CT. Seven patients showed definite pathology in a bone marrow biopsy. The parameters included the measurement of WBC, hemoglobin, platelet and cellularity of the bone marrow. Bone marrow FDG uptake was correlated with a low hemoglobin but not WBC, platelet. Histopathologic findings in marrow biopsies were various: normal finding (n=3), hyperplasia of granulocytic cells (n=2), eosinophilic hyperplasia (n=1), reactive lymphoid nodules (n=1), hypercelluar marrow (n=1), hypocelluar marrow (n=1). All patients except two, showed normal marrow celluarity. FDG uptake by bone marrow correlated with anemia but not WBC, platelet, bone marrow cellularity.

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

    Science.gov (United States)

    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.

  15. Bone marrow transplantation in mice as a tool for studying the role of hematopoietic cells in metabolic and cardiovascular diseases

    NARCIS (Netherlands)

    Aparicio-Vergara, Marcela; Shiri-Sverdlov, Ronit; de Haan, Gerald; Hofker, Marten H.

    2010-01-01

    Hematopoietic cells have been established as major players in cardiovascular disease, with an important role in the etiology of atherosclerotic plaque. In addition, hematopoietic cells, and in particular the cells of monocyte and macrophage lineages, have recently been unmasked as one of the main ca

  16. Quantification of the Mutant CALR Allelic Burden by Digital PCR: Application to Minimal Residual Disease Evaluation after Bone Marrow Transplantation.

    Science.gov (United States)

    Mansier, Olivier; Migeon, Marina; Saint-Lézer, Arnaud; James, Chloé; Verger, Emmanuelle; Robin, Marie; Socié, Gérard; Bidet, Audrey; Mahon, François-Xavier; Cassinat, Bruno; Lippert, Eric

    2016-01-01

    With the recent discovery of CALR mutations, >80% of patients with myeloproliferative neoplasms carry a phenotype-driving mutation. For JAK2 V617F, the most frequent mutation in myeloproliferative neoplasms, accurate determination of mutational loads is of interest at diagnosis, for phenotypic and prognostic purposes, and during follow-up for minimal residual disease assessment. We developed a digital PCR technique that allowed the accurate determination of CALR allelic burdens for the main mutations (types 1 and 2). Compared with the commonly used fluorescent PCR product analysis, digital PCR is more precise, reproducible, and accurate. Furthermore, this method reached a very high sensitivity. We detected at least 0.025% CALR mutants. It can thus be used for patient characterization at diagnosis and for minimal residual disease monitoring. When applied to patients with primary myelofibrosis who underwent hematopoietic stem cell transplant, the digital PCR detected low levels of minimal residual disease. After negativation of the mutational load in all patients, the disease reappeared at a low level in one patient, preceding hematologic relapse. In conclusion, digital PCR adapted to type 1 and 2 CALR mutations is an inexpensive, highly precise, and sensitive technique suitable for evaluation of myeloproliferative neoplasm patients during follow-up.

  17. A critical damping approach for assessing the role of marrow fat on the mechanical strength of trabecular bone.

    Science.gov (United States)

    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.

  18. Bone Marrow Gene Therapy for HIV/AIDS.

    Science.gov (United States)

    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.

  19. Fusion of bone marrow-derived cells with cancer cells:metastasis as a secondary disease in cancer

    Institute of Scientific and Technical Information of China (English)

    John M. Pawelek

    2014-01-01

    This perspective article highlights the leukocyte-cancer cellhybrid theory as a mechanism for cancer metastasis. Beginning from the first proposal of the theory more than a century ago and continuing today with the first proof for this theory in a human cancer, the hybrid theory offers a unifying explanation for metastasis. In this scenario, leukocyte fusion with a cancer cellis a secondary disease superimposed upon the early tumor, giving birth to a new, malignant cellwith a leukocyte-cancer cellhybrid epigenome.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  2. Effects of Platelet Factor 4 on Expression of Bone Marrow Heparan Sulfate in Syngenic Bone Marrow Transplantation Mice

    Institute of Scientific and Technical Information of China (English)

    孟凡凯; 孙汉英; 刘文励; 袁慧玲; 徐惠珍; 孙岚; 周银莉; 任天华

    2002-01-01

    Summary: To explore the effects of platelet factor 4(PF4) on hematopoietic reconstitution and its mechanism in syngenic bone marrow transplantation (BMT). The syngenic BMT mice models were established. 20 and 26 h before irradiation, the mice were injected 20 μg/kg PF4 or PBS twice into abdominal cavity, then the donor bone marrow nuclear cells (BMNC) were transplanted. On the 7th day, spleen clone forming units (CFU-S) were counted. On the 7th, 14th and 21st day after BMT, the BMNC and megakaryoryocytes in bone marrow tissue were counted and the percentage of hematopoietic tissue and expression level of heparan sulfate in bone marrow tissue were assessed. In PF4-treated groups, the CFU-S counts on the 7th day were higher than those in BMT groups after BMT. The BMNC and megakaryoryocyte counts and the percentage of hematopoietic tissue and heparan sulfate expression level were higher than those in BMT group on the 7th, 14th and 21st day after BMT (P<0. 01 or P<0. 05). PF4 could accelerate hematopoietic reconstitution of syngenic bone marrow transplantation. The promotion of the heparan sulfate expression in bone marrow may be one of mechanisms of PF4.

  3. Bone and bone marrow function of reconstructed chest wall after surgical correction of pectus excavatum

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Yoh; Magara, Tatsuo; Kobayashi, Hiroaki; Ichihashi, Takumi; Hikishima, Hiroshi (Kanazawa Univ. (Japan). School of Medicine)

    1984-03-01

    Bone and bone marrow functions of the reconstructed chest wall after surgical correction of the funnel chest deformities were evaluated by scanning method. In our series, three kinds of operative procedures were employed; strut method for adult cases, sternal turnover method with and without muscle pedicle for infant cases. Bone function was scanned by sup(99m)Tc-methylene-diphosphonate and bone marrow function was evaluated by sup(99m)Tc-sulfur-colloid. For the cases undergone each surgical procedure, bone and bone marrow scan were done at short term after surgery (within 30 days), at intermediate stage (one month to 12 months), and at long term stage (beyond one year). The results were as follows: By the evaluation at the long term stage of the cases undergoing strut method, bone as well as bone marrow scan visualized normal view of the reconstructed sternum. Regarding the cases undergone sternal turnover method without muscle pedicle, or free graft implantation of the plastron, the bone scan at the long term follow-up stage showed abnormal finding, i.e. hypo-, or defect-visualization of the inverted sternum, in 11.5% of the cases. Furthermore, bone marrow scan showed abnormality in 33.3% of the cases. On the other hand, the cases undergone sternal turnover method with muscle pedicle, in which blood supply to the plastron were preserved by the connection from superior epigastric artery to internal mammary artery, showed no abnormality as far as at the long term follow-up study neither in bone scan nor bone marrow scan. However, in the evaluation at short term after surgery, 50% of the cases undergoing bone scan showed abnormality. In addition, in this stage 85.7% of the bone marrow scan showed abnormal finding. These abnormality, however, normalized within 6 months for bone scan and 12 months for bone marrow scan, in contrast to the results of the cases undergone sternal turnover without pedicle.

  4. Intranasal delivery of bone marrow-derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimer's and Parkinson's disease.

    Science.gov (United States)

    Danielyan, Lusine; Beer-Hammer, Sandra; Stolzing, Alexandra; Schäfer, Richard; Siegel, Georg; Fabian, Claire; Kahle, Philipp; Biedermann, Tilo; Lourhmati, Ali; Buadze, Marine; Novakovic, Ana; Proksch, Barbara; Gleiter, Christoph H; Frey, William H; Schwab, Matthias

    2014-01-01

    In view of the rapid preclinical development of cell-based therapies for neurodegenerative disorders, traumatic brain injury, and tumors, the safe and efficient delivery and targeting of therapeutic cells to the central nervous system is critical for maintaining therapeutic efficacy and safety in the respective disease models. Our previous data demonstrated therapeutically efficacious and targeted delivery of mesenchymal stem cells (MSCs) to the brain in the rat 6-hydroxydopamine model of Parkinson's disease (PD). The present study examined delivery of bone marrow-derived MSCs, macrophages, and microglia to the brain in a transgenic model of PD [(Thy1)-h[A30P] αS] and an APP/PS1 model of Alzheimer's disease (AD) via intranasal application (INA). INA of microglia in naive BL/6 mice led to targeted and effective delivery of cells to the brain. Quantitative PCR analysis of eGFP DNA showed that the brain contained the highest amount of eGFP-microglia (up to 2.1 × 10(4)) after INA of 1 × 10(6) cells, while the total amount of cells detected in peripheral organs did not exceed 3.4 × 10(3). Seven days after INA, MSCs expressing eGFP were detected in the olfactory bulb (OB), cortex, amygdala, striatum, hippocampus, cerebellum, and brainstem of (Thy1)-h[A30P] αS transgenic mice, showing predominant distribution within the OB and brainstem. INA of eGFP-expressing macrophages in 13-month-old APP/PS1 mice led to delivery of cells to the OB, hippocampus, cortex, and cerebellum. Both MSCs and macrophages contained Iba-1-positive population of small microglia-like cells and Iba-1-negative large rounded cells showing either intracellular amyloid β (macrophages in APP/PS1 model) or α-synuclein [MSCs in (Thy1)-h[A30P] αS model] immunoreactivity. Here, we show, for the first time, intranasal delivery of cells to the brain of transgenic PD and AD mouse models. Additional work is needed to determine the optimal dosage (single treatment regimen or repeated

  5. Pericyte coverage of abnormal blood vessels in myelofibrotic bone marrows

    DEFF Research Database (Denmark)

    Zetterberg, Eva; Vannucchi, Alessandro M; Migliaccio, Anna Rita

    2007-01-01

    BACKGROUND AND OBJECTIVES: Myelofibrotic bone marrow displays abnormal angiogenesis but the pathogenic mechanisms of this are poorly understood. Since pericyte abnormalities are described on solid tumor vessels we studied whether vessel morphology and pericyte coverage in bone marrow samples from...... patients with myelofibrosis differed from that in samples from controls. DESIGN AND METHODS: We assessed the microvascular density (MVD), vessel morphology and pericyte coverage in bone marrows from 19 myelofibrosis patients and nine controls. We also studied the same parameters in two mouse models...... of myelofibrosis, with genetic alterations affecting megakaryocyte differentiation (i.e. one model with low GATA-1 expression and the other with over-expression of thrombopoietin). RESULTS: In myelofibrotic marrows, MVD was 3.8-fold greater than in controls (pvessels displayed 5.9-fold larger mean...

  6. Proteinase activated receptor 1 mediated fibrosis in a mouse model of liver injury: a role for bone marrow derived macrophages.

    Directory of Open Access Journals (Sweden)

    Yiannis N Kallis

    Full Text Available Liver fibrosis results from the co-ordinated actions of myofibroblasts and macrophages, a proportion of which are of bone marrow origin. The functional effect of such bone marrow-derived cells on liver fibrosis is unclear. We examine whether changing bone marrow genotype can down-regulate the liver's fibrotic response to injury and investigate mechanisms involved. Proteinase activated receptor 1 (PAR1 is up-regulated in fibrotic liver disease in humans, and deficiency of PAR1 is associated with reduced liver fibrosis in rodent models. In this study, recipient mice received bone marrow transplantation from PAR1-deficient or wild-type donors prior to carbon tetrachloride-induced liver fibrosis. Bone marrow transplantation alone from PAR1-deficient mice was able to confer significant reductions in hepatic collagen content and activated myofibroblast expansion on wild-type recipients. This effect was associated with a decrease in hepatic scar-associated macrophages and a reduction in macrophage recruitment from the bone marrow. In vitro, PAR1 signalling on bone marrow-derived macrophages directly induced their chemotaxis but did not stimulate proliferation. These data suggest that the bone marrow can modulate the fibrotic response of the liver to recurrent injury. PAR1 signalling can contribute to this response by mechanisms that include the regulation of macrophage recruitment.

  7. High frequency of parvovirus B19 DNA in bone marrow samples from rheumatic patients

    DEFF Research Database (Denmark)

    Lundqvist, Anders; Isa, Adiba; Tolfvenstam, Thomas;

    2005-01-01

    BACKGROUND: Human parvovirus B19 (B19) polymerase chain reaction (PCR) is now a routine analysis and serves as a diagnostic marker as well as a complement or alternative to B19 serology. The clinical significance of a positive B19 DNA finding is however dependent on the type of tissue or body fluid...... analysed and of the immune status of the patient. OBJECTIVES: To analyse the clinical significance of B19 DNA positivity in bone marrow samples from rheumatic patients. STUDY DESIGN: Parvovirus B19 DNA was analysed in paired bone marrow and serum samples by nested PCR technique. Serum was also analysed...... negative group. A high frequency of parvovirus B19 DNA was thus detected in bone marrow samples in rheumatic patients. The clinical data does not support a direct association between B19 PCR positivity and rheumatic disease manifestation. Therefore, the clinical significance of B19 DNA positivity in bone...

  8. Histopathological perspective on bone marrow oedema, reactive bone change and haemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Thiryayi, W.A.; Thiryayi, S.A. [Department of Histopathology, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL (United Kingdom); Freemont, A.J. [Division of Regenerative Medicine, University of Manchester, Oxford Road, Manchester M13 9PT (United Kingdom)], E-mail: tony.freemont@manchester.ac.uk

    2008-07-15

    This article presents a systematic review of the current biomedical literature surrounding the aetiopathogenesis and histopathological features of bone marrow oedema, reactive bone change and haemorrhage. Bone marrow oedema is generally demonstrated as a non-specific finding on magnetic resonance imaging in association with infections, tumours and avascular necrosis. When it occurs in isolation as a primary event not triggered by any obvious bony pathology in the clinical setting of debilitating joint pain, it constitutes the 'bone marrow oedema syndrome'. Although the latter diagnosis is based on magnetic resonance (MR) imaging, showing the lesion as areas of signal hyperintensity within the marrow, recent radiology-histology correlational studies have shown variably interstitial marrow oedema, necrosis, fibrosis and trabecular bone abnormalities. In light of these facts, the use of the term bone marrow oedema syndrome in a radiological context might be considered questionable, but histopathological techniques are not sensitive in detecting increased extracellular fluid. Reactive bone changes may be focal or diffuse and usually amount to increased bone formation. Bone marrow haemorrhage, due to trauma, results in bone bruising, a condition in which the size of the bruise and associated osteochondral injury determines the outcome, although the natural history of these lesions is still being researched.

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

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    Wang FJ

    2015-12-01

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

  10. Correlation of plasma FL expression with bone marrow irradiation dose.

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    Mary Sproull

    Full Text Available PURPOSE: Ablative bone marrow irradiation is an integral part of hematopoietic stem cell transplantation. These treatment regimens are based on classically held models of radiation dose and the bone marrow response. Flt-3 ligand (FL has been suggested as a marker of hematopoiesis and bone marrow status but the kinetics of its response to bone marrow irradiation has yet to be fully characterized. In the current study, we examine plasma FL response to total body and partial body irradiation in mice and its relationship with irradiation dose, time of collection and pattern of bone marrow exposure. MATERIALS/METHODS: C57BL6 mice received a single whole body or partial body irradiation dose of 1-8 Gy. Plasma was collected by mandibular or cardiac puncture at 24, 48 and 72 hr post-irradiation as well as 1-3 weeks post-irradiation. FL levels were determined via ELISA assay and used to generate two models: a linear regression model and a gated values model correlating plasma FL levels with radiation dose. RESULTS: At all doses between 1-8 Gy, plasma FL levels were greater than control and the level of FL increased proportionally to the total body irradiation dose. Differences in FL levels were statistically significant at each dose and at all time points. Partial body irradiation of the trunk areas, encompassing the bulk of the hematopoietically active bone marrow, resulted in significantly increased FL levels over control but irradiation of only the head or extremities did not. FL levels were used to generate a dose prediction model for total body irradiation. In a blinded study, the model differentiated mice into dose received cohorts of 1, 4 or 8 Gy based on plasma FL levels at 24 or 72 hrs post-irradiation. CONCLUSION: Our findings indicate that plasma FL levels might be used as a marker of hematopoietically active bone marrow and radiation exposure in mice.

  11. Opposite effects of bone marrow-derived cells transplantation in MPTP-rat model of Parkinson's disease: a comparison study of mononuclear and mesenchymal stem cells.

    Science.gov (United States)

    Capitelli, Caroline Santos; Lopes, Carolina Salomão; Alves, Angélica Cristina; Barbiero, Janaína; Oliveira, Lucas Felipe; da Silva, Valdo José Dias; Vital, Maria Aparecida Barbato Frazão

    2014-01-01

    The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model is a useful tool to study Parkinson's disease (PD) and was used in the present study to investigate the potential beneficial as well as deleterious effects of systemic bone-marrow mononuclear cell (BMMC) or mesenchymal stem cell (BM-MSC) transplantation. MPTP administration resulted in a breakdown of the blood-brain barrier and motor impairment in the open field test 24 h after surgery. Three and 7 days after receiving the lesion, the injured animals showed remaining motor impairment compared to the sham groups along with a significant loss of tyrosine hydroxylase-immunoreactive (TH-ir) cells in the substantia nigra pars compacta (SNpc). The MPTP-lesioned rats treated with BMMCs immediately after lesioning exhibited motor impairment similar to the MPTP-saline group, though they presented a significantly higher loss of TH-ir cells in the SNpc compared to the MPTP-saline group. This increased loss of TH-ir cells in the SNpc was not observed when BMMC transplantation was performed 24 h after MPTP administration. In contrast, in the MPTP animals treated early with systemic BM-MSCs, no loss of TH-ir cells was observed. BMMCs and BM-MSCs previously labeled with CM-DiI cell tracker were found in brain sections of all transplanted animals. In addition, cells expressing CD45, an inflammatory white blood cell marker, were found in all brain sections analyzed and were more abundant in the MPTP-BMMC animals. In these animals, Iba1+ microglial cells showed also marked morphological changes indicating increased microglial activation. These results show that systemic BMMC transplantation did not ameliorate or prevent the lesion induced by MPTP. Instead, BMMC transplantation in MPTP-lesioned rats accelerated dopaminergic neuronal damage and induced motor impairment and immobility behavior. These findings suggest that caution should be taken when considering cell therapy using BMMCs to treat PD. However, systemic

  12. In vivo lipid diffusion coefficient measurements in rat bone marrow.

    Science.gov (United States)

    Ababneh, Zaid Q; Beloeil, Helene; Berde, Charles B; Ababneh, Anas M; Maier, Stephan E; Mulkern, Robert V

    2009-07-01

    The diffusion coefficient of lipids, D(l), within bone marrow, fat deposits and metabolically active intracellular lipids in vivo will depend on several factors including the precise chemical composition of the lipid distribution (chain lengths, degree of unsaturation, etc.) as well as the temperature. As such, D(l) may ultimately prove of value in assessing abnormal fatty acid distributions linked to diseases such as cystic fibrosis, diabetes and coronary heart disease. A sensitive temperature dependence of D(l) may also prove of value for MR-guided thermal therapies for bone tumors or disease within other fatty tissues like the breast. Measuring diffusion coefficients of high molecular weight lipids in vivo is, however, technically difficult for a number of reasons. For instance, due to the much lower diffusion coefficients compared to water, much higher b factors than those used for central nervous system applications are needed. In addition, the pulse sequence design must incorporate, as much as possible, immunity to motion, susceptibility and chemical shift effects present whenever body imaging is performed. In this work, high b-factor line scan diffusion imaging sequences were designed, implemented and tested for D(l) measurement using a 4.7-T horizontal bore animal scanner. The gradient set available allowed for b factors as high as 0.03 micros/nm(2) (30,000 s/mm(2)) at echo times as short as 42 ms. The methods were used to measure lipid diffusion coefficients within the marrow of rat paws in vivo, yielding lipid diffusion coefficients approximately two orders of magnitude smaller than typical tissue water diffusion coefficients. Phantom experiments that demonstrate the sensitivity of lipid diffusion coefficients to chain length and temperature were also performed.

  13. Bone marrow granulomas in infiltrating lobular breast cancer.

    OpenAIRE

    Kettle, P.; Allen, D C

    1997-01-01

    A 50 year old woman with a history of infiltrating lobular breast carcinoma presented with back pain. Bone scan and magnetic resonance imaging were not conclusive. A bone marrow aspirate appeared normal. A routine trephine biopsy specimen showed granulomas but no obvious infiltration by carcinoma. Immunohistochemical staining with epithelial markers demonstrated carcinoma cells in the trephine specimen. This case illustrates the difficulty of detecting infiltrating lobular carcinoma in bone m...

  14. A Survey of Bacterial Infections in Bone Marrow Transplant Recipients

    Directory of Open Access Journals (Sweden)

    MH Shirazi

    2007-09-01

    Full Text Available "nBackground: Bone marrow transplant (BMT recipients are prone to bacterial, viral and fungal infections. Bacterial infec­tion is considered as one of the common and serious complications in bone marrow transplant recipients. The aim of this study was to determine the rate of bacterial infections in bone marrow transplant recipients."nMethods: Fifty-two blood and 25 catheter samples were obtained from 23 patients who were hospitalized in bone marrow trans­plantation unit in Shariati Hospital in Tehran. Bacterial strains were isolated and identified by the standard conven­tional bacteriological methods. Antimicrobial susceptibility was performed according to the guidelines from NCCLS using 18 different antibiotics."nResults:  The strains of Staphylococci, Streptococcus viridans, Pseudomonas aeruginosa and Escherichia coli were isolated from 8(66.7%, 1(8.3%, 2 (16.7% and the 1(8.3% cases, respectively."nConclusion: Current study indicated that the bacterial infections particularly those caused by the Gram-positive cocci were still as important problem in bone marrow transplant.

  15. Transplantable NK cell progenitors in murine bone marrow.

    Science.gov (United States)

    Moore, T; Bennett, M; Kumar, V

    1995-02-15

    Differentiation of NK cells from pluripotent hematopoietic stem cells is a poorly understood process. Although it is known that NK cells are bone marrow derived and dependent upon an intact bone marrow microenvironment for complete maturation, it is not known if they arise from an intermediate lymphoid stem cell or from progenitors exclusively committed to the NK lineage. To determine whether phenotypically distinct committed NK progenitor cells exist in murine bone marrow, we sorted cells capable of repopulating recipient mice with mature NK cells upon i.v. transfer. We identified a rare population of bone marrow cells with the phenotype Ly6+ Lin- c-kit+ CD43high Fall-3high TSA-1- AA4.1low Rh123high that is highly enriched for the ability to generate NK cells after transplantation. Although these cells are relatively depleted of Rh123low pluripotent stem cells, they are highly enriched for both lymphoid and myeloid repopulating ability. Thus, we have found no evidence to support the existence of a phenotypically distinct transplantable progenitor population in mouse bone marrow that is either exclusively committed to the NK cell lineage or exhibits the functional characteristics of a common lymphoid stem cell.

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

    Science.gov (United States)

    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.

  17. Effect of mobilization of bone marrow stem cells by granulocyte colony stimulating factor on clinical symptoms, left ventricular perfusion and function in patients with severe chronic ischemic heart disease

    DEFF Research Database (Denmark)

    Wang, Yongzhong; Tägil, Kristina; Ripa, Rasmus S.

    2005-01-01

    OBJECTIVES: A phase I safety and efficacy study with granulocyte colony stimulating factor (G-CSF) mobilization of bone marrow stem cells to induce vasculogenesis in patients with severe ischemic heart disease (IHD) was conducted. DESIGN, PATIENTS AND RESULTS: 29 patients with IHD participated...... in 'mobilizers'. At the follow-up, G-CSF treated had improved in CCS classification, NTG consumption and angina attacks, but the controls only in CCS classification. No difference was seen between the two groups. The decline in NTG consumption tended to be significant in 'mobilizers' compared to controls...

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

    Science.gov (United States)

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

    1999-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Yi-Bin Chen

    2016-01-01

    Full Text Available 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.

  20. Bone marrow metastasis in nonhematologic malignancies: Data from a cancer hospital

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    Kriti Chauhan

    2016-01-01

    Full Text Available Background: Bone marrow metastasis by a nonhematologic malignancy signifies advanced stage of disease and confers a poor prognosis. The aim of this study was to analyze clinical presentation, hematological profile, biochemical profile, radiological presentation, and patterns of bone marrow involvement in patients with metastatic nonhematologic malignancies retrospectively. Materials and Methods: Ninety bone marrow procedures were done in cases of nonhematologic malignancies for suspected involvement or as a part of staging procedure. Results: Sixteen out of 90 patients showed metastasis by nonhematologic malignancies. The most common malignancy to metastasize was malignant small round cell tumor (Ewing's sarcoma and rhabdomyosarcoma followed by carcinoma breast and prostate. The most common clinical presentation was backache, fever anorexia, and abdominal pain. The biochemical findings included raised serum calcium and lactate dehydrogenase. 62.5% had anemia and 37.5% had thrombocytopenia. Leukocytosis was seen in 37.5% of patients. Leukoerythroblastic picture was seen in 43.75% cases. Of the eleven cases where both bone marrow aspirate and biopsies were done, 10 cases showed malignant cells in both. Immunohistochemistry was conclusive in four cases. The combined procedure of aspiration and biopsy gives a higher yield and are essential in patients with suspected bone marrow metastasis in nonhematologic malignancies.

