Bone marrow mesenchymal stem cells stimulate proliferation and neuronal differentiation of retinal progenitor cells.

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Jing Xia

Full Text Available During retina development, retinal progenitor cell (RPC proliferation and differentiation are regulated by complex inter- and intracellular interactions. Bone marrow mesenchymal stem cells (BMSCs are reported to express a variety of cytokines and neurotrophic factors, which have powerful trophic and protective functions for neural tissue-derived cells. Here, we show that the expanded RPC cultures treated with BMSC-derived conditioned medium (CM which was substantially enriched for bFGF and CNTF, expressed clearly increased levels of nuclear receptor TLX, an essential regulator of neural stem cell (NSC self-renewal, as well as betacellulin (BTC, an EGF-like protein described as supporting NSC expansion. The BMSC CM- or bFGF-treated RPCs also displayed an obviously enhanced proliferation capability, while BMSC CM-derived bFGF knocked down by anti-bFGF, the effect of BMSC CM on enhancing RPC proliferation was partly reversed. Under differentiation conditions, treatment with BMSC CM or CNTF markedly favoured RPC differentiation towards retinal neurons, including Brn3a-positive retinal ganglion cells (RGCs and rhodopsin-positive photoreceptors, and clearly diminished retinal glial cell differentiation. These findings demonstrate that BMSCs supported RPC proliferation and neuronal differentiation which may be partly mediated by BMSC CM-derived bFGF and CNTF, reveal potential limitations of RPC culture systems, and suggest a means for optimizing RPC cell fate determination in vitro.

Influence of chitosan-chitin nanofiber composites on cytoskeleton structure and the proliferation of rat bone marrow stromal cells.

Science.gov (United States)

Kiroshka, Victoria V; Petrova, Valentina A; Chernyakov, Daniil D; Bozhkova, Yulia O; Kiroshka, Katerina V; Baklagina, Yulia G; Romanov, Dmitry P; Kremnev, Roman V; Skorik, Yury A

2017-01-01

Chitosan scaffolds have gained much attention in various tissue engineering applications, but the effect of their microstructure on cell-material spatial interactions remains unclear. Our objective was to evaluate the effect of chitosan-based matrices doping with chitin nano-whiskers (CNW) on adhesion, spreading, cytoskeleton structure, and proliferation of rat bone marrow stromal cells (BMSCs). The behavior of BMSCs during culture on chitosan-CNW films was determined by the molecular mass, hydrophobicity, porosity, crosslinking degree, protonation degree and molecular structure of the composite chitosan-CNW films. The shape, spreading area, cytoskeleton structure, and proliferation of BMSCs on chitosan matrices with a crystalline structure and high porosity were similar to that observed for BMSCs cultured on polystyrene tissue culture plates. The amorphous polymer structure and high swelling led to a decrease in the spreading area and cell proliferation. Thus, we can control the behavior of cells in culture (adhesion, spreading, and proliferation) by changing the physico-chemical properties of the chitosan-CNW films.

Enhancing proliferation and optimizing the culture condition for human bone marrow stromal cells using hypoxia and fibroblast growth factor-2

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Jung-Seok Lee

2018-04-01

Full Text Available This study aimed to determine the cellular characteristics and behaviors of human bone marrow stromal cells (hBMSCs expanded in media in a hypoxic or normoxic condition and with or without fibroblast growth factor-2 (FGF-2 treatment. hBMSCs isolated from the vertebral body and expanded in these four groups were evaluated for cellular proliferation/migration, colony-forming units, cell-surface characterization, in vitro differentiation, in vivo transplantation, and gene expression. Culturing hBMSCs using a particular environmental factor (hypoxia and with the addition of FGF-2 increased the cellular proliferation rate while enhancing the regenerative potential, modulated the multipotency-related processes (enhanced chondrogenesis-related processes/osteogenesis, but reduced adipogenesis, and increased cellular migration and collagen formation. The gene expression levels in the experimental samples showed activation of the hypoxia-inducible factor-1 pathway and glycolysis in the hypoxic condition, with this not being affected by the addition of FGF-2. The concurrent application of hypoxia and FGF-2 could provide a favorable condition for culturing hBMSCs to be used in clinical applications associated with bone tissue engineering, due to the enhancement of cellular proliferation and regenerative potential. Keywords: Bone marrow stromal cells, Hypoxia, Fibroblast growth factor, Tissue regeneration, Microenvironment interactions

Distribution Atlas of Proliferating Bone Marrow in Non-Small Cell Lung Cancer Patients Measured by FLT-PET/CT Imaging, With Potential Applicability in Radiation Therapy Planning

International Nuclear Information System (INIS)

Campbell, Belinda A.; Callahan, Jason; Bressel, Mathias; Simoens, Nathalie; Everitt, Sarah; Hofman, Michael S.; Hicks, Rodney J.; Burbury, Kate; MacManus, Michael

2015-01-01

Purpose: Proliferating bone marrow is exquisitely sensitive to ionizing radiation. Knowledge of its distribution could improve radiation therapy planning to minimize unnecessary marrow exposure and avoid consequential prolonged myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)–positron emission tomography (PET) is a novel imaging modality that provides detailed quantitative images of proliferating tissues, including bone marrow. We used FLT-PET imaging in cancer patients to produce an atlas of marrow distribution with potential clinical utility. Methods and Materials: The FLT-PET and fused CT scans of eligible patients with non-small cell lung cancer (no distant metastases, no prior cytotoxic exposure, no hematologic disorders) were reviewed. The proportions of skeletal FLT activity in 10 predefined bony regions were determined and compared according to age, sex, and recent smoking status. Results: Fifty-one patients were studied: 67% male; median age 68 (range, 31-87) years; 8% never smokers; 70% no smoking in the preceding 3 months. Significant differences in marrow distribution occurred between sex and age groups. No effect was detected from smoking in the preceding 3 months. Using the mean percentages of FLT uptake per body region, we created an atlas of the distribution of functional bone marrow in 4 subgroups defined by sex and age. Conclusions: This atlas has potential utility for estimating the distribution of active marrow in adult cancer patients to guide radiation therapy planning. However, because of interindividual variation it should be used with caution when radiation therapy risks ablating large proportions of active marrow; in such cases, individual FLT-PET scans may be required

Distribution Atlas of Proliferating Bone Marrow in Non-Small Cell Lung Cancer Patients Measured by FLT-PET/CT Imaging, With Potential Applicability in Radiation Therapy Planning

Energy Technology Data Exchange (ETDEWEB)

Campbell, Belinda A., E-mail: Belinda.Campbell@petermac.org [Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Callahan, Jason [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Bressel, Mathias [Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, East Melbourne (Australia); Simoens, Nathalie [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Everitt, Sarah [Radiotherapy Services, Peter MacCallum Cancer Centre, East Melbourne (Australia); Hofman, Michael S.; Hicks, Rodney J. [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Burbury, Kate [Department of Haematology, Peter MacCallum Cancer Centre, East Melbourne (Australia); MacManus, Michael [Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia)

2015-08-01

Purpose: Proliferating bone marrow is exquisitely sensitive to ionizing radiation. Knowledge of its distribution could improve radiation therapy planning to minimize unnecessary marrow exposure and avoid consequential prolonged myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)–positron emission tomography (PET) is a novel imaging modality that provides detailed quantitative images of proliferating tissues, including bone marrow. We used FLT-PET imaging in cancer patients to produce an atlas of marrow distribution with potential clinical utility. Methods and Materials: The FLT-PET and fused CT scans of eligible patients with non-small cell lung cancer (no distant metastases, no prior cytotoxic exposure, no hematologic disorders) were reviewed. The proportions of skeletal FLT activity in 10 predefined bony regions were determined and compared according to age, sex, and recent smoking status. Results: Fifty-one patients were studied: 67% male; median age 68 (range, 31-87) years; 8% never smokers; 70% no smoking in the preceding 3 months. Significant differences in marrow distribution occurred between sex and age groups. No effect was detected from smoking in the preceding 3 months. Using the mean percentages of FLT uptake per body region, we created an atlas of the distribution of functional bone marrow in 4 subgroups defined by sex and age. Conclusions: This atlas has potential utility for estimating the distribution of active marrow in adult cancer patients to guide radiation therapy planning. However, because of interindividual variation it should be used with caution when radiation therapy risks ablating large proportions of active marrow; in such cases, individual FLT-PET scans may be required.

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

Energy Technology Data Exchange (ETDEWEB)

McGuire, S; Ponto, L; Menda, Y [University Of Iowa, Iowa City, IA (United States)

2016-06-15

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

Regulated proliferation of primitive hematopoietic progenitor cells in long-term human marrow cultures

International Nuclear Information System (INIS)

Cashman, J.; Eaves, A.C.; Eaves, C.J.

1985-01-01

We have examined the cycling status of various classes of erythroid and granulopoietic progenitor populations maintained for many weeks in standard normal long-term human marrow cultures. These were initiated with a single inoculum of marrow aspirate and were routinely fed by weekly removal of half of the nonadherent cells and replacement of half of the growth medium. Progenitors of large erythroid colonies (more than eight erythroblast clusters) present in the nonadherent fraction and progenitors of small granulocyte/macrophage colonies (fewer than 500 cells) present in both the nonadherent and adherent fractions were found to be actively cycling at all times examined (28% to 63% kill following a 20-minute exposure to 20 microCi/mL of high specific activity 3 H-thymidine). In contrast, progenitors of large granulocyte/macrophage colonies (more than 500 cells) and progenitors of large erythroid colonies (more than eight erythroblast clusters), present in the adherent layer, consistently alternated between a quiescent state at the time of each weekly medium change and a proliferating state two to three days later (0% to 13% kill and 21% to 49% kill, respectively). Additional experiments revealed that the activation of primitive progenitors in the adherent layer was not dependent on the addition of fresh glutamine or hydrocortisone, nor on the physical manipulations involved in changing the growth medium. These studies provide the first direct evidence that normal long-term human marrow cultures support the continued turnover of a variety of early hematopoietic progenitor cell types. Further, they indicate that the proliferative activity of the most primitive of these progenitors is regulated by stage-specific cell-cell interactions that are subject to manipulation

Osterix enhances proliferation and osteogenic potential of bone marrow stromal cells

International Nuclear Information System (INIS)

Tu Qisheng; Valverde, Paloma; Chen, Jake

2006-01-01

Osterix (Osx) is a zinc-finger-containing transcription factor that is expressed in osteoblasts of all endochondral and membranous bones. In Osx null mice osteoblast differentiation is impaired and bone formation is absent. In this study, we hypothesized that overexpression of Osx in murine bone marrow stromal cells (BMSC) would be able to enhance their osteoblastic differentiation and mineralization in vitro. Retroviral transduction of Osx in BMSC cultured in non-differentiating medium did not affect expression of Runx2/Cbfa1, another key transcription factor of osteoblast differentiation, but induced an increase in the expression of other markers associated with the osteoblastic lineage including alkaline phosphatase, bone sialoprotein, osteocalcin, and osteopontin. Retroviral transduction of Osx in BMSC also increased their proliferation, alkaline phosphatase activity, and ability to form bone nodules. These events occurred without significant changes in the expression of α1(II) procollagen or lipoprotein lipase, which are markers of chondrogenic and adipogenic differentiation, respectively

Low level light promotes the proliferation and differentiation of bone marrow derived mesenchymal stem cells

Science.gov (United States)

Ahn, Jin-Chul; Rhee, Yun-Hee; Choi, Sun-Hyang; Kim, Dae Yu; Chung, Phil-Sang

2015-03-01

Low-level light irradiation (LLLI) reported to stimulate the proliferation or differentiation of a variety of cell types. However, very little is known about the effect of light therapy on stem cells. The aim of the present study was to evaluate the effect of LLLI on the molecular physiological change of human bone marrow derived stem cells (hBMSC) by wavelength (470, 630, 660, 740 and 850, 50mW). The laser diode was performed with different time interval (0, 7.5, 15, 30J/cm2, 50mW) on hBMSC. To determine the molecular physiological changes of cellular level of hBMSC, the clonogenic assay, ATP assay, reactive oxygen species (ROS) detection, mitochondria membrane potential (MMPΦ) staining and calcium efflux assay were assessed after irradiation. There was a difference between with and without irradiation on hBMSCs. An energy density up to 30 J/cm² improved the cell proliferation in comparison to the control group. Among these irradiated group, 630 and 660nm were significantly increased the cell proliferation. The cellular level of ATP and calcium influx was increased with energy dose-dependent in all LLLI groups. Meanwhile, ROS and MMPΦ were also increased after irradiation except 470nm. It can be concluded that LLLI using infrared light and an energy density up to 30 J/cm² has a positive stimulatory effect on the proliferation or differentiation of hBMSCs. Our results suggest that LLLI may influence to the mitochondrial membrane potential activity through ATP synthesis and increased cell metabolism which leads to cell proliferation and differentiation.

Effects of BIO on proliferation and chondrogenic differentiation of mouse marrow derived mesenchymal stem cells

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Nasrin Fallah

2013-06-01

Full Text Available In vitroexpansion of mesenchymal stem cell (MSCs into large number is necessary fortheir application in cell-based treatment of articular cartilage defects. On the other hand,some studies have indicated that BIO (6-Bromoindirubin-3-Oxime possesses mitogeniceffects on cell culture. The objective of the present study was to examine the effect of BIO onin vitro expansion and chondrogenic differentiation of mouse marrow-derived MSCs. Theculture was established using bone marrow tissue obtained from 10 NMRI mice. MSC natureof the isolated cells was verified according to the minimal criteria proposed for MSC.Passaged-3 cells were seeded in 24-well culture plates and treated by 0.05, 0.01, 0.1, 1.0 and1.5 μM BIO forsevendays. The culture without BIO was taken as the control. At the end ofcultivation period, the cultures were examinedfor viable cell number which was then used tocalculate population doubling time (PDT. The BIO with higher proliferation-promoting effectwas investigated for its chondrogenic effect on MSC culture. There was significantly moreviable cells at the cultures treated by 0.1 μM BIO. At this culture the cells tended to doubletheir population in rapid rate (each 43.07 hr than the cells treated with the other BIOconcentrations (p< 0.05. Interestingly treatment of MSC chondrogenic culture with 0.1 μMBIO ledto the up-regulation of cartilage specific genes including aggrecan, collagen II andSox9. In conclusion BIO at 0.1 μM could enhance mouse MSC in vitro proliferation as well astheir chondrogenic differentiation. These findings would be of great importance for the fieldof regenerative medicine.

Clonal proliferation and karyotypic features of cells in bone marrow after irradiation

International Nuclear Information System (INIS)

Kohno, S.; Ishihara, T.

1979-01-01

Single stem cells in which chromosome abnormalities are induced by radiation may multiply to form the chromosomally abnormal clones of cells that may replace most of the cells in regenerating hematopoietic tissues after irradiation. It is only a limited number of karyotypes out of a variety of the cells with radiation-induced chromosome abnormalities that can persist as proliferative clones. Such clones in the bone marrows of irradiated rats were found to have aneusomic chromosome constitutions with trisomy or monosomy. This finding is contradictory to the general beliefs that the chromosomally abnormal clones surviving after irradiation would have the chromosome constitutions comparable to a normal diploid set making such clone cells selectively neutral, and that autosomally monosomic cells would not be able to compete against the cells in normal somatic tissues. The proliferation of aneusomic cells in hematopoietic tissues is a phenomenon observable in various blood disorders such as leukemia. The fact that almost all of the aneuploid clones observed possessed various chromosomal rearrangements in addition to their numerical changes appears to indicate that the chromosomal imbalance in original clones may predispose their chromosomes to non-disjunction. The process of the leukemic development of cells may require two steps: the leukemic transformation of cells and the proliferation of such transformed cells up to the manifestation of the disease. (Yamashita, S.)

Different Competitive Capacities of Stat4 and Stat6 Deficient CD4+ T Cells during Lymphophenia-Driven Proliferation

DEFF Research Database (Denmark)

Sanchez-Guajardo, Vanesa Maria; Borghans, J.A.M.; Marquez, M.-E.

2005-01-01

The outcome of an immune response relies on the competitive capacities acquired through differentiation of CD4ﰀ T cells into Th1 or Th2 effector cells. Because Stat4 and Stat6 proteins are implicated in the Th1 vs Th2 generation and maintenance, respectively, we compare in this study the kinetics...... of Stat4ﰐ/ﰐ and Stat6ﰐ/ﰐ CD4ﰀ T cells during competitive bone marrow reconstitution and lymphopenia-driven proliferation. After bone marrow transplantation, both populations reconstitute the peripheral T cell pools equally well. After transfer into lymphopenic hosts, wild-type and Stat6ﰐ/ﰐ CD4ﰀ T cells...... show a proliferation advantage, which is early associated with the expression of an active phospho-Stat4 and the down-regulation of Stat6. Despite these differences, Stat4- and Stat6-deficient T cells reach similar steady state numbers. However, when both Stat4ﰐ/ﰐ and Stat6ﰐ/ﰐ CD4ﰀ T cells...

Apatite formation on bioactive calcium-silicate cements for dentistry affects surface topography and human marrow stromal cells proliferation.

Science.gov (United States)

Gandolfi, Maria Giovanna; Ciapetti, Gabriela; Taddei, Paola; Perut, Francesca; Tinti, Anna; Cardoso, Marcio Vivan; Van Meerbeek, Bart; Prati, Carlo

2010-10-01

The effect of ageing in phosphate-containing solution of bioactive calcium-silicate cements on the chemistry, morphology and topography of the surface, as well as on in vitro human marrow stromal cells viability and proliferation was investigated. A calcium-silicate cement (wTC) mainly based on dicalcium-silicate and tricalcium-silicate was prepared. Alpha-TCP was added to wTC to obtain wTC-TCP. Bismuth oxide was inserted in wTC to prepare a radiopaque cement (wTC-Bi). A commercial calcium-silicate cement (ProRoot MTA) was tested as control. Cement disks were aged in DPBS for 5 h ('fresh samples'), 14 and 28 days, and analyzed by ESEM/EDX, SEM/EDX, ATR-FTIR, micro-Raman techniques and scanning white-light interferometry. Proliferation, LDH release, ALP activity and collagen production of human marrow stromal cells (MSC) seeded for 1-28 days on the cements were evaluated. Fresh samples exposed a surface mainly composed of calcium-silicate hydrates CSH (from the hydration of belite and alite), calcium hydroxide, calcium carbonate, and ettringite. Apatite nano-spherulites rapidly precipitated on cement surfaces within 5 h. On wTC-TCP the Ca-P deposits appeared thicker than on the other cements. Aged cements showed an irregular porous calcium-phosphate (Ca-P) coating, formed by aggregated apatite spherulites with interspersed calcite crystals. All the experimental cements exerted no acute toxicity in the cell assay system and allowed cell growth. Using biochemical results, the scores were: fresh cements>aged cements for cell proliferation and ALP activity (except for wTC-Bi), whereas fresh cementsproliferation than aged cements, probably favoured by the presence of Si-OH gel and the early formation of apatite nano-spherulites; (2) the alpha-TCP doped cement aged for 28 days displayed the highest bioactivity and cell proliferation; (3) the deleterious effect of bismuth on cell

[Effects of nicotine on bone marrow stromal cells proliferation and differentiation of chondrocyte in vitro].

Science.gov (United States)

Ying, Xiao-zhou; Peng, Lei; Cheng, Shao-wen; Chen, Qing-yu; Zhang, Wei; Kou, Dong-quan; Shen, Yue

2011-11-01

To examine the effects of various concentration of nicotine on bone marrow stromal cells (BMSCs) proliferation and differentiation of cartilaginous in vitro. BMSCs was obtained from femoral bone and tibia of New-Zealand albino rabbit. The cells of the 3rd generation were used in study. Different concentration of nicotine (0, 1 x 10(-7), 1 x 10(-6), 1 x 10(-5) M) were added into BMSCs. BMSCs proliferation was analyzed by MTT assay at the 1, 4, 7, 14 days. The expression of collagen type II and aggrecan as the marker genes of cartilaginous differentiation from BMSCs were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Microscope showed that BMSCs transformed from round to fusiform shape. The concentration of nicotine in 1 x 10(-7), 1 x 10(-6) M had a significant positive effect on cell proliferation and the expression of type II collagen in a time-dependent manner when supplemented in commonly used induction media (P<0.05). Concentrations of nicotine in 1 x 10(-7) can promote the expression of aggrecan at the 7th day after induction,and in 1 x 10(-5) M may inhibit the expression of type II collagen and aggrecan. It was implied that local application of nicotine at an appropriate concentration may be a promising approach for enhancing cartilaginous differentiation capacity of BMSCs in cartilage tissue engineering.

Effect of growth factors (BMP-4/7 & bFGF on proliferation & osteogenic differentiation of bone marrow stromal cells

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Shaohui Yuan

2013-01-01

Full Text Available Background & objectives: BMP (bone morphogenetic protein-4/7 and bFGF (basic fibroblast growth factor significantly promote the osteogenic activity and the proliferation of rabbit BMSCs (bone marrow stromal cells, respectively. However, their synergistic effects on the proliferation and the differentiation of BMSCs remain unclear. In the present study, the effects of bFGF and BMP-4/7 were investigated on the proliferation and the differentiation of rat BMSCs in vitro. Methods: BMSCs were isolated from New Zealand white rabbits and cultured to the third passage. The samples were divided into five groups according to the material implanted: (A 80 ng/ml BMP-4/7; (B 80 ng/ml bFGF; (C 30 ng/ml BMP-4/7 and 30 ng/ml bFGF; (D 50 ng/ml BMP-4/7 and 50 ng/ml bFGF; and (E 80 ng/ml BMP-4/7 and 80 ng/ml bFGF. Cell proliferation was analyzed using methyl thiazolyl tetrazolium (MTT assay. Alkaline phosphatase activity and osteocalcin (OC dynamics were also measured. Results: BMP-4/7 alone significantly (P<0.05 promoted the proliferation of BMSCs. At the same time, it also promoted or inhibited the osteogenic differentiation of BMSCs. The synergistic effects of BMP-4/7 and bFGF significantly promoted both the proliferation and the osteogenic differentiation of BMSCs. The treatment of the synergistic effects was dose and time dependent. Interpretation & conclusions: A rational combination of BMP-4/7 and bFGF can promote the proliferation and the osteogenic differentiation of BMSCs. In addition, the synergistic functions are effective.

Sonic hedgehog protein promotes proliferation and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro.

Science.gov (United States)

Warzecha, Jörg; Göttig, Stephan; Brüning, Christian; Lindhorst, Elmar; Arabmothlagh, Mohammad; Kurth, Andreas

2006-10-01

Sonic hedgehog (Shh) protein is known to be an important signaling protein in early embryonic development. Also, Shh is involved in the induction of early cartilaginous differentiation of mesenchymal cells in the limb and in the spine. The impact of Shh on adult stem cells, human bone marrow-derived mesenchymal stem cells (MSCs), was tested. The MSCs were treated either with recombinant Sonic hedgehog protein (r-Shh) or with transforming growth factor-beta 1 (TGF-beta(1)) as a positive control in vitro for 3 weeks. The effects on cartilaginous differentiation and proliferation were assayed. MSCs when treated with either Shh or TGF-beta(1) showed expression of cartilage markers aggrecan, Sox9, CEP-68, and collagen type II and X within 3 weeks. Only r-Shh-treated cells showed a very strong cell proliferation and much higher BrdU incorporation in cell assay systems. These are the first data that indicate an important role of Shh for the induction of cartilage production by MSCs in vitro.

Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca).

Science.gov (United States)

Wang, Jun-Jie; Liu, Yu-Liang; Sun, Yuan-Chao; Ge, Wei; Wang, Yong-Yong; Dyce, Paul W; Hou, Rong; Shen, Wei

2015-01-01

It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro.

Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca)

Science.gov (United States)

Wang, Jun-Jie; Liu, Yu-Liang; Sun, Yuan-Chao; Ge, Wei; Wang, Yong-Yong; Dyce, Paul W.; Hou, Rong; Shen, Wei

2015-01-01

It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro. PMID:26375397

Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca.