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

    Science.gov (United States)

    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.

  2. [Value of hemophagocytosis in the morphological examination of the bone marrow (author's transl)].

    Science.gov (United States)

    Brugues, R M; Vives-Corrons, J L; Rozman, C; Jou, J M; Aguilar, J L; Cardellach, F; Urbano, A; Feliu, E

    1979-12-15

    The hemophagocytosis or the process of ingestion of blood cells by phagocytes and macrophages of the mononuclear phagocytic system (MFS), is a phenomenon that rarely could be observed in the morphological examination of the bone marrow aspirate. Occasionally it is present in certain pathologic conditions such as, malignant histiocitosis, autimmune hemolytic anemia, or some chronic inflammatory diseases. The capacity of ingestion is not an exlusive property of the phagocytes and macrophages of the MFS, so that different neoplastic cells can show it too. This study analyzes the presence of hemophagocytosis by neoplastic cells in a total of 552 bone marrow aspirates corresponding to a series of 130 patients with acute leukemia and 422 patients with diverse solid tumors. In the group of patients with acute leukemia, hemophagocytosis by blastic cells was observed in five cases with acute monocytic leukemia. In the other group with solid tumors, hemophagocytosis was present in three patients with oat-cell lung carcinomas and diffuse bone marrow metastases. The interest of the evaluation of hemophagocytosis by neoplastic cells in the morphological examination of the bone marrow is stressed, as well as it possible value in the cytological diagnosis of acute monocytic leukemia. However, in these circumstances a sdiffuse metastases by solid tumors should be always discarded, since their cytomorphological characteristics are in most cases superimposed to those of the leukemic bone marrow infiltrate.

  3. Analysis of {sup 18}F-FDG PET diffuse bone marrow uptake and splenic uptake in staging of Hodgkin's lymphoma: a reflection of disease infiltration or just inflammation?

    Energy Technology Data Exchange (ETDEWEB)

    Salaun, Pierre Y. [University Hospital of Brest, Nuclear Medicine Department, Brest (France); Rene Gauducheau Cancer Center, Nuclear Medicine Department, Nantes (France); Gastinne, Thomas [University Hospital of Nantes, Department of Haematology, Nantes (France); Bodet-Milin, Caroline [University Hospital of Nantes, Nuclear Medicine Department, Nantes (France); Campion, Loic [Rene Gauducheau Cancer Center, Biostatistics Unit, Nantes (France); INSERM UMR 892, CRCNA, Nantes (France); Cambefort, Pierre [University Hospital of Brest, Nuclear Medicine Department, Brest (France); Moreau, Anne [University Hospital of Nantes, Department of Histopathology, Nantes (France); Le Gouill, Steven; Moreau, Philippe [University Hospital of Nantes, Department of Haematology, Nantes (France); INSERM UMR 892, CRCNA, Nantes (France); Berthou, Christian [University Hospital of Brest, Department of Haematology, Brest (France); Kraeber-Bodere, Francoise [Rene Gauducheau Cancer Center, Nuclear Medicine Department, Nantes (France); University Hospital of Nantes, Nuclear Medicine Department, Nantes (France); INSERM UMR 892, CRCNA, Nantes (France)

    2009-11-15

    {sup 18}F-FDG PET has been successfully evaluated in the management of Hodgkin's lymphoma (HL) and the most recent international guidelines recommended {sup 18}F-FDG PET for initial staging and final therapeutic assessment. However, {sup 18}F-FDG PET diffuse bone marrow uptake (BMU) and splenic uptake (SU) are frequently observed at the initial imaging and remain difficult to analyse. The aim of this retrospective study was to evaluate the significance of {sup 18}F-FDG diffuse BMU and SU in initial staging of HL. A total of 106 patients (median age: 31 years, range: 9-81, 51 female, 55 male) underwent {sup 18}F-FDG PET/CT for initial staging of HL. BMU level was assessed visually according to liver uptake (1 = below liver uptake, 2 = corresponding to liver uptake, 3 = above liver uptake) and semi-quantitatively using the maximum standardized uptake value (SUV{sub max}) measured in the sacral area. SU was assessed visually according to liver uptake (1 = below liver uptake, 2 = corresponding to liver uptake, 3 = above liver uptake). These data were compared with the patient's characteristics including sex, age, Ann Arbor staging, bulky disease (tumour burden > 10 cm), presence of B symptoms, bone foci on PET (n = 106), bone marrow involvement (BMI) on biopsy (n = 75), leukocyte count (n = 74), lactic dehydrogenase (LDH) (n = 87), C-reactive protein (CRP) (n = 83) and fibrinogen (n = 60). Univariate and multivariate analyses were performed. Multivariate analysis found an independent correlation between BMU visual grading and CRP level (p = 0.007). For semi-quantitative BMU evaluation, multivariate analysis found an independent correlation between sacral SUVs and CRP level (p = 0.032) and Ann Arbor stage (p = 0.005). No BMI was found in patients who presented with SUV{sub max} below 3.4. For splenic evaluation, multivariate analysis found an independent correlation between SU and splenic foci (p = 0.034). No statistical link was found between SU and

  4. Bone marrow cells differentiation into organ cells using stem cell therapy.

    Science.gov (United States)

    Yang, Y-J; Li, X-L; Xue, Y; Zhang, C-X; Wang, Y; Hu, X; Dai, Q

    2016-07-01

    Bone marrow cells (BMC) are progenitors of bone, cartilage, skeletal tissue, the hematopoiesis-supporting stroma and adipocyte cells. BMCs have the potential to differentiate into neural cells, cardiac myocytes, liver hepatocytes, chondrocytes, renal, corneal, blood, and myogenic cells. The bone marrow cell cultures from stromal and mesenchymal cells are called multipotent adult progenitor cells (MAPCs). MAPCs can differentiate into mesenchymal cells, visceral mesoderm, neuroectoderm and endoderm in vitro. It has been shown that the stem cells derived from bone marrow cells (BMCs) can regenerate cardiac myocytes after myocardial infarction (MI). Adult bone marrow mesenchymal stem cells have the ability to regenerate neural cells. Neural stem/progenitor cells (NS/PC) are ideal for treating central nervous system (CNS) diseases, such as Alzheimer's, Parkinson's and Huntington disease. However, there are important ethical issues about the therapeutic use of stem cells. Neurons, cardiac myocytes, hepatocytes, renal cells, blood cells, chondrocytes and adipocytes regeneration from BMCs are very important in disease control. It is known that limbal epithelial stem cells in the cornea can repair the eye sight and remove symptoms of blindness. Stem cell therapy (SCT) is progressing well in animal models, but the use of SCT in human remains to be explored further.

  5. Qualitative Aspects of Bone Marrow Adiposity in Osteoporosis

    Directory of Open Access Journals (Sweden)

    Clifford J Rosen

    2016-10-01

    Full Text Available 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.

  6. Treatment of Bone Marrow Failure Syndrome with Integrated Traditional and Western Medicine

    Institute of Scientific and Technical Information of China (English)

    MA Rou

    2007-01-01

    @@ Aplastic anemia (AA) and myelodysplastic syndrome (MDS) are both included in the bone marrow failure syndromes (BMFS). AA is a group of diseases characterized by hematopoietic stem/progenitor cell damage,peripheral blood cytopenia, and clinical manifestations including anemia, bleeding and infection, which eventually lead to bone marrow failure.The incidence rate of AA in China is 7.4/106, higher than that in Western countries, among which the morbidity of acute AA and chronic AA (CAA) is 1.4/106 and 6.0/106,respectively.

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

    Science.gov (United States)

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

    2016-01-01

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

  8. Myeloma bone disease: Pathophysiology and management

    Science.gov (United States)

    Silbermann, Rebecca; Roodman, G. David

    2013-01-01

    Multiple myeloma bone disease is marked by severe dysfunction of both bone formation and resorption and serves as a model for understanding the regulation of osteoblasts (OBL) and osteoclasts (OCL) in cancer. Myeloma bone lesions are purely osteolytic and are associated with severe and debilitating bone pain, pathologic fractures, hypercalcemia, and spinal cord compression, as well as increased mortality. Interactions within the bone marrow microenvironment in myeloma are responsible for the abnormal bone remodeling in myeloma bone disease. Myeloma cells drive bone destruction that increases tumor growth, directly stimulates the OCL formation, and induces cells in the marrow microenvironment to produce factors that drive OCL formation and suppress OBL formation. Factors produced by marrow stromal cells and OCL promote tumor growth through direct action on myeloma cells and by increasing angiogenesis. Current therapies targeting MMBD focus on preventing osteoclastic bone destruction; however regulators of OBL inhibition in MMBD have also been identified, and targeted agents with a potential anabolic effect in MMBD are under investigation. This review will discuss the mechanisms responsible for MMBD and therapeutic approaches currently in use and in development for the management of MMBD. PMID:26909272

  9. A study of bone marrow failure syndrome in children

    Directory of Open Access Journals (Sweden)

    Gupta V

    2008-01-01

    Full Text Available Background: Bone marrow failure syndrome (BMFS, or aplastic anemia, includes peripheral blood single cytopenias, as well as pancytopenia due to inability of the marrow to effectively produce blood cells. Aim: To study the clinico-hematological profile and etiological factors of bone marrow failure syndrome in children. Setting and Design: This prospective study was carried out in the Department of Pediatrics of a university teaching hospital over 36 months. Materials and Methods: Children with pancytopenia (Hb < 10 g/dl, absolute neutrophil count < 1.5 x 10 9 /L, platelet count < 100 x 10 9 /L and bone marrow cellularity < 25% were included in the study. History of exposure to drugs, socioeconomic status, ethnicity and occupation of father were noted. Bone marrow aspiration; trephine biopsy; Ham test; viral studies for hepatitis A, B and C; and cytogenetic investigations were carried out. Statistical Analysis: Relative risk was estimated by odds ratio (OR with 95% confidence interval (CI in matched cases and controls. Results: Of the 53 children studied, 6 (11.3% were diagnosed as Fanconi anemia. Two cases had features of myelodysplastic syndrome. Forty-five children were labeled as acquired aplastic anemia, of whom one had evidence of hepatitis B infection and two patients (5.8% had paroxysmal nocturnal hemoglobinuria. Aplastic anemia was more common in children from family with lower socioeconomic status; in Muslims; and where the father′s occupation was weaving, dyeing and painting. However, the number was small to make statistically significant conclusions. No correlation could be established with exposure to drugs. Conclusion: Fanconi anemia was responsible for approximately one-tenth of the cases of bone marrow failure syndrome. Majority of the patients had acquired aplastic anemia. Hepatitis B infection was an uncommon cause of acquired aplastic anemia.

  10. Are bone marrow regenerative cells ideal seed cells for the treatment of cerebral ischemia?★

    OpenAIRE

    Li, Yi; Hua, Xuming; Hua, Fang; Mao, Wenwei; Wan, Liang; Li, Shiting

    2013-01-01

    Bone marrow cells for the treatment of ischemic brain injury may depend on the secretion of a large number of neurotrophic factors. Bone marrow regenerative cells are capable of increasing the secretion of neurotrophic factors. In this study, after tail vein injection of 5-fluorouracil for 7 days, bone marrow cells and bone marrow regenerative cells were isolated from the tibias and femurs of rats, and then administered intravenously via the tail vein after focal cerebral ischemia. Immunohist...

  11. Analysis of 110 Cases of Hematological Diseases in Children With Bone Marrow Cytology%110例儿童血液病的骨髓细胞学调查分析

    Institute of Scientific and Technical Information of China (English)

    曹玉琳

    2016-01-01

    目的:调查分析110例儿童血液病的骨髓细胞学,总结并分析儿童血液病的种类及临床表现。方法选取我院2013年4月~2015年7月收治的110例液病患儿,对患儿骨髓细胞学调查结果实行分析。结果所有患儿血液病类型中,血小板、巨核细胞疾病占有比例较高,其次为红细胞系统和白细胞系统疾病。结论儿童血液病多在男性儿童中发病,且多发生于血小板和红细胞、白细胞系统,临床主要表现为淋巴结大、发热、出血等。%Objective To investigate and analyze the bone marrow cytology of 110 children with hematological diseases, to summarize and analyze the types and clinical manifestations of children's hematological diseases. Methods In our hospital from April 2013 to July 2015 were treated 110 cases of children with liquid, analysis of the results of the investigation of the bone marrow cytology in children. Results In all patients with hematological diseases, platelet, giant cell disease has a higher proportion of disease, the second was the red cell system and the white blood cell system disease.Conclusion Children with hematologic diseases are more common in male children, and more in the platelet and red blood cells,white blood cell system, the main clinical manifestations were lymph node, fever, bleeding and so on.

  12. Late effects on human bone marrow after extended field radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Parmentier, C.; Morardet, N.; Tubiana, M.

    1983-09-01

    Thirty-two patients with lymphoma were treated by extended radiotherapy (RT) at a dose of 40 Gy and were studied by ferrokinetic studies and surface counting at various times following irradiation. Loss of hematopoietic activity in the irradiated areas is compensated by increased activity in the non-irradiated areas. Despite the return of peripheral blood counts to normal, the hyperactivity of the non-irradiated bone marrow persists over up to 13 years after RT, while the hematopoietic activity of the irradiated areas remains depressed and is only slightly higher than immediately after RT. The hypoactivity persisted even when the hemopoietic tissues had been subjected to the intense stimulation provoked by an aplasia caused by chemotherapy. However, a recovery was observed for dose of 20 Gy or lower. The hemopoietic activity of the irradiated bone marrow appears to be related to the volume of the marrow irradiated and is higher after a mantle + inverted Y field than after a mantle field. Bone marrow scintigraphies with /sup 59/Fe in 7 out of 9 patients studied revealed an extension of hematopoiesis into a normally dormant area of the marrow, such as the femora. In 2 patients an erythropoietic activity was observed in spleens which had received a dose of 40 Gy, and extra medullary erythropoiesis was found in approximately two-thirds of the patients.

  13. Bone Marrow Transplantation for Severe Aplastic Anemia Secondary to Temozolomide

    OpenAIRE

    Morris, E. Brannon; Kasow, Kimberly; Reiss, Ulrike; Ellison, David; Broniscer, Alberto

    2008-01-01

    Radiotherapy (RT) and concomitant/adjuvant therapy with temozolomide (Temodar) is a common treatment regimen for children and adults with glioma. Although temozolomide is generally well tolerated with temporary myelosuppression as the primary dose-limiting toxicity, irreversible bone-marrow aplasia after treatment with temozolomide has been reported. We report the case of an adolescent patient with a high-grade glioma who, after > 2 years of event-free survival, underwent successful bone marr...

  14. Noninvasive measurement of skin physiological parameters on children and adolescents before and after bone marrow transplantation

    OpenAIRE

    2014-01-01

    Transplantation of hematopoietic stem cells is a therapy with curative intention for many malignant and non-malignant diseases. Side effects, however, frequently involve skin and mucosa. In the Department of Pediatric Dermatology, Charité-Universitätsmedizin Berlin, we observed that young receivers of bone marrow transplants presented themselves not only for treatment of transplantation-specific diseases such as Graft-versus-Host-Disease, but with unspecific skin disorders and complaints incl...

  15. File list: ALL.Bld.50.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

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  16. File list: His.Bld.05.AllAg.Leukemic_bone_marrow [Chip-atlas[Archive

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  18. File list: ALL.Bld.10.AllAg.Bone_Marrow_Cells [Chip-atlas[Archive

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

    Science.gov (United States)

    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...

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  14. Bone marrow transplantation reverses new-onset immunoinflammatory diabetes in a mouse model.

    Science.gov (United States)

    Lv, Cheng-Lan; Wang, Jing; Xie, Ting; Ouyang, Jian

    2014-01-01

    Bone marrow transplantation might be an effective method to cure type 1 diabetes mellitus. This study aimed to investigate whether bone marrow transplantation could reverse hyperglycemia in diabetic mice and whether high-dose total body irradiation followed by high-dose bone marrow mononuclear cell infusion could improve the efficiency of bone marrow transplantation in treating diabetic mice. Diabetic mice after multiple low doses of streptozotocin injection were irradiated followed by infusion with approximately 1×10(7) bone marrow mononuclear cells intravenously. Before and after bone marrow transplantation, fasting blood glucose, intraperitoneal glucose tolerance test, serum insulin, pancreatic histology, and the examination of insulin and glucagon in islets were processed. All recipients returned to near euglycemic within 1 week after undergoing bone marrow transplantation. No mice became hyperglycemia again during investigation period. The change of serum insulin, glucose tolerance test, pancreatic histology and the expression of insulin and glucagon in recipient islets after bone marrow transplantation all revealed islets regeneration and significant amelioration when compared respectively with those of diabetic mice without bone marrow transplantation. Bone marrow transplantation contributed to reduce blood glucose, prevent further blood glucose hike in diabetic recipients, and promote islets regeneration. High-dose total body irradiation in combination with high-dose bone marrow monoclear cell infusion could improve the efficiency of bone marrow transplantation in treating streptozotocin-induced diabetes.

  15. Markers for Characterization of Bone Marrow Multipotential Stromal Cells

    Directory of Open Access Journals (Sweden)

    Sally A. Boxall

    2012-01-01

    Full Text Available Given the observed efficacy of culture-expanded multipotential stromal cells, also termed mesenchymal stem cells (MSCs, in the treatment of graft-versus host and cardiac disease, it remains surprising that purity and potency characterization of manufactured cell batches remains rather basic. In this paper, we will initially discuss surface and molecular markers that were proposed to serve as the indicators of the MSC potency, in terms of their proliferative potential or the ability to differentiate into desired lineages. The second part of this paper will be dedicated to a critical discussion of surface markers of uncultured (i.e., native bone marrow (BM MSCs. Although no formal consensus has yet been reached on which markers may be best suited for prospective BM MSC isolation, markers that cross-react with MSCs of animal models (such as CD271 and W8-B2/MSCA-1 may have the strongest translational value. Whereas small animal models are needed to discover the in vivo function on these markers, large animal models are required for safety and efficacy testing of isolated MSCs, particularly in the field of bone and cartilage tissue engineering.

  16. Bone marrow-derived cells are differentially involved in pathological and physiological retinal angiogenesis in mice

    Energy Technology Data Exchange (ETDEWEB)

    Zou, He [Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8507 (Japan); Otani, Atsushi, E-mail: otan@kuhp.kyoto-u.ac.jp [Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8507 (Japan); Oishi, Akio; Yodoi, Yuko; Kameda, Takanori; Kojima, Hiroshi; Yoshimura, Nagahisa [Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8507 (Japan)

    2010-01-08

    bone marrow cells are involved in the pathology or severity of retinal angiogenic diseases.

  17. Leishmania donovani infection induces anemia in hamsters by differentially altering erythropoiesis in bone marrow and spleen.

    Directory of Open Access Journals (Sweden)

    William P Lafuse

    Full Text Available Leishmania donovani is a parasite that causes visceral leishmaniasis by infecting and replicating in macrophages of the bone marrow, spleen, and liver. Severe anemia and leucopenia is associated with the disease. Although immune defense mechanisms against the parasite have been studied, we have a limited understanding of how L. donovani alters hematopoiesis. In this study, we used Syrian golden hamsters to investigate effects of L. donovani infection on erythropoiesis. Infection resulted in severe anemia and leucopenia by 8 weeks post-infection. Anemia was associated with increased levels of serum erythropoietin, which indicates the hamsters respond to the anemia by producing erythropoietin. We found that infection also increased numbers of BFU-E and CFU-E progenitor populations in the spleen and bone marrow and differentially altered erythroid gene expression in these organs. In the bone marrow, the mRNA expression of erythroid differentiation genes (α-globin, β-globin, ALAS2 were inhibited by 50%, but mRNA levels of erythroid receptor (c-kit, EpoR and transcription factors (GATA1, GATA2, FOG1 were not affected by the infection. This suggests that infection has a negative effect on differentiation of erythroblasts. In the spleen, erythroid gene expression was enhanced by infection, indicating that the anemia activates a stress erythropoiesis response in the spleen. Analysis of cytokine mRNA levels in spleen and bone marrow found that IFN-γ mRNA is highly increased by L. donovani infection. Expression of the IFN-γ inducible cytokine, TNF-related apoptosis-inducing ligand (TRAIL, was also up-regulated. Since TRAIL induces erythroblasts apoptosis, apoptosis of bone marrow erythroblasts from infected hamsters was examined by flow cytometry. Percentage of erythroblasts that were apoptotic was significantly increased by L. donovani infection. Together, our results suggest that L. donovani infection inhibits erythropoiesis in the bone marrow by

  18. Bone marrow dysfunction in chronic heart failure patients

    NARCIS (Netherlands)

    Westenbrink, B. Daan; Voors, Adriaan A.; de Boer, Rudolf A.; Schuringa, Jan J.; Klinkenberg, Theo; van der Harst, Pim; Vellenga, Edo; van Veldhuisen, Dirk J.; van Gilst, Wiek H.

    2010-01-01

    To investigate whether chronic heart failure (CHF) is associated with a general dysfunction of the haematopoietic compartment. Bone marrow was obtained during coronary artery bypass graft surgery from 20 patients with CHF (age 67 +/- 6 years, 75% NYHA class >= III, LVEF 32 +/- 6%), and 20 age- and g

  19. Pain During Bone Marrow Aspiration: Prevalence and Prevention

    NARCIS (Netherlands)

    Vanhelleputte, P.; Nijs, K.A.N.D.; Delforge, M.; Evers, G.; Vanderschueren, S.

    2003-01-01

    The Prevalence, intensity, determinants and prevention of pain during bone marrow aspiration (BMA) in adults are not well defined. In the first part of this prospective study (observational phase), 132 adult hematological patients undergoing BMA after local anesthesia scored the procedural pain by m

  20. Successful nonsibling bone marrow transplantation in severe combined immunodeficiency

    DEFF Research Database (Denmark)

    Ramsøe, K; Skinhøj, P; Andersen, V

    1978-01-01

    Severe combined immunodeficiency (SCID) was diagnosed in a girl immediately after birth; her older brother had SCID and was successfully reconstituted by bone marrow transplantation from his uncle. She was isolated in a laminar air flow bench and decontaminated. The father differed by one HLA...

  1. Increased rejection of murine allogeneic bone marrow in presensitized recipients

    NARCIS (Netherlands)

    vanOs, R; deWitte, T; Dillingh, JH; Mauch, PM; Down, JD

    1997-01-01

    The role of presensitizing murine recipients with donor spleen cells prior to T cell-depleted or -repleted H-2 compatible allogeneic bone marrow transplantation (BMT) was investigated at two different doses of total body irradiation (TBI). Recipients that were presensitized with 2 x 10(7) irradiated

  2. Bone marrow failure syndromes and refractory cytopenia of childhood

    NARCIS (Netherlands)

    A.M. Aalbers (Anna Maartje)

    2014-01-01

    markdownabstract__Abstract__ Hematopoiesis, or blood cell production, is sustained through hematopoietic stem cells, which are self-renewing cells that reside in the bone marrow, and that are capable of producing daughter cells that proliferate and mature to provide all adult blood effector cells,

  3. A Role For Photodynamic Therapy In Autologous Bone Marrow Transplantation

    Science.gov (United States)

    Sieber, Fritz

    1988-02-01

    Simultaneous exposure to the amphipathic fluorescent dye merocyanine 540 (MC 540) and light of a suitable wavelength rapidly kills leukemia, lymphoma, and neuroblastoma cells but spares normal pluripotent hematopoietic stem cells. Tests in several preclinical models and early results of a phase I clinical trial suggest that MC 540-mediated photosensitization may be useful for the extracorporeal purging of autologous remission bone marrow grafts.

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

    OpenAIRE

    Xinchun Ye; Jinxia Hu; Guiyun Cui

    2016-01-01

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

  5. Neurokinin-1 receptor signalling impacts bone marrow repopulation efficiency.

    Directory of Open Access Journals (Sweden)

    Alexandra Berger

    Full Text Available Tachykinins are a large group of neuropeptides with both central and peripheral activity. Despite the increasing number of studies reporting a growth supportive effect of tachykinin peptides in various in vitro stem cell systems, it remains unclear whether these findings are applicable in vivo. To determine how neurokinin-1 receptor (NK-1R deficient hematopoietic stem cells would behave in a normal in vivo environment, we tested their reconstitution efficiency using competitive bone marrow repopulation assays. We show here that bone marrow taken from NK-1R deficient mice (Tacr1(-/- showed lineage specific B and T cell engraftment deficits compared to wild-type competitor bone marrow cells, providing evidence for an involvement of NK-1R signalling in adult hematopoiesis. Tachykinin knockout mice lacking the peptides SP and/or HK-1 (Tac1 (-/-, Tac4 (-/- and Tac1 (-/-/Tac4 (-/- mice repopulated a lethally irradiated wild-type host with similar efficiency as competing wild-type bone marrow. The difference between peptide and receptor deficient mice indicates a paracrine and/or endocrine mechanism of action rather than autocrine signalling, as tachykinin peptides are supplied by the host environment.

  6. SPONTANEOUS TRANSFORMATION OF CULTURED PORCINE BONE MARROW STROMAL CELLS

    DEFF Research Database (Denmark)

    Zou, Lijin; Zou, Xuenong; Li, Haisheng;

    INTRODUCTION Recently, the possibility that tumors originate from cancer stem cells (CSCs) has been proposed. Stem cells and CSCs share certain features such as self-renewal and differentiation potential. The aim of this study was to evaluate whether bone marrow stromal cells (BMSC) after long-te...

  7. Lipopolysaccharide-activated microglial-induced neuroglial cell differentiation in bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Xiaoguang Luo; Chunlin Ge; Yan Ren; Hongmei Yu; Zhe Wu; Qiushuang Wang; Chaodong Zhang

    2008-01-01

    BACKGROUND: Microglia are very sensitive to environmental changes, often becoming activated by pathological conditions. Activated microglia can exert a dual role in injury and repair in various diseases of the central nervous system, including cerebral ischemia, Parkinson's disease, and Alzheimer's disease. OBJECTIVE: An immortal microglial cell line, BV2, was treated with varying concentrations of lipopolysaccharide (LPS) to induce a pathological situation. Supernatant was harvested and incubated with bone marrow mesenchymal stem cells and, concomitantly, bone marrow mesenchymal stem cell differentiation was observed. DESIGN: A controlled observation, in vitro experiment. SETTING: Department of Neurology, First Affiliated Hospital of China Medical University. MATERIALS: Five male 2-3-week-old Sprague Dawley rats were purchased from Animal Laboratory Center of China Medical University and included in this study. The protocol was performed in accordance with ethical guidelines for the use and care of animals. The microglial cell line BV2 was produced by Cell Research Institute of Chinese Academy of Sciences. LPS was produced by Sigma Company, USA. METHODS: This study was performed in the Central Laboratory of China Medical University from September 2006 to March 2007. Rat femoral and tibial bone marrow was collected for separation and primary culture of bone marrow mesenchymal stem cells. Bone marrow mesenchymal stem cell cultures were divided into 5 groups: control group, non-activated group, as well as low-, medium-, and high-dose LPS groups. In the control group, bone marrow mesenchymal stem cells were cultured with Dulbecco's modified Eagle's medium (DMEM) supplemented with fetal bovine serum (volume fraction 0.1). In the non-activated group, bone marrow mesenchymal stem cells were incubated with non-activated BV2 supernatant. In the low-, medium-, and high-dose LPS groups, bone marrow mesenchymal stem cells were incubated with LPS (0.01, 0.1 and 1

  8. Visceral Leishmaniasis: A Differential Diagnosis to Remember after Bone Marrow Transplantation

    Directory of Open Access Journals (Sweden)

    Margarida Dantas Brito

    2014-01-01

    Full Text Available Leishmania infection in immunocompromised hosts is reported in the literature, mostly concerning human immunodeficiency virus infected patients. It is not well characterized in the context of stem cell transplantation. We report a rare case clinical case of visceral leishmaniasis after allogeneic bone marrow transplantation. A 50-year-old Caucasian male was referred to allogeneic bone marrow transplantation with a high-risk acute lymphoblastic B leukemia in first complete remission. Allogeneic SCT was performed with peripheral blood stem cells from an unrelated Portuguese matched donor. In the following months, patient developed mild fluctuating cytopenias, mostly thrombocytopenia (between 60 and 80∗109/L. The only significant complaint was intermittent tiredness. The common causes for thrombocytopenia in this setting were excluded—no evidence of graft versus host disease, no signs of viral or bacterial infection, and no signs of relapsed disease/dysplastic changes. The bone marrow smear performed 12 months after transplantation revealed an unsuspected diagnosis: a massive bone marrow infiltration with amastigotes.

  9. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma.

    Science.gov (United States)

    Nysom, K; Holm, K; Hesse, B; Ulrik, C S; Jacobsen, N; Bisgaard, H; Hertz, H

    1996-05-01

    Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary damage after transplantation. None developed chronic graft-versus-host disease. Transfer factor and lung volumes were reduced immediately after bone marrow transplantation, but increased during the following years. However, at the last follow up, 4-13 years (median 8) after transplantation, patients had significantly reduced transfer factor, total lung capacity, and forced vital capacity (-1.0, -1.2, and -0.8 SD score, respectively), and increased ratio of forced expiratory volume in one second to forced vital capacity (+0.9 SD score). None of the patients had pulmonary symptoms, and changes were unrelated to their age at bone marrow transplantation. In conclusion, patients had subclinical restrictive pulmonary disease at a median of eight years after total body irradiation and allogeneic bone marrow transplantation.

  10. Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure

    Directory of Open Access Journals (Sweden)

    Bechtold Astrid

    2007-01-01

    Full Text Available Abstract Background DNA Ligase IV deficiency syndrome is a rare autosomal recessive disorder caused by hypomorphic mutations in the DNA ligase IV gene (LIG4. The clinical phenotype shows overlap with a number of other rare syndromes, including Seckel syndrome, Nijmegen breakage syndrome, and Fanconi anemia. Thus the clinical diagnosis is often delayed and established by exclusion. Methods We describe a patient with pre- and postnatal growth retardation and dysmorphic facial features in whom the diagnoses of Seckel-, Dubowitz-, and Nijmegen breakage syndrome were variably considered. Cellular radiosensitivity in the absence of clinical manifestations of Ataxia telangiectasia lead to the diagnosis of DNA ligase IV (LIG4 deficiency syndrome, confirmed by compound heterozygous mutations in the LIG4 gene. At age 11, after a six year history of progressive bone marrow failure and increasing transfusion dependency the patient was treated with matched sibling donor hematopoetic stem cell transplantation (HSCT using a fludarabine-based conditioning regimen without irradiation. Results The post-transplantation course was uneventful with rapid engraftment leading to complete and stable chimerism. Now at age 16, the patient has gained weight and is in good clinical condition. Conclusion HSCT using mild conditioning without irradiation qualifies as treatment of choice in LIG4-deficient patients who have a matched sibling donor.

  11. Recruitment of bone marrow derived cells during anti-angiogenic therapy in GBM : Bone marrow derived cell in GBM

    NARCIS (Netherlands)

    Boer, Jennifer C.; Walenkamp, Annemiek M. E.; den Dunnen, Wilfred F. A.

    2014-01-01

    Glioblastoma (GBM) is a highly vascular tumor characterized by rapid and invasive tumor growth, followed by oxygen depletion, hypoxia and neovascularization, which generate a network of disorganized, tortuous and permeable vessels. Recruitment of bone marrow derived cells (BMDC) is crucial for vascu

  12. Bone marrow cells produce nerve growth factor and promote angiogenesis around transplanted islets

    Institute of Scientific and Technical Information of China (English)

    Naoaki; Sakata; Nathaniel; K; Chan; John; Chrisler; Andre; Obenaus; Eba; Hathout

    2010-01-01

    AIM:To clarify the mechanism by which bone marrow cells promote angiogenesis around transplanted islets.METHODS: Streptozotocin induced diabetic BALB/ c mice were transplanted syngeneically under the kidney capsule with the following: (1) 200 islets (islet group: n=12), (2) 1-5×106 bone marrow cells (bone marrow group: n=11), (3) 200 islets and 1-5×106 bone marrow cells (islet + bone marrow group: n= 13), or (4) no cells (sham group:n=5). All mice were evaluated for blood glucose, serum insulin, serum nerve...

  13. Bone marrow MR imaging findings in disuse osteoporosis

    Energy Technology Data Exchange (ETDEWEB)

    Abreu, Marcelo R. de [Hospital Mae de Deus, Porto Alegre (Brazil); Wesselly, Michelle; Chung, Christine B.; Resnick, Donald [University of California, San Diego, CA (United States)

    2011-05-15

    To demonstrate MR imaging findings in the cortical and trabecular bone as well as marrow changes in patients with disuse osteoporosis (DO). Sixteen patients (14 men, 2 women, aged 27-86 years) with clinical and radiographic evidence of DO of a lower limb joint (10 knees, 6 ankles) with MR examination of the same joint performed within a 1-month period were selected, as well as 16 healthy volunteers (7 men, 9 women, aged 25-75 years, 10 knees and 6 ankles). MR imaging findings of the bone marrow were analyzed by 2 musculoskeletal radiologists in consensus regarding: diffuse or focal signal alteration, reinforcement of vertical or longitudinal trabecular lines, and presence of abnormal vascularization. All patients (100%,16/16) with DO presented MR imaging abnormalities of the bone marrow, such as: accentuation of vertical trabecular lines (50%, 8/16), presence of subchondral lobules of fat (37.5%, 6/16), presence of horizontal trabecular lines (31%, 5/16), prominence of bone vessels (25%, 4/16), and presence of dotted areas of high signal intensity on T2-weighted fat-suppressed sequences (12.5%, 2/16). Such MR findings did not appear in the control individuals. There are several MR imaging findings in bones with DO that range from accentuation of vertical and horizontal marrow lines, presence of subchondral lobules of fat, prominent bone vascularization and the presence of dotted foci of high signal intensity on T2-weighted fat-suppressed sequences. Recognition of these signs may prove helpful in the identification of DO as well as distinguishing these findings from other entities. (orig.)

  14. Degenerative disc disease in the lumbar spine: Another cause for focally reduced activity on marrow scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, M. (Addenbrookes Hospital, Cambridge (United Kingdom). Dept. of Radiology); Miles, K.A. (Addenbrookes Hospital, Cambridge (United Kingdom). Dept. of Radiology Addenbrookes Hospital, Cambridge (United Kingdom). Dept. of Nuclear Medicine); Wraight, E.P. (Addenbrookes Hospital, Cambridge (United Kingdom). Dept. of Nuclear Medicine); Dixon, A.K. (Addenbrookes Hospital, Cambridge (United Kingdom). Dept. of Radiology Cambridge Univ. (United Kingdom))

    1992-05-01

    A patient is presented in whom a focal reduction in marrow activity in the lumbar spine on both leucocyte and nanocolloid marrow scintigraphy was subsequently shown to be due to fatty infiltration of marrow in association with disc degeneration. Degenerative disease in the lumbar spine has not been previously described as a cause of abnormal bone marrow distribution by such means and needs to be distinguished from a more serious pathology, such as malignant infiltration and vertebral infection, which it may mimic. In a retrospective review of 33 nanocolloid bone marrow and 117 leucocyte scintigrams, 8 showed a degree of reduced marrow activity in the lumbar spine consistent with that caused by degenerative changes. (orig.).

  15. CXCR2 modulates bone marrow vascular repair and haematopoietic recovery post-transplant.

    Science.gov (United States)

    Hale, Sarah J M; Hale, Ashley B H; Zhang, Youyi; Sweeney, Dominic; Fisher, Nita; van der Garde, Mark; Grabowska, Rita; Pepperell, Emma; Channon, Keith; Martin-Rendon, Enca; Watt, Suzanne M

    2015-05-01

    Murine models of bone marrow transplantation show that pre-conditioning regimens affect the integrity of the bone marrow endothelium and that the repair of this vascular niche is an essential pre-requisite for successful haematopoietic stem and progenitor cell engraftment. Little is known about the angiogenic pathways that play a role in the repair of the human bone marrow vascular niche. We therefore established an in vitro humanized model, composed of bone marrow stromal and endothelial cells and have identified several pro-angiogenic factors, VEGFA, ANGPT1, CXCL8 and CXCL16, produced by the stromal component of this niche. We demonstrate for the first time that addition of CXCL8 or inhibition of its receptor, CXCR2, modulates blood vessel formation in our bone marrow endothelial niche model. Compared to wild type, Cxcr2(-/-) mice displayed a reduction in bone marrow cellularity and delayed platelet and leucocyte recovery following myeloablation and bone marrow transplantation. The delay in bone marrow recovery correlated with impaired bone marrow vascular repair. Taken together, our data demonstrate that CXCR2 regulates bone marrow blood vessel repair/regeneration and haematopoietic recovery, and clinically may be a therapeutic target for improving bone marrow transplantation.

  16. GPR18 Controls Reconstitution of Mouse Small Intestine Intraepithelial Lymphocytes following Bone Marrow Transplantation.

    Directory of Open Access Journals (Sweden)

    Amy M Becker

    Full Text Available Specific G protein coupled receptors (GPRs regulate the proper positioning, function, and development of immune lineage subsets. Here, we demonstrate that GPR18 regulates the reconstitution of intraepithelial lymphocytes (IELs of the small intestine following bone marrow transplantation. Through analysis of transcriptional microarray data, we find that GPR18 is highly expressed in IELs, lymphoid progenitors, and mature follicular B cells. To establish the physiological role of this largely uncharacterized GPR, we generated Gpr18-/- mice. Despite high levels of GPR18 expression in specific hematopoietic progenitors, Gpr18-/- mice have no defects in lymphopoiesis or myelopoiesis. Moreover, antibody responses following immunization with hapten-protein conjugates or infection with West Nile virus are normal in Gpr18-/- mice. Steady-state numbers of IELs are also normal in Gpr18-/- mice. However, competitive bone marrow reconstitution experiments demonstrate that GPR18 is cell-intrinsically required for the optimal restoration of small intestine TCRγδ+ and TCRαβ+ CD8αα+ IELs. In contrast, GPR18 is dispensable for the reconstitution of large intestine IELs. Moreover, Gpr18-/- bone marrow reconstitutes small intestine IELs similarly to controls in athymic recipients. Gpr18-/- chimeras show no changes in susceptibility to intestinal insults such as Citrobacter rodentium infections or graft versus host disease. These data reveal highly specific requirements for GPR18 in the development and reconstitution of thymus-derived intestinal IEL subsets in the steady-state and after bone marrow transplantation.

  17. Bone marrow uptake of {sup 99m}Tc-MIBI in patients with multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Fonti, R. [Medicina Nucleare, Facolta di Medicina, Univ. Federico II, Naples (Italy); Centro per la Medicina Nucleare C.N.R., Cattedra di Medicina Nucleare, Napoli (Italy); Del Vecchio, S.; Zannetti, A.; Di Gennaro, F.; Pace, L.; Salvatore, M. [Centro per la Medicina Nucleare C.N.R., Cattedra di Medicina Nucleare, Napoli (Italy); De Renzo, A.; Catalano, L.; Califano, C.; Rotoli, B. [Cattedra di Ematologia, Dipt. di Medicina Clinica e Sperimentale, Napoli (Italy)

    2001-02-01

    In a previous study, we showed the ability of technetium-99m methoxyisobutylisonitrile ({sup 99m}Tc-MIBI) scan to identify active disease in patients with multiple myeloma (Eur J Nucl Med 1998; 25: 714-720). In particular, a semiquantitative score of the extension and intensity of bone marrow uptake was derived and correlated with both the clinical status of the disease and plasma cell bone marrow infiltration. In order to estimate quantitatively {sup 99m}Tc-MIBI bone marrow uptake and to verify the intracellular localization of the tracer, bone marrow samples obtained from 24 multiple myeloma patients, three patients with monoclonal gammopathy of undetermined significance (MGUS) and two healthy donors were studied for in vitro uptake. After centrifugation over Ficoll-Hypaque gradient, cell suspensions were incubated with {sup 99m}Tc-MIBI and the uptake was expressed as the percentage of radioactivity specifically retained within the cells. The cellular localization of the tracer was assessed by micro-autoradiography. Twenty-two out of 27 patients underwent {sup 99m}Tc-MIBI scan within a week of bone marrow sampling. Whole-body images were obtained 10 min after intravenous injection of 555 MBq of the tracer; the extension and intensity of {sup 99m}Tc-MIBI uptake were graded using the semiquantitative score. A statistically significant correlation was found between in vitro uptake of {sup 99m}Tc-MIBI and both plasma cell infiltration (Pearson's coefficient of correlation r=0.69, P<0.0001) and in vivo score (Spearman rank correlation coefficient r=0.60, P<0.01). No specific tracer uptake was found in bone marrow samples obtained from the two healthy donors. Micro-autoradiography showed localization of {sup 99m}Tc-MIBI inside the plasma cells infiltrating the bone marrow. Therefore, our findings show that the degree of tracer uptake both in vitro and in vivo is related to the percentage of infiltrating plasma cells which accumulate the tracer in their inner

  18. Functional status of bone marrow mesenchymal stem cells from osteoarthritis patients and disease development%骨关节炎患者骨髓间充质干细胞的功能状态与病情进展

    Institute of Scientific and Technical Information of China (English)

    王治洲; 关振鹏; 徐超; 韩亚军; 帖小佳; 郭洪亮; 伊力哈木托合提; 王军锋; 闫斌; 毕晓娟

    2015-01-01

    背景:骨髓间充质干细胞对骨和软骨在细胞水平的发育和再生至关重要,其数量缺失和功能受损被广泛认为是骨关节炎病因之一。目的:探讨骨关节炎患者骨髓间充质干细胞功能状态与病情进展的关系。方法:2013年7月至2014年10月间收集3组病例,每组10例,分别为对照组、轻度骨关节炎患者组、重度骨关节炎患者组。获取3组患者股骨或胫骨骨髓5 mL分离培养骨髓间充质干细胞,培养至3代时采用CCK-8法检测各组患者骨髓间充质干细胞的增殖能力,成软骨诱导14 d后行甲苯胺蓝染色鉴定,Real time PCR法检测对照组诱导后软骨细胞特征基因Aggrecan、Col2A1的表达。结果与结论:骨髓间充质干细胞体外培养后贴壁生长,胞浆含有较大的颗粒,核卵圆形,细胞呈多角形、梭形,有多个大小不一的突起,细胞分裂相多见。对照组增殖能力最强,重度骨关节炎患者组增殖能力最弱,但均在培养1周后进入平台期。成软骨诱导14 d后细胞呈多角形、类圆形改变,紫红色异染颗粒分布于胞浆外围。对照组诱导后软骨细胞特征基因 Aggrecan、Col2A1有高表达趋势。结果表明骨关节炎患者骨髓间充质干细胞功能状态与病情严重程度成负相关,其功能状态影响骨关节炎患者的病情进展。%BACKGROUND:Bone marrow mesenchymal stem cels are crucial for bone and cartilage development and regeneration at a celular level. Insufficient quantity and functional impairment of bone marrow mesenchymal stem cels is widely considered to be one of osteoarthritis causes. OBJECTIVE: To explore the relationship between the functional status of bone marrow mesenchymal stem cels and disease progression in osteoarthritis patients.METHODS: Thirty patients with osteoarthritis were enroled from July 2013 to October 2014, and divided into control, mild osteoarthritis, and severe osteoarthritis

  19. Bone marrow-derived mesenchymal stem cells increase dopamine synthesis in the injured striatum

    Institute of Scientific and Technical Information of China (English)

    Yue Huang; Cheng Chang; Jiewen Zhang; Xiaoqun Gao

    2012-01-01

    Previous studies showed that tyrosine hydroxylase or neurturin gene-modified cells transplanted into rats with Parkinson's disease significantly improved behavior and increased striatal dopamine content. In the present study, we transplanted tyrosine hydroxylase and neurturin gene-modified bone marrow-derived mesenchymal stem cells into the damaged striatum of Parkinson's disease model rats. Several weeks after cell transplantation, in addition to an improvement of motor function, tyrosine hydroxylase and neurturin proteins were up-regulated in the injured striatum, and importantly, levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid increased significantly. Furthermore, the density of the D2 dopamine receptor in the postsynaptic membranes of dopaminergic neurons was decreased. These results indicate that transplantation of tyrosine hydroxylase and neurturin gene-modified bone marrow-derived mesenchymal stem cells increases dopamine synthesis and significantly improves the behavior of rats with Parkinson's disease.

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

    Science.gov (United States)

    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

  1. Pneumatosis intestinalis in children after allogeneic bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Yeager, A.M.; Kanof, M.E.; Lake, A.M.; Kramer, S.S.; Jones, B.; Saral, R.; Santos, G.W.

    1987-01-01

    Four children, ages 3 to 8 years, developed pneumatosis intestinalis (PI) after allogeneic bone marrow transplantation (BMT) for acute leukemia or severe aplastic anemia. PI was detected at a median of 48 days (range, 10-63 days) after BMT and was associated with abdominal symptoms and clinical signs. All patients had severe systemic and/or highgrade cutaneous acute graft-versus-host disease (AGVHD) at some time after BMT and were receiving corticosteroids at the time of development of PI; however, PI was associated with concomitant severe AGVHD in only one patient. One patient with PI had Hafnia alvei bacteremia and another patient had gastroenteritis due to rotavirus and adenovirus. All patients were treated with supportive care and systemic broad-spectrum antibiotics, and PI resolved 2-16 days after onset. Two patients died with BMT-associated complications unrelated to PI. Multiple factors contribute to the development of PI after BMT, and the prognosis for recovery from PI is good with medical management alone. Overall survival in these patients is dependent on the frequency and severity of other conditions, such as AGVHD and opportunistic infections, after BMT.

  2. In Vivo Osteoinductive Effect and In Vitro Isolation and Cultivation Bone Marrow Mesenchymal Stem Cells

    OpenAIRE

    Redžić, Amira; Smajilagić, Amer; Aljičević, Mufida; Berberović, Ljubomir

    2010-01-01

    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 Zeeland Rabbits, and then in second part of study to iso...

  3. Organotins Are Potent Activators of PPARγ and Adipocyte Differentiation in Bone Marrow Multipotent Mesenchymal Stromal Cells

    OpenAIRE

    2011-01-01

    Adipocyte differentiation in bone marrow is potentially deleterious to both bone integrity and lymphopoiesis. Here, we examine the hypothesis that organotins, common environmental contaminants that are dual ligands for peroxisome proliferator–activated receptor (PPAR) γ and its heterodimerization partner retinoid X receptor (RXR), are potent activators of bone marrow adipogenesis. A C57Bl/6-derived bone marrow multipotent mesenchymal stromal cell (MSC) line, BMS2, was treated with rosiglitazo...

  4. Bone marrow hypoplasia associated with fenbendazole administration in a dog.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  6. Human bone-marrow-derived mesenchymal stem cells

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Abdallah, Basem M

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of cells present in bone-marrow stroma and the stroma of various organs with the capacity for mesoderm-like cell differentiation into, for example, osteoblasts, adipocytes, and chondrocytes. MSC are being introduced in the clinic for the treatment of a var......Mesenchymal stem cells (MSC) are a group of cells present in bone-marrow stroma and the stroma of various organs with the capacity for mesoderm-like cell differentiation into, for example, osteoblasts, adipocytes, and chondrocytes. MSC are being introduced in the clinic for the treatment...... of a variety of clinical conditions. The aim of this review is to provide an update regarding the biology of MSC, their identification and culture, and mechanisms controlling their proliferation and differentiation. We also review the current status of their clinical use. Areas in which research is needed...

  7. Differentiation of Bone Marrow Mesenchymal Cells to Neural Cells

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To explore the possibility and condition of differentiation of bone marrow mesenchymal cells (BMSCs) to neural cells in vitro, BMSCs from whole bone marrow of rats were cultured. The BMSCs of passage 3 were identified with immunocytochemical staining of CD44 ( + ), CD71 ( + )and CD45(-). There were type Ⅰ and type Ⅱ cells in BMSCs. Type Ⅰ BMSCs were spindleshaped and strong positive in immunocytochemical staining of CD44 and CD71, whereas flat and big type Ⅱ BMSCs were lightly stained. The BMSCs of same passage were induced to differentiate into neural cells by β-mercaptoethanol (BME). After induction by BME, the type Ⅰ BMSCs withdrew to form neuron-like round soma and axon-like and dendrite-like processes, and were stained positively for neurofilament (NF). The type Ⅱ BMSCs did not change in the BME medium and were negatively or slightly stained of NF.

  8. Quantitative analysis of protein and gene expression in salivary glands of Sjogren's-like disease NOD mice treated by bone marrow soup.