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Jun-Jie Wang

Full Text Available It has been widely known that the giant panda (Ailuropoda melanoleuca is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF, a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide (MTT cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro.

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

International Nuclear Information System (INIS)

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

1987-01-01

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

Normalizing the bone marrow microenvironment with p38 inhibitor reduces multiple myeloma cell proliferation and adhesion and suppresses osteoclast formation

International Nuclear Information System (INIS)

Nguyen, Aaron N.; Stebbins, Elizabeth G.; Henson, Margaret; O'Young, Gilbert; Choi, Sun J.; Quon, Diana; Damm, Debby; Reddy, Mamatha; Ma, Jing Y.; Haghnazari, Edwin; Kapoun, Ann M.; Medicherla, Satyanarayana; Protter, Andy; Schreiner, George F.; Kurihara, Noriyoshi; Anderson, Judy; Roodman, G. David; Navas, Tony A.; Higgins, Linda S.

2006-01-01

The multiple myeloma (MM) bone marrow (BM) microenvironment plays a critical role in supporting tumor growth and survival as well as in promoting formation of osteolytic lesions. Recent results suggest that the p38 mitogen-activated protein kinase (MAPK) is an important factor in maintaining this activated environment. In this report, we demonstrate that the p38α MAPK inhibitor, SCIO-469, suppresses secretion of the tumor-supportive factors IL-6 and VEGF from BM stromal cells (BMSCs) as well as cocultures of BMSCs with MM cells, resulting in reduction in MM cell proliferation. Additionally, we show that SCIO-469 prevents TNFα-induced adhesion of MM cells to BMSCs through an ICAM-1- and VCAM-1-independent mechanism. Microarray analysis revealed a novel set of TNFα-induced chemokines in BMSCs that is strongly inhibited by SCIO-469. Furthermore, reintroduction of chemokines CXCL10 and CCL8 to BMSCs overcomes the inhibitory effect of SCIO-469 on TNFα-induced MM adhesion. Lastly, we show that SCIO-469 inhibits secretion and expression of the osteoclast-activating factors IL-11, RANKL, and MIP-1α as well as prevents human osteoclast formation in vitro. Collectively, these results suggest that SCIO-469 treatment can suppress factors in the bone marrow microenvironment to inhibit MM cell proliferation and adhesion and also to alleviate osteolytic activation in MM

Dual effect of LPS on murine myeloid leukemia cells: Pro-proliferation and anti-proliferation

International Nuclear Information System (INIS)

Yu, Lingling; Zhao, Yingmin; Gu, Xin; Wang, Jijun; Pang, Lei; Zhang, Yanqing; Li, Yaoyao; Jia, Xiaoqin; Wang, Xin; Gu, Jian; Yu, Duonan

2016-01-01

Modification of the bone marrow microenvironment is considered as a promising strategy to control leukemic cell proliferation, diseases progression and relapse after treatment. However, due to the diversity and complexity of the cellular and molecular compartments in the leukemic microenvironment, it is extremely difficult to dissect the role of each individual molecule or cell type in vivo. Here we established an in vitro system to dissect the role of lipopolysaccharide (LPS), stromal cells and endothelial cells in the growth of mouse myeloid tumor cells and B-lymphoma cells. We found that either LPS or bone marrow stromal cells as a feeder layer in culture is required for the proliferation of myeloid tumor cells. Surprisingly, the growth of myeloid leukemic cells on stromal cells is strongly inhibited when coupled with LPS in culture. This opposing effect of LPS, a complete switch from pro-proliferation to antitumor growth is due, at least in part, to the rapidly increased production of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells stimulated by LPS. These results demonstrate that LPS can either facilitate or attenuate tumor cell proliferation, thus changing the disease course of myeloid leukemias through its direct effect or modulation of the tumor microenvironment. - Highlights: • LPS alone in culture is required for the proliferation of murine myeloid tumor cells. • Bone marrow stromal cells as a feeder layer is also required for the proliferation of myeloid tumor cells. • However, the growth of myeloid tumor cells is inhibited when LPS and stromal cells are both available in culture. • Thus LPS can either facilitate or attenuate tumor growth through its direct effect or modulation of tumor microenvironment.

Dual effect of LPS on murine myeloid leukemia cells: Pro-proliferation and anti-proliferation

Energy Technology Data Exchange (ETDEWEB)

Yu, Lingling [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Zhao, Yingmin [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Gu, Xin; Wang, Jijun; Pang, Lei; Zhang, Yanqing; Li, Yaoyao; Jia, Xiaoqin; Wang, Xin [Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Gu, Jian [Department of Hematology, Yangzhou University School of Clinical Medicine, Yangzhou 225001 (China); Yu, Duonan, E-mail: duonan@yahoo.com [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Disease, Yangzhou 225001 (China); Institute of Comparative Medicine, Yangzhou University, Yangzhou 225001 (China); Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonosis, Yangzhou 225001 (China)

2016-06-10

Modification of the bone marrow microenvironment is considered as a promising strategy to control leukemic cell proliferation, diseases progression and relapse after treatment. However, due to the diversity and complexity of the cellular and molecular compartments in the leukemic microenvironment, it is extremely difficult to dissect the role of each individual molecule or cell type in vivo. Here we established an in vitro system to dissect the role of lipopolysaccharide (LPS), stromal cells and endothelial cells in the growth of mouse myeloid tumor cells and B-lymphoma cells. We found that either LPS or bone marrow stromal cells as a feeder layer in culture is required for the proliferation of myeloid tumor cells. Surprisingly, the growth of myeloid leukemic cells on stromal cells is strongly inhibited when coupled with LPS in culture. This opposing effect of LPS, a complete switch from pro-proliferation to antitumor growth is due, at least in part, to the rapidly increased production of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells stimulated by LPS. These results demonstrate that LPS can either facilitate or attenuate tumor cell proliferation, thus changing the disease course of myeloid leukemias through its direct effect or modulation of the tumor microenvironment. - Highlights: • LPS alone in culture is required for the proliferation of murine myeloid tumor cells. • Bone marrow stromal cells as a feeder layer is also required for the proliferation of myeloid tumor cells. • However, the growth of myeloid tumor cells is inhibited when LPS and stromal cells are both available in culture. • Thus LPS can either facilitate or attenuate tumor growth through its direct effect or modulation of tumor microenvironment.

Polyamines and post-irradiation cell proliferation

International Nuclear Information System (INIS)

Rosiek, O.; Wronowski, T.; Lerozak, K.; Kopec, M.

1978-01-01

The results of three sets of experiments will be presented. Firstly polyamines and DNA content was determined in bone marrow, mesenteric lymph nodes, spleen, liver and kidney of rabbits at the 1, 5, 10 and 20th day after exposure to 600 R of X-irradiation. Polyamine concentration in bone marrow, spleen and lymph nodes was found to be markedly increased during the period of postirradiation recovery. Secondly, effect of 10 -5 M methyl glyoxalbis, guanylhydrazone (MGBG), an inhibitor of spermidine and spermine synthesis, on multiplication of X-irradiated cultures of murine lymphoblaste L5178Y-S was assessed. MGBG-induced inhibition of cell proliferation could be prevented by concurrent administration of 10 -4 M spermidine. Thirdly the influence of putrescine on bone marrow cellularity and 3 H-thymidine incorporation into bone marrow cells was investigated in X-irradiated mice. The results obtained indicate close relation of polyamines to cell proliferation processes after irradiation. (orig./AJ) [de

Functional evaluation of bone marrow derived DC of tumor bearing mice after immunotherapy

International Nuclear Information System (INIS)

Li Min; Chen Cheng; Gu Tao; Zhou Huan; Zhang Feng; Zhu Yibei; Yu Gehua; Zhang Xueguang; Gu Zongjiang

2006-01-01

Objective: To evaluate the function of bone marrow derived DC of tumor bearing mice after immunotherapy. Methods: Tumor bearing mice were immunized with DC vaccine plus injection of agonistic anti-4-1BB monoclonal antibody. The proliferation of T cells primed with bone marrow derived DC of tumor bearing mice after immunotherapy was tested by 3 H-TdR incorporation. ELISA was employed to determine the levels of IL-2, IFN-γ and IL-10 secreted by DC primed T cells. Results: Bone marrow derived DC of tumor bearing mice was less efficient in stimulating the proliferation of T cells and IL-2 and IFN-γ secretion made by T cells. After immunotherapy, the proliferation of cells and IL-2 and IFN-γ secretionmade by T cells were enhanced. Conclusion: The function of bone marrow derived DC of tumor bearing mice after immunotherapy was ameliorated. (authors)

Overexpression of FABP3 inhibits human bone marrow derived mesenchymal stem cell proliferation but enhances their survival in hypoxia

International Nuclear Information System (INIS)

Wang, Suna; Zhou, Yifu; Andreyev, Oleg; Hoyt, Robert F.; Singh, Avneesh; Hunt, Timothy; Horvath, Keith A.

2014-01-01

Studying the proliferative ability of human bone marrow derived mesenchymal stem cells in hypoxic conditions can help us achieve the effective regeneration of ischemic injured myocardium. Cardiac-type fatty acid binding protein (FABP3) is a specific biomarker of muscle and heart tissue injury. This protein is purported to be involved in early myocardial development, adult myocardial tissue repair and responsible for the modulation of cell growth and proliferation. We have investigated the role of FABP3 in human bone marrow derived mesenchymal stem cells under ischemic conditions. MSCs from 12 donors were cultured either in standard normoxic or modified hypoxic conditions, and the differential expression of FABP3 was tested by quantitative RT PCR and western blot. We also established stable FABP3 expression in MSCs and searched for variation in cellular proliferation and differentiation bioprocesses affected by hypoxic conditions. We identified: (1) the FABP3 differential expression pattern in the MSCs under hypoxic conditions; (2) over-expression of FABP3 inhibited the growth and proliferation of the MSCs; however, improved their survival in low oxygen environments; (3) the cell growth factors and positive cell cycle regulation genes, such as PCNA, APC, CCNB1, CCNB2 and CDC6 were all down-regulated; while the key negative cell cycle regulation genes TP53, BRCA1, CASP3 and CDKN1A were significantly up-regulated in the cells with FABP3 overexpression. Our data suggested that FABP3 was up-regulated under hypoxia; also negatively regulated the cell metabolic process and the mitotic cell cycle. Overexpression of FABP3 inhibited cell growth and proliferation via negative regulation of the cell cycle and down-regulation of cell growth factors, but enhances cell survival in hypoxic or ischemic conditions. - Highlights: • FABP3 expression pattern was studied in 12 human hypoxic-MSCs. • FABP3 mRNA and proteins are upregulated in the MSCs under hypoxic conditions. �

Carbon nanotubes functionalized with fibroblast growth factor accelerate proliferation of bone marrow-derived stromal cells and bone formation

International Nuclear Information System (INIS)

Hirata, Eri; Takita, Hiroko; Watari, Fumio; Yokoyama, Atsuro; Ménard-Moyon, Cécilia; Venturelli, Enrica; Bianco, Alberto

2013-01-01

Multi-walled carbon nanotubes (MWCNTs) were functionalized with fibroblast growth factor (FGF) and the advantages of their use as scaffolds for bone augmentation were evaluated in vitro and in vivo. The activity of FGF was assessed by measuring the effect on the proliferation of rat bone marrow stromal cells (RBMSCs). The presence of FGF enhanced the proliferation of RBMSCs and the FGF covalently conjugated to the nanotubes (FGF–CNT) showed the same effect as FGF alone. In addition, FGF–CNT coated sponges were implanted between the parietal bone and the periosteum of rats and the formation of new bone was investigated. At day 14 after implantation, a larger amount of newly formed bone was clearly observed in most pores of FGF–CNT coated sponges. These findings indicated that MWCNTs accelerated new bone formation in response to FGF, as well as the integration of particles into new bone during its formation. Scaffolds coated with FGF–CNT could be considered as promising novel substituting materials for bone regeneration in future tissue engineering applications. (paper)

Carbon nanotubes functionalized with fibroblast growth factor accelerate proliferation of bone marrow-derived stromal cells and bone formation

Science.gov (United States)

Hirata, Eri; Ménard-Moyon, Cécilia; Venturelli, Enrica; Takita, Hiroko; Watari, Fumio; Bianco, Alberto; Yokoyama, Atsuro

2013-11-01

Multi-walled carbon nanotubes (MWCNTs) were functionalized with fibroblast growth factor (FGF) and the advantages of their use as scaffolds for bone augmentation were evaluated in vitro and in vivo. The activity of FGF was assessed by measuring the effect on the proliferation of rat bone marrow stromal cells (RBMSCs). The presence of FGF enhanced the proliferation of RBMSCs and the FGF covalently conjugated to the nanotubes (FGF-CNT) showed the same effect as FGF alone. In addition, FGF-CNT coated sponges were implanted between the parietal bone and the periosteum of rats and the formation of new bone was investigated. At day 14 after implantation, a larger amount of newly formed bone was clearly observed in most pores of FGF-CNT coated sponges. These findings indicated that MWCNTs accelerated new bone formation in response to FGF, as well as the integration of particles into new bone during its formation. Scaffolds coated with FGF-CNT could be considered as promising novel substituting materials for bone regeneration in future tissue engineering applications.

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.

[Acute unclassified leukemia with bone marrow necrosis].

Science.gov (United States)

Uoshima, N; Yamazaki, N; Iinuma, S; Kimura, S; Wada, K; Kobayashi, Y; Ozawa, M; Horiuchi, H; Maruo, N; Kondo, M

1991-01-01

Massive bone marrow necrosis was seen in a 42-year-old male with acute leukemia. In December, 1988, on admission, laboratory data revealed pancytopenia and a high level of serum LDH and ALKP. Bone marrow aspiration resulted in dry-tap and showed bone marrow necrosis in the bone marrow biopsy specimen. A bone marrow scintigraphy with 111In faintly visualized the bone marrow but visualized area was expanded in the extremities compared with normal subjects. The second bone marrow biopsy showed proliferation of blasts. In the middle of March, blasts began to appear in peripheral blood. The blasts were cytochemically negative for POX, Es, PAS, AcP, TdT and had surface markers CD3-, CD19-, CD33-, CD13-, LCA-, HLA-DR-. Even by investigation on rearrangement of the immunoglobulin heavy chain region, an origin of the blasts could not be determined. In April, the number of blasts in peripheral blood increased and hepatosplenomegaly developed rapidly. Therefore, he was put on the chemotherapy with vincristine and prednisolone, but he died of cerebral hemorrhage. The autopsy revealed widespread bone marrow necrosis. It has rarely been reported that massive bone marrow necrosis is found prior to the occurrence of acute unclassified leukemia.

Bone Marrow Mesenchymal Stromal Cells Stimulate Skeletal Myoblast Proliferation through the Paracrine Release of VEGF

Science.gov (United States)

Chellini, Flaminia; Mazzanti, Benedetta; Nistri, Silvia; Nosi, Daniele; Saccardi, Riccardo; Quercioli, Franco; Zecchi-Orlandini, Sandra; Formigli, Lucia

2012-01-01

Mesenchymal stromal cells (MSCs) are the leading cell candidates in the field of regenerative medicine. These cells have also been successfully used to improve skeletal muscle repair/regeneration; however, the mechanisms responsible for their beneficial effects remain to be clarified. On this basis, in the present study, we evaluated in a co-culture system, the ability of bone-marrow MSCs to influence C2C12 myoblast behavior and analyzed the cross-talk between the two cell types at the cellular and molecular level. We found that myoblast proliferation was greatly enhanced in the co-culture as judged by time lapse videomicroscopy, cyclin A expression and EdU incorporation. Moreover, myoblasts immunomagnetically separated from MSCs after co-culture expressed higher mRNA and protein levels of Notch-1, a key determinant of myoblast activation and proliferation, as compared with the single culture. Notch-1 intracellular domain and nuclear localization of Hes-1, a Notch-1 target gene, were also increased in the co-culture. Interestingly, the myoblastic response was mainly dependent on the paracrine release of vascular endothelial growth factor (VEGF) by MSCs. Indeed, the addition of MSC-derived conditioned medium (CM) to C2C12 cells yielded similar results as those observed in the co-culture and increased the phosphorylation and expression levels of VEGFR. The treatment with the selective pharmacological VEGFR inhibitor, KRN633, resulted in a marked attenuation of the receptor activation and concomitantly inhibited the effects of MSC-CM on C2C12 cell growth and Notch-1 signaling. In conclusion, this study provides novel evidence for a role of MSCs in stimulating myoblast cell proliferation and suggests that the functional interaction between the two cell types may be exploited for the development of new and more efficient cell-based skeletal muscle repair strategies. PMID:22815682

Homing of bone marrow lymphoid cells

International Nuclear Information System (INIS)

Yoshida, Y.; Osmond, D.G.

1978-01-01

DNA labeling, bone marrow fractionation, and radioautography were used to follow the fate of transfused, newly formed marrow lymphocytes in irradiated hosts. After infusing donor Hartley guinea pigs with 3 H-thymidine for 3 to 5 days, high concentrations of labeled small lymphocytes and large lymphoid cells were separated from marrow by sedimentation in sucrose-serum gradients and injected into lethally x-irradiated syngeneic recipients. Most labeled small lymphocytes and large lymphoid cells rapidly left the circulation. They appeared to be mainly in the marrow and spleen, increasing in incidence from 1 to 3 days, but declining in mean grain count. Labeled cells were scattered throughout the recipient marrow; in the spleen they localized initially in the red pulp, and subsequently in peripheral areas of white pulp, often in clusters. Labeled small lymphocytes showed a delayed migration into the mesenteric lymph node, mainly in the superficial cortex and medulla; they also appeared in small numbers in Peyer's patches, but rarely in the thymus or thoracic duct lymph. It is concluded that a rapid selective homing of newly formed marrow lymphoid cells occurs in both the marrow and certain areas of the spleen of irradiated hosts, followed by a continuing proliferation of large lymphoid cells and production of small lymphocytes. The results are discussed with respect to the life history of marrow lymphocytes and the use of adoptive immune assays of marrow cells to characterize B lymphocyte maturation

Lectin-like oxidized LDL receptor-1 expresses in mouse bone marrow-derived mesenchymal stem cells and stimulates their proliferation

International Nuclear Information System (INIS)

Zhang, Fenxi; Wang, Congrui; Jing, Suhua; Ren, Tongming; Li, Yonghai; Cao, Yulin; Lin, Juntang

2013-01-01

The bone marrow-derived mesenchymal stem cells (bmMSCs) have been widely used in cell transplant therapy, and the proliferative ability of bmMSCs is one of the determinants of the therapy efficiency. Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) as a transmembrane protein is responsible for binding, internalizing and degrading oxidized low density lipoprotein (ox-LDL). It has been identified that LOX-1 is expressed in endothelial cells, vascular smooth muscle cells, cardiomyocytes, fibroblasts and monocytes. In these cells, low concentration of ox-LDL (<40 μg/mL) stimulates their proliferation via LOX-1 activation. However, it is poor understood that whether LOX-1 is expressed in bmMSCs and which role it plays. In this study, we investigated the status of LOX-1 expression in bmMSCs and its function on bmMSC proliferation. Our results showed that primary bmMSCs exhibiting a typical fibroblast-like morphology are positive for CD44 and CD90, but negative for CD34 and CD45. LOX-1 in both mRNA and protein levels is highly expressed in bmMSCs. Meanwhile, bmMSCs exhibit a strong potential to take up ox-LDL. Moreover, LOX-1 expression in bmMSCs is upregulated by ox-LDL with a dose- and time-dependent manner. Presence of ox-LDL also enhances the proliferation of bmMSCs. Knockdown of LOX-1 expression significantly inhibits ox-LDL-induced bmMSC proliferation. These findings indicate that LOX-1 plays a role in bmMSC proliferation. - Highlights: ► LOX-1 expresses in bmMSCs and mediates uptake of ox-LDL. ► Ox-LDL stimulates upregulation of LOX-1 in bmMSCs. ► Ox-LDL promotes bmMSC proliferation and expression of Mdm2, phosphor-Akt, phosphor-ERK1/2 and phosphor-NF-κB. ► LOX-1 siRNA inhibits ox-LDL-induced bmMSC proliferation and expression cell survival signals

Lectin-like oxidized LDL receptor-1 expresses in mouse bone marrow-derived mesenchymal stem cells and stimulates their proliferation

Energy Technology Data Exchange (ETDEWEB)

Zhang, Fenxi [Department of Anatomy, Sanquan College, Xinxiang Medical University, Xinxiang 453003 (China); Stem Cell and Biotheraphy Technology Research Center, College of Lifescience and Technology, Xinxiang Medical University, Xinxiang 453003 (China); Wang, Congrui [Stem Cell and Biotheraphy Technology Research Center, College of Lifescience and Technology, Xinxiang Medical University, Xinxiang 453003 (China); Jing, Suhua [ICU Center, The Third Hospital of Xinxiang Medical University, Xinxiang 453003 (China); Ren, Tongming [Department of Anatomy, Sanquan College, Xinxiang Medical University, Xinxiang 453003 (China); Li, Yonghai; Cao, Yulin [Stem Cell and Biotheraphy Technology Research Center, College of Lifescience and Technology, Xinxiang Medical University, Xinxiang 453003 (China); Lin, Juntang, E-mail: juntang.lin@googlemail.com [Stem Cell and Biotheraphy Technology Research Center, College of Lifescience and Technology, Xinxiang Medical University, Xinxiang 453003 (China)

2013-04-15

The bone marrow-derived mesenchymal stem cells (bmMSCs) have been widely used in cell transplant therapy, and the proliferative ability of bmMSCs is one of the determinants of the therapy efficiency. Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) as a transmembrane protein is responsible for binding, internalizing and degrading oxidized low density lipoprotein (ox-LDL). It has been identified that LOX-1 is expressed in endothelial cells, vascular smooth muscle cells, cardiomyocytes, fibroblasts and monocytes. In these cells, low concentration of ox-LDL (<40 μg/mL) stimulates their proliferation via LOX-1 activation. However, it is poor understood that whether LOX-1 is expressed in bmMSCs and which role it plays. In this study, we investigated the status of LOX-1 expression in bmMSCs and its function on bmMSC proliferation. Our results showed that primary bmMSCs exhibiting a typical fibroblast-like morphology are positive for CD44 and CD90, but negative for CD34 and CD45. LOX-1 in both mRNA and protein levels is highly expressed in bmMSCs. Meanwhile, bmMSCs exhibit a strong potential to take up ox-LDL. Moreover, LOX-1 expression in bmMSCs is upregulated by ox-LDL with a dose- and time-dependent manner. Presence of ox-LDL also enhances the proliferation of bmMSCs. Knockdown of LOX-1 expression significantly inhibits ox-LDL-induced bmMSC proliferation. These findings indicate that LOX-1 plays a role in bmMSC proliferation. - Highlights: ► LOX-1 expresses in bmMSCs and mediates uptake of ox-LDL. ► Ox-LDL stimulates upregulation of LOX-1 in bmMSCs. ► Ox-LDL promotes bmMSC proliferation and expression of Mdm2, phosphor-Akt, phosphor-ERK1/2 and phosphor-NF-κB. ► LOX-1 siRNA inhibits ox-LDL-induced bmMSC proliferation and expression cell survival signals.

Migration of bone marrow cells to the thymus in sublethally irradiated mice

International Nuclear Information System (INIS)

Varlet, Andree; Lenaerts, Patrick; Houben-Defresne, M.P.; Boniver, Jacques

1982-01-01

In sublethally irradiated mice, thymus repopulation is due first to the proliferation of surviving thymocytes followed by the multiplication of bone marrow derived prothymocytes. The migration of bone marrow cells to the thymus after a single sublethal whole-body X irradiation was studied by using fluorescein isothiocyanate as a cell marker. Irradiation increases the permissiveness of the thymus to the immigration of bone marrow cells. Furthermore, the post-Rx regenerating bone marrow cells exhibit migration capacities greater than the normal ones. The radiation induced changes in the bone marrow thymus interaction might play an important role in thymus regeneration after sublethal irradiation [fr

LIGHT (TNFSF14 Increases the Survival and Proliferation of Human Bone Marrow-Derived Mesenchymal Stem Cells.