    Directory of Open Access Journals (Sweden)

    Kaori Misuno

    Full Text Available BACKGROUND: Bone marrow cell extract (termed as BM Soup has been demonstrated to repair irradiated salivary glands (SGs and restore saliva secretion in our previous study. In the present study, we aim to investigate if the function of damaged SGs in non-obese diabetic (NOD mice can be restored by BM Soup treatment and the molecular alterations associated with the treatment. METHODS: Whole BM cells were lysed and soluble intracellular contents ("BM Soup" were injected I.V. into NOD mice. Tandem mass tagging with 2-D liquid chromatography-mass spectrometry was used to quantify proteins in the submandibular glands (SMGs between untreated and BM Soup-treated mice. Quantitative PCR was used to identify genes with altered expression in the treated mice. RESULTS BM SOUP: restored salivary flow rates to normal levels and significantly reduced the focus scores of SMGs in NOD mice. More than 1800 proteins in SMG cells were quantified by the proteomic approach. Many SMG proteins involved in inflammation and apoptosis were found to be down-regulated whereas those involved in salivary gland biology and development/regeneration were up-regulated in the BM Soup-treated mice. qPCR analysis also revealed expression changes of growth factors and cytokines in the SMGs of the treated NOD mice. CONCLUSION: BM Soup treatment is effective to restore the function of damaged SGs in NOD mice. Through gene/protein expression analysis, we have found that BM Soup treatment might effectuate via inhibiting apoptosis, focal adhesion and inflammation whereas promoting development, regeneration and differentiation of the SG cells in NOD mice. These findings provide important insights on the potential mechanisms underlying the BM Soup treatment for functional restoration of damaged SGs in NOD mice. Additional studies are needed to further confirm the identified target genes and their related signaling pathways that are responsible for the BM Soup treatment.

  9. Glucocorticoids induce autophagy in rat bone marrow mesenchymal stem cells

    DEFF Research Database (Denmark)

    Wang, L.; Fan, J.; Lin, Y. S.;

    2015-01-01

    and their responses to diverse stimuli, however, the role of autophagy in glucocorticoidinduced damage to bone marrow mesenchymal stem cells (BMSCs) remains unclear. The current study confirmed that glucocorticoid administration impaired the proliferation of BMSCs. Transmission electron microscopy......Glucocorticoidinduced osteoporosis (GIOP) is a widespread clinical complication following glucocorticoid therapy. This irreversible damage to boneforming and resorbing cells is essential in the pathogenesis of osteoporosis. Autophagy is a physiological process involved in the regulation of cells...

  10. Primary cutaneous aspergillosis and idiopathic bone marrow aplasia*

    Science.gov (United States)

    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

  11. Occupational therapy and the pediatric division of bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Thais Clemente Idemori

    2016-04-01

    Full Text Available Introduction: Bone Marrow Transplantation may cause a series of restrictions to patients. The child’s illness and hospitalization may further change daily life activities, playing and school routine; and social interaction, which will interfere in occupational roles. The occupational therapy procedures seek to provide a more accessible experience in hospital concerning the possibilities of involvement, favoring the child’s development through activities. Objective: This study aimed to describe the practice of an occupational therapist during therapeutic process with a school age child who has undergone bone marrow transplantation. Method: This is a qualitative research with a case study approach. Data was collected with a short form of personal and professional identification and characterization, and a semi-structured interview script. The interview was fully transcribed, and analyzed under the content analysis overview. Through the content obtained in the interviews, it was possible to raise four categories: occupational roles affected by illness, hospitalization; occupational therapy processes; benefits to children by the occupational therapy activities; and, successful practices: essential factors and theoretical principles. Results: The results showed that the occupational therapist took on roles as mediator between the hospital and the child’s original environment, and the relations to family, hospital team, towards the child’s needs and his/her life experience (school, family, hospital. Conclusion: It is expected that this study may contribute to the knowledge and propagation of the practice being developed by the therapists in children with bone marrow transplantation.

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

    Science.gov (United States)

    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.

  13. Are bone marrow regenerative cells ideal seed cells for the treatment of cerebral ischemia?

    Institute of Scientific and Technical Information of China (English)

    Yi Li; Xuming Hua; Fang Hua; Wenwei Mao; Liang Wan; Shiting Li

    2013-01-01

    Bone marrow cells for the treatment of ischemic brain injury may depend on the secretion of a large number of neurotrophic factors. Bone marrow regenerative cells are capable of increasing the secretion of neurotrophic factors. In this study, after tail vein injection of 5-fluorouracil for 7 days, bone marrow cells and bone marrow regenerative cells were isolated from the tibias and femurs of rats, and then administered intravenously via the tail vein after focal cerebral ischemia. Immunohistological staining and reverse transcription-PCR detection showed that transplanted bone marrow cells and bone marrow regenerative cells could migrate and survive in the ischemic regions, such as the cortical and striatal infarction zone. These cells promote vascular endothelial cell growth factor mRNA expression in the ischemic marginal zone surrounding the ischemic penumbra of the cortical and striatal infarction zone, and have great advantages in promoting the recovery of neurological function, reducing infarct size and promoting angiogenesis. Bone marrow regenerative cells exhibited stronger neuroprotective effects than bone marrow cells. Our experimental findings indicate that bone marrow regenerative cells are preferable over bone marrow cells for cell therapy for neural regeneration after cerebral ischemia. Their neuroprotective effect is largely due to their ability to induce the secretion of factors that promote vascular regeneration, such as vascular endothelial growth factor.

  14. Differentiation of rat bone marrow stem cells in liver after partial hepatectomy

    Institute of Scientific and Technical Information of China (English)

    Yu-Tao Zhan; Yu Wang; Lai Wei; Bin Liu; Hong-Song Chen; Xu Cong; Ran Fei

    2006-01-01

    AIM: To investigate the differentiation of rat bone marrow stem cells in liver after partial hepatectomy.METHODS: Bone marrow cells were collected from the tibia of rat with partial hepatectomy, the medial and left hepatic lobes were excised. The bone marrow stem cells (Thy+CD3-CD45RA- cells) were enriched from the bone marrow cells by depleting red cells and fluorescence-activated cell sorting. The sorted bone marrow stem cells were labeled by PKH26-GL in vitro and autotransplanted by portal vein injection. After 2wk, the transplanted bone marrow stem cells in liver were examined by the immunohistochemistry of albumin (hepatocyte-specific marker).RESULTS: The bone marrow stem cells (Thy+CD3-CD45RA- cells) accounted for 2.8% of bone marrow cells without red cells. The labeling rate of 10μM PKH26-GL on sorted bone marrow stem cells was about 95%.There were sporadic PKH26-GL-labeled cells among hepatocytes in liver tissue section, and some of the cells expressed albumin.CONCLUSION: Rat bone marrow stem cells can differentiate into hepatocytes in regenerative environment and may participate in liver regeneration after partial hepatectomy.

  15. Cigarette Smoking Is Associated with a Lower Concentration of CD105+ Bone Marrow Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Shaul Beyth

    2015-01-01

    Full Text Available Cigarette smoking is associated with musculoskeletal degenerative disorders, delayed fracture healing, and nonunion. Bone marrow progenitor cells (BMPCs, known to express CD105, are important in local trophic and immunomodulatory activity and central to musculoskeletal healing/regeneration. We hypothesized that smoking is associated with lower levels of BMPC. Iliac bone marrow samples were collected from individuals aged 18–65 years during the first steps of pelvic surgery, under IRB approval with informed consent. Patients with active infectious or neoplastic disease, a history of cytotoxic or radiation therapy, primary or secondary metabolic bone disease, or bone marrow dysfunction were excluded. Separation process purity and the number of BMPCs recovered were assessed with FACS. BMPC populations in self-reported smokers and nonsmokers were compared using the two-tailed t-test. 13 smokers and 13 nonsmokers of comparable age and gender were included. The average concentration of BMPCs was 3.52 × 105/mL ± 2.45 × 105/mL for nonsmokers versus 1.31 × 105/mL ± 1.61 × 105/mL for smokers (t= 3.2, P=0.004. This suggests that cigarette smoking is linked to a significant decrease in the concentration of BMPCs, which may contribute to the reduced regenerative capacity of smokers, with implications for musculoskeletal maintenance and repair.

  16. Cigarette Smoking Is Associated with a Lower Concentration of CD105+ Bone Marrow Progenitor Cells

    Science.gov (United States)

    Beyth, Shaul; Mosheiff, Rami; Safran, Ori; Daskal, Anat; Liebergall, Meir

    2015-01-01

    Cigarette smoking is associated with musculoskeletal degenerative disorders, delayed fracture healing, and nonunion. Bone marrow progenitor cells (BMPCs), known to express CD105, are important in local trophic and immunomodulatory activity and central to musculoskeletal healing/regeneration. We hypothesized that smoking is associated with lower levels of BMPC. Iliac bone marrow samples were collected from individuals aged 18–65 years during the first steps of pelvic surgery, under IRB approval with informed consent. Patients with active infectious or neoplastic disease, a history of cytotoxic or radiation therapy, primary or secondary metabolic bone disease, or bone marrow dysfunction were excluded. Separation process purity and the number of BMPCs recovered were assessed with FACS. BMPC populations in self-reported smokers and nonsmokers were compared using the two-tailed t-test. 13 smokers and 13 nonsmokers of comparable age and gender were included. The average concentration of BMPCs was 3.52 × 105/mL ± 2.45 × 105/mL for nonsmokers versus 1.31 × 105/mL ± 1.61 × 105/mL for smokers (t = 3.2,  P = 0.004). This suggests that cigarette smoking is linked to a significant decrease in the concentration of BMPCs, which may contribute to the reduced regenerative capacity of smokers, with implications for musculoskeletal maintenance and repair. PMID:26346476

  17. Neural Crest Cells Isolated from the Bone Marrow of Transgenic Mice Express JCV T-Antigen.

    Directory of Open Access Journals (Sweden)

    Jennifer Gordon

    Full Text Available JC virus (JCV, a common human polyomavirus, is the etiological agent of the demyelinating disease, progressive multifocal leukoencephalopathy (PML. In addition to its role in PML, studies have demonstrated the transforming ability of the JCV early protein, T-antigen, and its association with some human cancers. JCV infection occurs in childhood and latent virus is thought to be maintained within the bone marrow, which harbors cells of hematopoietic and non-hematopoietic lineages. Here we show that non-hematopoietic mesenchymal stem cells (MSCs isolated from the bone marrow of JCV T-antigen transgenic mice give rise to JCV T-antigen positive cells when cultured under neural conditions. JCV T-antigen positive cells exhibited neural crest characteristics and demonstrated p75, SOX-10 and nestin positivity. When cultured in conditions typical for mesenchymal cells, a population of T-antigen negative cells, which did not express neural crest markers arose from the MSCs. JCV T-antigen positive cells could be cultured long-term while maintaining their neural crest characteristics. When these cells were induced to differentiate into neural crest derivatives, JCV T-antigen was downregulated in cells differentiating into bone and maintained in glial cells expressing GFAP and S100. We conclude that JCV T-antigen can be stably expressed within a fraction of bone marrow cells differentiating along the neural crest/glial lineage when cultured in vitro. These findings identify a cell population within the bone marrow permissible for JCV early gene expression suggesting the possibility that these cells could support persistent viral infection and thus provide clues toward understanding the role of the bone marrow in JCV latency and reactivation. Further, our data provides an excellent experimental model system for studying the cell-type specificity of JCV T-antigen expression, the role of bone marrow-derived stem cells in the pathogenesis of JCV-related diseases

  18. A genetic variant in the IL-17 promoter is functionally associated with acute graft-versus-host disease after unrelated bone marrow transplantation.

    Directory of Open Access Journals (Sweden)

    J Luis Espinoza

    Full Text Available Interleukin IL-17 is a proinflammatory cytokine that has been implicated in the pathogenesis of various autoimmune diseases. The single nucleotide polymorphism (SNP, rs2275913, in the promoter region of the IL-17 gene is associated with susceptibility to ulcerative colitis. When we examined the impact of rs2275913 in a cohort consisting of 438 pairs of patients and their unrelated donors transplanted through the Japan Marrow Donor Program, the donor IL-17 197A allele was found to be associated with a higher risk of acute graft-versus-host disease (GVHD; hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.00 to 2.13; P = 0.05. Next, we investigated the functional relevance of the rs2275913 SNP. In vitro stimulated T cells from healthy individuals possessing the 197A allele produced significantly more IL-17 than those without the 197A allele. In a gene reporter assay, the 197A allele construct induced higher luciferase activity than the 197G allele, and the difference was higher in the presence of T cell receptor activation and was abrogated by cyclosporine treatment. Moreover, the 197A allele displayed a higher affinity for the nuclear factor activated T cells (NFAT, a critical transcription factor involved in IL-17 regulation. These findings substantiate the functional relevance of the rs2275913 polymorphism and indicate that the higher IL-17 secretion by individuals with the 197A allele likely accounts for their increased risk for acute GVHD and certain autoimmune diseases.

  19. ETIOLOGICAL EVALUATION IN 120 CASES OF PANCYTOPENIA BY BONE MARROW EXAMINATION

    Directory of Open Access Journals (Sweden)

    Surya Babu

    2014-11-01

    Full Text Available BACKGROUND: Pancytopenia is a relatively common hematological entity resulting from a variety of disease processes. The present study is carried out to find out the causes of pancytopenia by bone marrow examination. MATERIALS AND METHODS: Bone marrow examination is carried out in 120 cases of pancytopenia over a period of 3 years. Age of patients ranged from 2 to 75 years with a mean of 32 years. Most of the patients presented with generalized weakness and fever. Commonest physical finding was pallor followed by splenomegaly. Dimorphic anemia was the predominant blood picture. The commonest marrow finding was megaloblastic erythroid hyperplasia. The commonest cause of pancytopenia was megaloblastic anemia (58.3% followed by aplastic anemia (18.3%. Others include acute leukemia, myelodysplasia, non-Hodgkin’s lymphoma and disseminated tuberculosis. CONCLUSION: The present study shows the importance of bone marrow examination in evaluating pancytopenia and the geographical variation in the etiology as megaloblastic anemia is the predominant cause of pancytopenia in Indian subcontinent.

  20. Comparison of adenovirus viruria in bone marrow transplant patients before and after transplantation

    OpenAIRE

    Saderi, H; Owlia, P.; K.A. Moghadam; B Bahar; S Faghih Zadeh

    2005-01-01

    Baekgrouund & purpose: In recent years, the role of adenoviruses in infection and disease in recipients of bone marrow transplantation (BMT) has been studied. It suppose that adenoviral infections are prevalant in these patients Due to using medicines for preventing transplant rejection. This study was performed to compare the incidence of adenoviruses in urine samples taken before and after BMT from individuals undergoing BMT. In addition, The correlation between age, sex, etiology and kind...

  1. MRI of the femoral bone marrow in the assessment of aplastic anemia

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Osamu; Matsuura, Katsuhiko; Ichikawa, Tamaki; Kobayashi, Yasuyuki; Nagai, Jun; Takagi, Shojiro [Jichi Medical School, Saitama (Japan) Omiya Medical Center

    1995-11-01

    MR imaging of the femoral bone marrow was performed in 12 patients with untreated aplastic anemia and six patients with hypoplastic myelodysplastic syndrome (MDS). The MRI appearance was classified into four patterns; fatty marrow faint signal, nodular pattern and heterogeneous infiltration. The MRI patterns of aplastic anemia were evaluated and compared with those of hypoplastic MDS. In spite of hypocellular biopsies, MRI of the femoral marrow showed unexpected abnormal signal intensities in aplastic anemia; nodular pattern in five and heterogeneous infiltration pattern in two patients. Completely fatty marrow was depicted in four patients mainly with severe aplastic anemia. The nodular pattern with a background of fatty marrow was commonly seen in moderate or severe cases, while the heterogeneous infiltration pattern was noted in mild cases of the disease. Compared with hypoplastic MDS, asymmetrical nodular pattern suggesting patchy hematopoiesis was thought to be a characteristic finding of aplastic anemia. One patient clinically diagnosed as aplastic anemia, who had shown heterogeneous infiltration pattern, evolved to acute myeloid leukemia. We concluded that MRI of the femoral marrow could be useful in the assessment of aplastic anemia and detection of myelodysplastic or leukemic transformation. (author).

  2. Osteopetrosis (marble bone disease

    Directory of Open Access Journals (Sweden)

    Alexey Nikolayevich Kalyagin

    2014-01-01

    Full Text Available We report the data of the history of describing osteopetrosis (marble bone disease, its clinical features, diagnosis, and possible therapy approaches. Our own clinical case is presented.

  3. Metastatic Bone Disease

    Science.gov (United States)

    ... begin in bone are much less common in adults older than 45 years. Other diseases, such as Paget’s sarcoma, post-radiation sarcoma, hyperparathyroidism, and fractures due to osteoporosis, are also possibilities. Additional tests will likely be ...

  4. A history of bone marrow transplantation.

    Science.gov (United States)

    de la Morena, M Teresa; Gatti, Richard A

    2011-02-01

    The last 40 years has seen the emergence of hematopoietic stem cell transplantation as a therapeutic modality for fatal diseases and as a curative option for individuals born with inherited disorders that carry limited life expectancy and poor quality of life. Despite the rarity of many primary immunodeficiency diseases, these disorders have led the way toward innovative therapies and further provide insights into mechanisms of immunologic reconstitution applicable to all hematopoietic stem cell transplants. This article represents a historical perspective of the early investigators and their contributions. It also reviews the parallel work that oncologists and immunologists have undertaken to treat both primary immunodeficiencies and hematologic malignancies.

  5. ENRICHMENT AND CHARACTERIZATION OF THYMUS-REPOPULATING CELLS IN STROMA-DEPENDENT CULTURES OF RAT BONE-MARROW

    NARCIS (Netherlands)

    PRAKAPAS, Z; DENOYELLE, M; DARGEMONT, C; KROESE, FGM; THIERY, JP; DEUGNIER, MA

    1993-01-01

    The bone marrow precursor cells seeding the thymus have been difficult to investigate using fresh bone marrow and in vivo thymus reconstitution assays. We have therefore designed a short-term bone marrow culture system allowing the study of thymus-repopulating cells in the marrow microenvironment. L

  6. HLA Typing for Bone Marrow Transplantation

    Science.gov (United States)

    2011-07-21

    ISBT International Society Blood Transfusion IT Information Technology KIR Killer Immunoglobulin-like Receptor LR Low Resolution mHAg Minor...National Institute of Allergy and Infectious Diseases, Division of Allergy, Immunology, and Transplantation NAT Nucleic Acid Test NCI National Cancer ...important research study funded by this grant investigated the allelic diversity of the Killer Immunoglobulin-like Receptor ( KIR ) ligands. During the

  7. Organotypic culture of human bone marrow adipose tissue.

    Science.gov (United States)

    Uchihashi, Kazuyoshi; Aoki, Shigehisa; Shigematsu, Masamori; Kamochi, Noriyuki; Sonoda, Emiko; Soejima, Hidenobu; Fukudome, Kenji; Sugihara, Hajime; Hotokebuchi, Takao; Toda, Shuji

    2010-04-01

    The precise role of bone marrow adipose tissue (BMAT) in the marrow remains unknown. The purpose of the present study was therefore to describe a novel method for studying BMAT using 3-D collagen gel culture of BMAT fragments, immunohistochemistry, ELISA and real-time reverse transcription-polymerase chain reaction. Mature adipocytes and CD45+ leukocytes were retained for >3 weeks. Bone marrow stromal cells (BMSC) including a small number of lipid-laden preadipocytes and CD44+/CD105+ mesenchymal stem cell (MSC)-like cells, developed from BMAT. Dexamethasone (10 micromol/L), but not insulin (20 mU/mL), significantly increased the number of preadipocytes. Dexamethasone and insulin also promoted leptin production and gene expression in BMAT. Adiponectin production by BMAT was BMAT, in which adiponectin protein secretion is normally very low, and that BMAT may exhibit a different phenotype from that of the visceral and subcutaneous adipose tissues. BMAT-osteoblast interactions were also examined, and it was found that osteoblasts inhibited the development of BMSC and reduced leptin production, while BMAT inhibited the growth and differentiation of osteoblasts. The present novel method proved to be useful for the study of BMAT biology.

  8. Safety of autologous bone marrow aspiration concentrate transplantation: initial experiences in 101 patients

    Directory of Open Access Journals (Sweden)

    Christian Hendrich

    2009-12-01

    Full Text Available The clinical application of cellular based therapies with ex vivo cultivation for the treatment of diseases of the musculoskeletal system has until now been limited. In particular, the advanced laboratory and technical effort necessary, regulatory issues as well as high costs are major obstacles. On the other hand, newly developed cell therapy systems permit intra-operative enrichment and application of mesenchymal and progenitor stem cells from bone marrow aspirate concentrate (BMAC in one single operative session. The objective of the present clinical surveillance study was to evaluate new bone formation after the application of BMAC as well as to record any possible therapy-specific complications For this purpose, the clinical-radiological progress of a total of 101 patients with various bone healing disturbances was documented (surveillance study. The study included 37 necrosis of the head of the femur, 32 avascular necroses/bone marrow edema of other localization, 12 non-unions, 20 other defects. The application of BMAC was performed in the presence of osteonecrosis via a local injection as part of a core decompression (n=72 or by the local adsorption of intra-operative cellular bone substitution material (scaffold incubated with BMAC during osteosynthesis (n=17 or in further surgery (n=12. After an average of 14 months (2-24 months, the patients were re-examined clinically and radiologically and interviewed. Further surgery was necessary in 2 patients within the follow-up period. These were due to a progression of a collapsed head of the femur with initial necrosis in ARCO Stage III, as well as inadequate new bone formation with secondary loss of correction after periprosthetic femoral fracture. The latter healed after repeated osteosynthesis plus BMAC application without any consequences. Other than these 2 patients, no further complications were observed. In particular, no infections, no excessive new bone formation, no induction of

  9. Bone disease in haemoglobin disorders

    Directory of Open Access Journals (Sweden)

    Ersi Voskaridou

    2013-03-01

    Full Text Available Bone disease represents a prominent cause of morbidity in patients with thalassaemia and other haemoglobin disorders. The delay in sexual maturation, the presence of diabetes and hypothyroidism, the parathyroid gland dysfunction, the haemolytic anaemia, the progressive marrow expansion, the iron toxicity on osteoblasts, the iron chelators, and the deficiency of growth hormone or insulin growth factors have been identified as major causes of osteoporosis in thalassaemia. Adequate hormonal replacement, effective iron chelation, improvement of hemoglobin levels, calcium and vitamin D administration, physical activity, and smoking cessation are the main to-date measures for the management of the disease. During the last decade, novel pathogenetic data suggest that the reduced osteoblastic activity, which is believed to be the basic mechanism of bone loss in thalassemia, is accompanied by a comparable or even greater increase in bone resorption. Therefore, potent inhibitors of osteoclast activation, such as the aminobisphosphonates, arise as key drugs for the management of osteoporosis in thalassaemia patients and other haemoglobin disorders.

  10. Possible mechanisms of retinal function recovery with the use of cell therapy with bone marrow-derived stem cells

    Directory of Open Access Journals (Sweden)

    Rubens Camargo Siqueira

    2010-10-01

    Full Text Available Bone marrow has been proposed as a potential source of stem cells for regenerative medicine. In the eye, degeneration of neural cells in the retina is a hallmark of such widespread ocular diseases as age-related macular degeneration (AMD and retinitis pigmentosa. Bone marrow is an ideal tissue for studying stem cells mainly because of its accessibility. Furthermore, there are a number of well-defined mouse models and cell surface markers that allow effective study of hematopoiesis in healthy and injured mice. Because of these characteristics and the experience of bone marrow transplantation in the treatment of hematological disease such as leukemia, bone marrow-derived stem cells have also become a major tool in regenerative medicine. Those cells may be able to restore the retina function through different mechanisms: A cellular differentiation, B paracrine effect, and C retinal pigment epithelium repair. In this review, we described these possible mechanisms of recovery of retinal function with the use of cell therapy with bone marrow-derived stem cells.

  11. Bone Marrow Cells in Acute Lymphoblastic Leukemia Create a Proinflammatory Microenvironment Influencing Normal Hematopoietic Differentiation Fates

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    Armando Vilchis-Ordoñez

    2015-01-01

    Full Text Available B-cell acute lymphoblastic leukemia (B-ALL is a serious public health problem in the pediatric population worldwide, contributing to 85% of deaths from childhood cancers. Understanding the biology of the disease is crucial for its clinical management and the development of therapeutic strategies. In line with that observed in other malignancies, chronic inflammation may contribute to a tumor microenvironment resulting in the damage of normal processes, concomitant to development and maintenance of neoplastic cells. We report here that hematopoietic cells from bone marrow B-ALL have the ability to produce proinflammatory and growth factors, including TNFα, IL-1β, IL-12, and GM-CSF that stimulate proliferation and differentiation of normal stem and progenitor cells. Our findings suggest an apparently distinct CD13+CD33+ population of leukemic cells contributing to a proinflammatory microenvironment that may be detrimental to long-term normal hematopoiesis within B-ALL bone marrow.