Directory of Open Access Journals (Sweden)

Sook-Kyoung Heo

Full Text Available LIGHT (HVEM-L, TNFSF14, or CD258, an entity homologous to lymphotoxins, with inducible nature and the ability to compete with herpes simplex virus glycoprotein D for herpes virus entry mediator (HVEM/tumor necrosis factor (TNF-related 2, is a member of the TNF superfamily. It is expressed as a homotrimer on activated T cells and dendritic cells (DCs, and has three receptors: HVEM, LT-β receptor (LTβR, and decoy receptor 3 (DcR3. So far, three receptors with distinct cellular expression patterns are known to interact with LIGHT. Follicular DCs and stromal cells bind LIGHT through LTβR. We monitored the effects of LIGHT on human bone marrow-derived mesenchymal stem cells (BM-MSCs. At first, we checked the negative and positive differentiation markers of BM-MSCs. And we confirmed the quality of MSCs by staining cells undergoing adipogenesis (Oil Red O staining, chondrogenesis (Alcian blue staining, and osteogenesis (Alizarin red staining. After rhLIGHT treatment, we monitored the count, viability, and proliferation of cells and cell cycle distribution. PDGF and TGFβ production by rhLIGHT was examined by ELISA, and the underlying biological mechanisms were studied by immunoblotting by rhLIGHT treatment. LTβR was constitutively expressed on the surface of human BM-MSCs. Cell number and viability increased after rhLIGHT treatment. BM-MSC proliferation was induced by an increase in the S/G2/M phase. The expression of not only diverse cyclins such as cyclin B1, D1, D3, and E, but also CDK1 and CDK2, increased, while that of p27 decreased, after rhLIGHT treatment. RhLIGHT-induced PDGF and TGFβ production mediated by STAT3 and Smad3 activation accelerated BM-MSC proliferation. Thus, LIGHT and LTβR interaction increases the survival and proliferation of human BM-MSCs, and therefore, LIGHT might play an important role in stem cell therapy.

Autologous bone marrow Th cells can support multiple myeloma cell proliferation in vitro and in xenografted mice.

Science.gov (United States)

Wang, D; Fløisand, Y; Myklebust, C V; Bürgler, S; Parente-Ribes, A; Hofgaard, P O; Bogen, B; Taskén, K; Tjønnfjord, G E; Schjesvold, F; Dalgaard, J; Tveita, A; Munthe, L A

2017-10-01

Multiple myeloma (MM) is a plasma cell malignancy where MM cell growth is supported by the bone marrow (BM) microenvironment with poorly defined cellular and molecular mechanisms. MM cells express CD40, a receptor known to activate autocrine secretion of cytokines and elicit proliferation. Activated T helper (Th) cells express CD40 ligand (CD40L) and BM Th cells are significantly increased in MM patients. We hypothesized that activated BM Th cells could support MM cell growth. We here found that activated autologous BM Th cells supported MM cell growth in a contact- and CD40L-dependent manner in vitro. MM cells had retained the ability to activate Th cells that reciprocated and stimulated MM cell proliferation. Autologous BM Th cells supported MM cell growth in xenografted mice and were found in close contact with MM cells. MM cells secreted chemokines that attracted Th cells, secretion was augmented by CD40-stimulation. Within 14 days of culture of whole BM aspirates in autologous serum, MM cells and Th cells mutually stimulated each other, and MM cells required Th cells for further expansion in vitro and in mice. The results suggest that Th cells may support the expansion of MM cells in patients.

Study of /sup 201/Tl uptake by bone and bone marrow on /sup 201/Tl scintigraphy. With special reference to bone marrow abnormalities

Energy Technology Data Exchange (ETDEWEB)

Fujii, Tadashige; Tanaka, Masao; Hirose, Yoshiki; Hirayama, Jiro; Handa, Kenjiro; Nakanishi, Fumiko; Yano, Kesato; Ueda, Hitoshi

1989-04-01

Thallium-201 (Tl-201) uptake in the bone and bone marrow was examined in a total of 93 patients with various diseases. Sternal uptake of Tl-201 was observed when patients had bone marrow abnormality especially associated with hematopoietic disease. It was associated with proliferation of immature cells and of various types of bone marrow cells, especially erythroblastic and plasma cells. Whole-body Tl-201 scanning showed a high uptake (82%) in the sternum, chest, lumbar vertebrae, and pelvis. Thallium-201 was definitively taken up by the sternum in polycythemia (5/41), hemolytic anemia (2/2), iron deficiency anemia (2/2), and multiple myeloma (2/5). For leukemia, Tl-201 uptake was slight or negative. Thallium-201 scanning proved useful in visualizing bone marrow abnormality, although careful interpretation of bone and bone marrow uptake is required. (Namekawa, K).

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.

Conditioned media from differentiating craniofacial bone marrow stromal cells influence mineralization and proliferation in periodontal ligament stem cells.

Science.gov (United States)

Jin, Zhenyu; Feng, Yuan; Liu, Hongwei

2016-10-01

Previous reports have mainly focused on the behavioral responses of human periodontal ligament stem cells (hPDLSCs) in interaction with tibia bone marrow stromal cells (BMSCs). However, there is little study on the biologic features of hPDLSCs under the induction of maxilla BMSCs (M-BMSCs) at different phases of osteogenic differentiation. We hypothesized that M-BMSCs undergoing osteogenic differentiation acted on the proliferation, differentiation, and bone-forming capacity of hPDLSCs. In this paper, primary hPDLSCs and human M-BMSCs (hM-BMSCs) were expanded in vitro. After screening of surface markers for characterization, hPDLSCs were cocultured with different phases of differentiating hM-BMSCs. Cell proliferation and alkaline phosphatase activity were examined, and mineralization-associated markers such as osteocalcin and runt-related transcription factor 2 of hPDLSCs in coculture with uninduced/osteoinduced hM-BMSCs were evaluated. hPDLSCs in hM-BMSCs-conditioned medium (hM-BMSCs-CM) group showed a reduction in proliferation compared with untreated hPDLSCs, while osteoinduced hM-BMSCs for 10 day-conditioned medium (hM-BMSCs-CM-10ds) and osteoinduced hM-BMSCs for 15 day-conditioned medium (hM-BMSCs-CM-15ds) enhance the proliferation of hPDLSCs. hM-BMSCs of separate differentiation stages temporarily inhibited osteogenesis of hPDLSCs in the early days. Upon extending time periods, uninduced/osteoinduced hM-BMSCs markedly enhanced osteogenesis of hPDLSCs to different degrees. The transplantation results showed hM-BMSCs-CM-15ds treatment promoted tissue regeneration to generate cementum/periodontal ligament-like structure characterized by hard-tissue formation. This research supported the notion that hM-BMSCs triggered osteogenesis of hPDLSCs suggesting important implications for periodontal engineering.

Parental bone marrow growth in young hybrid mice

International Nuclear Information System (INIS)

Chervenak, R.P.

1979-01-01

When bone marrow is transplated from certain inbred mouse strains to F 1 hybrids of that strain, the graft often fails to proliferate. It has been reported that this phenomenon, known as Poor Growth, is not demonstrable in recipients less than three weeks of age. The purpose of the present study was to investigate some of the parameters involved in this phenomenon and its sudden appearance at three weeks of age. By employing 125 IUdR uptake and hemopoietic colony assays following transplantation of marrow to mice of various ages and treatment groups, the following conclusions were drawn. (1) Parental marrow grew equally well in both parental strain and F 1 hybrid recipients less than three weeks old; (2) The observed growth of hemopoietic tissue was not due to endogeneous stem cell proliferation; (3) Changes in radiation sensitivity did not account for the fluctuations of hemopoiesis seen in mice from one to five weeks of age; (4) Neither stimulator cells in mice less than three weeks of age nor graft destroying cells in older mice could be demonstrated. Two mechanistic models of Poor Growth are presented and discussed and a new model is proposed

Graphene coating on the surface of CoCrMo alloy enhances the adhesion and proliferation of bone marrow mesenchymal stem cells.

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Zhang, Qi; Li, Kewen; Yan, Jinhong; Wang, Zhuo; Wu, Qi; Bi, Long; Yang, Min; Han, Yisheng

2018-03-18

The objective was to investigate whether a graphene coating could improve the surface bioactivity of a cobalt-chromium-molybdenum-based alloy (CoCrMo). Graphene was produced by chemical vapor deposition and transferred to the surface of the CoCrMo alloy using an improved wet transfer approach. The morphology of the samples was observed, and the adhesion force and stabilization of graphene coating were analyzed by a nanoscratch test and ultrasonication test. In an in vitro study, the adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs) cultured on the samples were quantified via an Alamar Blue assay and cell counting kit-8 (CCK-8) assay. The results showed that it is feasible to apply graphene to modify the surface of a CoCrMo alloy, and the enhancement of the adhesion and proliferation of BMSCs was also shown in the present study. In conclusion, graphene exhibits considerable potential for enhancing the surface bioactivity of CoCrMo alloy. Copyright © 2018 Elsevier Inc. All rights reserved.

Neurotrophin-3 promotes proliferation and cholinergic neuronal differentiation of bone marrow- derived neural stem cells via notch signaling pathway.

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Yan, Yu-Hui; Li, Shao-Heng; Gao, Zhong; Zou, Sa-Feng; Li, Hong-Yan; Tao, Zhen-Yu; Song, Jie; Yang, Jing-Xian

2016-12-01

Recently, the potential for neural stem cells (NSCs) to be used in the treatment of Alzheimer's disease (AD) has been reported; however, the therapeutic effects are modest by virtue of the low neural differentiation rate. In our study, we transfected bone marrow-derived NSCs (BM-NSCs) with Neurotrophin-3 (NT-3), a superactive neurotrophic factor that promotes neuronal survival, differentiation, and migration of neuronal cells, to investigate the effects of NT-3 gene overexpression on the proliferation and differentiation into cholinergic neuron of BM-NSCs in vitro and its possible molecular mechanism. BM-NSCs were generated from BM mesenchymal cells of adult C57BL/6 mice and cultured in vitro. After transfected with NT-3 gene, immunofluorescence and RT-PCR method were used to determine the ability of BM-NSCs on proliferation and differentiation into cholinergic neuron; Acetylcholine Assay Kit was used for acetylcholine (Ach). RT-PCR and WB analysis were used to characterize mRNA and protein level related to the Notch signaling pathway. We found that NT-3 can promote the proliferation and differentiation of BM-NSCs into cholinergic neurons and elevate the levels of acetylcholine (ACh) in the supernatant. Furthermore, NT-3 gene overexpression increase the expression of Hes1, decreased the expression of Mash1 and Ngn1 during proliferation of BM-NSCs. Whereas, the expression of Hes1 was down-regulated, and Mash1 and Ngn1 expression were up-regulated during differentiation of BM-NSCs. Our findings support the prospect of using NT-3-transduced BM-NSCs in developing therapies for AD due to their equivalent therapeutic potential as subventricular zone-derived NSCs (SVZ-NSCs), greater accessibility, and autogenous attributes. Copyright © 2016 Elsevier Inc. All rights reserved.

Probable impact of age and hypoxia on proliferation and microRNA expression profile of bone marrow-derived human mesenchymal stem cells

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Norlaily Mohd Ali

2016-01-01

Full Text Available Decline in the therapeutic potential of bone marrow-derived mesenchymal stem cells (MSC is often seen with older donors as compared to young. Although hypoxia is known as an approach to improve the therapeutic potential of MSC in term of cell proliferation and differentiation capacity, its effects on MSC from aged donors have not been well studied. To evaluate the influence of hypoxia on different age groups, MSC from young (60 years donors were expanded under hypoxic (5% O2 and normal (20% O2 culture conditions. MSC from old donors exhibited a reduction in proliferation rate and differentiation potential together with the accumulation of senescence features compared to that of young donors. However, MSC cultured under hypoxic condition showed enhanced self-renewing and proliferation capacity in both age groups as compared to normal condition. Bioinformatic analysis of the gene ontology (GO and KEGG pathway under hypoxic culture condition identified hypoxia-inducible miRNAs that were found to target transcriptional activity leading to enhanced cell proliferation, migration as well as decrease in growth arrest and apoptosis through the activation of multiple signaling pathways. Overall, differentially expressed miRNA provided additional information to describe the biological changes of young and aged MSCs expansion under hypoxic culture condition at the molecular level. Based on our findings, the therapeutic potential hierarchy of MSC according to donor’s age group and culture conditions can be categorized in the following order: young (hypoxia > young (normoxia > old aged (hypoxia > old aged (normoxia.

Postradiation recovery of the bone marrow of man and morphodynamics of the pool of undifferentiated cells

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

1981-01-01

Peculiarities of postradiation recovery of bone marrow parenchyma and stroma in persons who have been exposed to uniform gamma irradiation and nonuniform gamma-neutron irradiation at doses of 2-5 and more than 5 Gy are described on the basis of quantitive characteristics of bone marrow trepanates which have been investigated in different periods of acute radiation sickness (from 2 to 43 days). A special attention is paid to the description of the behaviour of clones composed of nondifferentiated cells that appear in bone marrow of the 4th - 6th day of sickness and participate in its repair. The obtained results attest that clone-forming nondifferentiated cells are the basis for hemopoetic parenchyma recovery. The number of trunk hemopoetic cells in this or that area of bone marrow exposed to the irradiation at different doses can be determined with a high degree of probability by the number of clones.

Postirradiation bone marrow damage in chickens

International Nuclear Information System (INIS)

Skardova, I.; Ojeda, F.

1994-01-01

The frequency of bone marrow damage induced by the continuous gamma irradiation was studied. Effect of dose rate and level of cumulated doses of radiation was evaluated in clinical and hematological examinations and bone marrow damage was determined by chromosome aberrations in anaphase. The regulative ability of hematopoiesis of many cytokines are discussed. Positive regulators are inducers of cell proliferation, and negative regulators are inducers of apoptosis /programmed cell death/. Birds corresponding with similarities in thymus-T and bursal-B cells appear to be an interesting model for studying the possible participation of apoptosis in radiation disease. Our recent experimental studies continue to progress in this direction. (author) 17 refs.; 3 figs.; 2 tabs

[Progesterone Promotes Human Bone Marrow Mesenchymal Stem Cells to Synthesize Fibronectin via ERK Pathway].

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Wu, Zhen-Yong; Chen, Jing-Li; Huang, Shu; Zhang, Hui; Wang, Fang; Wang, Yan; Bi, Xiao-Yun; Guo, Zi-Kuan

2015-12-01

To investigate whether the progesterone can promote fibronection (FN) synthesis by human bone marrow mesenchymal stem cells (MSCs) and to explore the potential underlying mechanism. The human bone marrow MSCs were cultured in a serum-free medium with progesterone for 72 hours, the MTT test was performed to observe the proliferation status and adhension ability of the treated cells. Western blot was used to detect the content of FN in MSDs with GAPDH as the internal reference, the phosphorylation of ERK1/2, as well as the FN content in MSC treated by PD98059, a specific inhibitor of ERK1/2. The progesterone at a range of certain doses not effect on the proliferation of human bone marrow MSCs. Progesterone (25 µg/L) treatment enhanced the FN expression and adherent ability of marrow MSCs. Progesterone could induce prompt phosphorylation of ERK 1/2 and its promoting effects on FN synthesis was reversed by PD98059. The progesterone can promote FN synthesis by human bone marrow MSCs via ERK 1/2 pathway, and it might be used to culture MSCs in serum-free medium.

Effect of some chemical radioprotectors on mouse bone marrow

International Nuclear Information System (INIS)

Lata, Manju; Ghose, A.; Khanna, C.M.

1993-01-01

Effect of 5-hydroxy-L-tryptophan (HT), AET and Se on mice bone marrow has been studied by counting bone marrow micronucleated cells and endogenous spleen colony count (CFU-S). Combination of HT and AET used as a radioprotector has not caused any significant variation in any of the parameter studied when administered once, it increases bone marrow micronucleated cells and decreases CFU-S slightly after daily administration for 7 days. The individual constituent of the combination administered singly does not increase micronucleated cell number. Seven consecutive doses of HT+AET and same in combination with Se enhances micronucleated cells to a higher level. Daily injection of Se alone up to 7 days also causes an increase in micronucleated cells up to same level. CFU-S pool does not show any significant change in number of bone marrow cells through out the study except in the groups where animals were treated with Se. (author). 15 refs., 3 tabs

Noradrenergic and cholinergic innervation of the bone marrow.

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Artico, Marco; Bosco, Sandro; Cavallotti, Carlo; Agostinelli, Enzo; Giuliani-Piccari, Gabriella; Sciorio, Salvatore; Cocco, Lucio; Vitale, Marco

2002-07-01

Bone marrow is supplied by sensory and autonomic innervation. Although it is well established that hematopoiesis is regulated by cytokines and cell-to-cell contacts, the role played by neuromediators on the proliferation, differentiation and release of hematopoietic cells is still controversial. We studied the innervation of rat femur bone marrow by means of fluorescence histochemistry and immunohistochemistry. Glyoxylic acid-induced fluorescence was used to demonstrate catecholaminergic nerve fibers. The immunoperoxidase method with nickel amplification was applied to detect the distribution of nerve fibers using antibodies against the general neuronal marker PGP 9.5 (neuron-specific cytoplasmic protein), while the cholinacetyltransferase immunoreactivity was studied by immunohistochemistry. Our results show the presence of an extensive network of innervation in the rat bone marrow, providing a morphological basis for the neural modulation of hemopoiesis.

Changes of the proliferation kinetics of human bone marrow in vivo through hydroxyurea

International Nuclear Information System (INIS)

Ertl, E.

1982-01-01

A 10-hour oral continuous infusion with hydroxyurea (HU) at a non-toxic concentration was performed in 20 malignoma patients with undisturbed bone marrow. Bone marrow taken before, during and after HU-administration was examined for 3H-TdR incorporation by means of autoradiography and liquid scintimetry, for cell phase distribution by means of flow cytophotometry, morphologically and by means of CFUc. 3H-TdR incorporation into bone marrow cells dropped to 16% of the initial value under HU and rose to 156% 10 h after HU-effect terminated. Cytophotometry did not furnish any proof of a decrease of S-phase cells or increase of cells in G 1 -to-S-transition during HU. S-cells rise to 129% of the initial value 10 h after having fallen below minimum inhibition concentration. Under HU, there is an equal number of cells in S which incorporate much less 3H-thymidine; after HU more S-cells incorporate more 3H-thymidine than before HU. During HU action, DNA synthesis activity is reduced to 17% and reaches the initial value with 105% afterwards. In human bone marrow, hydroxyurea in non-toxic concentration causes a temporary DNA synthesis inhibition in terms of activity reduction and partial arrest in S. A stop-and-go of the cell cycle effected by HU does not occur; the effect is rather a slow-down of DNA synthesis. (orig./MG) [de

Marrow fat cell: response to x-ray induced aplasia

International Nuclear Information System (INIS)

Bathija, A.; Ohanian, M.; Davis, S.; Trubowitz, S.

1979-01-01

Adipose tissue is an integral structural component of normal rabbit marrow and is believed to behave primarily as a cushion in response to hemopoietic proliferation, accommodating to changes in hemopoiesis by change in either size or number or both of the fat cells in order to maintain constancy of the marrow volume. To test this hypothesis, aplasia of the right femur of New Zealand white rabbits was induced by x irradiation with 8000 rads; the left unirradiated limb served as control. Twenty-four hours before sacrifice 50 μCi of palmitate-114C was administered intravenously and the marrow of both femurs removed. Samples of perinephric fat were taken for comparison. Fat cell volume, C14 palmitate turnover and fatty acid composition were determined. The total number of fat cells in the entire marrow of both femurs was calculated. The measurements showed no difference in size or fatty acid turnover of the fat cells in the irradiated aplastic marrow from the cells of the control marrow. The number of fat cells in both the irradiated and the unirradiated control femurs was essentially the same. These findings do not support the view that marrow fat cells respond to diminished hematopoiesis by either increase in their volume or number. In addition, the findings suggest that both marrow and subcutaneous fat cells are fairly resistant to high doses of x-ray irradiation

Local regulation of haemopoietic stem cell proliferation in mice following irradiation

International Nuclear Information System (INIS)

Ali, A.M.; Riches, A.C.; Wright, E.G.

1989-01-01

Changes in the kinetic state of pluripotent haemopoietic spleen colony forming cells (CFU-S) and of the CFU-S proliferation stimulator have been studied following whole-body X-irradiation. Rapid recruitment of CFU-S into cell cycle by 30 min after irradiation was observed following low doses (0.5 Gy) but a delay of 6 h occurred after higher doses (1.5 and 4.5 Gy). These changes in proliferative state correlated with the presence of the CFU-S proliferation stimulator. CFU-S irradiated in vitro in bone marrow plugs were also recruited into cycle illustrating directly the local nature of the feedback mechanism. CFU-S removed from 1.5 Gy irradiated recipients at a time when they were not in cycle were not responsive to the CFU-S proliferation stimulator. The CFU-S proliferation stimulator was produced by Ia positive cells in the irradiated bone marrow. The regulation changes occurring shortly after irradiation cannot simply be controlled by the size of the CFU-S compartment. (author)

Use of long-term human marrow cultures to demonstrate progenitor cell precursors in marrow treated with 4-hydroperoxycyclophosphamide

International Nuclear Information System (INIS)

Winton, E.F.; Colenda, K.W.

1987-01-01

The continued retrieval of progenitor cells (CFU-GEMM, BFU-E, CFU-E, CFU-GM) from human long-term marrow cultures (LTMC) is not uncommonly used as evidence that proliferation and differentiation are occurring in more primitive hematopoietic stem cells (HSC) in these cultures. Alternatively, the continued presence of progenitors in LTMC could be the result of survival and/or limited self-renewal of progenitor cells present when the culture was initiated, and such progenitors would have little relevance to the parent HSC. The following studies were designed to determine the relative contributions of precursors of progenitor cells to the total progenitor cells present in LTMC using a two-stage regeneration model. The adherent layer in LTMC was established over 3 weeks, irradiated (875 rad) to permanently eliminate resident hematopoietic cells, and recharged with autologous cryo-preserved marrow that was either treated or not treated (control) with 4-hydroperoxycyclophosphamide (4-HC, 100 micrograms/ml for 30 min). The 4-HC-treated marrow contained no progenitor cells, yet based on clinical autologous bone marrow transplant experience, has intact HSC. Within 1-3 weeks, progenitor cells reappeared in the irradiated LTMC recharged with 4-HC-treated marrow, and were preferentially located in the adherent layer. By 2-6 weeks, the number of progenitor cells in the adherent layer of LTMC recharged with 4-HC marrow was equivalent to control LTMC. The progenitors regenerating in the irradiated LTMC recharged with 4-HC-treated marrow appear to originate from precursors of progenitor cells, perhaps HSC. We propose this model may be useful in elucidating cellular and molecular correlates of progenitor cell regeneration from precursors

Human amnion mesenchymal stem cells promote proliferation and osteogenic differentiation in human bone marrow mesenchymal stem cells.

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Wang, Yuli; Yin, Ying; Jiang, Fei; Chen, Ning

2015-02-01

Human amnion mesenchymal stem cells (HAMSCs) can be obtained from human amniotic membrane, a highly abundant and readily available tissue. HAMSC sources present fewer ethical issues, have low immunogenicity, anti-inflammatory properties, considerable advantageous characteristics, and are considered an attractive potential treatment material in the field of regenerative medicine. We used a co-culture system to determine whether HAMSCs could promote osteogenesis in human bone marrow mesenchymal stem cells (HBMSCs). We isolated HAMSCs from discarded amnion samples and collected them using pancreatin/collagenase digestion. We cultured HAMSCs and HBMSCSs in basal medium. Activity of alkaline phosphatase (ALP), an early osteogenesis marker, was increased in the co-culture system compared to the control single cultures, which we also confirmed by ALP staining. We used immunofluorescence testing to investigate the effects of co-culturing with HAMSCs on HBMSC proliferation, which revealed that the co-culturing enhanced EdU expression in HBMSCs. Western blotting and quantitative real-time PCR indicated that co-culturing promoted osteogenesis in HBMSCs. Furthermore, Alizarin red S staining revealed that extracellular matrix calcium levels in mineralized nodule formation produced by the co-cultures were higher than that in the controls. Using the same co-culture system, we further observed the effects of HAMSCs on osteogenic differentiation in primary osteoblasts by Western blotting, which better addressed the mechanism for HAMSCs in bone regeneration. The results showed HAMSCs are osteogenic and not only play a role in promoting HBMSC proliferation and osteogenic differentiation but also in osteoblasts, laying the foundation for new regenerative medicine methods.