  12. The prostate cancer bone marrow niche: more than just ‘fertile soil’

    Institute of Scientific and Technical Information of China (English)

    Elisabeth A Pedersen; Yusuke Shiozawa; Kenneth J Pienta; Russell S Taichman

    2012-01-01

    The hematopoietic stem cell (HSC) niche in the bone marrow has been studied extensively over the past few decades,yet the bone marrow micmenvironment that supports the growth of metastatic prostate cancer (PCa) has only been recently considered to be a specialized ‘niche' as well.New evidence supports the fact that disseminated tumor cells (DTCs) of PCa actually target the HSC niche,displace the occupant HSCs and take up residence in the pre-existing niche space.This review describes some of the evidence and mechanisms by which DTCs act as molecular parasites of the HSC niche.Furthermore,the interactions between DTCs,HSCs and the niche may provide new targets for niche-directed therapy,as well as insight into the perplexing clinical manifestations of metastatic PCa disease.

  13. Bone Marrow Transplantation in Mice as a Tool to Generate Genetically Modified Animals

    Science.gov (United States)

    Rőszer, Tamás; Pintye, Éva; Benkő, Ilona

    2008-12-01

    Transgenic mice can be used either as models of known inherited human diseases or can be applied to perform phenotypic tests of genes with unknown function. In some special applications of gene modification we have to create a tissue specific mutation of a given gene. In some cases however the gene modification can be lethal in the intrauterine life, therefore we should engraft the mutated cells in the postnatal life period. After total body irradiation transplantation of bone marrow cells can be a solution to introduce mutant hematopoietic stem cells into a mature animal. Bone marrow transplantation is a useful and novel tool to study the role of hematopoietic cells in the pathogenesis of inflammation, autoimmune syndromes and many metabolic alterations coupled recently to leukocyte functions.

  14. Factors that influence Greeks' decision to register as potential bone marrow donors.

    Science.gov (United States)

    Galanis, P A; Sparos, L D; Katostaras, T; Velonakis, E; Kalokerinou, A

    2008-06-01

    Hemopoietic stem cells can be used from bone marrow or blood or umbilical cord blood of matched siblings or appropriately matched unrelated volunteers. Today, large bone marrow registries have been established to help identify volunteer unrelated bone marrow donors for patients lacking a family donor. Despite there being almost 10 million registered potential bone marrow donors (PBMD) worldwide, only 50% of white patients have a suitable bone marrow match. Growth in the number of PBMD increases the likelihood of finding a compatible donor for a patient. The attitudes and knowledge of 250 registered PBMD and 315 not registered PBMD toward bone marrow donation, tissues and organs donation, and blood donation were surveyed, using a questionnaire with 27 items. Multivariate logistic regression identified gender (females more often than males), regular blood donation, having a relative or a friend who has already been registered as PBMD, having a relative or a friend who needs bone marrow transplantation, family discussion about tissue and organ donation, knowledge about bone marrow transplantation, information about bone marrow transplantation, and trust in health professionals were independent predictive factors influencing people's decision to register as PBMD. Knowledge of these factors is important to target recruitment efforts.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Guihong Li

    2016-01-01

    Full Text Available 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.

  17. A stepwise procedure for isolation of murine bone marrow and generation of dendritic cells

    Directory of Open Access Journals (Sweden)

    Alka Madaan

    2014-02-01

    Full Text Available Bone marrow derived Dendritic cells (BMDCs are routinely employed in cell based assays to evaluate immunomodulatory and anti-inflammatory activities. Hence, simplified, stepwise, defined and standardized methods are required for isolation of bone marrow cells from mice, propagating them in presence of growth factors and obtaining high and reproducible yields of BMDCs. Here, we describe a detailed, stepwise protocol with pictorial representation to isolate bone marrow from mouse femur and development of dendritic cells. Mouse bone marrow cells are cultured in presence of granulocyte-macrophage colony stimulating factor (GM-CSF for 6 days to generate BMDCs.

  18. Endocrine dysfunction after bone marrow transplantation during childhood and adolescence

    Directory of Open Access Journals (Sweden)

    Hye Young Jin

    2010-03-01

    Full Text Available Purpose : Several complications can occur in patients who received bone marrow transplantation (BMT during childhood and adolescence. This study aims to investigate endocrine dysfunctions after BMT so that better care can be provided to care for long-term survivors of BMT. Methods : One hundred patients (61 males, 39 females were included in this study. Clinical parameters such as initial diagnosis, age at BMT, conditioning regimen, presence of graft-versus-host disease (GVHD, growth pattern, thyroid function, and pubertal status were retrospectively reviewed to evaluate risk factors associated with endocrine dysfunction. Results : Height standard deviation score (SDS at BMT, after 1 year of BMT, and at the last visit were 0.08¡?#?.04;, -0.09¡?#?1.0;2, and -0.27¡?#?.18;, respectively (P=0.001. Height SDS significantly decreased in patients who received total body irradiation (TBI (P=0.017. One of the patients who received TBI demonstrated growth hormone deficiency. Thirty (31.9% of 94 patients had compensated hypothyroidism. Incidence of compensated hypothyroidism was higher among those who had GVHD (odds ratio 2.82, P=0.025. Of the 32 patients (17 males, 15 females who were over 14 years in male and 13 years in female at the last visit, 16 (3 males, 13 females had increased luteinizing hormone (LH or follicle-stimulating hormone (FSH. Abnormal elevation of LH or FSH was more common in females (odds ratio 30.3, P=0.001. Conclusion : The most common endocrine dysfunction was ovarian insufficiency. Regular check-up for endocrine function needs to be required due to high incidence of endocrine dysfunction in patients with BMT.

  19. Hypercalciuric Bone Disease

    Science.gov (United States)

    Favus, Murray J.

    2008-09-01

    Hypercalciuria plays an important causal role in many patients with calcium oxalate (CaOx) stones. The source of the hypercalciuria includes increased intestinal Ca absorption and decreased renal tubule Ca reabsorption. In CaOx stone formers with idiopathic hypercalciuria (IH), Ca metabolic balance studies have revealed negative Ca balance and persistent hypercalciuria in the fasting state and during low dietary Ca intake. Bone resorption may also contribute to the high urine Ca excretion and increase the risk of bone loss. Indeed, low bone mass by DEXA scanning has been discovered in many IH patients. Thiazide diuretic agents reduce urine Ca excretion and may increase bone mineral density (BMD), thereby reducing fracture risk. Dietary Ca restriction that has been used unsuccessfully in the treatment of CaOx nephrolithiasis in the past may enhance negative Ca balance and accelerate bone loss. DEXA scans may demonstrate low BMD at the spine, hip, or forearm, with no predictable pattern. The unique pattern of bone histologic changes in IH differs from other causes of low DEXA bone density including postmenopausal osteoporosis, male hypogonadal osteoporosis, and glucocorticoid-induced osteoporosis. Hypercalciuria appears to play an important pathologic role in the development of low bone mass, and therefore correction of urine Ca losses should be a primary target for treatment of the bone disease accompanying IH.

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

    Science.gov (United States)

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

    2016-01-01

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

  1. Bone marrow transplantation in patients with Thalassemia

    Directory of Open Access Journals (Sweden)

    Ghavamzadeh A

    1993-05-01

    Full Text Available During April, 1991 and September, 1993, eighteen patients with major thalassemia admitted to Shariati BMT center. Seventeen patients were transplanted were from HLA identical siblings and one from. his HLA identical father. Eleven of the donors were the known cases of minor thalassemia. The range of patients' age was within 3-10 years (with the average of 5 years and 11 months. Among them, seven patients were male and eleven were female. As the other international BMT centers, we classified our patients into three classes. Our criteria for this classification were hepatomegaly, ferretin, and liver fibrous; 60% of our patients were put in class I and 40% in class II. All of our patients revealed a GVHD (severe graft vs. host disease three weeks post-BMT as pruritus, diarrhea, and skin erythema especially in hands and feet. Two of the patients showed severe GVHD. One of the patients had chimerism after BMT. Although one year after BMT has passed, the patients is still depended on blood transfusion. One patient, despite graft rejection, died nine months post-BMT; another one died after +70 due to GVHD. During 2.5 years, the overall graft survival rate was 88% in our center

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

    Science.gov (United States)

    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.

  3. Bone marrow and nonbone marrow Toll like receptor 4 regulate acute hepatic injury induced by endotoxemia.

    Directory of Open Access Journals (Sweden)

    Edith Hochhauser

    Full Text Available BACKGROUND: Toll-like receptors (TLRs are expressed in immune cells and hepatocytes. We examined whether hepatic Toll-like receptor 4 (TLR4 is involved in the acute hepatic injury caused by the administration of lipopolysaccharide (LPS (septic shock model. METHODS: Wild type (WT, TLR4-deficient and chimera mice underwent myeloablative bone marrow transplantation to dissociate between TLR4 expression in the liver or in the immune-hematopoietic system. Mice were injected with LPS and sacrificed 4 hours later. RESULTS: Compared to TLR4 deficient mice, WT mice challenged with LPS displayed increased serum liver enzymes and hepatic cellular inflammatory infiltrate together with increased serum and hepatic levels of interleukin 1β (IL-1β, tumor necrosis factor α (TNFα ,Up-regulation of hepatic mRNA encoding TLR4, IκB and c-jun expressions. TLR4 mutant mice transplanted with WT bone marrow were more protected than WT chimeric mice bearing TLR4 mutant hemopoietic cells from LPS, as seen by IL-1β and TNFα levels. We then used hepatocytes (Huh7 and macrophages from monocytic cell lines to detect TLR mRNA expression. Macrophages expressed a significantly higher level of TLR4 mRNA and TLR2 (more than 3000- and 8000-fold respectively compared with the hepatocyte cell line. LPS administration induced TLR4 activation in a hepatocyte cell line in a dose dependent manner while TLR2 mRNA hardly changed. CONCLUSIONS: These results suggest that TLR4 activation of hepatocytes participate in the immediate response to LPS induced hepatic injury. However, in this response, the contribution of TLR4 on bone marrow derived cells is more significant than those of the hepatocytes. The absence of the TLR4 gene plays a pivotal role in reducing hepatic LPS induced injury.

  4. Bone marrow transplantation for thalassemia: a global perspective

    Directory of Open Access Journals (Sweden)

    Mohamed Hamed Hussein

    2013-03-01

    Full Text Available Even though severe thalassemia is a preventable disease, over 100,000 new cases are born yearly, particularly in the Middle East and South-East Asia. Most of these children may not reach adulthood because long-term appropriate supportive care is either inaccessible or unaffordable. Bone marrow transplantation (BMT remains the only available definitive cure and success rates can be very high in appropriately selected patients, i.e. low-risk younger children with a matched family donor. In these circumstances BMT may be justified medically, ethically as well as financially, in fact, the cost of low-risk BMT is equivalent to that of a few years of non-curative supportive. This manuscript will briefly review the current status of bone marrow transplantation for thalassemia major with particular emphasis on a global prospective and present the experience of the Cure2Children Foundation supporting sustainable and scalable start up BMT programs in low-resource settings. The initial twelve consecutive patients managed in two start up BMT units in Pakistan (Children’s Hospital of the Pakistan Institute of Medical Sciences, Islamabad and India (South East Asia Institute for Thalassemia, Jaipur were included in this analysis. These initial six patients per each institution where purposely chosen as the focus of this report because they represent the steepest phase of the learning curve. The median age at transplant was 3.9 years, range 0.9 to 6.0, liver was no greater than 2 cm from costal margin, and all received matched related BMT. A structured on-site focused training program as well as ongoing intensive on-line cooperation was provided by the Cure2Children team of professionals. At a median follow-up of 7.5 months (range 3.5 to 33.5 months both thalassemia-free and overall survival are 92%, one patient died of encephalitis-meningitis of unknown cause. No rejections where observed. Neutrophil recovery occurred at a median of 15.5 days (range 13

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  7. Contribution of bone marrow derived cells to pancreatic carcinogenesis

    Directory of Open Access Journals (Sweden)

    Christopher J Scarlett

    2013-03-01

    Full Text Available Pancreatic cancer is a complex, aggressive and heterogeneous malignancy driven by the multifaceted interactions within the tumor microenvironment. While it is known that the tumor microenvironment accommodates many cell types, each playing a key role in tumorigenesis, the major source of these stromal cells is not well understood. This review examines the contribution of bone marrow-derived cells (BMDC to pancreatic carcinogenesis, with respect to their role in constituting the tumor microenvironment. In particular, their role in supporting fibrosis, immunosuppression and neovascularisation will be discussed.

  8. Late health effects of chronic radiation exposure of bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Yarmoshenko, Ilia V.; Malinovsky, Georgy P.; Konshina, Lidia G.; Zhukovsky, Michael V. [Institute of Industrial Ecology UB RAS, 620219, 20, Sophy Kovalevskoy St., Ekaterinburg (Russian Federation); Tuzankina, Irina A. [Institute of Immunology and Physiology UB RAS, 620049, 106, Pervomayskaya St., Ekaterinburg (Russian Federation)

    2014-07-01

    infectious etiology, which are unexpected due to low doses absorbed in those organs and tissues. To analyze the unexpected results recent findings on strong attributability of stomach, liver and cervix cancers to bacterial and viral infections was taken into account. According to IARC, stomach cancer relative risk associated with helicobacter pillory is 5.6, liver cancer relative risks associated with HBV and HCV are 23 and 17 respectively, cervix cancer relative risk associated with HPV is >100. At the same time association of lung cancer, colon cancer and some other common malignancies with infections is either not established or of low significance. To explain observed effects we suggested that excess mortality due to cancer and non-cancer diseases of infectious etiology is associated with radiation exposure of bone marrow due to Sr-90. Irradiation of hematopoietic stem cells and progenitor cells damages hematopoiesis and suppresses the immune response. Secondary immune deficiency induced by chronic radiation increases susceptibility to the bacterial and viral infections. Such late effect of radiation exposure can be considered within the concept of deterministic tissue reactions. (Under support of UB RAS project 12-P-2-1033). (authors)

  9. Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

    Science.gov (United States)

    Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

    2016-01-01

    Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone-fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues - subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT - is differently associated with bone mineral density (BMD) variations. However, compared with the other fat depots, BMAT displays striking features that makes it a substantial actor in bone alterations. BMAT quantity is well associated with BMD loss in aging, menopause, and other metabolic conditions, such as anorexia nervosa. Consequently, BMAT is sensed as a relevant marker of a compromised bone integrity. However, analyses of BMAT development in metabolic diseases (obesity and diabetes) are scarce and should be, thus, more systematically addressed to better apprehend the bone modifications in that pathophysiological contexts. Moreover, bone marrow (BM) adipogenesis occurs throughout the whole life at different rates. Following an ordered spatiotemporal expansion, BMAT has turned to be a heterogeneous fat depot whose adipocytes diverge in their phenotype and their response to stimuli according to their location in bone and BM. In vitro, in vivo, and clinical studies point to a detrimental role of BM adipocytes (BMAs) throughout the release of paracrine factors that modulate osteoblast and/or osteoclast formation and function. However, the anatomical dissemination and the difficulties to access BMAs still hamper our understanding of the relative contribution of BMAT secretions compared with those of peripheral adipose tissues. A further characterization of the phenotype and the functional regulation of BMAs are ever more required. Based on currently available data and comparison with other fat tissues

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

    Science.gov (United States)

    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 (P0.05). 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 (Pregeneration, although the combined approach seems to be relevant, especially to bone formation out of the implant threads.

  11. Further development of a model of chronic bone marrow aplasia in the busulphan-treated mouse.

    Science.gov (United States)

    Turton, John A; Sones, William R; Andrews, Charles M; Pilling, Andrew M; Williams, Thomas C; Molyneux, Gemma; Rizzo, Sian; Gordon-Smith, Edward C; Gibson, Frances M

    2006-02-01

    Aplastic anaemia (AA) in man is an often fatal disease characterized by pancytopenia of the peripheral blood and aplasia of the bone marrow. AA is a toxic effect of many drugs and chemicals (e.g. chloramphenicol, azathioprine, phenylbutazone, gold salts, penicillamine and benzene). However, there are no widely used or convenient animal models of drug-induced AA. Recently, we reported a new model of chronic bone marrow aplasia (CBMA = AA) in the busulphan (BU)-treated mouse: eight doses of BU (10.50 mg/kg) were administered to female BALB/c mice over a period of 23 days; CBMA was evident at day 91/112 post-dosing with significantly reduced erythrocytes, platelets, leucocytes and nucleated bone marrow cell counts. However, mortality was high (49.3%). We have now carried out a study to modify the BU-dosing regime to induce CBMA without high mortality, and investigated the patterns of cellular responses in the blood and marrow in the post-dosing period. Mice (n = 64/65) were dosed 10 times with BU at 0 (vehicle control), 8.25, 9.0 and 9.75 mg/kg over 21 days and autopsied at day 1, 23, 42, 71, 84, 106 and 127 post-dosing (n = 7-15); blood and marrow samples were examined. BU induced a predictable bone marrow depression at day 1 post-dosing; at day 23/42 post-dosing, parameters were returning towards normal during a period of recovery. At day 71, 84, 106 and 127 post-dosing, a stabilized, late-stage, nondose-related CBMA was evident in BU-treated mice, with decreased erythrocytes, platelets and marrow cell counts, and increased MCV. At day 127 post-dosing, five BU-treated mice showed evidence of lymphoma. In this study, mortality was low, ranging from 3.1% (8.25 mg/kg BU) to 12.3% (9.75 mg/kg BU). It is concluded that BU at 9.0 mg/kg (or 9.25 mg/kg) is an appropriate dose level to administer (10 times over 21 days) to induce CBMA at approximately day 50-120 post-dosing.

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

    Science.gov (United States)

    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.

  13. Bone-Marrow-Derived Mesenchymal Stem Cells for Organ Repair

    Directory of Open Access Journals (Sweden)

    Ming Li

    2013-01-01

    Full Text Available Mesenchymal stem cells (MSCs are prototypical adult stem cells with the capacity for self-renewal and differentiation with a broad tissue distribution. MSCs not only differentiate into types of cells of mesodermal lineage but also into endodermal and ectodermal lineages such as bone, fat, cartilage and cardiomyocytes, endothelial cells, lung epithelial cells, hepatocytes, neurons, and pancreatic islets. MSCs have been identified as an adherent, fibroblast-like population and can be isolated from different adult tissues, including bone marrow (BM, umbilical cord, skeletal muscle, and adipose tissue. MSCs secrete factors, including IL-6, M-CSF, IL-10, HGF, and PGE2, that promote tissue repair, stimulate proliferation and differentiation of endogenous tissue progenitors, and decrease inflammatory and immune reactions. In this paper, we focus on the role of BM-derived MSCs in organ repair.

  14. Gene-modified bone marrow cell therapy for prostate cancer.

    Science.gov (United States)

    Wang, H; Thompson, T C

    2008-05-01

    There is a critical need to develop new and effective cancer therapies that target bone, the primary metastatic site for prostate cancer and other malignancies. Among the various therapeutic approaches being considered for this application, gene-modified cell-based therapies may have specific advantages. Gene-modified cell therapy uses gene transfer and cell-based technologies in a complementary fashion to chaperone appropriate gene expression cassettes to active sites of tumor growth. In this paper, we briefly review potential cell vehicles for this approach and discuss relevant gene therapy strategies for prostate cancer. We further discuss selected studies that led to the conceptual development and preclinical testing of IL-12 gene-modified bone marrow cell therapy for prostate cancer. Finally, we discuss future directions in the development of gene-modified cell therapy for metastatic prostate cancer, including the need to identify and test novel therapeutic genes such as GLIPR1.

  15. Autologous bone marrow stem cell intralesional transplantation repairing bisphosphonate related osteonecrosis of the jaw

    Directory of Open Access Journals (Sweden)

    Cella Luigi

    2011-08-01

    Full Text Available Abstract Purpose Bisphosphonate - related osteonecrosis of the JAW (BRONJ is a well known side effect of bisphosphonate therapies in oncologic and non oncologic patients. Since to date no definitive consensus has been reached on the treatment of BRONJ, novel strategies for the prevention, risk reduction and treatment need to be developed. We report a 75 year old woman with stage 3 BRONJ secondary to alendronate and pamidronate treatment of osteoporosis. The patient was unresponsive to recommended treatment of the disease, and her BRONJ was worsening. Since bone marrow stem cells are know as being multipotent and exhibit the potential for differentiation into different cells/tissue lineages, including cartilage, bone and other tissue, we performed autologous bone marrow stem cell transplantation into the BRONJ lesion of the patient. Methods Under local anesthesia a volume of 75 ml of bone marrow were harvested from the posterior superior iliac crest by aspiration into heparinized siringes. The cell suspension was concentrated, using Ficoll - Hypaque® centrifugation procedures, in a final volume of 6 ml. Before the injection of stem cells into the osteonecrosis, the patient underwent surgical toilet, local anesthesia was done and spongostan was applied as a carrier of stem cells suspension in the bone cavity, then 4 ml of stem cells suspension and 1 ml of patient's activated platelet-rich plasma were injected in the lesion of BRONJ. Results A week later the residual spongostan was removed and two weeks later resolution of symptoms was obtained. Then the lesion improved with progressive superficialization of the mucosal layer and CT scan, performed 15 months later, shows improvement also of bone via concentric ossification: so complete healing of BRONJ (stage 0 was obtained in our patient, and 30 months later the patient is well and without signs of BRONJ. Conclusion To our knowledge this is the first case of BRONJ successfully treated with

  16. Natural killer function following allogeneic bone marrow transplantation. Very early reemergence but strong dependence of cytomegalovirus infection

    DEFF Research Database (Denmark)

    Hokland, M; Jacobsen, N; Ellegaard, J;

    1988-01-01

    Natural killer (NK) cell function was followed sequentially after allogeneic bone marrow transplantation (BMT) using three approaches: (1) chromium-release assay with purified mononuclear effector cells, (2) chromium-release assay with whole blood effectors, and 3) enumeration of lymphocytes......) infections (primary or reactivated). In contrast, the presence of graft-versus-host (GVH) disease did not associate with consistent changes in the NK parameters measured here. After the first month of increase, NK declined reaching levels near those observed in their respective bone marrow donors at day 90...

  17. Immunoglobulin M concentration in Waldenström macroglobulinemia: correlation with bone marrow B cells and plasma cells.

    Science.gov (United States)

    de Tute, Ruth M; Rawstron, Andy C; Owen, Roger G

    2013-04-01

    Serum immunoglobulin (Ig) M levels vary considerably among patients with Waldenström macroglobulinemia, and previous studies have failed to demonstrate a correlation with overall bone marrow disease burden. In this study, bone marrow B cells and plasma cells were enumerated by flow cytometry and correlated with serum IgM concentrations. Monotypic B cells comprised a median of 6% of bone marrow leukocytes but did not correlate with IgM levels (r = 0.071, P = .5). Plasma cells, although typically present in lower numbers (median, 0.52%) did show a correlation with IgM (r = 0.452, P = .01). IgM levels in Waldenström macroglobulinemia, at least in part, correlate with the degree of plasma cell differentiation seen within the tumor.

  18. [Role of Bone Marrow Mesenchymal Stem Cells in Resistance of Chronic Myeloid Leukemia to Tyrosine Kinase Inhibitors -Review].

    Science.gov (United States)

    Zhang, Xiao-Yan; Wan, Qian; Fang, Li-Jun; Li, Jian

    2016-12-01

    Chronic myeloid leukemia (CML) is a disease originated from malignant hematopoietic stem cell disorder. In CML, mesenchymal stem cells(MSC) have been changed in the bone marrow microenvironment, which can protect the leukemia cells from apoptosis induced by tyrosine kinase inhibitors (TKI) and lead to the resistance to TKI by the secretion of soluble factors, involvement in cell-cell adhesion, and so on. This review mainly focuses on the changes of the bone marrow mesenchymal stem cells in CML, as well as the role and mechanism of MSC in the CML resistance of TKI. The concrete probrems dicussing in this review are role of MSC in bone marrow microenviroment, characteristics of MSC in CML, the related mechanisms of MSC in drug resistance and so on.

  19. Quantitative and phenotypic analysis of bone marrow-derived cells in the intact and inflamed central nervous system.

    Science.gov (United States)

    Short, Martin A; Campanale, Naomi; Litwak, Sara; Bernard, Claude C A

    2011-01-01

    Bone marrow has been proposed as a possible source of cells capable of replacing injured neural cells in diseases such as Multiple Sclerosis (MS). Previous studies have reported conflicting results regarding the transformation of bone marrow cells into neural cells in vivo. This study is a detailed analysis of the fate of bone marrow derived cells (BMDC) in the CNS of C57Bl/6 mice with and without experimental autoimmune encephalomyelitis using flow cytometry to identify GFP-labeled BMDC that lacked the pan-hematopoietic marker, CD45 and co-expressed neural markers polysialic acid-neural cell adhesion molecule or A2B5. A small number of BMDC displaying neural markers and lacking CD45 expression was identified within both the non-inflamed and inflamed CNS. However, the majority of BMDC exhibited a hematopoietic phenotype.