Osteoinduction and proliferation of bone-marrow stromal cells in three-dimensional poly (ε-caprolactone)/ hydroxyapatite/collagen scaffolds.

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Wang, Ting; Yang, Xiaoyan; Qi, Xin; Jiang, Chaoyin

2015-05-08

Osteoinduction and proliferation of bone-marrow stromal cells (BMSCs) in three-dimensional (3D) poly(ε-caprolactone) (PCL) scaffolds have not been studied throughly and are technically challenging. This study aimed to optimize nanocomposites of 3D PCL scaffolds to provide superior adhesion, proliferation and differentiation environment for BMSCs in this scenario. BMSCs were isolated and cultured in a novel 3D tissue culture poly(ε-caprolactone) (PCL) scaffold coated with poly-lysine, hydroxyapatite (HAp), collagen and HAp/collagen. Cell morphology was observed and BMSC biomarkers for osteogenesis, osteoblast differentiation and activation were analyzed. Scanning Electron Microscope (SEM) micrographs showed that coating materials were uniformly deposited on the surface of PCL scaffolds and BMSCs grew and aggregated to form clusters during 3D culture. Both mRNA and protein levels of the key players of osteogenesis and osteoblast differentiation and activation, including runt-related transcription factor 2 (Runx2), alkaline phosphates (ALP), osterix, osteocalcin, and RANKL, were significantly higher in BMSCs seeded in PCL scaffolds coated with HAp or HAp/collagen than those seeded in uncoated PCL scaffolds, whereas the expression levels were not significantly different in collagen or poly-lysine coated PCL scaffolds. In addition, poly-lysine, collagen, HAp/collagen, and HAp coated PCL scaffolds had significantly more viable cells than uncoated PCL scaffolds, especially scaffolds with HAp/collagen and collagen-alone coatings. That BMSCs in HAp or HAp/collagen PCL scaffolds had remarkably higher ALP activities than those in collagen-coated alone or uncoated PCL scaffolds indicating higher osteogenic differentiation levels of BMSCs in HAp or HAp/collagen PCL scaffolds. Moreover, morphological changes of BMSCs after four-week of 3D culture confirmed that BMSCs successfully differentiated into osteoblast with spread-out phenotype in HAp/collagen coated PCL scaffolds

Wip1 knockout inhibits the proliferation and enhances the migration of bone marrow mesenchymal stem cells

International Nuclear Information System (INIS)

Tang, Yiting; Liu, Lan; Sheng, Ming; Xiong, Kai; Huang, Lei; Gao, Qian; Wei, Jingliang; Wu, Tianwen; Yang, Shulin; Liu, Honglin; Mu, Yulian; Li, Kui

2015-01-01

Mesenchymal stem cells (MSCs), a unique population of multipotent adult progenitor cells originally found in bone marrow (BM), are extremely useful for multifunctional therapeutic approaches. However, the growth arrest and premature senescence of MSCs in vitro prevent the in-depth characterization of these cells. In addition, the regulatory factors involved in MSCs migration remain largely unknown. Given that protein phosphorylation is associated with the processes of MSCs proliferation and migration, we focused on wild-type p53-inducible phosphatase-1 (Wip1), a well-studied modulator of phosphorylation, in this study. Our results showed that Wip1 knockout significantly inhibited MSCs proliferation and induced G2-phase cell-cycle arrest by reducing cyclinB1 expression. Compared with WT-MSCs, Wip1 −/− MSCs displayed premature growth arrest after six passages in culture. Transwell and scratch assays revealed that Wip1 −/− MSCs migrate more effectively than WT-MSCs. Moreover, the enhanced migratory response of Wip1 −/− MSCs may be attributed to increases in the induction of Rac1-GTP activity, the pAKT/AKT ratio, the rearrangement of filamentous-actin (f-actin), and filopodia formation. Based on these results, we then examined the effect of treatment with a PI3K/AKT and Rac1 inhibitor, both of which impaired the migratory activity of MSCs. Therefore, we propose that the PI3K/AKT/Rac1 signaling axis mediates the Wip1 knockout-induced migration of MSCs. Our findings indicate that the principal function of Wip1 in MSCs transformation is the maintenance of proliferative capacity. Nevertheless, knocking out Wip1 increases the migratory capacity of MSCs. This dual effect of Wip1 provides the potential for purposeful routing of MSCs. - Highlights: • Wip1 knockout inhibited MSCs proliferation through reducing cyclinB1 expression. • Wip1 −/− MSCs displayed premature growth arrest in vitro after six passages. • Knocking out Wip1 increases the migratory

Wip1 knockout inhibits the proliferation and enhances the migration of bone marrow mesenchymal stem cells

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Tang, Yiting [College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China); State Key Laboratory of Animal Nutrition and Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193 (China); Liu, Lan [State Key Laboratory of Animal Nutrition and Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193 (China); Sheng, Ming [College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China); Xiong, Kai [Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Grønnegårdsvej 7, 1870 Frederiksberg C (Denmark); Huang, Lei; Gao, Qian; Wei, Jingliang; Wu, Tianwen; Yang, Shulin [State Key Laboratory of Animal Nutrition and Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193 (China); Liu, Honglin, E-mail: liuhonglinnjau@163.com [College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China); Mu, Yulian, E-mail: muyulian76@iascaas.net.cn [State Key Laboratory of Animal Nutrition and Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193 (China); Li, Kui [State Key Laboratory of Animal Nutrition and Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193 (China)

2015-06-10

Mesenchymal stem cells (MSCs), a unique population of multipotent adult progenitor cells originally found in bone marrow (BM), are extremely useful for multifunctional therapeutic approaches. However, the growth arrest and premature senescence of MSCs in vitro prevent the in-depth characterization of these cells. In addition, the regulatory factors involved in MSCs migration remain largely unknown. Given that protein phosphorylation is associated with the processes of MSCs proliferation and migration, we focused on wild-type p53-inducible phosphatase-1 (Wip1), a well-studied modulator of phosphorylation, in this study. Our results showed that Wip1 knockout significantly inhibited MSCs proliferation and induced G2-phase cell-cycle arrest by reducing cyclinB1 expression. Compared with WT-MSCs, Wip1{sup −/−} MSCs displayed premature growth arrest after six passages in culture. Transwell and scratch assays revealed that Wip1{sup −/−} MSCs migrate more effectively than WT-MSCs. Moreover, the enhanced migratory response of Wip1{sup −/−} MSCs may be attributed to increases in the induction of Rac1-GTP activity, the pAKT/AKT ratio, the rearrangement of filamentous-actin (f-actin), and filopodia formation. Based on these results, we then examined the effect of treatment with a PI3K/AKT and Rac1 inhibitor, both of which impaired the migratory activity of MSCs. Therefore, we propose that the PI3K/AKT/Rac1 signaling axis mediates the Wip1 knockout-induced migration of MSCs. Our findings indicate that the principal function of Wip1 in MSCs transformation is the maintenance of proliferative capacity. Nevertheless, knocking out Wip1 increases the migratory capacity of MSCs. This dual effect of Wip1 provides the potential for purposeful routing of MSCs. - Highlights: • Wip1 knockout inhibited MSCs proliferation through reducing cyclinB1 expression. • Wip1{sup −/−} MSCs displayed premature growth arrest in vitro after six passages. • Knocking out Wip1

Potential Effect of CD271 on Human Mesenchymal Stromal Cell Proliferation and Differentiation.

Science.gov (United States)

Calabrese, Giovanna; Giuffrida, Raffaella; Lo Furno, Debora; Parrinello, Nunziatina Laura; Forte, Stefano; Gulino, Rosario; Colarossi, Cristina; Schinocca, Luciana Rita; Giuffrida, Rosario; Cardile, Venera; Memeo, Lorenzo

2015-07-09

The Low-Affinity Nerve Growth Factor Receptor (LNGFR), also known as CD271, is a member of the tumor necrosis factor receptor superfamily. The CD271 cell surface marker defines a subset of multipotential mesenchymal stromal cells and may be used to isolate and enrich cells derived from bone marrow aspirate. In this study, we compare the proliferative and differentiation potentials of CD271+ and CD271- mesenchymal stromal cells. Mesenchymal stromal cells were isolated from bone marrow aspirate and adipose tissue by plastic adherence and positive selection. The proliferation and differentiation potentials of CD271+ and CD271- mesenchymal stromal cells were assessed by inducing osteogenic, adipogenic and chondrogenic in vitro differentiation. Compared to CD271+, CD271- mesenchymal stromal cells showed a lower proliferation rate and a decreased ability to give rise to osteocytes, adipocytes and chondrocytes. Furthermore, we observed that CD271+ mesenchymal stromal cells isolated from adipose tissue displayed a higher efficiency of proliferation and trilineage differentiation compared to CD271+ mesenchymal stromal cells isolated from bone marrow samples, although the CD271 expression levels were comparable. In conclusion, these data show that both the presence of CD271 antigen and the source of mesenchymal stromal cells represent important factors in determining the ability of the cells to proliferate and differentiate.

Proliferation kinetics and cyclic AMP as prognostic factors in adult acute leukemia.

Science.gov (United States)

Paietta, E; Mittermayer, K; Schwarzmeier, J

1980-07-01

In 41 adult patients with acute leukemia (myeloblastic, lymphoblastic, and undifferentiated), proliferation kinetics (as determined by double-label autoradiography) and cyclic adenosine 3',5'-monophosphate (cAMP) concentration were studied for their significance in the prediction of responsiveness to cytostatic therapy. Patients with good clinical response had significantly shorter turnover times and higher labeling indices in the bone marrow than did those who failed to respond to treatment. Cases for which cell kinetics did not correlate with clinical response were explained by variance in the distribution of leukemic blasts between the proliferative cell cycle and the resting pool. Good clinical response was also found to be associated with low levels of cAMP in leukemic cells prior to therapy, whereas high cAMP contents predicted failure. Low cAMP concentrations, however, did not necessarily correlate with short turnover times and vice versa. This might be due to fluctuations of the cAMP concentrations during the cell cycle.

Effects of radiations on bone marrow

International Nuclear Information System (INIS)

Tubiana, M.; Frindel, E.; Croizat, H.; Parmentier, C.

1979-01-01

After total body irradiation for kidney transplant, the initial decrease of circulating blood cells is more rapid, the nadir is reached sooner and the regeneration occurs earlier when the doses are higher than a few hundred rads. The LD 50 in man seems to be higher than 450 rads. The in vivo and in vitro assays of hemopoietic stem cells have greatly increasedd the understanding of acute and late effects. Multipotential stem cells are very radiosensitive, furthermore the differentiation of the surviving stem cells is accelerated after irradiation. This results in a severe depletion of the stem cell compartment. When this stem cell number falls below a critical value, the stem cell no longer differentiates till the completion of the regeneration of the stem cell compartment. Stem cell proliferation is regulated by inhibitors and stimulators. Release of stimulators by irradiated bone marrow has been demonstrated. Severe sequellae are observed after irradiation of animal and human bone marrow. They seem to be due either to the damage of the stromal cell or to the stem cell population. In patients, four compensating mechanisms are observed after a regional bone marrow irradiation: stimulation of non irradiated bone marrow, extension of hemopoietic areas, regeneration of irradiated bone marrow when the irradiated volume is large and increase in the amplification factor resulting in an increase in the output of mature cells for one stem cell input. Assay of progenitor cells provides useful information and a reduction in their number is still observed many years after a large regional irradiation

Biocompatibility of various hydoxyapatite scaffolds evaluated by proliferation of rat’s bone marrow mesenchymal stem cells: an in vitro study

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Achmad F. Kamal

2013-12-01

Full Text Available Background: Scaffold (biomaterial biocompatibility test should be performed in vitro prior to in vivo stem cell application in animal or clinical trial. These test consists of direct and indirect toxicity test (MTT assay [3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide]. Those tests were used to identify cell morphological changes, cell-substrate adhesion impairment, and reduction in cell proliferation activity.Methods: The tested scaffolds were hydroxyapatite-calcium sulphate (HA-CaSO4 (scaffold I, nano-particular HA paste (scaffold II, synthetic HA granule (scaffold III, bovine HA granule (scaffold IV, and morsellized bovine xenograft (scaffold V. Direct contact toxicity test and MTT assay [3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide] were performed on those groups. In direct contact toxicity test, we put granules of various scaffolds within plates and incubated together with mesenchymal stem cells (MSCs. In MTT assay we included phenol 20 mg/mL and 100 mg/mL group as positive control. Morphology, cell adhesion impairment, and cell growth were monitored daily until day-7. Cells counting in the direct contact toxicity test was conducted on day-7.Results: There were no changes on 24 hours observation after direct contact. On day-7, an impairment of cell adhesion to plastic substrates, changes in cell morphology, and cell death were observed, especially in scaffold I, scaffold II, and scaffold V. In MTT assay, only scaffold I, phenol 20 mg/mL, and phenol 100 mg/mL showed more than 50% inhibition at 24-hour and 7-day-observation. Extracts from scaffold II, III, IV, and V did not affect the viability and proliferation of bone marrow MSCs (inhibition value < 50%. Scaffold II, III, IV and V were proven non-cytotoxic and have good biocompatibility in vitro,  no statistical significant differences were observed among the scaffold groups (p > 0.05.Conclusion: We understand which scaffold was nontoxic or the least toxic to

Animal experimental model of a graft-versus-host (GVH) reaction after allogenic transplantation of bone marrow in lethally irradiated mice

International Nuclear Information System (INIS)

Schwenke, H.; Muench, S.; Haubold, S.; Weber, B.

1977-01-01

The graft-versus-host (GVH) disease represents a serious still unsolved problem in the human allogenic transplantation of bone marrow. An experimental model of GVH reaction after an allogenic transplantation of bone marrow in the adult mouse has been worked out as a prerequisite for further studies on the therapeutic influence of this syndrome. 3 groups have been formed out of 82 lethally X-irradiated C57 Bl mice. The non-transplanted control group died to a hundred per cent within 12 days. While out of the 2nd group treated with syngenic bone marrow 55 per cent survived from the 22nd day, 30 per cent of the third animal group, allogenicly transplanted with histoincompatible AKR donor marrow developed a chronic GVH syndrome. The following symptoms were observed: retardation, alterations of the skin, diarrhea, edemas of the legs, failing increase of leukocytes in blood and proliferation of lymphocytes in bone marrow of about 60 per cent (18 per cent in syngenically transplanted animals), in lacking proliferation of hematopoiesis. The increase of liver and especially spleen index is not characteristic in comparison with the syngenically transplanted group, since in the latter there is also an increase of the values on account of a strong hematopoetic proliferation. The model is suitable and sufficiently well characterized for the performance of further experimental studies. (author)

Long-term culture and differentiation of porcine red bone marrow hematopoietic cells co-cultured with immortalized mesenchymal cells.

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Garba, Abubakar; Acar, Delphine D; Roukaerts, Inge D M; Desmarets, Lowiese M B; Devriendt, Bert; Nauwynck, Hans J

2017-09-01

Mesenchymal cells are multipotent stromal cells with self-renewal, differentiation and immunomodulatory capabilities. We aimed to develop a co-culture model for differentiating hematopoietic cells on top of immortalized mesenchymal cells for studying interactions between hematopoietic and mesenchymal cells, useful for adequately exploring the therapeutic potential of mesenchymal cells. In this study, we investigated the survival, proliferation and differentiation of porcine red bone marrow hematopoietic cells co-cultured with immortalized porcine bone marrow mesenchymal cells for a period of five weeks. Directly after collection, primary porcine bone marrow mesenchymal cells adhered firmly to the bottom of the culture plates and showed a fibroblast-like appearance, one week after isolation. Upon immortalization, porcine bone marrow mesenchymal cells were continuously proliferating. They were positive for simian virus 40 (SV40) large T antigen and the mesenchymal cell markers CD44 and CD55. Isolated red bone marrow cells were added to these immortalized mesenchymal cells. Five weeks post-seeding, 92±6% of the red bone marrow hematopoietic cells were still alive and their number increased 3-fold during five weekly subpassages on top of the immortalized mesenchymal cells. The red bone marrow hematopoietic cells were originally small and round; later, the cells increased in size. Some of them became elongated, while others remained round. Tiny dendrites appeared attaching hematopoietic cells to the underlying immortalized mesenchymal cells. Furthermore, weekly differential-quick staining of the cells indicated the presence of monoblasts, monocytes, macrophages and lymphocytes in the co-cultures. At three weeks of co-culture, flow cytometry analysis showed an increased surface expression of CD172a, CD14, CD163, CD169, CD4 and CD8 up to 37±0.8%, 40±8%, 41±4%, 23±3% and 19±5% of the hematopoietic cells, respectively. In conclusion, continuous mesenchymal cell

Effect of hydroxyurea and vinblastine on the proliferation of the pluripotential stem cells

International Nuclear Information System (INIS)

Necas, E.; Neuwirt, J.

1977-01-01

The population of the pluripotential hemopoietic stem cells in mice, i.e., cells forming colonies in the spleens of lethally irradiated mice (colony forming cells CFc) proliferates relatively slowly. After partial damage the population regenerates which is achieved by an increased proliferation rate. The effect of damage caused by different doses of hydroxyurea or vinblastine to the proliferation of the CFc was investigated. CFc population was measured in femur bone marrow after the grafting of a bone marrow sample into lethally irradiated mice recipients (spleen colony method). The proliferation rate was estimated either according to the magnitude of the fraction of cells synthesizing DNA in the S phase of the cell cycle, or according to the sensitivity of the population to repeated injections of vinblastine. Data showed that even after very minute damage by hydroxyurea the stem cells started to proliferate intensively. The effect was dose dependent. The comparable damage caused by vinblastine had a significantly weaker effect on the proliferation of the stem cells. It is concluded from the results that the proliferation response of the pluripotential stem cells depends on two factors: the extent of the damage caused to the hemopoietic tissue and the position of the killed cells in the cell cycle. (author)

Potential Effect of CD271 on Human Mesenchymal Stromal Cell Proliferation and Differentiation

Directory of Open Access Journals (Sweden)

Giovanna Calabrese

2015-07-01

Full Text Available The Low-Affinity Nerve Growth Factor Receptor (LNGFR, also known as CD271, is a member of the tumor necrosis factor receptor superfamily. The CD271 cell surface marker defines a subset of multipotential mesenchymal stromal cells and may be used to isolate and enrich cells derived from bone marrow aspirate. In this study, we compare the proliferative and differentiation potentials of CD271+ and CD271− mesenchymal stromal cells. Mesenchymal stromal cells were isolated from bone marrow aspirate and adipose tissue by plastic adherence and positive selection. The proliferation and differentiation potentials of CD271+ and CD271− mesenchymal stromal cells were assessed by inducing osteogenic, adipogenic and chondrogenic in vitro differentiation. Compared to CD271+, CD271− mesenchymal stromal cells showed a lower proliferation rate and a decreased ability to give rise to osteocytes, adipocytes and chondrocytes. Furthermore, we observed that CD271+ mesenchymal stromal cells isolated from adipose tissue displayed a higher efficiency of proliferation and trilineage differentiation compared to CD271+ mesenchymal stromal cells isolated from bone marrow samples, although the CD271 expression levels were comparable. In conclusion, these data show that both the presence of CD271 antigen and the source of mesenchymal stromal cells represent important factors in determining the ability of the cells to proliferate and differentiate.

Selective interactions between epithelial tumour cells and bone marrow mesenchymal stem cells

OpenAIRE

Hombauer, H; Minguell, J J

2000-01-01

This work is a comparative study on the features displayed by an epithelial metastatic breast cancer cell line (MCF-7) when set in co-culture with human bone marrow mesenchymal stem cells (MSC) or a feeder layer of 3T3 fibroblasts. MSC, a subset of non-haematopoietic cells in the marrow stroma, display a potential for self-renewal, proliferation and differentiation into precursors for bone, cartilage, connective and muscular tissue. Adhesion of MCF-7 cells to monolayers of MSC or 3T3 was high...

Bone marrow mesenchymal stem cells differentiation and proliferation on the surface of coral implant

International Nuclear Information System (INIS)

Al-Salihi, K.A.; Samsudin, A.R.

2004-01-01

This study was designed to evaluate the ability of natural coral implant to provide an environment for marrow cells to differentiate into osteoblasts and function suitable for mineralized tissue formation. DNA content, alkaline phosptatase (ALP) activity, calcium (Ca) content and mineralized nodules, were measured at day 3, day 7 and day 14, in rat bone marrow stromal cells cultured with coral discs glass discs, while cells alone and coral disc alone cultured as control. DNA content, ALP activity, Ca content measurements showed no difference between coral, glass and cells groups at 3 day which were higher than control (coral disc alone), but there were higher asurement at day 7 and 14 in the cell cultured on coral than on glass discs, control cells and control coral discs. Mineralized nodules formation (both in area and number) was more predominant on the coral surface than in control groups. These results showed that natural coral implant provided excellent and favorable situation for marrow cell to differentiate to osteoblasts, lead to large amount of mineralized tissue formation on coral surface. This in vitro result could explain the rapid bone bonding of coral in vivo. (Author)

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

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

2012-01-01

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

Bone marrow-derived multipotent mesenchymal stromal cells from horses after euthanasia.

Science.gov (United States)

Schröck, Carmen; Eydt, Carina; Geburek, Florian; Kaiser, Lena; Päbst, Felicitas; Burk, Janina; Pfarrer, Christiane; Staszyk, Carsten

2017-11-01

Allogeneic equine multipotent mesenchymal stromal cells (eMSCs) have been proposed for use in regenerative therapies in veterinary medicine. A source of allogeneic eMSCs might be the bone marrow from euthanized horses. The purpose of this study was to compare in vitro characteristics of equine bone marrow derived eMSC (eBM-MSCs) from euthanized horses (eut-MSCs) and from narcotized horses (nar-MSCs). Eut-MSCs and nar-MSCs showed typical eMSC marker profiles (positive: CD44, CD90; negative: CD11a/CD18 and MHCII) and possessed tri-lineage differentiation characteristics. Although CD105 and MHCI expression varied, no differences were detected between eut-MSCs and nar-MSCs. Proliferation characteristics did not differ between eut-MSCs and nar-MSCs, but age dependent decrease in proliferation and increase in MHCI expression was detected. These results suggest the possible use of eut-MSCs for therapeutic applications and production of commercial available eBM-MSC products.

Histamine protects bone marrow against cellular damage induced by Ionizing radiation

International Nuclear Information System (INIS)

Medina, Vanina; Sambuco, Lorena; Massari, Noelia; Cricco, Graciela; Martin, Gabriela; Bergoc, Rosa; Rivera, Elena S.

2008-01-01

After surgery, radiotherapy is arguably one of the most important treatments for cancer, especially for localized disease that has not spread. However, ionizing radiation is toxic not only to tumor cells but also to healthy tissues causing serious adverse effects to patients. We have recently reported that histamine prevents ionizing radiation-induced toxicity on mouse small intestine. The aim of the present work was to determine whether histamine is able to protect bone marrow cells against ionizing radiation damage. For that purpose 56 mice were divided into 4 groups. Histamine and Histamine-10Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 20 hours before irradiation and continued till the end of experimental period; untreated group received saline. Histamine-10Gy and untreated-10Gy groups were irradiated with a single dose on whole-body using Cesium-137 source (7 Gy/min) and were sacrificed 3 days after irradiation. Bone marrow was removed, fixed and stained with hematoxylin and eosin. The number of megacariocytes per 40x field, bone marrow tropism, edema, vascular damage, and other histological characteristics of bone marrow cells were evaluated. We further determined by immunohistochemistry the expression of proliferating cell nuclear antigen (PCNA) and cells in the S phase of the cell cycle were identified by immunohistochemical detection of 5-bromo-2'-deoxyuridine (BrdU) incorporation. Results indicate that histamine treatment substantially reduced the grade of aplasia, the edema and the vascular damage induced by ionizing radiation on bone marrow. Additionally, histamine preserved medullar components increasing significantly the number of megacariocytes per field (5.4 ± 0.4 vs. 2.8 ± 0.4 in Control-10 Gy, P<0.01). This effect was associated with an increased proliferation rate determined by the augmented PCNA expression and BrdU incorporation of bone marrow cells. On the basis of these results, we conclude that histamine

Proliferation differentiation and therapeutic effect of short-term cultured murine bone marrow cells

International Nuclear Information System (INIS)

Zhao Zekun; Cong Jianbo

1986-01-01

Murine bone marrow cells were cultured in conditioned medium of muscle. After 24 hours of culture, both adherent and suspended cells appeared in the culture. The adherent cells mainly consisted of macrophages and the suspended cells were predominantly granulocytes. After 6 days, the total number of nucleated cells and CFU-C in the culture increased about 400% and 600% respectively, but CFU-S reduced to 21% approximately. Lymphocytes persisted only for 4 days. The stem cells (CFU-S) from 6-day culture were injected into the lethally irradiated syngenic mice. The 30 day survival rate of the treated mice was 89% whereas that of the controls was only 7%. The bone marrow cells in 2/8 of recipients sacrificed at 30 or 60 days were of donor type and 6/8 of the recipients were chimeras

In vitro migration and proliferation ("wound healing") potential of mesenchymal stromal cells generated from human CD271(+) bone marrow mononuclear cells.

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Latifi-Pupovci, Hatixhe; Kuçi, Zyrafete; Wehner, Sibylle; Bönig, Halvard; Lieberz, Ralf; Klingebiel, Thomas; Bader, Peter; Kuçi, Selim

2015-09-25

Emerging evidence indicates that mesenchymal stromal cells (MSCs) isolated from different tissue sources may be used in vivo as tissue restorative agents. To date, there is no evidence, however, on migration and proliferation ("wound healing") potential of different subsets of MSCs. The main goal of this study was therefore to compare the in vitro "wound healing" capacity of MSCs generated from positively selected CD271(+) bone marrow mononuclear cells (CD271-MSCs) and MSCs generated by plastic adherence (PA-MSCs). The in vitro model of wound healing (CytoSelect™ 24-Well Wound Healing Assay) was used in order to compare the migration and proliferation potential of CD271-MSCs and PA-MSCs of passage 2 and 4 cultured in presence or absence of growth factors or cytokines. CD271-MSCs of both passages when compared to PA-MSCs demonstrated a significantly higher potential to close the wound 12 and 24 h after initiation of the wound healing assay (P MSCs of second passage was significantly improved after stimulation with FGF-2 (P MSCs of P4 12 h after the treatment (P MSCs of both passages with growth factors or cytokines did not affect their migratory potential. Our in vitro data provide the first evidence that CD271-MSCs are significantly more potent in "wound healing" than their counterparts PA-MSCs.

The long and the short of telomeres in bone marrow recipient SCID patients.

Science.gov (United States)

Sarzotti-Kelsoe, Marcella; Daniell, Xiaoju G; Whitesides, John F; Buckley, Rebecca H

2011-04-01

Telomeres are noncoding DNA regions at the end of the chromosomes that are crucial for genome stability. Since telomere length decreases with cell division, they can be used as a signature of cell proliferation history. T-cell reconstitution in severe combined immunodeficiency (SCID) subjects, recipients of T-cell-depleted, allogeneic-related bone marrow cells, is due to the development and maturation of donor T-cell precursors in the infant's vestigial thymus and to homeostatic proliferation of mature T cells in the peripheral organs. Since T-cell function, thymic output, and T-cell clonal diversity are maintained long term in these patients, we investigated whether donor T-cell engraftment resulted in increased telomere shortening. Our study of seven SCID patients, following successful bone marrow transplantation, demonstrates that the patients' peripheral T cells did not exhibit greater than normal telomere shortening.

Macrophage-Lineage Cells Negatively Regulate the Hematopoietic Stem Cell Pool in Response to Interferon Gamma at Steady State and During Infection.

Science.gov (United States)

McCabe, Amanda; Zhang, Yubin; Thai, Vinh; Jones, Maura; Jordan, Michael B; MacNamara, Katherine C

2015-07-01

Bone marrow (BM) resident macrophages (Mϕs) regulate hematopoietic stem cell (HSC) mobilization; however, their impact on HSC function has not been investigated. We demonstrate that depletion of BM resident Mϕs increases HSC proliferation as well as the pool of quiescent HSCs. At the same time, during bacterial infection where BM resident Mϕs are selectively increased we observe a decrease in HSC numbers. Moreover, strategies that deplete or reduce Mϕs during infection prevent HSC loss and rescue HSC function. We previously found that the transient loss of HSCs during infection is interferon-gamma (IFNγ)-dependent. We now demonstrate that IFNγ signaling specifically in Mϕs is critical for both the diminished HSC pool and maintenance of BM resident Mϕs during infection. In addition to the IFNγ-dependent loss of BM HSC and progenitor cells (HSPCs) during infection, IFNγ reduced circulating HSPC numbers. Importantly, under infection conditions AMD3100 or G-CSF-induced stem cell mobilization was impaired. Taken together, our data show that IFNγ acts on Mϕs, which are a negative regulator of the HSC pool, to drive the loss in BM and peripheral HSCs during infection. Our findings demonstrate that modulating BM resident Mϕ numbers can impact HSC function in vivo, which may be therapeutically useful for hematologic conditions and refinement of HSC transplantation protocols. © 2015 AlphaMed Press.

Gene expression deregulation in postnatal skeletal muscle of TK2 deficient mice reveals a lower pool of proliferating myogenic progenitor cells.

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João A Paredes

Full Text Available Loss of thymidine kinase 2 (TK2 causes a heterogeneous myopathic form of mitochondrial DNA (mtDNA depletion syndrome (MDS in humans that predominantly affects skeletal muscle tissue. In mice, TK2 deficiency also affects several tissues in addition to skeletal muscle, including brain, heart, adipose tissue, kidneys and causes death about 3 weeks after birth. We analysed skeletal muscle and heart muscle tissues of Tk2 knockout mice at postnatal development phase and observed that TK2 deficient pups grew slower and their skeletal muscles appeared significantly underdeveloped, whereas heart was close to normal in size. Both tissues showed mtDNA depletion and mitochondria with altered ultrastructure, as revealed by transmission electron microscopy. Gene expression microarray analysis showed a strong down-regulation of genes involved in cell cycle and cell proliferation in both tissues, suggesting a lower pool of undifferentiated proliferating cells. Analysis of isolated primary myoblasts from Tk2 knockout mice showed slow proliferation, less ability to differentiate and signs of premature senescence, even in absence of mtDNA depletion. Our data demonstrate that TK2 deficiency disturbs myogenic progenitor cells function in postnatal skeletal muscle and we propose this as one of the causes of underdeveloped phenotype and myopathic characteristic of the TK2 deficient mice, in addition to the progressive mtDNA depletion, mitochondrial damage and respiratory chain deficiency in post-mitotic differentiated tissue.

Gene expression deregulation in postnatal skeletal muscle of TK2 deficient mice reveals a lower pool of proliferating myogenic progenitor cells.

Science.gov (United States)

Paredes, João A; Zhou, Xiaoshan; Höglund, Stefan; Karlsson, Anna

2013-01-01

Loss of thymidine kinase 2 (TK2) causes a heterogeneous myopathic form of mitochondrial DNA (mtDNA) depletion syndrome (MDS) in humans that predominantly affects skeletal muscle tissue. In mice, TK2 deficiency also affects several tissues in addition to skeletal muscle, including brain, heart, adipose tissue, kidneys and causes death about 3 weeks after birth. We analysed skeletal muscle and heart muscle tissues of Tk2 knockout mice at postnatal development phase and observed that TK2 deficient pups grew slower and their skeletal muscles appeared significantly underdeveloped, whereas heart was close to normal in size. Both tissues showed mtDNA depletion and mitochondria with altered ultrastructure, as revealed by transmission electron microscopy. Gene expression microarray analysis showed a strong down-regulation of genes involved in cell cycle and cell proliferation in both tissues, suggesting a lower pool of undifferentiated proliferating cells. Analysis of isolated primary myoblasts from Tk2 knockout mice showed slow proliferation, less ability to differentiate and signs of premature senescence, even in absence of mtDNA depletion. Our data demonstrate that TK2 deficiency disturbs myogenic progenitor cells function in postnatal skeletal muscle and we propose this as one of the causes of underdeveloped phenotype and myopathic characteristic of the TK2 deficient mice, in addition to the progressive mtDNA depletion, mitochondrial damage and respiratory chain deficiency in post-mitotic differentiated tissue.

The Nerve Supply of the Bone Marrow in Different Laboratory Animals

Energy Technology Data Exchange (ETDEWEB)

Calvo, W. [Forschungsgruppe Freiburg, Institut fuer Haematologie der Gesellschaft fuer Strahlenforschung Assoziation mit EURATOM, Freiburg/Breisgau, Federal Republic of Germany (Germany)

1967-07-15

The proliferation and release of the different types of cells from the bone marrow presents so many obscurities in the explanation of the maintenance of homeostasis at the level of the blood corpuscles that one wonders if this difficulty is due to a lack of information in some important area. The function of an organ, and the influence that other organs may have on its physiological and pathological changes, cannot be understood if the role of the nervous system and the hormones are not taken into consideration; but when we study the bone marrow and speak about its function as a blood-forming organ, the nervous system is continually ignored. The situation is such that the first question that comes to mind is this: Are there nerves in the bone marrow? The answer of the old anatomists was: Yes. The description of nerves entering into the bone cavity can be found in papers published more than one hundred years ago, but the description of their distribution and relation with the different elements of the marrow is vague and contradictory. Consequently we considered it worthwhile to study the problem of the innervation of the bone marrow anew.

Ginsenoside Rg1 improves bone marrow haematopoietic activity via extramedullary haematopoiesis of the spleen.

Science.gov (United States)

Liu, Hua-Hsing; Chen, Fei-Peng; Liu, Rong-Kai; Lin, Chun-Lin; Chang, Ko-Tung

2015-11-01

Cyclophosphamide (CY) is a chemotherapeutic agent used for cancer and immunological diseases. It induces cytotoxicity of bone marrow and causes myelosuppression and extramedullary haematopoiesis (EMH) in treated patients. EMH is characterized with the emergence of multipotent haematopoietic progenitors most likely in the spleen and liver. Previous studies indicated that a Chinese medicine, ginsenoside Rg1, confers a significant effect to elevate the number of lineage (Lin(-) ) Sca-1(+) c-Kit(+) haematopoietic stem and progenitor cells (HSPCs) and restore the function of bone marrow in CY-treated myelosuppressed mice. However, whether the amelioration of bone marrow by Rg1 accompanies an alleviation of EMH in the spleen was still unknown. In our study, the cellularity and weight of the spleen were significantly reduced after Rg1 treatment in CY-treated mice. Moreover, the number of c-Kit(+) HSPCs was significantly decreased but not as a result of apoptosis, indicating that Rg1 alleviated EMH of the spleen induced by CY. Unexpectedly, the proliferation activity of c-Kit(+) HSPCs was only up-regulated in the spleen, but not in the bone marrow, after Rg1 treatment in CY-treated mice. We also found that a fraction of c-Kit(+) /CD45(+) HSPCs was simultaneously increased in the circulation after Rg1 treatment. Interestingly, the effects of Rg1 on the elevation of HSPCs in bone marrow and in the peripheral blood were suppressed in CY-treated splenectomized mice. These results demonstrated that Rg1 improves myelosuppression induced by CY through its action on the proliferation of HSPCs in EMH of the spleen and migration of HSPCs from the spleen to the bone marrow. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Dynamics of Cellular Proliferation during 'Acute Homologous Disease' in Mice

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Vitale, B.; Silobrcic, V.; Jurin, M.; Matosic, M.; Tomazic, Vesna [Laboratory for Transplantation and Tumour Immunology, Department of Biology, Institute Ruder Boskovic, Zagreb, Yugoslavia (Croatia)

1968-08-15

CBA mice, lethally irradiated and injected with 20 x 10{sup 6} bone-marrow cells derived from C57BL donors, develop a chronic form of 'homologous disease' and die between 20 and 40 days after treatment. If 10 x 10{sup 6} lymph node cells are added to the bone-marrow suspension, all recipients develop 'acute' homologous disease and die 6 to 10 days after irradiation. Different parameters of the disease were systematically observed. Among them, changes in spleen weight indicated early cell proliferation, which reached its maximum on day 4 and progressively decreased later on. Chromosomal analysis showed that all dividing cells in the spleen were of donor origin. Their number decreased concomitantly with the shrinkage and devastation of the organ, which started on day 6. The period of devastation of the spleen fully corresponds to the time in which all animals die. The use of cyclophosphamide in the treatment of 'acute' homologous disease transformed the disease into a chronic form with a mortality very similar to that obtained when only bone-marrow cells were injected. Among other effects, treatment with cyclophosphamide prevented early proliferation of donor cells in the spleen, and delayed spleen weight increase for about 10 days. After that period spleen weight increased, reaching its maximum on day 12. At first only donor type cells could be detected, but towards the end of the period in which spleen weight increase was registered host type cells appeared among the cells in mitosis. Their number gradually increased, and in some cases the majority or all of the dividing cells were of the host type. After a transitional decrease in spleen weight, another peak in cellular proliferation consisting of either host or donor or both types of cells was observed about day 30. In spite of the observed irregularities in the origin of dividing cells, all animals died by day 40 after application of cyclophosphamide. The relationship between proliferation of injected lymph node

The long and the short of telomeres in bone marrow recipient SCID patients

OpenAIRE

Sarzotti-Kelsoe, Marcella; Daniell, Xiaoju G.; Whitesides, John F.; Buckley, Rebecca H.

2011-01-01

Telomeres are noncoding DNA regions at the end of the chromosomes that are crucial for genome stability. Since telomere length decreases with cell division, they can be used as a signature of cell proliferation history. T-cell reconstitution in severe combined immunodeficiency (SCID) subjects, recipients of T-cell-depleted, allogeneic-related bone marrow cells, is due to the development and maturation of donor T-cell precursors in the infant’s vestigial thymus and to homeostatic proliferation...

Characteristics of cells producing stimulator for the proliferation of colony forming unit-spleen (CFU-S)

International Nuclear Information System (INIS)

Abdul Manaf Ali; Wright, E.G.; Riches, A.C.

1994-01-01

The presence of stimulator for haemopoietic stem cell (CFU-S) proliferation in regenerating bone marrow was assayed by incubating the conditioned medium (CM) prepared from bone marrow with quiescent CFU-S from normal bone marrow. The percentage of CFU-S normal bone marrow in DNA synthesis increased more than 30 percent after incubating with CM of 4.5 Gy regenerating bone marrow. Stimulator was also present in bone marrow of mice at 9.0 Gy whole body X-irradiation. However the conditioned medium prepared from regenerating bone marrow without Fc and Ia-2k cells failed to increase the percentage of CFU-S in DNA synthesis. On the other hand, elimination of Thy 1.2 positive cells with complement cytolysis did not affect the ability of regenerating bone marrow to produce stimulator. These observations suggest that the stimulator producing cells are radio-resistant, Thy 1.2 negative, Fc and Ia-2k positive

Fusion of intestinal epithelial cells with bone marrow derived cells is dispensable for tissue homeostasis

NARCIS (Netherlands)

de Jong, Joan H.; Rodermond, Hans M.; Zimberlin, Cheryl D.; Lascano, Valeria; de Sousa E Melo, Felipe; Richel, Dick J.; Medema, Jan Paul; Vermeulen, Louis

2012-01-01

The epithelial lining of the intestine is characterized by an immense cellular turn-over ascertaining an extensive regenerative capacity. Multiple reports suggest that besides the local intestinal stem cell pool, circulating cells of bone marrow origin (BMDCs) contribute to this process by fusing

Bone marrow stromal elements in murine leukemia; Decreased CSF-producing fibroblasts and normal IL-1 expression by macrophages

Energy Technology Data Exchange (ETDEWEB)

Ben-Ishay, Z [Laboratory of Experimental Hematology, Department of Anatomy and Embryology, Hebrew University-Hadassah Medical School (Israel); Barak, V [Laboratory of Immunology, Department of Oncology, Hadassah University Hospital (Israel); Shoshan, S [Faculty of Dental Medicine, Connective Tissue Research Laboratory, Hebrew University, Jerusalem (Israel); Prindull, G [Department of Pediatrics, University of Gottingen, Gottingen (Germany, F.R.)

1990-01-01

A study of bone marrow stromal elements in murine acute myeloid leukemia (AML) was carried out. Our previous studies had indicated marrow stromal deficiency in murine AML. In the current investigation, separate stromal cells were cultured and the results obtained have shown that, while marrow stromal macrophages are normal in leukemia and express adequate amounts of IL-1, the fibroblasts are markedly reduced. However, if sufficient fibroblasts are pooled in vitro, they produce adequate amounts of CSF. Test of TNF{alpha} in leukemic cells CM, as possible cause of marrow stromal inhibition in leukemia, had not disclosed this cytokine. Further, it was observed that total body lethal irradiation of leukemic mice aggravates the stromal deficiency, confirming results of our previous investigations. It is concluded that bone marrow stromal deficiency in murine AML is due to decreased fibroblasts and, implicity, reduced CSF production. (author).

Influence of age on the proliferation and peripheralization of thymic T cells

International Nuclear Information System (INIS)

Hirokawa, K.; Utsuyama, M.; Katsura, Y.; Sado, T.

1988-01-01

Bone marrow cells obtained from B10.Thy-1.1 mice (H-2b, Thy-1.1) were injected directly into the thymus of C57BL/6 mice (H-2b,Thy 1.2) of various ages. Thymocyte precursors in the injected donor-bone marrow cells could proliferate in the thymic microenvironment in the following manner: first, preferentially proliferating into the subcapsular cortex; and second, spreading to the whole layer of the cortex, a portion of them gradually moving into the medulla. The proliferation of donor-type thymocytes was most pronounced when intrathymic injection of bone marrow cells (ITB) was performed in newborn mice and especially prominent in week-old mice; it took approximately ten weeks for donor-type thymocytes to finish the whole course of proliferation, differentiation, and emigration to the periphery. When ITB was performed in mice 4 weeks of age and older, the proliferation of donor-type thymocytes was retarded at onset, less pronounced in magnitude, and disappeared earlier. Emigration of donor-type T cells from the thymus to the peripheral lymphoid tissues occurred most rapidly when ITB was performed in newborn mice, and these T cells continued to reside thereafter in the peripheral lymphoid tissues. However, when ITB was performed in mice 4 weeks of age and older, the number of emigrated T cells in the spleen decreased (about a tenth of that in newborn mice) and, moreover, these T cells resided only transiently in the spleen. It was suggested that T cells emigrating from the thymus of mice from newborn to 2 weeks of age are long-lived, whereas those from the thymus in mice 4 weeks of age and older are short-lived. However, when 4-week-old young adult mice were treated by irradiation or hydrocortisone, the thymic capacity was enhanced in terms of proliferation and peripheralization of thymocytes, and emigrated T cells became long-lived

Modeling Dynamics and Function of Bone Marrow Cells in Mouse Liver Regeneration

NARCIS (Netherlands)

Pedone, Elisa; Olteanu, Vlad-Aris; Marucci, Lucia; Muñoz-Martin, Maria Isabel; Youssef, Sameh A; de Bruin, Alain; Cosma, Maria Pia

2017-01-01

In rodents and humans, the liver can efficiently restore its mass after hepatectomy. This is largely attributed to the proliferation and cell cycle re-entry of hepatocytes. On the other hand, bone marrow cells (BMCs) migrate into the liver after resection. Here, we find that a block of BMC

TU-F-12A-02: Quantitative Characterization of Normal Bone Marrow Proliferative Activity with FLT PET/CT

Energy Technology Data Exchange (ETDEWEB)

Weisse, N; Jeraj, R [Department of Medical Physics, University of Wisconsin, Madison, WI (United States)

2014-06-15

Purpose: [F-18]FLT PET is a tool for assessing health of bone marrow by evaluating its proliferative activity. This study establishes a baseline quantitative characterization of healthy marrow proliferation to aid in diagnosis of hematological disease. Methods: 31 patients (20 male, 11 female, 41–76 years) being treated for solid cancers with no history of hematological disease, osseous metastatic disease, or radiation therapy received pre-treatment FLT PET/CT scans. Total bone marrow was isolated from whole body FLT PET images by manually removing organs and applying a standardize uptake value (SUV) threshold of 1.0. Because adult marrow is concentrated in the axial skeleton, quantitative total bone marrow analysis (QTBMA) was used to isolate marrow in the lumbar spine, thoracic spine, sacrum, and pelvis for analysis. SUV_mean, SUV_max, and SUV_CV were used to quantify bone marrow proliferation. Correlations were explored between SUV and patient characteristics including age, weight, height, and BMI using the Spearman coefficient (ρ). Results: The population-averaged whole-skeleton SUV_mean, SUV_max, and SUV_CV were 3.0±0.6, 18.4±5.7, and 0.6±0.1, respectively. Uptake values in the axial skeleton were similar to the whole-skeleton demonstrated by SUV_mean in the thoracic spine (3.6±0.6), lumbar spine (3.3±0.5), sacrum (3.0±0.6), and pelvis regions (2.8±0.5). Whole-skeleton SUV_max correlated with patient weight (ρ=0.47, p<0.01) and BMI (ρ=0.60, p<0.01), suggesting marrow activity is related to the body's burden. SUV measures in the thoracic spine, lumbar spine, sacrum, and pelvis were negatively correlated with age (ρ:−0.41 to −0.46, p≤0.02). These negative correlations reflect the fact that active marrow in the adult skeleton is localized in the axial skeleton and decreases with age. Conclusions: Normal bone marrow characterizations were determined using FLT

Influence of the dose rate on the proliferation capacity of haematopoietic elementary cells in vivo after partial body irradiation

International Nuclear Information System (INIS)

Sauer, R.

1977-01-01

During direct irradiation of the bone marrow, the dose rate effect was so paradoxical that a temporally protracted exposure has a stronger influence on the proliferation capacity of the elementary cells than one with high dose performance. During the recreation process, the elementary cells proliferated in the sense of a rebound-phaenomenon. This was also referred to the observation that in the non-irradiated bone marrow of animals exposed to partial body irradiation, an activation of the elementary cells started. The results have consequences for the oncological radiotherapy. (orig.) [de

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

Differential gene expression profile associated with the abnormality of bone marrow mesenchymal stem cells in aplastic anemia.

Directory of Open Access Journals (Sweden)

Jianping Li

Full Text Available Aplastic anemia (AA is generally considered as an immune-mediated bone marrow failure syndrome with defective hematopoietic stem cells (HSCs and marrow microenvironment. Previous studies have demonstrated the defective HSCs and aberrant T cellular-immunity in AA using a microarray approach. However, little is known about the overall specialty of bone marrow mesenchymal stem cells (BM-MSCs. In the present study, we comprehensively compared the biological features and gene expression profile of BM-MSCs between AA patients and healthy volunteers. In comparison with healthy controls, BM-MSCs from AA patients showed aberrant morphology, decreased proliferation and clonogenic potential and increased apoptosis. BM-MSCs from AA patients were susceptible to be induced to differentiate into adipocytes but more difficult to differentiate into osteoblasts. Consistent with abnormal biological features, a large number of genes implicated in cell cycle, cell division, proliferation, chemotaxis and hematopoietic cell lineage showed markedly decreased expression in BM-MSCs from AA patients. Conversely, more related genes with apoptosis, adipogenesis and immune response showed increased expression in BM-MSCs from AA patients. The gene expression profile of BM-MSCs further confirmed the abnormal biological properties and provided significant evidence for the possible mechanism of the destruction of the bone marrow microenvironment in AA.