  20. Review of Preclinical and Clinical Studies of Bone Marrow-Derived Cell Therapies for Intracerebral Hemorrhage

    Directory of Open Access Journals (Sweden)

    Paulo Henrique Rosado-de-Castro

    2016-01-01

    Full Text Available Stroke is the second leading cause of mortality worldwide, causing millions of deaths annually, and is also a major cause of disability-adjusted life years. Hemorrhagic stroke accounts for approximately 10 to 27% of all cases and has a fatality rate of about 50% in the first 30 days, with limited treatment possibilities. In the past two decades, the therapeutic potential of bone marrow-derived cells (particularly mesenchymal stem cells and mononuclear cells has been intensively investigated in preclinical models of different neurological diseases, including models of intracerebral hemorrhage and subarachnoid hemorrhage. More recently, clinical studies, most of them small, unblinded, and nonrandomized, have suggested that the therapy with bone marrow-derived cells is safe and feasible in patients with ischemic or hemorrhagic stroke. This review discusses the available evidence on the use of bone marrow-derived cells to treat hemorrhagic strokes. Distinctive properties of animal studies are analyzed, including study design, cell dose, administration route, therapeutic time window, and possible mechanisms of action. Furthermore, clinical trials are also reviewed and discussed, with the objective of improving future studies in the field.

  1. Safety assessment of bone marrow derived MSC grown in platelet-rich plasma

    Directory of Open Access Journals (Sweden)

    Shoji Fukuda

    2015-06-01

    Full Text Available The injection of endothelial progenitor cells and mononuclear cells derived from bone marrow at the ischemic region of peripheral artery disease patients is reported to be effective for therapeutic angiogenesis; however, these cell therapies require large amounts of bone marrow to obtain sufficient numbers of cells. To solve this problem, we attempted to culture bone-marrow-derived mesenchymal stem cells (BM-MSC, which are supposed to secrete several cytokines that promote angiogenesis. We also focused on using platelet-rich plasma (PRP as a supplement for cell culture instead of fetal bovine serum. Human BM-MSC obtained from healthy volunteers expanded rapidly when cultured with 10% PRP prepared from their own blood. FACS analysis revealed that these cultured human MSC were homogeneous populations, and chromosomal analysis showed a normal karyotype. Moreover, the angiogenetic effect was apparent two weeks after human BM-MSC were injected into the ischemic muscle in SCID mice. Tumor formation was not detected three months after injection into SCID mice either subcutaneously or intramuscularly. To simulate clinical settings, canine BM-MSC were grown with canine PRP and injected into their ischemic muscles. We confirmed that donor cells existed in situ two and six weeks after operation without any side effects. These results suggest that cultured human BM-MSC can be a promising cell source for therapeutic angiogenesis.

  2. Review of Preclinical and Clinical Studies of Bone Marrow-Derived Cell Therapies for Intracerebral Hemorrhage

    Science.gov (United States)

    de Carvalho, Felipe Gonçalves; de Freitas, Gabriel Rodriguez

    2016-01-01

    Stroke is the second leading cause of mortality worldwide, causing millions of deaths annually, and is also a major cause of disability-adjusted life years. Hemorrhagic stroke accounts for approximately 10 to 27% of all cases and has a fatality rate of about 50% in the first 30 days, with limited treatment possibilities. In the past two decades, the therapeutic potential of bone marrow-derived cells (particularly mesenchymal stem cells and mononuclear cells) has been intensively investigated in preclinical models of different neurological diseases, including models of intracerebral hemorrhage and subarachnoid hemorrhage. More recently, clinical studies, most of them small, unblinded, and nonrandomized, have suggested that the therapy with bone marrow-derived cells is safe and feasible in patients with ischemic or hemorrhagic stroke. This review discusses the available evidence on the use of bone marrow-derived cells to treat hemorrhagic strokes. Distinctive properties of animal studies are analyzed, including study design, cell dose, administration route, therapeutic time window, and possible mechanisms of action. Furthermore, clinical trials are also reviewed and discussed, with the objective of improving future studies in the field. PMID:27698671

  3. Transcriptional profiling of bone marrow stromal cells in response to Porphyromonas gingivalis secreted products.

    Directory of Open Access Journals (Sweden)

    Durga Reddi

    Full Text Available Periodontitis is an infectious inflammatory disease that destroys the tooth-supporting (periodontal tissues. Porphyromonas gingivalis is an oral pathogen highly implicated in the pathogenesis of this disease. It can exert its effects to a number of cells, including osteogenic bone marrow stromal cells which are important for homeostastic capacity of the tissues. By employing gene microarray technology, this study aimed to describe the overall transcriptional events (>2-fold regulation elicited by P. gingivalis secreted products in bone marrow stromal cells, and to dissect further the categories of genes involved in bone metabolism, inflammatory and immune responses. After 6 h of challenge with P. gingivalis, 271 genes were up-regulated whereas 209 genes were down-regulated, whereas after 24 h, these numbers were 259 and 109, respectively. The early (6 h response was characterised by regulation of genes associated with inhibition of cell cycle, induction of apoptosis and loss of structural integrity, whereas the late (24 h response was characterised by induction of chemokines, cytokines and their associated intracellular pathways (such as NF-κB, mediators of connective tissue and bone destruction, and suppression of regulators of osteogenic differentiation. The most strongly up-regulated genes were lipocalin 2 (LCN2 and serum amyloid A3 (SAA3, both encoding for proteins of the acute phase inflammatory response. Collectively, these transcriptional changes elicited by P. gingivalis denote that the fundamental cellular functions are hindered, and that the cells acquire a phenotype commensurate with propagated innate immune response and inflammatory-mediated tissue destruction. In conclusion, the global transcriptional profile of bone marrow stromal cells in response to P. gingivalis is marked by deregulated homeostatic functions, with implications in the pathogenesis of periodontitis.

  4. Autologous bone marrow-derived stem cells in amyotrophic lateral sclerosis: A pilot study

    Directory of Open Access Journals (Sweden)

    Sudesh Prabhakar

    2012-01-01

    Full Text Available Background: Amyotrophic lateral sclerosis (ALS is a neurodegenerative disorder with no effective treatment. Stem cell therapy may be one of the promising treatment options for such patients. Aim: To assess the feasibility, efficacy and safety of autologous bone marrow-derived stem cells in patients of ALS. Settings and Design: We conducted an open-label pilot study of autologous bone marrow-derived stem cells in patients with ALS attending the Neurology Clinic of a tertiary care referral centre. Materials and Methods: Ten patients with ALS with mean revised ALS Functional Rating Scale (ALSFRS-R score of 30.2 (± 10.58 at baseline received intrathecal autologous bone marrow-derived stem cells. Primary end point was improvement in the ALSFRS-R score at 90, 180, 270 and 365 days post therapy. Secondary endpoints included ALSFRS-R subscores, time to 4-point deterioration, median survival and reported adverse events. Paired t-test was used to compare changes in ALSFRS-R from baseline and Kaplan-Meier analysis was used for survival calculations. Results: There was no significant deterioration in ALSFRS-R composite score from baseline at one-year follow-up (P=0.090. The median survival post procedure was 18.0 months and median time to 4-point deterioration was 16.7 months. No significant adverse events were reported. Conclusion: Autologous bone marrow-derived stem cell therapy is safe and feasible in patients of ALS. Short-term follow-up of ALSFRS-R scores suggests a trend towards stabilization of disease. However, the benefit needs to be confirmed in the long-term follow-up period.

  5. Investigation analysis of bone marrow cytology of 112 children with blood diseases%儿童血液病112例骨髓细胞学调查分析

    Institute of Scientific and Technical Information of China (English)

    刘静

    2015-01-01

    Objective To analyze the results of bone marrow cytology investigation of children with hematological diseases.Methods A total of 112 children in the department of hematology were selected as the research objects,the types of blood disease were analyzed,and bone marrow cytology was conducted.Results Among the 112 cases,there were 32 cases (28.57%) of red cell system diseases,28 cases (25.00%) of white cell system diseases,39 cases (34.82%) of macrophages andplatelets disease,12 cases (11.61%) of others.The red blood cell system disease mainly were hemolytic anemia and hereditary spherocytosis,accounting for 37.58%,18.75%;leukocyte diseases mainly were ALL,accounting for 60.71%;macrophages and platelet disorders mainly were idiopathic thrombocytopenic purpura,accounting for 74.36%.The incidence of bleeding symptoms,symptoms of anemia,hepatomegaly,fever was relatively high,respectively 38.39%,41.96%,45.54%,43.75%.The incidence of splenomegaly and lymphadenopathy was relatively low,accounting for 10.71% and 8.04%.Conclusions The accompanying system of children with hematological diseases were bleeding,anemia,fever,the incidence of macrophage and platelet diseases is the highest,and the type of the disease mainly is idiopathic thrombocytopenic purpura.%目的 分析儿童血液病的骨髓细胞学调查结果.方法 选择血液科收治的儿童患者112例为研究对象,分析血液病类型并行骨髓细胞学检查.结果 112例患儿中红细胞系统疾病32例(占28.57%),白细胞系统疾病28例(占25.00%),巨噬细胞与血小板疾病39例(占34.82%),其他12例(占11.61%).其中红细胞系统疾病以溶血性贫血、遗传性球形红细胞增多症为主,分别占37.58%、18.75%;白细胞系统疾病以ALL为主,占60.71%;巨噬细胞与血小板疾病以特发性血小板减少性紫癜为主,占74.36%.合并出血症状、贫血症状、肝肿大、发热的发生率相对较高,分别占38.39%、41.96

  6. Gluteal Compartment Syndrome following an Iliac Bone Marrow Aspiration

    Science.gov (United States)

    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

  7. Development of bone marrow mesenchymal stem cell culture in vitro

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li; PENG Li-pan; WU Nan; LI Le-ping

    2012-01-01

    Objective To review the in vitro development of bone marrow mesenchymal stem cells culture (BM-MSC).Data sources The data cited in this review were mainly obtained from articles listed in Medline and PubMed.The search terms were “bone marrow mesenchymal stem cell" and "cell culture".Study selection Articles regarding the in vitro development of BM-MSCs culture,as well as the challenge of optimizing cell culture environment in two-dimensional (2D) vs.3D.Results Improving the culture conditions increases the proliferation and reduces the differentiation.Optimal values for many culture parameters remain to be identified.Expansion of BM-MSCs under defined conditions remains challenging,including the development of optimal culture conditions for BMSC and large-volume production systems.Conclusions Expansion of BM-MSCs under defined conditions remains challenges,including the development of optimal culture conditions for BMSC and scale-up to large-volume production systems.Optimal values for many culture parameters remain to be identified.

  8. Gluteal Compartment Syndrome following an Iliac Bone Marrow Aspiration.

    Science.gov (United States)

    Berumen-Nafarrate, Edmundo; 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.

  9. Degradation of polysaccharide hydrogels seeded with bone marrow stromal cells.

    Science.gov (United States)

    Jahromi, Shiva H; Grover, Liam M; Paxton, Jennifer Z; Smith, Alan M

    2011-10-01

    In order to produce hydrogel cell culture substrates that are fit for the purpose, it is important that the mechanical properties are well understood not only at the point of cell seeding but throughout the culture period. In this study the change in the mechanical properties of three biopolymer hydrogels alginate, low methoxy pectin and gellan gum have been assessed in cell culture conditions. Samples of the gels were prepared encapsulating rat bone marrow stromal cells which were then cultured in osteogenic media. Acellular samples were also prepared and incubated in standard cell culture media. The rheological properties of the gels were measured over a culture period of 28 days and it was found that the gels degraded at very different rates. The degradation occurred most rapidly in the order alginate > Low methoxy pectin > gellan gum. The ability of each hydrogel to support differentiation of bone marrow stromal cells to osteoblasts was also verified by evidence of mineral deposits in all three of the materials. These results highlight that the mechanical properties of biopolymer hydrogels can vary greatly during in vitro culture, and provide the potential of selecting hydrogel cell culture substrates with mechanical properties that are tissue specific.

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

    Science.gov (United States)

    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. Gluteal Compartment Syndrome following an Iliac Bone Marrow Aspiration

    Directory of Open Access Journals (Sweden)

    Edmundo Berumen-Nafarrate

    2013-01-01

    Full Text Available 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.

  12. Entonox as a sedative for bone marrow aspiration and biopsy.

    Science.gov (United States)

    Gudgin, E J; Besser, M W; Craig, J I O

    2008-02-01

    Bone marrow aspiration and biopsy can be a painful procedure. Sedation techniques may make this investigation more acceptable to patients, but have the potential to cause life-threatening complications, as well as requiring additional staff and equipment for safe administration. We assessed the use of Entonox, a 50 : 50 mix of nitrous oxide and oxygen, as a sedation and analgesic agent, and compared it to previous experience with the intravenous (i.v.) benzodiazepine midazolam. Patients' perception of pain, and both the operator and patient's views on the ease of the procedure and safety factors were recorded. Twenty-two patients who had previously required i.v. midazolam sedation (16), or who requested sedation (6) were studied. Fifteen of 16 (94%) found Entonox better or equal to midazolam, and only one patient (6%) found it worse. There were no serious adverse events due to Entonox. We have shown, in this small group of patients, that Entonox is an effective, safe alternative to intravenous midazolam for sedation during bone marrow biopsy, and is considered acceptable by both patients and staff. It has the major advantage that no additional staff or facilities are required for safe administration or monitoring the patient during or after the procedure.

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

    Science.gov (United States)

    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.

  14. Bone marrow findings in autoimmune lymphoproliferative syndrome with germline FAS mutation

    Science.gov (United States)

    Xie, Yi; Pittaluga, Stefania; Price, Susan; Raffeld, Mark; Hahn, Jamie; Jaffe, Elaine S.; Rao, V. Koneti; Maric, Irina

    2017-01-01

    Autoimmune lymphoproliferative syndrome is a rare genetic disorder characterized by defective FAS-mediated apoptosis, autoimmune disease, accumulation of mature T-cell receptor alpha/beta positive, CD4 and CD8 double-negative T cells and increased risk of lymphoma. Despite frequent hematologic abnormalities, literature is scarce regarding the bone marrow pathology in autoimmune lymphoproliferative syndrome. We retrospectively reviewed 3l bone marrow biopsies from a cohort of 240 patients with germline FAS mutations. All biopsies were performed for the evaluation of cytopenias or to rule out lymphoma. Clinical information was collected and morphological, immunohistochemical, flow cytometric and molecular studies were performed. Bone marrow lymphocytosis was the predominant feature, present in 74% (23/31) of biopsies. The lymphoid cells showed several different patterns of infiltration, most often forming aggregates comprising T cells in 15 cases, B cells in one and a mixture of T and B cells in the other seven cases. Double-negative T cells were detected by immunohistochemistry in the minority of cases (10/31; 32%); significantly, all but one of these cases had prominent double-negative T-lymphoid aggregates, which in four cases diffusely replaced the marrow space. One case showed features of Rosai-Dorfman disease, containing scattered S-100+ cells with emperipolesis and double-negative T cells. No clonal B or T cells were detected by polymerase chain reaction in any evaluated cases. Classical Hodgkin lymphoma was identified in three cases. Our results demonstrate that infiltrates of T cells, or rarely B cells, can be extensive in patients with autoimmune lymphoproliferative syndrome, mimicking lymphoma. A multi-modality approach, integrating clinical, histological, immunohistochemical as well as other ancillary tests, can help avoid this diagnostic pitfall. This study is registered at Clinicaltrials.gov ID # NCT00001350 PMID:27846610

  15. 2012478 Biological characteristics of bone marrow mesenchymal stem cells and JAK2 mutation in myeloproliferative neoplasms

    Institute of Scientific and Technical Information of China (English)

    田竑

    2012-01-01

    Objective To study the biological characteristics of bone marrow mesenchymal stem cells(BMSCs) and detect JAK2 mutation in BMSCs from myeloproliferative neoplasms(MPN) patients. Methods JAK2 V617F mutation and exon 12 mutation in 70 MPN patients’ blood or bone marrow samples were detected.

  16. Multiparameter Analysis of Human Bone Marrow Stromal Cells Identifies Distinct Immunomodulatory and Differentiation-Competent Subtypes

    NARCIS (Netherlands)

    S. James (Sally); J. Fox (James); F. Afsari (Farinaz); J. Lee (Jennifer); S. Clough (Sally); C. Knight (Charlotte); J. Ashmore (James); P. Ashton (Peter); O. Preham (Olivier); M.J. Hoogduijn (Martin); R.D.A.R. Ponzoni (Raquel De Almeida Rocha); Y. Hancock; M. Coles (Mark); P.G. Genever (Paul)

    2015-01-01

    textabstractBone marrow stromal cells (BMSCs, also called bone-marrow-derived mesenchymal stromal cells) provide hematopoietic support and immunoregulation and contain a stem cell fraction capable of skeletogenic differentiation. We used immortalized human BMSC clonal lines for multi-level analysis

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

    Science.gov (United States)

    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.

  18. B cell-autonomous somatic mutation deficit following bone marrow transplant

    NARCIS (Netherlands)

    Glas, A.M.

    2000-01-01

    The bone marrow is the major haematopoietic organ and is critically involved in the production of all formed blood elements in postnatal life. The bone marrow contains rapidly dividing cells and therefore is sensitive to DNA damaging agents. In certain types of cancers where a high dose of radiation

  19. CD34 defines an osteoprogenitor cell population in mouse bone marrow stromal cells

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Al-Shammary, Asma; Skagen, Peter

    2015-01-01

    Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) and their progenitors have been identified based on retrospective functional criteria. CD markers are employed to define cell populations with distinct functional characteristics. However, defining and pro...

  20. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Ya-jing Zhou

    2015-01-01

    Full Text Available Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

  1. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Ya-jing Zhou; Jian-min Liu; Shu-ming Wei; Yun-hao Zhang; Zhen-hua Qu; Shu-bo Chen

    2015-01-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administrationvia the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve ifbers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and lfuorogold-labeled nerve ifbers were increased and hindlimb motor function of spinal cord-injured rats was mark-edly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

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

    Science.gov (United States)

    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.

  3. A comparative study of diazepam levels in bone marrow versus serum, saliva and brain tissue.

    Science.gov (United States)

    Takatori, T; Tomii, S; Terazawa, K; Nagao, M; Kanamori, M; Tomaru, Y

    1991-01-01

    The distribution of diazepam in biological fluids and tissues of rats was examined 1, 2, 4 and 8 h after intraperitoneal administration by using a radioimmunoassay with specific anti-diazepam antibody. The diazepam levels in serum, saliva, brain and bone marrow decreased over a period of 2 h and levelled off 4 h after administration. The diazepam concentration in bone marrow was much higher than in serum, saliva and brain, suggesting an accumulation of diazepam in this tissue. This indicates that bone marrow could be a very useful material for the detection of diazepam in skeletonized remains. The diazepam concentrations in bone marrow, serum, saliva and brain showed a linear relationship (r = 0.860-0.997), indicating that a valid estimate of diazepam concentration in blood can be made from bone marrow samples.

  4. Chitosan-collagen porous scaffold and bone marrow mesenchymal stem cell transplantation for ischemic stroke

    Directory of Open Access Journals (Sweden)

    Feng Yan

    2015-01-01

    Full Text Available In this study, we successfully constructed a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold in vitro, transplanted either the composite or bone marrow mesenchymal stem cells alone into the ischemic area in animal models, and compared their effects. At 14 days after co-transplantation of bone marrow mesenchymal stem cells and the hitosan-collagen scaffold, neurological function recovered noticeably. Vascular endothelial growth factor expression and nestin-labeled neural precursor cells were detected in the ischemic area, surrounding tissue, hippocampal dentate gyrus and subventricular zone. Simultaneously, a high level of expression of glial fibrillary acidic protein and a low level of expression of neuron-specific enolase were visible in BrdU-labeled bone marrow mesenchymal stem cells. These findings suggest that transplantation of a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold has a neuroprotective effect following ischemic stroke.

  5. Chitosan-collagen porous scaffold and bone marrow mesenchymal stem cell transplantation for ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Feng Yan; Wei Yue; Yue-lin Zhang; Guo-chao Mao; Ke Gao; Zhen-xing Zuo; Ya-jing Zhang; Hui Lu

    2015-01-01

    In this study, we successfully constructed a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffoldin vitro, transplanted either the composite or bone marrow mesenchymal stem cells alone into the ischemic area in animal models, and compared their effects. At 14 days after co-transplantation of bone marrow mesenchymal stem cells and the hi-tosan-collagen scaffold, neurological function recovered noticeably. Vascular endothelial growth factor expression and nestin-labeled neural precursor cells were detected in the ischemic area, surrounding tissue, hippocampal dentate gyrus and subventricular zone. Simultaneously, a high level of expression of glial ifbrillary acidic protein and a low level of expression of neuron-spe-ciifc enolase were visible in BrdU-labeled bone marrow mesenchymal stem cells. These ifndings suggest that transplantation of a composite of bone marrow mesenchymal stem cells and a chi-tosan-collagen scaffold has a neuroprotective effect following ischemic stroke.

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

    Science.gov (United States)

    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.

  7. Organ-on-a-chip: development and clinical prospects toward toxicity assessment with an emphasis on bone marrow.

    Science.gov (United States)

    Kim, Jeehye; Lee, Hanna; Selimović, Šeila; Gauvin, Robert; Bae, Hojae

    2015-05-01

    Conventional approaches for toxicity evaluation of drugs and chemicals, such as animal tests, can be impractical due to the large experimental scale and the immunological differences between species. Organ-on-a-chip models have recently been recognized as a prominent alternative to conventional toxicity tests aiming to simulate the human in vivo physiology. This review focuses on the organ-on-a-chip applications for high-throughput screening of candidate drugs against toxicity, with a particular emphasis on bone-marrow-on-a-chip. Studies in which organ-on-a-chip models have been developed and utilized to maximize the efficiency and predictability in toxicity assessment are introduced. The potential of these devices to replace tests of acute systemic toxicity in animals, and the challenges that are inherent in simulating the human immune system are also discussed. As a promising approach to overcome the limitations, we further focus on an in-depth analysis of the development of bone-marrow-on-a-chip that is capable of simulating human immune responses against external stimuli due to the key roles of marrow in immune systems with hematopoietic activities. Owing to the complex interactions between hematopoietic stem cells and marrow microenvironments, precise control of both biochemical and physical niches that are critical in maintenance of hematopoiesis remains a key challenge. Thus, recently developed bone-marrow-on-a-chip models support immunogenicity and immunotoxicity testing in long-term cultivation with repeated antigen stimulation. In this review, we provide an overview of clinical studies that have been carried out on bone marrow transplants in patients with immune-related diseases and future aspects of clinical and pharmaceutical application of bone-marrow-on-a-chip.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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, pbone marrow plays a significant role in determining osteoblast and osteoclast activity.

  10. Photodynamic therapy of diseased bone

    Science.gov (United States)

    Bisland, Stuart K.; Yee, Albert; Siewerdsen, Jeffery; Wilson, Brian C.; Burch, Shane

    2005-08-01

    Objective: Photodynamic therapy (PDT) defines the oxygen-dependent reaction that occurs upon light-mediated activation of a photosensitizing compound, culminating in the generation of cytotoxic, reactive oxygen species, predominantly, singlet oxygen. We are investigating PDT treatment of diseased bone. Methods: Using a rat model of human breast cancer (MT-1)-derived bone metastasis we confirmed the efficacy of benzoporphyrin-derivative monoacid (BPD-MA)-PDT for treating metastatic lesions within vertebrae or long bones. Results: Light administration (150 J) 15 mins after BPDMA (2.5 mg/Kg, i.v.) into the lumbar (L3) vertebra of rats resulted in complete ablation of the tumour and surrounding bone marrow 48 hrs post-PDT without paralysis. Porcine vertebrae provided a model comparable to that of human for light propagation (at 150 J/cm) and PDT response (BPD-MA; 6 mg/m2, i.v.) in non-tumour vertebrae. Precise fibre placement was afforded by 3-D cone beam computed tomography. Average penetration depth of light was 0.16 +/- 0.04 cm, however, the necrotic/non-necrotic interface extended 0.6 cm out from the treatment fiber with an average incident fluence rate of 4.3 mW/cm2. Non-necrotic tissue damage was evident 2 cm out from the treatment fiber. Current studies involving BPD-MA-PDT treatment of primary osteosarcomas in the forelimbs of dogs are very promising. Magnetic resonance imaging 24 hr post treatment reveal well circumscribed margins of treatment that encompass the entire 3-4 cm lesion. Finally, we are also interested in using 5-aminolevulinic acid (ALA) mediated PDT to treat osteomyelitis. Response to therapy was monitored as changes in bioluminescence signal of staphylococcus aureus (SA)-derived biofilms grown onto 0.5 cm lengths of wire and subjected to ALA-PDT either in vitro or in vivo upon implant into the intramedullary space of rat tibia. Transcutaneous delivery of PDT (75 J/cm2) effectively eradicated SAbiofilms within bone. Conclusions: Results support

  11. Comparisons of Mouse Mesenchymal Stem Cells in Primary Adherent Culture of Compact Bone Fragments and Whole Bone Marrow

    Directory of Open Access Journals (Sweden)

    Yiting Cai

    2015-01-01

    Full Text Available The purification of mouse bone marrow mesenchymal stem cells (BMSCs by using the standard method of whole bone marrow adherence to plastic still remains ineffective. An increasing number of studies have indicated compact bone as an alternative source of BMSCs. We isolated BMSCs from cultured compact bone fragments and investigated the proliferative capacity, surface immunophenotypes, and osteogenic and adipogenic differentiations of the cells after the first trypsinization. The fragment culture was based on the fact that BMSCs were assembled in compact bones. Thus, the procedure included flushing bone marrow out of bone cavity and culturing the fragments without any collagenase digestion. The cell yield from cultured fragments was slightly less than that from cultured bone marrow using the same bone quantity. However, the trypsinized cells from cultured fragments exhibited significantly higher proliferation and were accompanied with more CD90 and CD44 expressions and less CD45 expression. The osteogenic and adipogenic differentiation capacity of cells from cultured fragments were better than those of cells from bone marrow. The directly adherent culture of compact bone is suitable for mouse BMSC isolation, and more BMSCs with potentially improved proliferation capacity can be obtained in the primary culture.