Pooled human platelet lysate versus fetal bovine serum—investigating the proliferation rate, chromosome stability and angiogenic potential of human adipose tissue-derived stem cells intended for clinical use

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Trojahn Kølle, Stig-Frederik; Oliveri, Roberto S; Glovinski, Peter V

2013-01-01

Because of an increasing focus on the use of adipose-derived stem cells (ASCs) in clinical trials, the culture conditions for these cells are being optimized. We compared the proliferation rates and chromosomal stability of ASCs that had been cultured in Dulbecco's modified Eagle's Medium (DMEM) ......) supplemented with either pooled human platelet lysate (pHPL) or clinical-grade fetal bovine serum (FBS) (DMEM(pHPL) versus DMEM(FBS))....

Prostacyclin Suppresses Twist Expression in the Presence of Indomethacin in Bone Marrow-Derived Mesenchymal Stromal Cells

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Kemper, Oliver; Herten, Monika; Fischer, Johannes; Haversath, Marcel; Beck, Sascha; Classen, Tim; Warwas, Sebastian; Tassemeier, Tjark; Landgraeber, Stefan; Lensing-Höhn, Sabine; Krauspe, Rüdiger; Jäger, Marcus

2014-01-01

Background Iloprost, a stable prostacyclin I2 analogue, seems to have an osteoblast-protective potential, whereas indomethacin suppresses new bone formation. The aim of this study was to investigate human bone marrow stromal cell (BMSC) proliferation and differentiation towards the osteoblastic lineage by administration of indomethacin and/or iloprost. Material/Methods Human bone marrow cells were obtained from 3 different donors (A=26 yrs/m; B=25 yrs/f, C=35 yrs/m) via vacuum aspiration of t...

Effects of cyclic stretch on proliferation of mesenchymal stem cells and their differentiation to smooth muscle cells

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Ghazanfari, Samane; Tafazzoli-Shadpour, Mohammad; Shokrgozar, Mohammad Ali

2009-01-01

Bone marrow mesenchymal stem cells (MSCs) are capable of differentiating into a variety of cell types such as vascular smooth muscle cells (SMCs). In this study, we investigated influence of cyclic stretch on proliferation of hMSCs for different loading conditions, alignment of actin filaments, and consequent differentiation to SMCs. Isolated cells from bone marrow were exposed to cyclic stretch utilizing a customized device. Cell proliferation was examined by MTT assay, alignment of actin fibers by a designed image processing code, and cell differentiation by fluorescence staining. Results indicated promoted proliferation of hMSCs by cyclic strain, enhanced by elevated strain amplitude and number of cycles. Such loading regulated smooth muscle α-actin, and reoriented actin fibers. Cyclic stretch led to differentiation of hMSCs to SMCs without addition of growth factor. It was concluded that applying appropriate loading treatment on hMSCs could enhance proliferation capability, and produce functional SMCs for engineered tissues.

1,25-Dihydroxyvitamin D3 stimulates the production of insulin-like growth factor-binding proteins-2, -3 and -4 in human bone marrow stromal cells

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Kveiborg, Marie; Flyvbjerg, Allan; Eriksen, E F

2001-01-01

1,25-Dihydroxyvitamin D3 (calcitriol) inhibits proliferation and stimulates differentiation of multiple cell types, including osteoblasts. Human (h) bone marrow stromal cells (MSCs) are a homogenous non-hematopoietic population of cells present in the bone marrow and exhibit a less differentiated...

Glucocorticoids induce autophagy in rat bone marrow mesenchymal stem cells

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

2015-01-01

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...... 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...... that in response to glucocorticoid administration, induced autophagy aids to maintain proliferation and prevent apoptosis of BMSCs. Thus, it is hypothesized that autophagy may be a novel target in the treatment or prevention of osteoporosis....

An abnormal bone marrow microenvironment contributes to hematopoietic dysfunction in Fanconi anemia.

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Zhou, Yuan; He, Yongzheng; Xing, Wen; Zhang, Peng; Shi, Hui; Chen, Shi; Shi, Jun; Bai, Jie; Rhodes, Steven D; Zhang, Fengqui; Yuan, Jin; Yang, Xianlin; Zhu, Xiaofan; Li, Yan; Hanenberg, Helmut; Xu, Mingjiang; Robertson, Kent A; Yuan, Weiping; Nalepa, Grzegorz; Cheng, Tao; Clapp, D Wade; Yang, Feng-Chun

2017-06-01

Fanconi anemia is a complex heterogeneous genetic disorder with a high incidence of bone marrow failure, clonal evolution to acute myeloid leukemia and mesenchymal-derived congenital anomalies. Increasing evidence in Fanconi anemia and other genetic disorders points towards an interdependence of skeletal and hematopoietic development, yet the impact of the marrow microenvironment in the pathogenesis of the bone marrow failure in Fanconi anemia remains unclear. Here we demonstrated that mice with double knockout of both Fancc and Fancg genes had decreased bone formation at least partially due to impaired osteoblast differentiation from mesenchymal stem/progenitor cells. Mesenchymal stem/progenitor cells from the double knockout mice showed impaired hematopoietic supportive activity. Mesenchymal stem/progenitor cells of patients with Fanconi anemia exhibited similar cellular deficits, including increased senescence, reduced proliferation, impaired osteoblast differentiation and defective hematopoietic stem/progenitor cell supportive activity. Collectively, these studies provide unique insights into the physiological significance of mesenchymal stem/progenitor cells in supporting the marrow microenvironment, which is potentially of broad relevance in hematopoietic stem cell transplantation. Copyright© Ferrata Storti Foundation.

Short-term myeloid growth factor mediated expansion of bone marrow haemopoiesis studied by localized magnetic resonance proton spectroscopy

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Jensen, K E; Hansen, P B; Larsen, V A

1994-01-01

-density cell proliferation rate in marrow samples increased from median 21.9 (range 4.5-31) x 10(3) cpm to 54.7 (range 13.9-94) x 10(3) cpm and the total number of myeloid progenitors enumerated as day 7/14 GM-CFUs per volume aspirated marrow increased from median 11/8 x 10(3) (range 4.0-87.5/2.2-103.0) to 64...

Identification of a murine CD45-F4/80lo HSC-derived marrow endosteal cell associated with donor stem cell engraftment.

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Overholt, Kathleen M; Otsuru, Satoru; Olson, Timothy S; Guess, Adam J; Velazquez, Victoria M; Desbourdes, Laura; Dominici, Massimo; Horwitz, Edwin M

2017-12-26

Hematopoietic stem cells (HSCs) reside in specialized microenvironments within the marrow designated as stem cell niches, which function to support HSCs at homeostasis and promote HSC engraftment after radioablation. We previously identified marrow space remodeling after hematopoietic ablation, including osteoblast thickening, osteoblast proliferation, and megakaryocyte migration to the endosteum, which is critical for effective engraftment of donor HSCs. To further evaluate the impact of hematopoietic cells on marrow remodeling, we used a transgenic mouse model (CD45Cre/iDTR) to selectively deplete hematopoietic cells in situ. Depletion of hematopoietic cells immediately before radioablation and hematopoietic stem cell transplantation abrogated donor HSC engraftment and was associated with strikingly flattened endosteal osteoblasts with preserved osteoblast proliferation and megakaryocyte migration. Depletion of monocytes, macrophages, or megakaryocytes (the predominant hematopoietic cell populations that survive short-term after irradiation) did not lead to an alteration of osteoblast morphology, suggesting that a hematopoietic-derived cell outside these lineages regulates osteoblast morphologic adaptation after irradiation. Using 2 lineage-tracing strategies, we identified a novel CD45 - F4/80 lo HSC-derived cell that resides among osteoblasts along the endosteal marrow surface and, at least transiently, survives radioablation. This newly identified marrow cell may be an important regulator of HSC engraftment, possibly by influencing the shape and function of endosteal osteoblasts.

The prognostic value of p53 mutation in pediatric marrow hypoplasia

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Sharaf Alzahraa EA

2011-06-01

Full Text Available Abstract Background The tumor suppressor gene p53 is involved in the control of cell proliferation, particularly in stressed cells. p 53 gene mutations are the most frequent genetic event found in human cancers. Fanconi Anemia (FA is the most common representative of inherited bone marrow failure syndromes (IBMFS with a leukemic propensity. P 53 DNA alteration has not been studied before in Egyptian children with FA. Patients and methods we investigated p53 mutation in the bone marrow and peripheral blood of forty children, FA (n = 10, acquired aplastic anemia (AAA (n = 10, and immune thrombocytopenia (ITP as a control (n = 20, using real-time PCR by TaqMan probe assay Results Mutation of p53 gene was demonstrated in the BM of 90% (9/10 of children with FA, compared to 10% (1/10 in AAA (p Conclusion mutation of p53 gene in hypoplastic marrow especially FA may represent an early indicator of significant DNA genetic alteration with cancer propensity.

Radiation effect on the generation and expression of bone marrow stromal cells

International Nuclear Information System (INIS)

Xu Xiaoya; Jin Weilao; Gao Jianjun; Zhou Yi; Sheng Hui

2009-01-01

In order to investigate focal flushing dose radiation effect on the generation, differentiation and gene expression of bone marrow stromal cells the femoral head of rats was irradiated at 30 Gy by 137 Cs γ-rays (dose rate: 0.83 Gy/min). Then the bone marrow stromal cells (BMSCs) was cultured. The ability of proliferation and colony formation was observed and the expression level of Cbf-α1, PPAR-γ, VEGF-a and KDR was detected by RT-PCR technology in two weeks later. It has been found that after partly irradiated by 137 Cs γ-rays the proliferation and the number of colony of BMSCs in irradiated group decreases obviously meanwhile the expression level of Cbf-α1, PPAR-γ and VEGF-a in irradiated BMSCs obviously decreases by 18.98 %, 9.46 %, 57.34 % and 5.56 % respectively compared to the normal BMSCs (p<0.05). It shows that the focal great radiation could damage the BMSCs and depress the generation, differentiation and the expression of the related genes obviously. (authors)

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

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

1981-09-01

The results of clinical follow-up of a group of subjects who had been exposed to uncontrolled radiation in accident situations were published in the Soviet literature: 1 patient was exposed to relative uniform gamma radiation, 8 to nonuniform gamma-neutron radiation in doses of the order of 2-5 Gy or more. Summarized are the hematological data referable to the same clinical observations and details on histological structural distinctions of bone marrow, using quantitative characteristics to describe the behavior of different hemopoietic stem cells.

Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation

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Feng Xue

2015-01-01

Full Text Available We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 (Schwann cell marker and glial fibrillary acidic protein (glial cell marker at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvironment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury.

Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation

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Xue, Feng; Wu, Er-jun; Zhang, Pei-xun; Li-ya, A; Kou, Yu-hui; Yin, Xiao-feng; Han, Na

2015-01-01

We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 (Schwann cell marker) and glial fibrillary acidic protein (glial cell marker) at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvironment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury. PMID:25788929

Marrow-derived mesenchymal stem cells: role in epithelial tumor cell determination.

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Fierro, Fernando A; Sierralta, Walter D; Epuñan, Maria J; Minguell, José J

2004-01-01

Marrow stroma represents an advantageous environment for development of micrometastatic cells. Within the cellular structure of marrow stroma, mesenchymal stem cells (MSC) have been postulated as an interacting target for disseminated cancer cells. The studies reported here were performed to gain more information on the interaction of the human breast cancer cell line MCF-7 with human bone marrow-derived MSC cells and to investigate whether this interaction affects tumor cell properties. The results showed that after co-culture with MSC, changes were detected in the morphology, proliferative capacity and aggregation pattern of MCF-7 cells, but these parameters were not affected after the co-culture of MSC cells with a non-tumorigenic breast epithelial cell line, MCF-10. Since the indirect culture of MCF-7 with MSC or its products also resulted in functional changes in the tumor cells, we evaluated whether these effects could be attributed to growth factors produced by MSC cells. It was found that VEGF and IL-6 mimic the effects produced by MSC or its products on the proliferation and aggregation properties of MCF-7, cells, respectively. Thus, it seems that after entry of disseminated tumor cells into the marrow space, their proliferative and morphogenetic organization patterns are modified after interaction with distinct stromal cells and/or with specific signals from the marrow microenvironment.

In vitro proliferation of normal and leukemic human leukocytes controlled by an inhibitory endopeptide. [/sup 3/H-TdR incorporation

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Balazs, A; Mann, J; Takacsi-Nagy, L; Zimonyi, I; Molnar, A; Klupp, T [Inst. of Experimental Medicine, Budapest (Hungary); Istvan Municipal Hospital, Budapest (Hungary); Heim Pal Children' s Hospital Budapest, (Hungary))

1983-01-01

GI-3, an endogenous inhibitory fraction isolated from leukocytes, selectively inhibits the proliferation of granuloid precursor cells in a non-toxic manner. Its active principle is an acidic chlor-tolidine positive decapeptide. The in vitro effect on normal and acute leukemic human bone marrow and blood cells was examined. A dose dependent inhibition by GI-3 of /sup 3/H-TdR incorporation into myeloid cells of normal bone marrow was found, the sensitivity of human cells being higher than that of rat cells. The proliferation of the target leukemic bone marrow and blood cells was also decreased by the endogenous inhibitor in a dose-dependent manner in untreated subjects as well as in patients in remission or relapse. The rate of inhibition of leukemic cell proliferation in the short-term suspension system examined almost coincided with the action of well-known cytostatics applied for comparison. Beyond its direct cytostatic effect, GI-3 could be used in the differential diagnosis of blastic leukemias, complementing the routine cytochemical methods.

Bone marrow from Balb/c mice radiocontaminated with 241Am in utero shows a deficient in vitro haemopoiesis

International Nuclear Information System (INIS)

Heuvel, R.L. van den

1990-01-01

Radiation damage from 241 Am to bone marrow cells was manifest in long-term bone marrow cultures (LTC) from offspring of mice radiocontaminated at 14th day of gestation (119, 479, 803, 1754 kBq 241 Am kg). Offspring were reared by their own contaminated mother for 3 weeks postnatal. LTC from these offspring were less able to support in vitro CFC proliferation than control LTC. This radiation damage persisted 71 weeks after radiocontamination in utero. Damage was observed at lower doses if 241 Am contamination occurred at foetal rather than adult ages. Radiation damage was observed only using LTC. After culturing LTC in 25% FCS and recharging the stromal adherent layer with bone marrow cell suspensions originating either from control offspring or from offspring contaminated with 241 Am in utero evidence was found that the proliferation capacity of haemopoietic cells was diminished. However, the nature of effects on the stromal elements is currently somewhat equivocal. Following in utero contamination stromal adherent cells appeared to support better production of in vitro CFC. (author)

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

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

2015-01-01

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

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

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

2017-07-01

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

Stimulation of murine stem cell proliferation by circulating activities produced during the recovery of a radiation-induced hemopoietic injury

International Nuclear Information System (INIS)

Grande Azanedo, M.T.

1988-01-01

The proliferative activity of CFU-S, low in normal steady state, increases after treatment with different aggressors, i.e. radiation. This stimulation has been attributed in part to a local regulation system of stem cell proliferation, and at least in part to a humoral regulatory system. In the present work it has been investigated the role that circulating activities have in the CFU- S stimulation, by means of in vitro and in vivo incubation assays with diffusion chambers. The results show that bone marrow of mice irradiated with 5 Gy produces in vitro diffusible activities capable of stimulating the CFU-S proliferation. As well with this same dose circulating activities are also produced in vivo. In addition we have observed that these activities are only released during the periods of active hemopoietic regeneration that follow irradiation with moderate doses (1.5 and 5 Gy). In another set of experiments we saw that the stimulating activities are also detected in serum of mice irradiated with 5 Gy. These serum activities modify the proliferative state of very primitive precursors (12 d CFU-S). When the serum activities are added to long term bone marrow cultures the CFU-S) are also stimulated to proliferate. Finally, we observed that the radiation-induced serum activities stimulate the proliferation of bone marrow CFU-S when injected into normal mice, suggesting that such activities are involved in the regulation of CFU-S proliferation. (Author)

Glutathione S-transferase P influences redox and migration pathways in bone marrow.

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Jie Zhang

Full Text Available To interrogate why redox homeostasis and glutathione S-transferase P (GSTP are important in regulating bone marrow cell proliferation and migration, we isolated crude bone marrow, lineage negative and bone marrow derived-dendritic cells (BMDDCs from both wild type (WT and knockout (Gstp1/p2(-/- mice. Comparison of the two strains showed distinct thiol expression patterns. WT had higher baseline and reactive oxygen species-induced levels of S-glutathionylated proteins, some of which (sarco-endoplasmic reticulum Ca2(+-ATPase regulate Ca(2+ fluxes and subsequently influence proliferation and migration. Redox status is also a crucial determinant in the regulation of the chemokine system. CXCL12 chemotactic response was stronger in WT cells, with commensurate alterations in plasma membrane polarization/permeability and intracellular calcium fluxes; activities of the downstream kinases, ERK and Akt were also higher in WT. In addition, expression levels of the chemokine receptor CXCR4 and its associated phosphatase, SHP-2, were higher in WT. Inhibition of CXCR4 or SHP2 decreased the extent of CXCL12-induced migration in WT BMDDCs. The differential surface densities of CXCR4, SHP-2 and inositol trisphosphate receptor in WT and Gstp1/p2(-/- cells correlated with the differential CXCR4 functional activities, as measured by the extent of chemokine-induced directional migration and differences in intracellular signaling. These observed differences contribute to our understanding of how genetic ablation of GSTP causes different levels of myeloproliferation and migration [corrected

Pre-administration of safe exogenous substance minimizes radiation induced bone-marrow aplsia which may otherwise lead to hematopoietic disaster

International Nuclear Information System (INIS)

Gupta, Manju Lata; Verma, Savita; Ranjan, Rajiv

2014-01-01

Radiation induces injuries to biological system primarily by producing free radicals and also by directly interacting with cellular entities. In irradiated animals hematopoietic system gets severely affected leading to inactive microenvironment, damaged blood vessels and non functional endothelial cells of the marrow. Vascular damage inhibits the efficacy of stem cells to proliferate and differentiate. Release of pro-inflammatory cytokines and activation of fibroblast further contribute to the development of radiation-induced fibrosis. Various findings have revealed the occurrence of radiation induced aplasia and vascular damage cause large number of RBCs occupying the space and intrusion of fibrotic cells in the marrow of irradiated mice. Administration of effective radioprotective agents prior to irradiation has been amply reported for significant decline in the grade of vascular damage and inclusion of marrow fibrous tissues in these animals. In addition the formulations have also shown the presence stem cell population which is efficient to proliferate, differentiate and ultimately enrich bone marrow cellularity within 25-40 days depending on type of radiation and its dose and dose rate. Protection to bone marrow is multi-factorial phenomenon out of which inhibition of radiation induced free radical generation has been recognized as the key factor but essentially not the lone one. Protection to colony forming ability of bone marrow is also critically important which occurs mainly due to DNA protection and up-regulation of repair pathways. Preservation of microenvironment for providing stem cells to remain functional is lately reported as equally prominent factor. Our studies on a combination of two compounds of natural origin, administered to lethally irradiated animals have shown recovery in stem/precursor cells of all hematopoietic lineages. Major entities related to hematopoietic system were found nearly 90% recovered within 30 days. Current talk is focused

Low-level laser irradiation induces in vitro proliferation of mesenchymal stem cells

International Nuclear Information System (INIS)

Barboza, Carlos Augusto Galvão; Ginani, Fernanda; Soares, Diego Moura; Henriques, Águida Cristina Gomes; Freitas, Roseana de Almeida

2014-01-01

To evaluate the effect of low-level laser irradiation on the proliferation and possible nuclear morphological changes of mouse mesenchymal stem cells. Mesenchymal stem cells derived from bone marrow and adipose tissue were submitted to two applications (T0 and T48 hours) of low-level laser irradiation (660nm; doses of 0.5 and 1.0J/cm"2). The trypan blue assay was used to evaluate cell viability, and growth curves were used to analyze proliferation at zero, 24, 48, and 72 hours. Nuclear alterations were evaluated by staining with DAPI (4'-6-diamidino-2-phenylindole) at 72 hours. Bone marrow-derived mesenchymal stem cells responded to laser therapy in a dose-dependent manner. Higher cell growth was observed when the cells were irradiated with a dose of 1.0J/cm"2, especially after 24 hours (p<0.01). Adipose-derived mesenchymal stem cells responded better to a dose of 1.0J/cm"2, but higher cell proliferation was observed after 48 hours (p<0.05) and 72 hours (p<0.01). Neither nuclear alterations nor a significant change in cell viability was detected in the studied groups. Low-level laser irradiation stimulated the proliferation of mouse mesenchymal stem cells without causing nuclear alterations. The biostimulation of mesenchymal stem cells using laser therapy might be an important tool for regenerative therapy and tissue engineering

Hindlimb unloading in rat decreases preosteoblast proliferation assessed in vivo with BrdU incorporation.

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Barou, O; Palle, S; Vico, L; Alexandre, C; Lafage-Proust, M H

1998-01-01

Immobilization affects bone formation. However, the mechanisms regulating the decrease in osteoblast recruitment remain unclear. The aim of our study was to determine in vivo osteoblastic proliferation after short-term immobilization among the different bone compartments. Twelve Wistar 5-wk-old rats were assigned to two groups: six tail-suspended animals for 6 days and their six age-related controls. Osmotic minipumps, each containing 40 mg of bromodeoxyuridine (BrdU), were implanted intraperitoneally at day 4 until euthanasia. Histomorphometric measurements found a significantly lower bone volume in primary (ISP, -22%) and secondary spongiosa (IISP, -37%) in unloaded rats compared with their age-related controls. BrdU immunohistochemistry showed that the proliferation capacity of osteogenic precursors in ISP (-29%) and preosteoblasts in IISP (-80%) and in periosteum as well as bone marrow cells (-40%) was lowered by unloading. We demonstrated in vivo for the first time that 6-day tail suspension induced a significant decrease in proliferation of periosteal and trabecular preosteoblasts in ISP and IISP as well as in bone marrow cells.

Starvation marrow – gelatinous transformation of bone marrow

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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.

Down-regulation of mTOR leads to up-regulation of osteoprotegerin in bone marrow cells

International Nuclear Information System (INIS)

Mogi, Makio; Kondo, Ayami

2009-01-01

Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor regulates bone mass by inhibiting osteoclastic bone resorption. mTOR, which is the mammalian target of rapamycin, is a kinase and central regulator of cell growth, proliferation, and survival. By using Rapamycin, we studied whether mTOR pathway is associated with OPG protein production in the mouse bone marrow-derived stromal cell line ST2. Rapamycin markedly increased the level of soluble OPG in ST2 cells. This antibiotic treatment resulted in the suppression of phosphorylation of mTOR. Rapamycin had no effects on the proliferation, differentiation, or apoptosis of the cells. Treatment with bone morphogenetic protein-4, which can induce OPG protein in ST2 cells, also resulted in a decrease in the density of the phospho-mTOR-band, suggesting that the suppression of the phospho-mTOR pathway is necessary for OPG production in ST2 cells. Thus, suitable suppression of mTOR phosphorylation is a necessary requirement for OPG production in bone marrow stromal cells.

Silk fibroin/chitosan thin film promotes osteogenic and adipogenic differentiation of rat bone marrow-derived mesenchymal stem cells.