  12. Improved dopamine transporter binding activity after bone marrow mesenchymal stem cell transplantation in a rat model of Parkinson's disease: small animal positron emission tomography study with F-18 FP-CIT

    Energy Technology Data Exchange (ETDEWEB)

    Park, Bok-Nam; Lee, Kwanjae; An, Young-Sil [School of Medicine, Ajou University, Department of Nuclear Medicine and Molecular Imaging, Woncheon-dong, Yeongtong-gu, Gyeonggi-do, Suwon (Korea, Republic of); Kim, Jang-Hee; Park, So Hyun [Ajou University School of Medicine, Department of Pathology, Suwon (Korea, Republic of)

    2015-05-01

    We evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs) in a model of Parkinson's disease (PD) using serial F-18 fluoropropylcarbomethoxyiodophenylnortropane (FP-CIT) PET. Hemiparkinsonian rats were treated with intravenously injected BMSCs, and animals without stem cell therapy were used as the controls. Serial FP-CIT PET was performed after therapy. The ratio of FP-CIT uptake in the lesion side to uptake in the normal side was measured. The changes in FP-CIT uptake were also analyzed using SPM. Behavioural and histological changes were observed using the rotational test and tyrosine hydroxylase (TH)-reactive cells. FP-CIT uptake ratio was significantly different in the BMSCs treated group (n = 28) at each time point. In contrast, there was no difference in the ratio in control rats (n = 25) at any time point. SPM analysis also revealed that dopamine transporter binding activity was enhanced in the right basal ganglia area in only the BMSC therapy group. In addition, rats that received BMSC therapy also exhibited significantly improved rotational behaviour and preservation of TH-positive neurons compared to controls. The therapeutic effect of intravenously injected BMSCs in a rat model of PD was confirmed by dopamine transporter PET imaging, rotational functional studies, and histopathological evaluation. (orig.)

  13. IL-22 promoted CD3+ T cell infiltration by IL-22R induced STAT3 phosphorylation in murine acute graft versus host disease target organs after allogeneic bone marrow transplantation.

    Science.gov (United States)

    Zhao, Kai; Ruan, Suhong; Tian, Yu; Zhao, Dongmei; Chen, Chong; Pan, Bin; Yan, Zhiling; Yin, Lingling; Zhu, Shengyun; Xu, Kailin

    2016-10-01

    Graft versus host disease (GVHD) is a life threatening complication of bone marrow stem cell transplantation, in which considerable numbers of proinflammatory cytokines secreted by allo-reactive donor T cells are involved. We and other previous studies have found that interleukin-22 (IL-22) was able to aggravate the target organs damage of GVHD. However, the mechanism and the signal pathway of IL-22 in murine acute GVHD was not clear. Here, we observed that compared with GVHD group, more serious pathological damage and more CD3(+) T cells infiltrated in GVHD target organs were detected in the mice injected with IL-22. Meanwhile, transcription factor T-bet, RORγt and AhR respectively associated with Th1, Th17 and Th22 cells changed in varying degrees in different GVHD target organs. Furthermore, the increased expression of IL-22R and its downstream protein P-STAT3 were detected in GVHD mice with IL-22 treated. These results suggested that the pathological role of IL-22 in GVHD target organs contribute to exogenous injected IL-22 as well as secreted IL-22 from the infiltrated allo-reactive effector T cells. In addition, the IL-22R-STAT3 pathway may play important role in GVHD tissue injury and target this way may yield new approaches for reduction of GVHD.

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  17. Modeling Human Bone Marrow Failure Syndromes Using Pluripotent Stem Cells and Genome Engineering.

    Science.gov (United States)

    Jung, Moonjung; Dunbar, Cynthia E; Winkler, Thomas

    2015-12-01

    The combination of epigenetic reprogramming with advanced genome editing technologies opened a new avenue to study disease mechanisms, particularly of disorders with depleted target tissue. Bone marrow failure syndromes (BMFS) typically present with a marked reduction of peripheral blood cells due to a destroyed or dysfunctional bone marrow compartment. Somatic and germline mutations have been etiologically linked to many cases of BMFS. However, without the ability to study primary patient material, the exact pathogenesis for many entities remained fragmentary. Capturing the pathological genotype in induced pluripotent stem cells (iPSCs) allows studying potential developmental defects leading to a particular phenotype. The lack of hematopoietic stem and progenitor cells in these patients can also be overcome by differentiating patient-derived iPSCs into hematopoietic lineages. With fast growing genome editing techniques, such as CRISPR/Cas9, correction of disease-causing mutations in iPSCs or introduction of mutations in cells from healthy individuals enable comparative studies that may identify other genetic or epigenetic events contributing to a specific disease phenotype. In this review, we present recent progresses in disease modeling of inherited and acquired BMFS using reprogramming and genome editing techniques. We also discuss the challenges and potential shortcomings of iPSC-based models for hematological diseases.

  18. Brain-derived neurotrophic factor (BDNF) gene delivery into the CNS using bone marrow cells as vehicles in mice.

    Science.gov (United States)

    Makar, T K; Trisler, D; Eglitis, M A; Mouradian, M M; Dhib-Jalbut, S

    2004-02-19

    Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is protective in animal models of neurodegenerative diseases. However, BDNF has a short half-life and its efficacy in the CNS when delivered peripherally is limited due to the blood-brain barrier. In the present study, bone marrow cells were used as vehicles to deliver the BDNF gene into the CNS. Marrow cells obtained from 6 to 8 week-old SJL/J mice were transduced with BDNF expressing pro-virus. RT-PCR analysis revealed that BDNF mRNA was expressed in transduced but not in non-transduced marrow cells. Additionally, virus transduced marrow cells expressed the BDNF protein (296+/-1.2 unit/ml). BDNF-transduced marrow cells were then transplanted into irradiated mice through the tail vein. Three months post-transplantation, significant increases in BDNF as well as glutamic acid decarboxylase (GAD(67)) mRNA were detected in the brains of BDNF transplanted mice compared to untransplanted animals, indicating biological activity of the BDNF transgene. Thus, bone marrow cells can be used as vehicles to deliver the BDNF gene into the brain with implications for the treatment of neurological diseases.

  19. Mast Cell-activated Bone Marrow Mesenchymal Stromal Cells Regulate Proliferation and Lineage Commitment of CD34+ Progenitor cells

    Directory of Open Access Journals (Sweden)

    Zoulfia eAllakhverdi

    2013-12-01

    Full Text Available Background: Shortly after allergen exposure, the number of bone marrow and circulating CD34+ progenitors increases. We aim to analyze the possible mechanism whereby the allergic reaction stimulates bone marrow to release these effector cells in increased numbers. We hypothesize that mast cells may play a predominant role in this process. Objective: To examine the effect of IgE-activated mast cells on bone marrow mesenchymal stromal cells which regulate proliferation and differentiation of CD34+ progenitors. Methods: Primary mast cells were derived from CD34+ precursors and activated with IgE/anti-IgE. Bone marrow mesenchymal stromal cells were co-cultured with CD34+ progenitor cells and stimulated with IL1/TNF or IgE/anti-IgE activated mast cells in Transwell system. Results: Bone marrow mesenchymal stromal cells produce low level of TSLP under steady state conditions, which is markedly increased by stimulation with proinflammatory cytokines IL-1 and TNF or IgE-activated mast cells. The latter also triggers BM-MSCs production of G-CSF, and GM-CSF while inhibiting SDF-1. Mast cell-activated mesenchymal stromal cells stimulate CD34+ cells to proliferate and to regulate their expression of early allergy-associated genes. Conclusion and Clinical Relevance: This in vitro study indicates that IgE-activated mast cells trigger bone marrow mesenchymal stromal cells to release TSLP and hematopoietic growth factors and to regulate the proliferation and lineage commitment of CD34+ precursor cells. The data predict that the effective inhibition of mast cells should impair mobilization and accumulation of allergic effector cells and thereby reduce the severity of allergic diseases.

  20. Immunophenotypic analysis of abnormal plasma cell clones in bone marrow of primary systemic light chain amyloidosis patients

    Institute of Scientific and Technical Information of China (English)

    Hu Yang; Wang Mangju; Chen Yan; Chen Xue; Fang Fang; Liu Shiqin; Zhang Ying

    2014-01-01

    Background Primary systemic light chain amyloidosis (AL) is a rare plasma cell disease,our purpose was to analyze the immunophenotypic characteristics of the plasma cells in bone marrow in AL patients,and explore whether the detection of abnormal plasma cell clones in bone marrow by flow cytometry (FCM) could be used as an important indicator of AL diagnosis.Methods Fresh bone marrow samples were collected from 51 AL,21 multiple myeloma (MM),and 5 Waldenstr(o)m's macroglobulinemia (WM) patients.The immunophenotype of bone marrow cells were analyzed and compared by FCM using a panel of antibodies including CD45,CD38,CD138,CD117,CD56,and CD19.Results In AL,light chain restriction could be identified in 31 cases (60.9%),in which the λ light chain restriction was found in 24 cases (77.4%).In MM,κ light chain restriction was found in 13 cases (61.9%),and λ light chain restriction in eight cases.CD45 on abnormal plasma cells was negative to weakly positive in both AL and MM,but was positive to strongly positive in WM.In the bone marrow plasma cells of the 51 AL,78.4% were CD56+,68.6% were CD117+,and 88.2% were CD19-.While in the 21 MM cases,66.7% were CD56+,38.1% were CD117+,and 90.4% were CD19-.The plasmacytoid lymphocytes in the five WM patients were CD19+ and CD56-,CD117-.Conclusion Detection of abnormal plasma cell clones in bone marrow by FCM is valuable for the diagnosis of AL.

  1. Quality of harvest and role of cell dose in unrelated bone marrow transplantation: an Italian Bone Marrow Donor Registry-Gruppo Italiano Trapianto di Midollo Osseo Study.

    Science.gov (United States)

    Fagioli, Franca; Quarello, Paola; Pollichieni, Simona; Lamparelli, Teresa; Berger, Massimo; Benedetti, Fabio; Barat, Veronica; Marciano, Renato; Rambaldi, Alessandro; Bacigalupo, Andrea; Sacchi, Nicoletta

    2014-01-01

    In this study, we investigated the factors affecting cell dose harvest and the role of cell dose on outcome. We analysed data from a cohort of 703 patients who underwent unrelated bone marrow transplantation facilitated by IBMDR in GITMO centers between 2002 and 2008. The median-infused cell doses is 3.7 × 10(8)/kg, the correlation between the nucleated cells requested from transplant centers and those harvested by collection centers was adequate. A harvested/requested cells ratio lower than 0.5 was observed only in 3% of harvests. A volume of harvested marrow higher than the median value of 1270 ml was related to a significant lower infused cell dose (χ(2): 44.4; P < 0.001). No patient- or donor-related variables significantly influenced the cell dose except for the recipient younger age (χ(2): 95.7; P < 0.001) and non-malignant diseases (χ(2): 33.8; P < 0.001). The cell dose resulted an independent predictor factor for a better outcome in patients affected by non-malignant disease (P = 0.05) while early disease malignant patients receiving a lower cell dose showed a higher risk of relapse (P = 0.05).

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

    Science.gov (United States)

    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.

  3. Bone Marrow Vascular Niche: Home for Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Ningning He

    2014-01-01

    Full Text Available Though discovered later than osteoblastic niche, vascular niche has been regarded as an alternative indispensable niche operating regulation on hematopoietic stem cells (HSCs. As significant progresses gained on this type niche, it is gradually clear that the main work of vascular niche is undertaking to support hematopoiesis. However, compared to what have been defined in the mechanisms through which the osteoblastic niche regulates hematopoiesis, we know less in vascular niche. In this review, based on research data hitherto we will focus on component foundation and various functions of vascular niche that guarantee the normal hematopoiesis process within bone marrow microenvironments. And the possible pathways raised by various research results through which this environment undergoes its function will be discussed as well.

  4. Bone marrow processing on the Haemonetics V50 cell separator.

    Science.gov (United States)

    Anderson, N A; Cornish, J M; Godwin, V; Gunstone, M J; Oakhill, A; Pamphilon, D H

    1990-01-01

    We have processed 27 bone marrow (BM) harvests using the Haemonetics V50 cell separator with a paediatric plasmapheresis set and programmed for lymphocyte collection. The mean starting volume of 843 mL was processed in 6-8 cycles to a buffy coat (BC) with a mean volume of 230 mL. The mean starting mononuclear cell (MNC) count was 1.22 x 10 8/kg recipient weight, and recovery was 92%. Clonogenic potential of the BC was assessed using CFU-GM assays and recovery was measured after cryopreservation or purging. On 4 occasions where major ABO incompatibility existed between donor and recipient, both BM and BC were consecutively diluted in compatible blood and processed twice. This achieved a calculated reduction in donor erythrocytes of 98%. The procedure was efficient and yielded a BC fraction suitable for cryopreservation and purging. Adequate stem-cells were retained as verified by CFU-GM assays and documentation of stable engraftment.

  5. MRI of intracranial toxoplasmosis after bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Dietrich, U.; Doerfler, A.; Forsting, M. [Department of Neuroradiology, University Hospital, Essen (Germany); Maschke, M. [Department of Neurology, University Hospital Essen (Germany); Prumbaum, M. [Department of Bone Marrow Transplantation, University Hospital Essen (Germany)

    2000-01-01

    Toxoplasma encephalitis was confirmed by biopsy in three patients with bone marrow (BMT) or peripheral blood stem-cell transplantation (PBSCT). All had MRI before antimicrobial therapy. The intensity of contrast enhancement was very variable. One patient had one large, moderately enhancing cerebral lesion and several smaller almost nonenhancing lesions. The second had small nodular and haemorrhagic lesions without any enhancement. The third had late cerebral toxoplasmosis and showed multiple lesions with marked contrast enhancement. The moderate or absent contrast enhancement in the two patients in the early phase of cerebral toxoplasmosis may be related to a poor immunological response, with a low white blood cell count in at least one patient. Both received higher doses of prednisone than the patient with late infection, leading to a reduced inflammatory response. In patients with a low leukocyte count and/or high doses of immunosuppressive therapy, typical contrast enhancement may be absent. (orig.)

  6. Assessment of bone marrow inflammation in patients with myelofibrosis: an {sup 18}F-fluorodeoxyglucose PET/CT study

    Energy Technology Data Exchange (ETDEWEB)

    Derlin, Thorsten [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany); University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Alchalby, Haefaa; Triviai, Ioanna; Kroeger, Nicolaus [University Medical Center Hamburg-Eppendorf, Clinic for Stem Cell Transplantation, Hamburg (Germany); Bannas, Peter [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Veldhoen, Simon [University Medical Center Wuerzburg, Department of Diagnostic and Interventional Radiology, Wuerzburg (Germany); Apostolova, Ivayla [Otto-von-Guericke University, Department of Radiology and Nuclear Medicine, Magdeburg (Germany); Bengel, Frank M. [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany)

    2015-04-01

    Myelofibrosis is a haematopoietic stem cell neoplasm characterized by bone marrow inflammation, reactive marrow fibrosis and extramedullary haematopoiesis. The aim of this study was to determine if {sup 18}F-FDG PET/CT can be used to noninvasively visualize and quantify the extent and activity of bone marrow involvement. In 30 patients, the biodistribution of {sup 18}F-FDG was analysed by measuring the standardized uptake value in the bone marrow compartment and spleen. Imaging findings were compared with laboratory, cytogenetic and histopathological data. Retention of {sup 18}F-FDG was observed in bone marrow and spleen. Bone marrow involvement varied, ranging from mildly increased uptake in the central skeleton to extensive uptake in most parts of the skeleton. The extent of bone marrow involvement decreased over time from initial diagnosis (r{sub s} = -0.43, p = 0.019). Metabolic activity of the bone marrow decreased as the histopathological grade of fibrosis increased (r{sub s} = -0.37, p = 0.04). There was a significant positive correlation between the metabolic activity of the bone marrow and that of the spleen (p = 0.04). {sup 18}F-FDG PET/CT is as a promising technique for the quantitation of bone marrow inflammation in myelofibrosis. Our data indicate that the intensity of bone marrow {sup 18}F-FDG uptake decreases as bone marrow fibrosis increases. Further evaluation in prospective studies is required to determine the potential clinical impact and prognostic significance of PET. (orig.)

  7. Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

    Science.gov (United States)

    Popov, Dmitri

    Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

  8. Vancomycin Utilization Review in Patients Undergoing Bone MarrowTransplantation

    Directory of Open Access Journals (Sweden)

    Saghar Taheri

    2015-10-01

    Full Text Available Background:  Infections  in  neutropenic  patients  are  considered  as  major  causes  of  mortality and the emergence of drug resistance. Gram positive bacterial infections are crucially important to be covered if indicated. Vancomycin is active against most Gram positive bacteria including Methicillin Resistant Staphylococcus Aureus (MRSA. In this study, we evaluated the appropriate utilization of this agent in bone marrow transplantation (BMT patients.Methods: In a cross sectional study, all patients who received vancomycin in a seven months period at bone marrow transplantation research center in Shariati teaching hospital in Tehran, Iran, were entered to the study. Clinical and preclinical parameters such as serum creatinine, microbial culture, antibacterial sensitivity, WBC count and fever were collected and recorded for analysis. We also measured vancomycin trough level after administration of three doses.Results: Fifty one patients were entered in the study and reviewed in two adult BMT wards. The age range was 18 to 65 years. Most patients received allogenic versus autologous transplantation (56.9%, 43.1%. About 80% of the vancomycin used for the patients with febrile neutropenia was compatible with National Comprehensive Cancer Network (NCCN guideline. 21.6% of patients received appropriate doses. Vancomycin trough serum concentration range was 15.0±11.9 μg/mL.Conclusion: Vancomycin is an antibiotic used to treat resistant gram-positive infections and must be prescribed by a specialist. Vancomycin wrong dosing or initiation prescribing with dose 1 gr/q12h increases the resistance and toxicity to drug, and cause an inappropriate response to the drug.

  9. Histologia da medula óssea Bone marrow histology

    Directory of Open Access Journals (Sweden)

    Antonio C. Alves

    2009-01-01

    Full Text Available A biópsia de medula óssea, após a utilização da agulha de Jamshidi, tornou- se um evento de rotina em virtude da simplificação na obtenção do material. A adequação das dimensões da amostra e a diminuição do tempo de descalcificação melhoraram muito a qualidade histológica e possibilitaram ao patologista um aprofundamento da interpretação morfológica das doenças hematológicas e não hematológicas. Para um laudo correto é necessário o conhecimento do tecido hematopoético normal, suas diferentes linhagens celulares, variações dependentes da idade e integração com outros dados clínicos e laboratoriais.The bone marrow biopsy after the introduction of the Jamshidi needle has come into a routine practice due to the facilitation to obtain good sample. Due to the adequate size of the sample, the decalcification time decreased and consequently the histological quality improved allowing to the pathologist a more deep and precise morphological interpretation and diagnosis of the hematological and non- hematological disorders. For a correct diagnosis, the pathologist should be acquainted with the normal histology of the bone marrow parenchyma, it variations depending on age, as well as with the clinico- laboratorial data to integrate them with the morphological features.

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

    NARCIS (Netherlands)

    Song, G.; Habibovic, P.; Bao, C.; Hu, J.; Blitterswijk, van C.A.; Yuan, H.; Chen, W.; Xu, H.H.K.

    2013-01-01

    Osteoinductive biomaterials are promising for bone repair. There is no direct proof that bone marrow mesenchymal stem cells (BMSCs) home to non-osseous sites and participate in ectopic bone formation induced by osteoinductive bioceramics. The objective of this study was to use a sex-mismatched beagl

  11. Late Adherent Human Bone Marrow Stromal Cells Form Bone and Restore the Hematopoietic Microenvironment In Vivo

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    Verônica Fernandes Vianna

    2013-01-01

    Full Text Available Bone marrow stromal cells (BMSCs are a valuable resource for skeletal regenerative medicine because of their osteogenic potential. In spite of the very general term “stem cell,” this population of cells is far from homogeneous, and different BMSCs clones have greatly different phenotypic properties and, therefore, potentially different therapeutic potential. Adherence to a culture flask surface is a primary defining characteristic of BMSCs. We hypothesized that based on the adherence time we could obtain an enriched population of cells with a greater therapeutic potential. We characterized two populations of bone marrow-derived cells, those that adhered by three days (R-cells and those that did not adhere by three days but did by six days (L-cells. Clones derived from L-cells could be induced into adipogenic, chondrogenic, and osteogenic differentiation in vitro. L-cells appeared to have greater proliferative capacity, as manifested by larger colony diameter and clones with higher CD146 expression. Only clones from L-cells developed bone marrow stroma in vivo. We conclude that the use of late adherence of BMSCs is one parameter that can be used to enrich for cells that will constitute a superior final product for cell therapy in orthopedics.

  12. The Nature of Expansion of Paget’s Disease of Bone

    Science.gov (United States)

    2013-04-01

    cell line or normal marrow from uninvolved bones from PDB (5). We obtained the PSV10 cell line from Dr. G. David Roodman (Indiana University...H, Boykin CS, Zhang H, Ishizuka S, Dempster DW, Roodman GD, Windle JJ. A SQSTM1/p62 mutation linked to Paget’s disease increases the...Singer FR, Bruder JM, Roodman GD. Enhanced RANK ligand expression and responsivity of bone marrow cells in Paget’s disease of bone. J Clin Invest

  13. Ischemic colitis as a manifestation of thrombotic microangiopathy following bone marrow transplantation.

    Science.gov (United States)

    Komeno, Yukiko; Ogawa, Seishi; Ishida, Tateru; Takeuchi, Kengo; Tsujino, Shiho; Kurokawa, Mineo; Aoki, Katsunori; Kanda, Yoshinobu; Chiba, Shigeru; Motokura, Toru; Fukayama, Masashi; Hirai, Hisamaru

    2003-12-01

    Thrombotic microangiopathy (TMA) is a microvascular disorder characterized by platelet aggregation and hemolytic anemia. In the setting of bone marrow transplantation (BMT), ischemic colitis due to TMA is difficult to differentiate from acute graft-versus-host disease. We report a 32-year-old man who presented ischemic colitis due to TMA after unrelated BMT for myelodysplastic syndrome. He suffered from treatment-resistant bloody diarrhea, and died of renal failure and Aspergillus pleuritis on day 253 post-BMT. Autopsy revealed endothelial injuries of arterioles and ischemic changes in the intestines and kidneys. Clinical and pathological characteristics of ischemic colitis due to BMT-associated TMA are described.

  14. Quantitative and qualitative assessment of reactive hematopoietic bone marrow in aplastic anemia using MR spectroscopy with variable echo times

    Energy Technology Data Exchange (ETDEWEB)

    Amano, Yasuo; Kumazaki, Tatsuo [Department of Radiology, Nippon Medical School, Tokyo (Japan)

    2002-01-01

    Objective: To assess quantitative and qualitative differences in water components between normal bone marrow and reactive hematopoietic marrow in aplastic anemia using magnetic resonance (MR) spectroscopy with variable echo times (TEs). Design: Water content, T2 value of the water component, and signal change in water related to TE were assessed in normal bone marrow and reactive hematopoietic bone marrow by a stimulated echo acquisition mode with TEs of 30, 45, 60, and 90 ms. Patients: Six patients with aplastic anemia (13-84 years) and seven normal volunteers (25-38 years) were examined. Results and conclusion: Reactive hematopoietic marrow showed significantly higher water content than normal bone marrow. The T2 value of water components tended to be longer in reactive hematopoietic marrow. Water signal ratio related to TE was significantly higher in reactive hematopoietic marrow. These results suggest a quantitative and qualitative difference in water components between normal and reactive hematopoietic bone marrow. (orig.)

  15. Tumour necrosis factor-alpha (TNFα stimulates the growth of human bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    F. Rougier

    1997-01-01

    Full Text Available This study reports that TNF-α is a potent mitogen for human bone marrow sternal cells in vitro (assessed by [3H]-thymidine incorporation into DNA and cell counts. In contrast, cytokines such as IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, LIF, SCF, M-CSF, G-CSF and GM-CSF had no effect. The effect of TNF-α on the growth of human bone marrow stromal cells could be of importance during inflammatory processes which take place in the marrow, for example marrow fibrosis.

  16. Oral Health and Bone Disease

    Science.gov (United States)

    ... low bone mass. Research suggests a link between osteoporosis and bone loss in the jaw. The bone in the jaw supports and anchors the teeth. When the jawbone becomes less dense, tooth loss can occur, a common occurrence in older adults. Skeletal Bone Density and Dental Concerns Periodontal Disease ...

  17. Aspectos morfológicos da infiltração da medula óssea por condições exibindo diferenciação plasmocitária e gamopatia monoclonal Morphological aspects of bone marrow infiltration by diseases characterized by plasma cell proliferation and monoclonal gamopathy

    Directory of Open Access Journals (Sweden)

    Victor P. Andrade

    2009-08-01

    Full Text Available As doenças linfoproliferativas com diferenciação plasmocitária e pico monoclonal são causas de dificuldade diagnóstica no estudo de espécimes de medula óssea. Conhecer os aspectos clínicos, morfológicos, imunofenotípicos e citogenéticos é fundamental para o diagnóstico correto. Descrevemos os aspectos práticos mais relevantes para a interpretação de biópsias de medula óssea frente às situações mais frequentes.Some lymphoproliferative diseases with plasma cell differentiation and monoclonal gammopathy are challenging to diagnose when dealing with bone marrow biopsies. Knowledge of clinical, morphological, phenotypic and cytogenetic aspects is crucial to establish the correct diagnosis. We describe practical relevant aspects that help in the interpretation of bone marrow biopsies in these situations.

  18. Experience of autologous bone marrow mononuclear cells implantation as a treatment in patients with peripheral arterial disease: one year follow-up = Tratamiento de la enfermedad arterial periférica de las extremidades inferiores con células mononucleares de médula ósea autólogas: reporte de seguimiento a un año

    Directory of Open Access Journals (Sweden)

    Sergio Jaramillo Velásquez,

    2012-10-01

    Full Text Available Introduction: Autologous bone marrow mononuclear cells have been shown to be safe and effective for treatment of patients with peripheral arterial disease (PAD. Angiogenesis can also be induced by growth factors synthesized by them.Objective: To determine in Colombia the feasibility, safety and outcome of the afore-mentioned treatment.Methods: After informed consent, bone marrow was obtained by aspiration under local anesthesia; mononuclear cells were concentrated and their number and viability were established. They were suspended in saline solution and implanted by intramuscular injection into the gastrocnemius muscles of ischemic legs. Control patients were left untreated. Clinical evaluation included several parameters. Flow cytometry was used for cell analysis.Results: Mean age of patients: 69 ± 11 years; cell viability: 99.15 ± 0.76%; total number of injected cells: 9.2 x 108 ± 6.2 x 108. After treatment, angiographic studies showed the formation of new collateral vessels in all patients, with minimal thickness increase. There were no complications from bone marrow aspiration and intramuscular administration of cells. All treated patients experienced increased in the walking distance and improvement of rest pain.Conclusions: These preliminary results demonstrate that autologous cell therapy is safe, feasible and positively changes the natural history of patients with advanced peripheral arterial disease. In order to establish this treatment as a current practice in Colombia, we suggest the study of a larger number of patients.

  19. Immune complex glomerulonephritis following bone marrow transplantation in C3 deficient mice.

    Directory of Open Access Journals (Sweden)

    Thomas R Welch

    Full Text Available BACKGROUND: The role of circulating complement in host defense and immune disease is well established. Although a number of cells and tissues are capable of synthesizing complement components locally, the importance of such local synthesis in immune disease has been difficult to establish. METHODOLOGY/PRINCIPAL FINDINGS: We used bone marrow transplantation (BMT between C3 knockout (C3KO and wild type (WT mice to construct animals that were discordant for systemic (hepatic and local (monocytic C3 synthetic capacity. An immune complex glomerulonephritis (GN was then induced using intraperitoneal injections of horse spleen apoferritin (HSA with a lipopolysaccharide (LPS adjuvant. All HSA/LPS animals developed a proliferative GN with glomerular infiltration by monocytes. By sensitive ELISA, monocyte C3 synthesis could be detected in C3KO animals transplanted with WT bone marrow cells. Despite this, there were no significant differences among groups of mice in measures of clinical (proteinuria, renal function or histologic (glomerular cellularity, crescents disease severity. CONCLUSIONS/SIGNIFICANCE: In this model of GN, local synthesis of C3 by infiltrating cells does not appear to be of pathologic importance.

  20. Effect of antithymocyte globulin source on outcomes of bone marrow transplantation for severe aplastic anemia.

    Science.gov (United States)

    Kekre, Natasha; Zhang, Ying; Zhang, Mei-Jie; Carreras, Jeanette; Ahmed, Parvez; Anderlini, Paolo; Atta, Elias Hallack; Ayas, Mouhab; Boelens, Jaap Jan; Bonfim, Carmem; Deeg, H Joachim; Kapoor, Neena; Lee, Jong-Wook; Nakamura, Ryotaro; Pulsipher, Michael A; Eapen, Mary; Antin, Joseph H

    2017-03-24

    For treatment of severe aplastic anemia, immunosuppressive therapy with horse antithymocyte globulin results in superior response and survival compared with rabbit antithymocyte globulin. This relative benefit may be different in the setting of transplantation as rabbit antithymocyte globulin results in more profound immunosuppression. We analyzed 833 severe aplastic anemia transplants between 2008 and 2013 using HLA-matched siblings (n=546) or unrelated donors (n=287) who received antithymocyte globulin as part of their conditioning regimen and bone marrow graft. There were no differences in hematopoietic recovery by type of antithymocyte globulin. Among recipients of HLA-matched sibling transplants, day 100 incidence of acute (17% versus 6%, p<0.001) and chronic (20% versus 9%, p<0.001) graft-versus-host disease were higher with horse compared to rabbit antithymocyte globulin. There were no differences in 3 year overall survival, 87% and 92%, p=0.76. Among recipients of unrelated donor transplants acute graft-versus-host disease was also higher with horse compared to rabbit antithymocyte globulin (42% versus 23%, p<0.001) but not chronic graft-versus-host disease (38% versus 32%, p=0.35). Survival was lower with horse antithymocyte globulin after unrelated donor transplantation, 75% versus 83%, p=0.02. These data support the use of rabbit antithymocyte globulin for bone marrow transplant conditioning for severe aplastic anemia.

  1. The bone marrow endosteal niche: how far from the surface?

    Science.gov (United States)

    Cordeiro-Spinetti, Eric; Taichman, Russell S; Balduino, Alex

    2015-01-01

    Hematopoietic stem cells (HSC) self-renewal takes place in the same microenvironment in which massive hematopoietic progenitor proliferation, commitment, and differentiation will occur. This is only made possible if the bone marrow microenvironment comprises different specific niches, composed by different stromal cells that work in harmony to regulate all the steps of the hematopoiesis cascade. Histological and functional assays indicated that HSC and multipotent progenitors preferentially colonize the endosteal and subendosteal regions, in close association with the bone surface. Conversely, committed progenitors and differentiated cells are distributed in the central and perisinusoidal regions, respectively. Over the last decade, many investigative teams sought to define which cell types regulate the HSC niche, how they are organized, and to what extent they interface with each other. System dynamics requires different stromal cells to operate distinct functions over similar HSC pools rather than a single stromal cell type controlling everything. Therefore, our focus herein is to depict the players in the endosteal and subendosteal regions, named the endosteal niche, a necessary step to better understand the interactions of the HSC within the niche and to identify potential targets to manipulate and/or modulate normal and malignant HSC behavior.

  2. Targeting the bone marrow: applications in stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Orchard, K. [Southampton University Hospital Trust, Southampton (United Kingdom). Department of Haematology; Cooper, M. [St. Bartholomew' s Hospital, London (United Kingdom). Pharmacy Department

    2004-12-01

    Therapeutic doses of radiation cab be selectively directed to the bone marrow either directly using vectors that bind to myeloid and/or lymphoid specific antigens or indirectly by targeting bone matrix. The combination of an accessible target tissue and relatively radiation sensitive malignant cells favours the use of targeted radiotherapy in the treatment of haematopoietic malignancies. Dose escalation of targeted radiation can increase tumour cell destruction and has led to the use of myelosuppressive and possibly myeloablative doses of targeted radiation. A natural development has been the use of targeted radiation in conditioning prior to haematopoietic stem cell transplantation (HSCT). Several groups are actively exploring the use of targeted radiotherapy in the context of HSCT as treatment for haematological malignancies. Although no randomised trials using targeted radiotherapy in HSCT have been published, phase I and II trials have shown very encouraging results stimulating further clinical research in this field. After more than a decade of translational research the optimal combination of therapeutic radioisotope and vector has not been determined. This review summarises the clinical experience of targeted radiotherapy in HSCT and discusses the problems that still need to be solved to maximise the potential of this new treatment modality in HSCT.

  3. Saliva suppresses osteoclastogenesis in murine bone marrow cultures.

    Science.gov (United States)

    Caballé-Serrano, J; Cvikl, B; Bosshardt, D D; Buser, D; Lussi, A; Gruber, R

    2015-01-01

    Saliva can reach mineralized surfaces in the oral cavity; however, the relationship between saliva and bone resorption is unclear. Herein, we examined whether saliva affects the process of osteoclastogenesis in vitro. We used murine bone marrow cultures to study osteoclast formation. The addition of fresh sterile saliva eliminated the formation of multinucleated cells that stained positive for tartrate-resistant acid phosphatase (TRAP). In line with the histochemical staining, saliva substantially reduced gene expression of cathepsin K, calcitonin receptor, and TRAP. Addition of saliva led to considerably decreased gene expression of receptor activator of nuclear factor kappa-B (RANK) and, to a lesser extent, that of c-fms. The respective master regulators of osteoclastogenesis (c-fos and NFATc1) and the downstream cell fusion genes (DC-STAMP and Atp6v0d2) showed decreased expression after the addition of saliva. Among the costimulatory molecules for osteoclastogenesis, only OSCAR showed decreased expression. In contrast, CD40, CD80, and CD86-all costimulatory molecules of phagocytic cells-were increasingly expressed with saliva. The phagocytic capacity of the cells was confirmed by latex bead ingestion. Based on these in vitro results, it can be concluded that saliva suppresses osteoclastogenesis and leads to the development of a phagocytic cell phenotype.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  6. LIVER AND BONE MARROW STEM/PROGENITOR CELLS AS REGULATORS OF REPARATIVE REGENERATION OF DAMAGED LIVER

    Directory of Open Access Journals (Sweden)

    А. V. Lundup

    2010-01-01

    Full Text Available In this review the modern information about effectiveness of liver insufficiency treatment by stem/ progenitor cells of liver (oval cells and bone marrow (hemopoietic cells and mesenchymal cells was presented. It is shown that medical action of these cells is referred on normalization of liver cell interaction and reorganization of processes of a reparative regeneration in damaged liver. It is believed that application of mesenchymal stromal cells from an autological bone marrow is the most perspective strategy. However, for definitive judgement about regenerative possibilities of the autological bone marrow cells it is necessary to carry out large-scale double blind clinical researches. 

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

    Science.gov (United States)

    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.

  8. Ultrastructural changes of bone marrow cells exposed for xenogenous cerebrospinal fluid

    Directory of Open Access Journals (Sweden)

    Shaymardanova L.R.

    2010-01-01

    Full Text Available Due to the scientifical investigations xenogenous cerebrospinal fluid was considered as possible substance for theproduction of powerful adaptogen of biological origin. One of the representative research in these field demonstrates morphologicaland functional changes of bone marrow as the central hemopoetic and immune organ. The article shows the ultramicroscopicchanges of bone marrow cells after the xenogenous cerebrospinal fluid exposure in Vistar rats of differentage. It was revealed the activation of synthetic processes in bone marrow cells of the first three age groups and exhaustion ofactivating mechanisms in the fourth age group, that was manifested in swelling and destruction of mytochondria, vacuolisationof cytoplasm, invagination of caryolemma.

  9. CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization

    DEFF Research Database (Denmark)

    Tormin, Ariane; Li, Ou; Brune, Jan Claas

    2011-01-01

    Nonhematopoietic bone marrow mesenchymal stem cells (BM-MSCs) are of central importance for bone marrow stroma and the hematopoietic environment. However, the exact phenotype and anatomical distribution of specified MSC populations in the marrow are unknown. We characterized the phenotype...... in perivascular regions, whereas bone-lining MSCs expressed CD271 alone. In both regions, CD34⁺ hematopoietic stem/progenitor cells were located in close proximity to MSCs. These novel findings show that the expression of CD146 differentiates between perivascular versus endosteal localization of non...

  10. Large-scale gene expression profiling data of bone marrow stromal cells from osteoarthritic donors.

    Science.gov (United States)

    Stiehler, Maik; Rauh, Juliane; Bünger, Cody; Jacobi, Angela; Vater, Corina; Schildberg, Theresa; Liebers, Cornelia; Günther, Klaus-Peter; Bretschneider, Henriette

    2016-09-01

    This data article contains data related to the research article entitled, "in vitro characterization of bone marrow stromal cells from osteoarthritic donors" [1]. Osteoarthritis (OA) represents the main indication for total joint arthroplasty and is one of the most frequent degenerative joint disorders. However, the exact etiology of OA remains unknown. Bone marrow stromal cells (BMSCs) can be easily isolated from bone marrow aspirates and provide an excellent source of progenitor cells. The data shows the identification of pivotal genes and pathways involved in osteoarthritis by comparing gene expression patterns of BMSCs from osteoarthritic versus healthy donors using an array-based approach.

  11. Bone marrow edema syndrome of the foot: one year follow-up with MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Canton, Guillermo; Casado, Oscar; Capelastegui, Ana; Astigarraga, Elena; Larena, Jose Alejandro; Merino, Amaya [OSATEK, Unidades de Resonancia Magnetica, Dr. Areilza 12-16, 48011, Bilbao, Basque Country (Spain)

    2003-05-01

    To describe the MR findings of bone marrow edema syndrome (BMES) of the foot and its evolution at 1 year follow-up.Design and patients Twenty-five of 32 patients with disabling foot and ankle pain unrelated to trauma diagnosed as BMES when MR imaging demonstrated a bone marrow edema pattern in one or more bones without any radiological or underlying clinical cause, were re-evaluated by MR imaging 1 year later. On the initial MR examinations an average of 4.7 individual bones were involved by bone marrow edema. Soft tissue edema was present in every patient and joint effusion in 10 patients. MR imaging at 1 year showed resolution of bone edema in 18 patients (72%), partial improvement in five (20%) and no improvement in two (8%). Six patients (24%) developed similar symptoms in the other foot during follow-up. Ten of 17 available plain radiographs showed some loss of radiodensity. Further bone marrow edema developed in bones of the same foot that were initially normal, or in uninvolved distant bone marrow areas in the same affected bone, in six of seven patients on follow-up MR imaging. The evolution of the MR findings of BMES of the foot is to complete resolution or partial improvement at 1 year in the majority of cases. Migration to the other foot occurs in up to a quarter of patients. (orig.)

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Maira L. Mendonça

    Full Text Available 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.

  14. Graft-versus-leukemia effects from donor lymphocyte infusion after nonmyeloablative allogeneic bone marrow transplantation in mice

    Institute of Scientific and Technical Information of China (English)

    DU Bing; LI De-peng; XU Kai-lin; PAN Xiu-ying

    2005-01-01

    Background Nonmyeloablative allogeneic bone marrow transplantation has been used since the 1990s as a new hematological stem cell transplantation strategy for treating hematological diseases. The purpose of this study was to explore the graft-versus-leukemia (GVL) effects of donor lymphocyte infusions (DLIs) after nonmyeloablative allogeneic bone marrow transplantations, while assessing the declines in treatment-associated morbidity, mortality, and graft-versus-host disease (GVHD).Methods A total of 615 (H-2k) mice were injected with L615 tumor cells and received 500 cGy (60Coγ-ray) irradiation three days later, followed by an allogeneic bone marrow transplantation (allo-BMT). The allo-grafts consisted of 3×107 bone marrow cells and 1×107 spleen cells from BALB/C (H-2d) donor mice. Two days after the allo-BMT, the recipient mice were given 200 mg/kg of cyclophosphamide. Subsequently, recipient mice were infused with either donor spleen cells (2×107) on day 14 or 21, or donor spleen cells (5×107) pretreated with hydrocortisone and cyclosporin A (CsA) in vitro on day 14 post-BMT.Results The median survival time of mice that received DLI on day 21 and pretreated DLI on day 14 post-BMT was longer than that of controls and the day 14 DLI group (P<0.01). No evidence of severe GVHD was observed in the day 21 DLI group nor in the day 14 treated DLI group. Mixed chimerism was confirmed in the day 14 DLI group, the day 14 treated DLI group, and the day 21 DLI group on the thirteenth day post-transplantation; full donor chimerism was observed two weeks after DLI.Conclusion Donor lymphocyte infusion after nonmyeloablative bone marrow transplantation may reduce transplantation-associated morbidity and mortality while strengthening graft-versus-leukemia effects.

  15. Endogenous n 3 polyunsaturated fatty acids PUFAs mitigate ovariectomy-induced bone loss by attenuating bone marrow adipogenesis in FAT1 transgenic mice

    Directory of Open Access Journals (Sweden)

    Chen TY

    2013-06-01

    Full Text Available Tian-yu Chen,1,2,* Zhong-min Zhang,1,2,* Xiao-chen Zheng,1,2 Liang Wang,1,2 Min-jun Huang,1,2 Si Qin,3 Jian Chen,1,2 Ping-lin Lai,4 Cheng-liang Yang,1,2 Jia Liu,1,2 Yi-fan Dai,5 Da-di Jin,1,2 Xiao-chun Bai1,2,4 1Department of Orthopaedic, the Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, People's Republic of China; 2Academy of Orthopaedics, Guangdong Province, Guangzhou, Guangdong, People's Republic of China; 3Department of Dermatology and STD, Guangdong No.2 Provincial People's Hospital, Guangzhou, Guangdong, People's Republic of China; 4Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, People's Republic of China; 5Center of Metabolic Disease Research, Nanjing Medical University, Jiangsu, People's Republic of China *These authors contributed equally to this work Aim: To investigate the effect of endogenous n-3 polyunsaturated fatty acids (PUFAs on bone marrow adipogenesis under osteoporosis conditions. Methods: A mouse osteoporosis model overexpressing the FAT1 gene from Caenorhabditis elegans and converting n-6 PUFAs to n-3 PUFAs endogenously was used. Results: The mice presented significantly lower bone marrow adiposity (adipocyte volume/tissue volume, mean adipocyte number but increased the bone parameters (bone mineral density, bone mineral content, bone volume/total volume in the distal femoral metaphysis. Conclusion: Endogenous n-3 PUFAs protect bone marrow adipogenesis, which provides a novel drug target. Keywords: antiosteoporosis, n-3 PUFAs, bone marrow, adipogenesis

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

    Science.gov (United States)

    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

  17. Third-party tolerogenic dendritic cells reduce allo-reactivity in vitro and ameliorate the severity of acute graft-versus-host disease in allo-bone marrow transplantation.

    Science.gov (United States)

    Yang, J; Li, R; Ren, Y; Yang, Y; Xie, R; Fan, H

    2013-12-01

    Tolerogenic dendritic cells (tDCs) potently induce and maintain tolerance based on their distinct characteristics compared with conventional DCs. Recent reports show that donor or host tDCs promote allograft survival in mice. In this study, the efficacy of third-party tDCs in the prevention of acute graft-versus-host disease (aGVHD) was evaluated. In vitro, tDCs derived from the bone marrow (BM) of D1 mice were induced by GM-CSF, IL-10 and TGF-β1. The phenotypes, expression of cytokines and suppression of tDCs were analysed. In vivo, the effects of adoptive transfer of third-party-tDCs were evaluated in an MHC-mismatched aGVHD mouse model. Survival, body weight, GVHD scoring, histopathological specimens and serum cytokines were analysed in tDC-treated mice and untreated controls. Tolerogenic DCs had low expression of MHC and co-stimulatory molecules, expressed high levels of 'immunosuppressive' cytokines and suppressed allo-CD4(+) T cell proliferation. In the B6→D2 mouse model, all aGVHD mice died within 18 days. Fortunately, third-party tDCs transferred at low doses (10(4)) effectively prolonged survival after allo-BMT. Furthermore, in the mice treated with 10(4) tDCs, serum levels of IL-10/TGF-β were significantly higher and the percentage of Foxp3(+) cells continually increased compared with the mice treated with other doses of tDCs. Third-party tDCs play a crucial role in reducing the severity of aGVHD by modulating the secretion of various cytokines and expanding Foxp3(+) regulatory T cells, which suggests the possibility of using third-party tDCs for therapeutic applications. Furthermore, special attention should be paid to the optimal range of tDCs for preventing allograft rejection.

  18. The composite of bone marrow concentrate and PRP as an alternative to autologous bone grafting.

    Directory of Open Access Journals (Sweden)

    Mohssen Hakimi

    Full Text Available One possible alternative to the application of autologous bone grafts represents the use of autologous bone marrow concentrate (BMC. The purpose of our study was to evaluate the potency of autologous platelet-rich plasma (PRP in combination with BMC. In 32 mini-pigs a metaphyseal critical-size defect was surgically created at the proximal tibia. The animals were allocated to four treatment groups of eight animals each (1. BMC+CPG group, 2. BMC+CPG+PRP group, 3. autograft group, 4. CPG group. In the BMC+CPG group the defect was filled with autologous BMC in combination with calcium phosphate granules (CPG, whereas in the BMC+CPG+PRP group the defect was filled with the composite of autologous BMC, CPG and autologous PRP. In the autograft group the defect was filled with autologous cancellous graft, whereas in the CPG group the defect was filled with CPG solely. After 6 weeks radiological and histomorphometrical analysis showed significantly more new bone formation in the BMC+CPG+PRP group compared to the BMC+CPG group and the CPG group. There were no significant differences between the BMC+CPG+PRP group and the autograft group. In the PRP platelets were enriched significantly about 4.7-fold compared to native blood. In BMC the count of mononuclear cells increased significantly (3.5-fold compared to the bone marrow aspirate. This study demonstrates that the composite of BMC+CPG+PRP leads to a significantly higher bone regeneration of critical-size defects at the proximal tibia in mini-pigs than the use of BMC+CPG without PRP. Furthermore, within the limits of the present study the composite BMC+CPG+PRP represents a comparable alternative to autologous bone grafting.

  19. The composite of bone marrow concentrate and PRP as an alternative to autologous bone grafting.

    Science.gov (United States)

    Hakimi, Mohssen; Grassmann, Jan-Peter; Betsch, Marcel; Schneppendahl, Johannes; Gehrmann, Sebastian; Hakimi, Ahmad-Reza; Kröpil, Patric; Sager, Martin; Herten, Monika; Wild, Michael; Windolf, Joachim; Jungbluth, Pascal

    2014-01-01

    One possible alternative to the application of autologous bone grafts represents the use of autologous bone marrow concentrate (BMC). The purpose of our study was to evaluate the potency of autologous platelet-rich plasma (PRP) in combination with BMC. In 32 mini-pigs a metaphyseal critical-size defect was surgically created at the proximal tibia. The animals were allocated to four treatment groups of eight animals each (1. BMC+CPG group, 2. BMC+CPG+PRP group, 3. autograft group, 4. CPG group). In the BMC+CPG group the defect was filled with autologous BMC in combination with calcium phosphate granules (CPG), whereas in the BMC+CPG+PRP group the defect was filled with the composite of autologous BMC, CPG and autologous PRP. In the autograft group the defect was filled with autologous cancellous graft, whereas in the CPG group the defect was filled with CPG solely. After 6 weeks radiological and histomorphometrical analysis showed significantly more new bone formation in the BMC+CPG+PRP group compared to the BMC+CPG group and the CPG group. There were no significant differences between the BMC+CPG+PRP group and the autograft group. In the PRP platelets were enriched significantly about 4.7-fold compared to native blood. In BMC the count of mononuclear cells increased significantly (3.5-fold) compared to the bone marrow aspirate. This study demonstrates that the composite of BMC+CPG+PRP leads to a significantly higher bone regeneration of critical-size defects at the proximal tibia in mini-pigs than the use of BMC+CPG without PRP. Furthermore, within the limits of the present study the composite BMC+CPG+PRP represents a comparable alternative to autologous bone grafting.

  20. Turning Marrow into Muscle

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@ In unexpected testimony2 to the versatility3 of the body's cells,researchers have found they can make bone marrow cells turn into muscle, causing mice with muscular dystrophy4 to produce correctly working muscle cells. The experiment suggests that a form of bone marrow transplant- - a well established surgical procedure5- - could in principle treat patients with a variety of diseases.