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Li, Da-Wei; He, Jin; He, Feng-Li; Liu, Ya-Li; Liu, Yang-Yang; Ye, Ya-Jing; Deng, Xudong; Yin, Da-Chuan

2018-04-01

As a biodegradable polymer thin film, silk fibroin/chitosan composite film overcomes the defects of pure silk fibroin and chitosan films, respectively, and shows remarkable biocompatibility, appropriate hydrophilicity and mechanical properties. Silk fibroin/chitosan thin film can be used not only as metal implant coating for bone injury repair, but also as tissue engineering scaffold for skin, cornea, adipose, and other soft tissue injury repair. However, the biocompatibility of silk fibroin/chitosan thin film for mesenchymal stem cells, a kind of important seed cell of tissue engineering and regenerative medicine, is rarely reported. In this study, silk fibroin/chitosan film was prepared by solvent casting method, and the rat bone marrow-derived mesenchymal stem cells were cultured on the silk fibroin/chitosan thin film. Osteogenic and adipogenic differentiation of rat bone marrow-derived mesenchymal stem cells were induced, respectively. The proliferation ability, osteogenic and adipogenic differentiation abilities of rat bone marrow-derived mesenchymal stem cells were systematically compared between silk fibroin/chitosan thin film and polystyrene tissue culture plates. The results showed that silk fibroin/chitosan thin film not only provided a comparable environment for the growth and proliferation of rat bone marrow-derived mesenchymal stem cells but also promoted their osteogenic and adipogenic differentiation. This work provided information of rat bone marrow-derived mesenchymal stem cells behavior on silk fibroin/chitosan thin film and extended the application of silk fibroin/chitosan thin film. Based on the results, we suggested that the silk fibroin/chitosan thin film could be a promising material for tissue engineering of bone, cartilage, adipose, and skin.

Effects of low-level (1.0 R) x-irradiation on the erythroid response of the rat bone marrow

International Nuclear Information System (INIS)

Gong, J.K.; Glomski, C.A.; Frederiksen, N.L.; Lawson, A.J.; Daley, J.P.

1976-01-01

The levels of normoblasts in the bone marrow of six groups of female Sprague--Dawley rats previously exposed to a 1.0 R dose of x rays were compared with those in sham-exposed animals at intervals from 14 hr to 10 weeks postirradiation. Four parameters were analyzed, the percentage of normoblasts in Wright's Giemsa stained marrow smears, and the number of erythroid precursors per milligram of isolated marrow sample, per whole femur, and per entire skeleton. The studies were based on marrow examinations and on 59 Fe tracer data. At all intervals except the earliest, [14 hr], significant elevations in the percentage of normoblasts were found in the bone marrow. In addition, at 6 and 10 weeks postirradiation increases were found in the number of normoblasts in the isolated marrow samples, whole femurs, and total skeletons. When compared 81 hr after phlebotomy, subnormal increases in normoblast levels were found in all four parameters of the irradiated subjects. The results suggest that x irradiation at this dose level can induce an abnormal marrow function manifested by an elevated number of normoblasts and, after phlebotomy, by a subnormal proliferation of the erythroid precursors

Characteristics of monolayer culture of bone marrow cells of rats bearing 239Pu-induced osteosarcoma

International Nuclear Information System (INIS)

Bukhtoyarova, Z.M.; Lemberg, V.K.

1984-01-01

The report is concerned with a monolayer culture of bone marrow cells of rats in which optimal blastogenic dose (92.5 kBq/kg) induced osteosarcoma. The cell culture showed an enhanced rate of fibroblast-like cell proliferation (increased number of mitoses and symplasts and larger colonies of cells), apparent signs of radiation in ury (pathologic mitoses, chromosome aberrations and gaps) as well as an increase in ploidy. Diffusion chamber measurements demonstrated osteogenic precursor-cells in osteosarcoma-bearing rats to be highly capable of bone formation. This relatively high ability seems to occur outside bone marrow as well

Cure of murine thalassemia by bone marrow transplantation without eradication of endogenous stem cells

International Nuclear Information System (INIS)

Wagemaker, G.; Visser, T.P.; van Bekkum, D.W.

1986-01-01

alpha-Thalassemic heterozygous (Hbath/+) mice were used to investigate the possible selective advantage of transplanted normal (+/+) hemopoietic cells. Without conditioning by total-body irradiation (TBI), infusion of large numbers of normal bone marrow cells failed to correct the thalassemic peripheral blood phenotype. Since the recipients' stem cells are normal with respect to number and differentiation capacity, it was thought that the transplanted stem cells were not able to lodge, or that they were not stimulated to proliferate. Therefore, a nonlethal dose of TBI was given to temporarily reduce endogenous stem cell numbers and hemopoiesis. TBI doses of 2 or 3 Gy followed by infusion of normal bone marrow cells proved to be effective in replacing the thalassemic red cells by normal red cells, whereas a dose of 1 Gy was ineffective. It is concluded that cure of thalassemia by bone marrow transplantation does not necessarily require eradication of thalassemic stem cells. Consequently, the objectives of conditioning regimens for bone marrow transplantation of thalassemic patients (and possibly other nonmalignant hemopoietic disorders) should be reconsidered

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

Science.gov (United States)

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

2012-09-01

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

Intensity of erythropoiesis in different erythropoietic regions following bone marrow transplantation

International Nuclear Information System (INIS)

Hola, J.; Vacha, J.; Lukas, P.

1982-01-01

By applying 59 Fe-citrate to irradiated mice it was found that irradiation suppresses iron incorporation especially in tubular bones. Following the transfusion of bone marrow cells there was a significant increase in 59 Fe incorporation in all bone groups, i.e., an increase in erythropoiesis. The graft with erythropoietic potency proliferated especially in places where there was a high intensity of erythropoiesis already before irradiation. (M.D.)

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

International Nuclear Information System (INIS)

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

1983-01-01

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

Intra-osseous injection of donor mesenchymal stem cell (MSC) into the bone marrow in living donor kidney transplantation; a pilot study

OpenAIRE

Lee, Hyunah; Park, Jae Berm; Lee, Sanghoon; Baek, Soyoung; Kim, HyunSoo; Kim, Sung Joo

2013-01-01

Background Mesenchymal stem cells (MSCs) are multi-potent non-hematopoietic progenitor cells possessing an immune-regulatory function, with suppression of proliferation of activated lymphocytes. In this study, adult living donor kidney transplantation (LDKT) recipients were given MSCs derived from the donor bone marrow to evaluate the safety and the feasibility of immunological changes related to the intra-osseous injection of MSC into the bone marrow. Methods MSCs were derived from negative ...

Angiotensin II Regulation of Proliferation, Differentiation, and Engraftment of Hematopoietic Stem Cells.

Science.gov (United States)

Kim, Seungbum; Zingler, Michael; Harrison, Jeffrey K; Scott, Edward W; Cogle, Christopher R; Luo, Defang; Raizada, Mohan K

2016-03-01

Emerging evidence indicates that differentiation and mobilization of hematopoietic cell are critical in the development and establishment of hypertension and hypertension-linked vascular pathophysiology. This, coupled with the intimate involvement of the hyperactive renin-angiotensin system in hypertension, led us to investigate the hypothesis that chronic angiotensin II (Ang II) infusion affects hematopoietic stem cell (HSC) regulation at the level of the bone marrow. Ang II infusion resulted in increases in hematopoietic stem/progenitor cells (83%) and long-term HSC (207%) in the bone marrow. Interestingly, increases of HSCs and long-term HSCs were more pronounced in the spleen (228% and 1117%, respectively). Furthermore, we observed higher expression of C-C chemokine receptor type 2 in these HSCs, indicating there was increased myeloid differentiation in Ang II-infused mice. This was associated with accumulation of C-C chemokine receptor type 2(+) proinflammatory monocytes in the spleen. In contrast, decreased engraftment efficiency of GFP(+) HSC was observed after Ang II infusion. Time-lapse in vivo imaging and in vitro Ang II pretreatment demonstrated that Ang II induces untimely proliferation and differentiation of the donor HSC resulting in diminished HSC engraftment and bone marrow reconstitution. We conclude that (1) chronic Ang II infusion regulates HSC proliferation, mediated by angiotensin receptor type 1a, (2) Ang II accelerates HSC to myeloid differentiation resulting in accumulation of C-C chemokine receptor type 2(+) HSCs and inflammatory monocytes in the spleen, and (3) Ang II impairs homing and reconstitution potentials of the donor HSCs. These observations highlight the important regulatory roles of Ang II on HSC proliferation, differentiation, and engraftment. © 2016 American Heart Association, Inc.

Graft rejection by cytolytic T cells. Specificity of the effector mechanism in the rejection of allogeneic marrow

International Nuclear Information System (INIS)

Nakamura, H.; Gress, R.E.

1990-01-01

Cellular effector mechanisms of allograft rejection remain incompletely described. Characterizing the rejection of foreign-marrow allografts rather than solid-organ grafts has the advantage that the cellular composition of the marrow graft, as a single cell suspension, can be altered to include cellular components with differing antigen expression. Rejection of marrow grafts is sensitive to lethal doses of radiation in the mouse but resistant to sublethal levels of radiation. In an effort to identify cells mediating host resistance, lymphocytes were isolated and cloned from spleens of mice 7 days after sublethal TBI (650 cGy) and inoculation with allogeneic marrow. All clones isolated were cytolytic with specificity for MHC encoded gene products of the allogeneic marrow donor. When cloned cells were transferred in vivo into lethally irradiated (1025 cGy) recipients unable to reject allogeneic marrow, results utilizing splenic 125IUdR uptake indicated that these MHC-specific cytotoxic clones could suppress marrow proliferation. In order to characterize the effector mechanism and the ability of the clones to affect final engraftment, double donor chimeras were constructed so that 2 target cell populations differing at the MHC from each other and from the host were present in the same marrow allograft. Results directly demonstrated an ability of CTL of host MHC type to mediate graft rejection and characterized the effector mechanism as one with specificity for MHC gene products

Troglitazone treatment increases bone marrow adipose tissue volume but does not affect trabecular bone volume in mice

DEFF Research Database (Denmark)

Erikstrup, Lise Tornvig; Mosekilde, Leif; Justesen, J

2001-01-01

proliferator activated receptor-gamma (PPARgamma). Histomorphometric analysis of proximal tibia was performed in order to quantitate the amount of trabecular bone volume per total volume (BV/TV %), adipose tissue volume per total volume (AV/TV %), and hematopoietic marrow volume per total volume (HV......Aging is associated with decreased trabecular bone mass and increased adipocyte formation in bone marrow. As osteoblasts and adipocytes share common precursor cells present in the bone marrow stroma, it has been proposed that an inverse relationship exists between adipocyte and osteoblast....../TV %) using the point-counting technique. Bone size did not differ between the two groups. In troglitazone-treated mice, AV/TV was significantly higher than in control mice (4.7+/-2.1% vs. 0.2+/-0.3%, respectively, mean +/- SD, P

Mechanism of stimulation of antibody-forming ability of bone marrow cells of mice immunized with staphylococci

International Nuclear Information System (INIS)

Lyashchenko, K.P.; Golovanova, T.A.; Bobrovnik, S.A.

1987-01-01

The purpose of this paper is to study the formation of the ability of the bone marrow cells of mice immunized with staphylococci to create antibodies to this antigen. The research includes a study of the effect of the irradiation in vitro of the bone marrow cells on their stimulating activity and the role played by the thymus and spleen in the formation of this activity. Experiments were carried out on CBA and BALB/c mice as well as on mice with congenital absence of the thymus. The bone marrow cell donors were immunized intravenously with staphylococcal corpuscular antigen. Receptor mice were irradiated with cobalt 60 gamma radiation and injected intravenously with bone marrow cell extract from the immunized donors and were immunized with the antigen. Spleen cells were labelled with chromium 51 and injected intravenously into intact syngeneic recipients together with as well as without the antigen. Three days later the level of radioactivity in the spleen and femora of the animals was determined by scintillation counting. Total radioactivity of the bone marrow was calculated. Irradiation of the bone marrow cells of immunized animals was shown to abolish their stimulating effect on the humoral immune response of intact syngeneic recipients to the staphylococcal corpuscular antigen. Consequently, the immunostimulating effect of bone marrow cells is realized through the proliferating and radiosensitive lymphoid cells rather than through the macrophages

Sphingosine-1-phosphate mediates proliferation maintaining the multipotency of human adult bone marrow and adipose tissue-derived stem cells.

Science.gov (United States)

He, Xiaoli; H'ng, Shiau-Chen; Leong, David T; Hutmacher, Dietmar W; Melendez, Alirio J

2010-08-01

High renewal and maintenance of multipotency of human adult stem cells (hSCs), are a prerequisite for experimental analysis as well as for potential clinical usages. The most widely used strategy for hSC culture and proliferation is using serum. However, serum is poorly defined and has a considerable degree of inter-batch variation, which makes it difficult for large-scale mesenchymal stem cells (MSCs) expansion in homogeneous culture conditions. Moreover, it is often observed that cells grown in serum-containing media spontaneously differentiate into unknown and/or undesired phenotypes. Another way of maintaining hSC development is using cytokines and/or tissue-specific growth factors; this is a very expensive approach and can lead to early unwanted differentiation. In order to circumvent these issues, we investigated the role of sphingosine-1-phosphate (S1P), in the growth and multipotency maintenance of human bone marrow and adipose tissue-derived MSCs. We show that S1P induces growth, and in combination with reduced serum, or with the growth factors FGF and platelet-derived growth factor-AB, S1P has an enhancing effect on growth. We also show that the MSCs cultured in S1P-supplemented media are able to maintain their differentiation potential for at least as long as that for cells grown in the usual serum-containing media. This is shown by the ability of cells grown in S1P-containing media to be able to undergo osteogenic as well as adipogenic differentiation. This is of interest, since S1P is a relatively inexpensive natural product, which can be obtained in homogeneous high-purity batches: this will minimize costs and potentially reduce the unwanted side effects observed with serum. Taken together, S1P is able to induce proliferation while maintaining the multipotency of different human stem cells, suggesting a potential for S1P in developing serum-free or serum-reduced defined medium for adult stem cell cultures.

Low-level laser irradiation induces in vitro proliferation of mesenchymal stem cells

Energy Technology Data Exchange (ETDEWEB)

Barboza, Carlos Augusto Galvão; Ginani, Fernanda [Universidade Federal do Rio Grande do Norte, Natal, RN (Brazil); Soares, Diego Moura [Universidade Federal de Pernambuco, Recife, PE (Brazil); Henriques, Águida Cristina Gomes; Freitas, Roseana de Almeida [Universidade Federal do Rio Grande do Norte, Natal, RN (Brazil)

2014-07-01

To evaluate the effect of low-level laser irradiation on the proliferation and possible nuclear morphological changes of mouse mesenchymal stem cells. Mesenchymal stem cells derived from bone marrow and adipose tissue were submitted to two applications (T0 and T48 hours) of low-level laser irradiation (660nm; doses of 0.5 and 1.0J/cm{sup 2}). The trypan blue assay was used to evaluate cell viability, and growth curves were used to analyze proliferation at zero, 24, 48, and 72 hours. Nuclear alterations were evaluated by staining with DAPI (4'-6-diamidino-2-phenylindole) at 72 hours. Bone marrow-derived mesenchymal stem cells responded to laser therapy in a dose-dependent manner. Higher cell growth was observed when the cells were irradiated with a dose of 1.0J/cm{sup 2}, especially after 24 hours (p<0.01). Adipose-derived mesenchymal stem cells responded better to a dose of 1.0J/cm{sup 2}, but higher cell proliferation was observed after 48 hours (p<0.05) and 72 hours (p<0.01). Neither nuclear alterations nor a significant change in cell viability was detected in the studied groups. Low-level laser irradiation stimulated the proliferation of mouse mesenchymal stem cells without causing nuclear alterations. The biostimulation of mesenchymal stem cells using laser therapy might be an important tool for regenerative therapy and tissue engineering.

Cell-Cycle-Specific Function of p53 in Fanconi Anemia Hematopoietic Stem and Progenitor Cell Proliferation

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Xiaoli Li

2018-02-01

Full Text Available Summary: Overactive p53 has been proposed as an important pathophysiological factor for bone marrow failure syndromes, including Fanconi anemia (FA. Here, we report a p53-dependent effect on hematopoietic stem and progenitor cell (HSPC proliferation in mice deficient for the FA gene Fanca. Deletion of p53 in Fanca−/− mice leads to replicative exhaustion of the hematopoietic stem cell (HSC in transplant recipients. Using Fanca−/− HSCs expressing the separation-of-function mutant p53515C transgene, which selectively impairs the p53 function in apoptosis but keeps its cell-cycle checkpoint activities intact, we show that the p53 cell-cycle function is specifically required for the regulation of Fanca−/− HSC proliferation. Our results demonstrate that p53 plays a compensatory role in preventing FA HSCs from replicative exhaustion and suggest a cautious approach to manipulating p53 signaling as a therapeutic utility in FA. : In this article, Pang and colleagues demonstrate a p53-dependent HSPC proliferation regulation in mice deficient for the Fanca gene in the Fanconi anemia (FA pathway. They show that the p53 cell-cycle function is specifically required for the regulation of FA HSC proliferation. These results suggest that overactive p53 may represent a compensatory checkpoint mechanism for FA HSC proliferation. Keywords: p53, bone marrow failure, Fanconi anemia, hematopoietic stem and progenitor cells, apoptosis, cell cycle, proliferation

Radiosensitivity of stromal cells responsible for in vitro maintenance of hemopoietic stem cells in continuous, long-term marrow culture. [/sup 137/Cs; Mice

Energy Technology Data Exchange (ETDEWEB)

Tavassoli, M

1982-05-01

Marrow stromal cells are generally thought to be radioresistant. However, when the marrow was irradiated in vivo or in vitro before its use for the continuous longterm marrow culture, doses of radiation as low as 500 rad interfered with the establishment of the adherent stromal layer. Moreover, when the stromal layer was permitted to establish, similar doses of radiation interfered with its potential to support the proliferation and maintenance of the hemopoietic stem cell. Thus, marrow stromal cells appear to be more radiosensitive than hitherto thought. The type of damage may vary, however, according to the dose of radiation. Small doses may interfere with such functions as adhesion or cell division while larger doses may completely destroy the cell.

Immediate bromodeoxyuridine labelling of unseparated human bone marrow cells ex vivo is superior to labelling after routine laboratory processing

DEFF Research Database (Denmark)

Jensen, P O; Mortensen, B T; Christensen, I J

1998-01-01

It is important to evaluate the proliferation of bone marrow cells in several disease conditions and during treatment of patients with for example cytokines. Labelling with bromodeoxyuridine (BrdUrd), immunocytochemical staining with anti-BrdUrd antibody and analysis by flow cytometry provides...... a reliable and reproducible technique for estimation of the fraction of cells that incorporated BrdUrd into DNA during S-phase. We have compared immediate BrdUrd labelling of unseparated bone marrow cells with the previously used labelling in the laboratory after routine separation of the mononuclear cells....... Bone marrow aspirates from seven lymphoma patients without bone marrow involvement were studied with these two methods. We found higher BrdUrd labelling indices (LI) in the mononuclear cells, when cells were labelled immediately. A large variation in LI was found between patients. Our results suggest...

Bone marrow ablation with Ho-166 pharmaceuticals as preparation for bone marrow transplants

International Nuclear Information System (INIS)

Parks, N.J.; Kawakami, T.; Avila, M.; White, R.; Cain, G.; Moore, P.F.

1991-01-01

Bone marrow ablation is required preparation for leukemia patients where bone marrow transplantation is to be the therapeutic modality. Presently, the total body irradiation that is used produces appreciable morbidity in terms of radiation sickness, but an evenly distributed dose to marrow. The authors have shown in Beagles that bone-seeking radiolanthanide (Ho-166, t 1/2 = 25 h, 1.8 MeB beta, carrier added) phosphonic acid chelates can be used to completely ablate bone marrow with little morbidity. The research plan, incorporating bone marrow ablation with bone-seeking radionuclides and in vitro purging of aspirated leukemic marrow for use in autologous marrow transplants, is presented. Phosphonic acid complexes of Sm-153 also localize in the skeleton and have found use in the palliation of bone pain. However, the dose distribution is uneven because these radiopharmaceuticals distribute according to available surface; 2-4 times the skeletal average in trabecular vs cortical bone. Thus, the marrow dose can vary. The authors' research group and the Radiation Interactions Division of NIST have announced the discovery that beta radiation-induced excited electrons are trapped in the hydroxyapatite mineral of bone and provide a potential direct dosimetric method for marrow dose when combined with routine bone marrow (and included bone) biopsies. The overall research plan sets the hypothesis that reduced morbidity marrow ablation can be successfully followed by bone marrow transplantation (BMT) with autologous marrow purged in vitro by antibody-targeted alpha emitters

Constant post-irradiation repopulation rates and linear relationship between cellular blood response and number of transplanted bone marrow cells in inbread mice

International Nuclear Information System (INIS)

Petersen, B.H.

1977-01-01

Graded doses of syngeneic bone marrow cells were transplanted into lethally irradiated mice. Repopulation curves of peripheral blood granulocytes and platelets were apparently exponential and parallel after doses larger than 5 x 10 5 cells. The blood platelet sub(d) was reduced from 111 h to 53-57 h, and granulocyte Tsub(d) from 57 to 40 h in transplanted groups. The mean blood cell counts were reproducible to be used as a biological assay of the amount of bone marrow cells transplanted. Linear relationship between increment of blood cells up to day 16 and number of bone marrow cells transplanted on day 1 was demonstrated (1,200 granulocytes and 14,300 platelets/μl blood per 10 5 bone marrow cells). The linearity suggested a mean Tsub(d) < 22.5 h of proliferating bone marrow cells, and allowed a rough estimation of mouse bone marrow stem cell radiosensitivity (Dsub(o) 76 rad). (author)

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

International Nuclear Information System (INIS)

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

1983-01-01

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

Bone Marrow Aspirate Concentrate-Enhanced Marrow Stimulation of Chondral Defects

Science.gov (United States)

Eichler, Hermann; Orth, Patrick

2017-01-01

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

Vascular endothelial growth factor regulates melanoma cell adhesion and growth in the bone marrow microenvironment via tumor cyclooxygenase-2

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Crende Olatz

2011-08-01

Full Text Available Abstract Background Human melanoma frequently colonizes bone marrow (BM since its earliest stage of systemic dissemination, prior to clinical metastasis occurrence. However, how melanoma cell adhesion and proliferation mechanisms are regulated within bone marrow stromal cell (BMSC microenvironment remain unclear. Consistent with the prometastatic role of inflammatory and angiogenic factors, several studies have reported elevated levels of cyclooxygenase-2 (COX-2 in melanoma although its pathogenic role in bone marrow melanoma metastasis is unknown. Methods Herein we analyzed the effect of cyclooxygenase-2 (COX-2 inhibitor celecoxib in a model of generalized BM dissemination of left cardiac ventricle-injected B16 melanoma (B16M cells into healthy and bacterial endotoxin lipopolysaccharide (LPS-pretreated mice to induce inflammation. In addition, B16M and human A375 melanoma (A375M cells were exposed to conditioned media from basal and LPS-treated primary cultured murine and human BMSCs, and the contribution of COX-2 to the adhesion and proliferation of melanoma cells was also studied. Results Mice given one single intravenous injection of LPS 6 hour prior to cancer cells significantly increased B16M metastasis in BM compared to untreated mice; however, administration of oral celecoxib reduced BM metastasis incidence and volume in healthy mice, and almost completely abrogated LPS-dependent melanoma metastases. In vitro, untreated and LPS-treated murine and human BMSC-conditioned medium (CM increased VCAM-1-dependent BMSC adherence and proliferation of B16M and A375M cells, respectively, as compared to basal medium-treated melanoma cells. Addition of celecoxib to both B16M and A375M cells abolished adhesion and proliferation increments induced by BMSC-CM. TNFα and VEGF secretion increased in the supernatant of LPS-treated BMSCs; however, anti-VEGF neutralizing antibodies added to B16M and A375M cells prior to LPS-treated BMSC-CM resulted in a

Studies on the distribution of hematopoietic bone marrow by bone marrow scintigraphy, 2. The bone marrow distribution in leukemia

Energy Technology Data Exchange (ETDEWEB)

Fujimori, K [Kyoto Univ. (Japan). Faculty of Medicine

1976-04-01

Distribution of the leukemic marrow was investigated in 42 cases by bone marrow scintigraphy using sup(99m)Tc sulfur colloid in association with clinical findings and ferrokinetics studies in order to clarify hematopoietic function in leukemia. 17 of chronic myelogenous leukemia, 3 of lymphatic leukemia, 2 of monocytic leukemia, 7 of atypical leukemia and one of erythroleukemia. 12 acute myelogenous leukemia were classified into 3 types A, B and C. Type A showed the distribution similar to those obtained with normal controls. Ferrokinetics studies, however, indicated complete absence of erythropoiesis. Type B showed complete lack of sup(99m)Tc activity in usual marrow sites, although ferrokinetics data showed normal erythropoeitic function. Type C showed abnormal concentration of sup(99m)Tc sulfur colloid in the tibiae. 17 chronic myelogenous leukemia showed reduced sup(99m)Tc activity in usual marrow sites and remarkable expanded marrow extending into distal femurs, proximal and distal tibiae and bones of feet. 2 acute lymphotic leukemia patients showed complete absence of sup(99m)Tc activity. The one chronic type showed almost normal distribution. Monocytic leukemia showed decreased marrow distribution in the sternum and vertebrae. Of 6 atypical leukemias one showed almost normal distribution. The others, including a case with hypoplastic luekemia, demonstrated marrow extension similar to that observed in chronic myelogenous leukemia or monocytic leukemia. Erythroleukemia showed increased concentrations of sup(99m)Tc activity in the usual marrow sites and marked marrow expansion throughout all long bones. These results suggest that there is a discrepancy between bone marrow distribution and hematopoietic function in the cases of acute myelogenous leukemia.

Marrow uptake index (MUI): A quantitative scintigraphic study of bone marrow in aplastic anaemia

International Nuclear Information System (INIS)

Padhy, A.K.; Garg, A.; Kochupillai, V.; Gopinath, P.G.; Basu, A.K.

1987-01-01

Aplastic anaemia affects the entire bone marrow. This prospective study was undertaken to develop and standardise a new nuclear medicine technique called 'dynamic bone marrow imaging'. Eleven patients and ten controls were studied. Serial images of the pelvis were obtained in frame mode following intravenous injection of 185-370 mBq of 99m Tc S. Colloid, and an index, called the bone marrow uptake index was calculated by taking into consideration the time activity curve obtained over the iliac crest. This was followed by static imaging of the entire bone marrow in all cases. It was possible to obtain excellent information regarding topographic distribution of bone marrow as well as detect early changes in bone marrow function following treatment. An attempt was also made to correlate bone marrow cellularity as obtained by bone marrow biopsy with results of dynamic bone marrow scintigraphy. On the basis of the encouraging results obtained in the present study, the authors feel that dynamic bone marrow imaging is an excellent technique for the objective evaluation of bone marrow in aplastic anaemia. 20 refs.; 4 figs.; 5 tabs

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

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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.

The depletion of nuclear glutathione impairs cell proliferation in 3t3 fibroblasts.

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Jelena Markovic

2009-07-01

Full Text Available Glutathione is considered essential for survival in mammalian cells and yeast but not in prokaryotic cells. The presence of a nuclear pool of glutathione has been demonstrated but its role in cellular proliferation and differentiation is still a matter of debate.We have studied proliferation of 3T3 fibroblasts for a period of 5 days. Cells were treated with two well known depleting agents, diethyl maleate (DEM and buthionine sulfoximine (BSO, and the cellular and nuclear glutathione levels were assessed by analytical and confocal microscopic techniques, respectively. Both agents decreased total cellular glutathione although depletion by BSO was more sustained. However, the nuclear glutathione pool resisted depletion by BSO but not with DEM. Interestingly, cell proliferation was impaired by DEM, but not by BSO. Treating the cells simultaneously with DEM and with glutathione ethyl ester to restore intracellular GSH levels completely prevented the effects of DEM on cell proliferation.Our results demonstrate the importance of nuclear glutathione in the control of cell proliferation in 3T3 fibroblasts and suggest that a reduced nuclear environment is necessary for cells to progress in the cell cycle.

Different expression of MIB1 in primary site of non-Hodgkin lymphoma and its bone marrow deposits, a pilot study

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Malysz J

2017-02-01

Full Text Available Jozef Malysz,1 Juanita J Evans,2 Malcolm Acon-Laws,3 Michael G Bayerl,1 Michael H Creer1 1Department of Pathology, Penn State Milton S Hershey Medical Center, Hershey, PA, 2Department of Pathology, St. John Heath – Providence, Southfield, MI, USA; 3Laboratorio de Patologia Hospital Cima, San Jose, Costa Rica Abstract: Evaluation of mindbomb E3 ubiquitin protein ligase 1 (MIB1 (Ki67 proliferation index (PI in B-cell non-Hodgkin lymphomas is increasingly a common addition to classification of lymphoma and staging procedures. Clinicians relay on PI as a surrogate marker of biologic activity; however, no established guidelines have been published whether PI at the primary site of the tumor gives the same answer as evaluation of tumor in staging marrow. In our study, dual immunohistochemical staining for MIB1 and CD20 was performed on tissue from primary site and bone marrow involved by B-cell non-Hodgkin lymphoma to compare PI for each individual patient. For all patients, MIB1 expression was higher at primary tumor site as compared to staging marrow. Additional analysis was performed to investigate the degree of difference depending on lymphoma morphology. Patients with large cell lymphoma at the primary site and large cell morphology in the marrow (LCL-L, those with large cell morphology at the primary site and small cell morphology in the marrow (LCL-S, and those with small cell morphology at the primary site and small cells in the marrow (SCL-S were compared. As expected, LCL cases had a higher mean PI at the primary site when compared to SCL cases (28.5% vs 2.8%, P=0.0001. In addition, the most significant difference between medullary and extramedullary PI was observed in cases with discordant morphology (LCL-S (21% vs 1.1%, P=0.009. Our results indicate that PI of lymphoma within the bone marrow should not be used as a surrogate prognostic indicator of lymphoma biology in its primary site. Keywords: proliferation index, biologic behavior

Secreted Clusterin protein inhibits osteoblast differentiation of bone marrow mesenchymal stem cells by suppressing ERK1/2 signaling pathway

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Abdallah, Basem; Alzahrani, Abdullah M; Kassem, Moustapha

2018-01-01

Secreted Clusterin (sCLU, also known as Apolipoprotein J) is an anti-apoptotic glycoprotein involved in the regulation of cell proliferation, lipid transport, extracellular tissue remodeling and apoptosis. sCLU is expressed and secreted by mouse bone marrow-derived skeletal (stromal or mesenchyma...

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

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

2014-01-01

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

Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow.

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Raphael P H Meier

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

Effects of Focused Extracorporeal Shock Waves on Bone Marrow Mesenchymal Stem Cells in Patients with Avascular Necrosis of the Femoral Head.

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Zhai, Lei; Sun, Nan; Zhang, Bo; Liu, Shui-Tao; Zhao, Zhe; Jin, Hai-Chao; Ma, Xin-Long; Xing, Geng-Yan

2016-03-01

To observe the effect of extracorporeal shock waves (ESWs) on bone marrow mesenchymal stem cells (MSCs) in patients with avascular necrosis of the femoral head, we collected bone marrow donated by patients and then cultivated and passaged MSCs in vitro using density gradient centrifugation combined with adherence screening methods. The P3 generation MSCs were divided into the ESW group and the control group. The cell counting kit for MSCs detected some proliferation differences. Cytochemistry, alkaline phosphatase staining and Alizarin red staining were used to determine alkaline phosphatase content. Simultaneously, real-time polymerase factor α1, osteocalcin and peroxisome proliferator-activated receptor γ. Together, the results of our study first indicate that moderate ESW intensity, which is instrumental in enhancing MSC proliferation, inducing conversion of MSCs into osteoblasts, and inhibiting differentiation of MSCs into adipocytes from MSCs, is one of the effective mechanisms for treating avascular necrosis of the femoral head. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Development of the Fetal Bone Marrow Niche and Regulation of HSC Quiescence and Homing Ability by Emerging Osteolineage Cells

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Süleyman Coşkun

2014-10-01

Full Text Available Hematopoietic stem cells (HSCs reside within a specialized niche where interactions with vasculature, osteoblasts, and stromal components regulate their self-renewal and differentiation. Little is known about bone marrow niche formation or the role of its cellular components in HSC development; therefore, we established the timing of murine fetal long bone vascularization and ossification relative to the onset of HSC activity. Adult-repopulating HSCs emerged at embryonic day 16.5 (E16.5, coincident with marrow vascularization, and were contained within the c-Kit+Sca-1+Lin− (KSL population. We used Osterix-null (Osx−/− mice that form vascularized marrow but lack osteolineage cells to dissect the role(s of these cellular components in HSC development. Osx−/− fetal bone marrow cells formed multilineage colonies in vitro but were hyperproliferative and failed to home to and/or engraft transplant recipients. Thus, in developing bone marrow, the vasculature can sustain multilineage progenitors, but interactions with osteolineage cells are needed to regulate long-term HSC proliferation and potential.

Development of the fetal bone marrow niche and regulation of HSC quiescence and homing ability by emerging osteolineage cells.

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Coşkun, Süleyman; Chao, Hsu; Vasavada, Hema; Heydari, Kartoosh; Gonzales, Naomi; Zhou, Xin; de Crombrugghe, Benoit; Hirschi, Karen K

2014-10-23

Hematopoietic stem cells (HSCs) reside within a specialized niche where interactions with vasculature, osteoblasts, and stromal components regulate their self-renewal and differentiation. Little is known about bone marrow niche formation or the role of its cellular components in HSC development; therefore, we established the timing of murine fetal long bone vascularization and ossification relative to the onset of HSC activity. Adult-repopulating HSCs emerged at embryonic day 16.5 (E16.5), coincident with marrow vascularization, and were contained within the c-Kit(+)Sca-1(+)Lin(-) (KSL) population. We used Osterix-null (Osx(-/-)) mice that form vascularized marrow but lack osteolineage cells to dissect the role(s) of these cellular components in HSC development. Osx(-/-) fetal bone marrow cells formed multilineage colonies in vitro but were hyperproliferative and failed to home to and/or engraft transplant recipients. Thus, in developing bone marrow, the vasculature can sustain multilineage progenitors, but interactions with osteolineage cells are needed to regulate long-term HSC proliferation and potential. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Bone Marrow Regeneration Promoted by Biophysically Sorted Osteoprogenitors From Mesenchymal Stromal Cells

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Poon, Zhiyong; Lee, Wong Cheng; Guan, Guofeng; Nyan, Lin Myint; Lim, Chwee Teck; Han, Jongyoon

2015-01-01

Human tissue repair deficiencies can be supplemented through strategies to isolate, expand in vitro, and reimplant regenerative cells that supplant damaged cells or stimulate endogenous repair mechanisms. Bone marrow-derived mesenchymal stromal cells (MSCs), a subset of which is described as mesenchymal stem cells, are leading candidates for cell-mediated bone repair and wound healing, with hundreds of ongoing clinical trials worldwide. An outstanding key challenge for successful clinical translation of MSCs is the capacity to produce large quantities of cells in vitro with uniform and relevant therapeutic properties. By leveraging biophysical traits of MSC subpopulations and label-free microfluidic cell sorting, we hypothesized and experimentally verified that MSCs of large diameter within expanded MSC cultures were osteoprogenitors that exhibited significantly greater efficacy over other MSC subpopulations in bone marrow repair. Systemic administration of osteoprogenitor MSCs significantly improved survival rates (>80%) as compared with other MSC subpopulations (0%) for preclinical murine bone marrow injury models. Osteoprogenitor MSCs also exerted potent therapeutic effects as “cell factories” that secreted high levels of regenerative factors such as interleukin-6 (IL-6), interleukin-8 (IL-8), vascular endothelial growth factor A, bone morphogenetic protein 2, epidermal growth factor, fibroblast growth factor 1, and angiopoietin-1; this resulted in increased cell proliferation, vessel formation, and reduced apoptosis in bone marrow. This MSC subpopulation mediated rescue of damaged marrow tissue via restoration of the hematopoiesis-supporting stroma, as well as subsequent hematopoiesis. Together, the capabilities described herein for label-freeisolation of regenerative osteoprogenitor MSCs can markedly improve the efficacy of MSC-based therapies. PMID:25411477

Peroxisome Proliferator-Activated Receptor Gamma Negatively Regulates the Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Toward Myofibroblasts in Liver Fibrogenesis

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Shuangshuang Jia

2015-11-01

Full Text Available Background/Aims: Bone marrow-derived mesenchymal stem cells (BMSCs have been confirmed to have capacity to differentiate toward hepatic myofibroblasts, which contribute to fibrogenesis in chronic liver diseases. Peroxisome proliferator-activated receptor gamma (PPARγ, a ligand-activated transcription factor, has gained a great deal of recent attention as it is involved in fibrosis and cell differentiation. However, whether it regulates the differentiation of BMSCs toward myofibroblasts remains to be defined. Methods: Carbon tetrachloride or bile duct ligation was used to induce mouse liver fibrosis. Expressions of PPARγ, α-smooth muscle actin, collagen α1 (I and collagen α1 (III were detected by real-time RT-PCR and Western blot or immunofluorescence assay. Results: PPARγ expression was decreased in mouse fibrotic liver. In addition, PPARγ was declined during the differentiation of BMSCs toward myofibroblasts induced by transforming growth factor β1. Activation of PPARγ stimulated by natural or synthetic ligands suppressed the differentiation of BMSCs. Additionally, knock down of PPARγ by siRNA contributed to BMSC differentiation toward myofibroblasts. Furthermore, PPARγ activation by natural ligand significantly inhibited the differentiation of BMSCs toward myofibroblasts in liver fibrogenesis and alleviated liver fibrosis. Conclusions: PPARγ negatively regulates the differentiation of BMSCs toward myofibroblasts, which highlights a further mechanism implicated in the BMSC differentiation.

Bone marrow mesenchymal stem cells repair spinal cord ischemia/reperfusion injury by promoting axonal growth and anti-autophagy

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Yin, Fei; Meng, Chunyang; Lu, Rifeng; Li, Lei; Zhang, Ying; Chen, Hao; Qin, Yonggang; Guo, Li

2014-01-01

Bone marrow mesenchymal stem cells can differentiate into neurons and astrocytes after transplantation in the spinal cord of rats with ischemia/reperfusion injury. Although bone marrow mesenchymal stem cells are known to protect against spinal cord ischemia/reperfusion injury through anti-apoptotic effects, the precise mechanisms remain unclear. In the present study, bone marrow mesenchymal stem cells were cultured and proliferated, then transplanted into rats with ischemia/reperfusion injury via retro-orbital injection. Immunohistochemistry and immunofluorescence with subsequent quantification revealed that the expression of the axonal regeneration marker, growth associated protein-43, and the neuronal marker, microtubule-associated protein 2, significantly increased in rats with bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Furthermore, the expression of the autophagy marker, microtubule-associated protein light chain 3B, and Beclin 1, was significantly reduced in rats with the bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Western blot analysis showed that the expression of growth associated protein-43 and neurofilament-H increased but light chain 3B and Beclin 1 decreased in rats with the bone marrow mesenchymal stem cell transplantation. Our results therefore suggest that bone marrow mesenchymal stem cell transplantation promotes neurite growth and regeneration and prevents autophagy. These responses may likely be mechanisms underlying the protective effect of bone marrow mesenchymal stem cells against spinal cord ischemia/reperfusion injury. PMID:25374587

Harmine stimulates proliferation of human neural progenitors

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Vanja Dakic

2016-12-01

Full Text Available Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A, which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY, and an irreversible selective inhibitor of monoamine oxidase (MAO but not DYRK1A (pargyline. INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

Blastema from rabbit ear contains progenitor cells comparable to marrow derived mesenchymal stem cells

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Mohamadreza Baghaban Eslaminejad

2012-09-01

Full Text Available Rabbits have the capacity to regenerate holes in their ears by forming a blastema, a tissue that is made up of a group of undifferentiated cells. The purpose of the present study was to isolate and characterize blastema progenitor cells and compare them with marrow mesenchymal stem cells (MSCs. Five New Zealand white male rabbits were used in the present study. A 2-mm hole was created in the animal ears. After 4 days, the blastema ring formed in the periphery of the hole was removed and cultivated. The cells were expanded through several subcultures and compared with the MSCs derived from the marrow of same animal in terms of in vitro differentiation capacity, growth kinetics and culture requirements for optimal proliferation. The primary cultures from both cells tended to be heterogeneous. Fibroblastic cells became progressively dominant with advancing passages. Similar to MSCs blastema passaged-3 cells succeeded to differentiate into bone, cartilage and adipose cell lineages. Even lineage specific genes tended to express in higher level in blastema cells compared to MSCs (p < 0.05. Moreover blastema cells appeared more proliferative; producing more colonies (p < 0.05. While blastema cells showed extensive proliferation in 15% fetal bovine serum (FBS, MSCs displayed higher expansion rate at 10% FBS. In conclusion, blastema from rabbit ear contains a population of fibroblastic cells much similar in characteristic to bone marrow mesenchymal stem cells. However, the two cells were different in the level of lineage-specific gene expression, the growth curve characteristics and the culture requirements.

Increased granulocytic, erythrocytic, and megakaryocytic progenitors in myelofibrosis with myeloid metaplasia

International Nuclear Information System (INIS)

Chikkappa, G.; Carsten, A.L.; Chanana, A.D.; Chandra, P.; Cronkite, E.P.

1978-01-01

Nucleated cells obtained from blood and/or bone marrow of patients with myelofibrosis with myeloid metaplasia (MMM) were cultured in diffusion chambers (DC) implanted into the peritoneal cavities of irradiated mice. A total of five blood studies and two bone marrow studies were performed using cells obtained from five patients. The DC were harvested at intervals from the host mice and the total and differential cellularity of DC contents were evaluated. The results obtained from MMM cultures were compared with those from similar cultures of blood cells and marrow cells of four and six normal individuals respectively. The proliferation and maturation of the granulocytic, erythrocytic, and megakaryocytic lines in MMM cultures occurred in an orderly fashion as they occur in vivo. The patterns of proliferation and maturation of the three cell lines in cultures after day 7 suggest that they primarily originate from progenitor cells. The numbers of granulocytes in the multiplicative pool, recognizable red cell precursors, and megakaryocytes recovered were significantly greater from the MMM cultures than those from the normal blood or marrow cultures. These results suggest that the blood and marrow cells of MMM patients have increased numbers of progenitors for granulocytes, erythrocytes and megakaryocytes

Pathological changes after bone marrow and skin allograft transplantation in rats inflicted with severe combined radiation-burn injury

International Nuclear Information System (INIS)

Zheng Huaien; Cheng Tianmin; Yan Yongtang

1994-01-01

Bone marrow and skin allografts from the same donor were transplanted to rats inflicted with 8 Gy γ-radiation combined with third degree burns of 15% body surface area within 6 hr post injury. Pathological changes of hematopoietic tissues and skin allografts were studied. All injured controls died within 7 days post injury without bone marrow regeneration; 50% of treated rats survived with living skin allografts on 50th day post injury. On days 100 and 480 post operation, grafted skin still survived well on recipients with normal ultrastructure. Epidermic cells of skin allografts proliferated on day 5, developed and repaired on day 10. Histological structure of the skin returned to normal on day 30 post operation. The regeneration of bone marrow appeared on 5th day, increased markedly on day 10, and almost completed on day 15 after bone marrow transplantation. However, the regeneration of lymphocytes in cortex of spleen and lymph nodes did not appear until day 15 of BMT. The results show that bone marrow and skin allograft transplantation at early time post injury in most severe combined radiation-burn injury have tremendous beneficial effects, and the skin allograft can survive for a long time

Bone marrow transplantation rescues intestinal mucosa after whole body radiation via paracrine mechanisms

International Nuclear Information System (INIS)

Chang, Ya Hui; Lin, Li-Mei; Lou, Chi-Wen; Chou, Chuan-Kai; Ch’ang, Hui-Ju

2012-01-01

Purpose: Our previous study reveals bone marrow transplantation (BMT) recruits host marrow-derived myelomonocytic cells to radiation-injured intestine, enhancing stromal proliferation, leading secondarily to epithelial regeneration. In this study, we propose BMT ameliorates intestinal damage via paracrine mechanisms. Materials and methods: Angiogenic cytokines within the intestinal mucosa of mice after whole body irradiation (WBI) with or without BMT were measured by cytokine array and ELISA. BM conditioned medium (BMCM) with or without treatment with neutralizing antibodies to angiogenic cytokines were continuously infused into mice for three days after radiation. Carrageenan was used to deplete myelomonocytic cells of mice. Results: BMT increased VEGF, bFGF and other angiogenic and chemotactic cytokines in the intestinal mucosa within 24 h after WBI. Infusion of BMCM ameliorated radiation-induced intestinal damage with improved stromal activity and prolonged survival of mice. Neutralization of bFGF, PDGF and other angiogenic cytokines within BMCM abolished the mitigating effect to the intestine. Pretreatment of carrageenan to recipient mice reversed some of the cytokine levels, including VEGF, bFGF and IGF within the intestinal mucosa after BMT. Conclusions: Our result suggests BMT recruits host myelomonocytic cells and enhances intestinal stroma proliferation after radiation by secreting cytokines enhancing angiogenesis and chemotaxis. Host myelomonocytic cells further uplift the paracrine effect to enhance intestinal mucosal recovery.

Cell proliferation and thymocyte subset reconstitution in sublethally irradiated mice: Compared kinetics of endogenous and intrathymically transferred progenitors

International Nuclear Information System (INIS)

Penit, C.; Ezine, S.

1989-01-01

After sublethal (6 Gy) whole-body irradiation, the C57BL/Ba (Thy-1.1) murine thymus regenerated in two waves, on days 3-10 and 25-32, separated by a severe relapse. The second phase of depletion-reconstitution reproduced the first one, in a less synchronous manner. The depletion affected all cell subsets, but CD4+ CD8- cells decreased later than immature cells. Cell proliferation, measured by BrdUrd incorporation, started on day 3 after irradiation and concerned CD4- CD8-, CD4- CD8+, and CD4+ CD8+ cells, sequentially. CD4+ CD8- cells never represented a significant percentage of cycling cells. When irradiation was immediately followed by an intrathymic injection of 10(5) C57BL/Ka (Thy-1.2) bone marrow cells, the relapse in thymus reconstitution was no longer observed. Detected with anti-Thy-1.2 antibodies, donor cells started cycling on day 14 and showed only one wave of proliferation. In these chimeras, recipient thymocytes behave exactly like thymocytes of solely irradiated mice. Intrathymically transferred CD4- CD8- thymocytes 10(5) showed the same proliferation kinetics as endogenous cells, with a peak in number on day 10 but completely disappeared from the thymus on days 14-21. These data reflect maturational differences between intrathymic and bone marrow precursor cells and suggest different radiosensitivities not linked to proliferative status. The resting state of the thymus immigrants was shown by the absence of Thy-1 acquisition by bone marrow cells continuously labeled for 10 days with BrdUrd in vivo before intrathymic transfer. When such labeled bone marrow cells were injected in the thymus, only the minor BrdUrd- subset gave rise to Thy-1+ cells

Evaluation of renal uptake on 111InCl3 bone marrow scintigraphy in patients with aplastic anemia and myelodysplastic syndrome

International Nuclear Information System (INIS)

Koizumi, Mitsuru; Goto, Masafumi; Nomura, Toshiharu; Watari, Tsutomu; Saito, Kenji

1993-01-01

High renal uptake on bone marrow scan with indium-111 chloride is often shown in patients with bone marrow abnormality. We evaluated the renal uptake on bone marrow scan in 27 cases of aplastic anemia, 20 cases of myelodysplastic syndrome (MDS) and 10 cases of other diseases. The high renal uptake was observed in patients not only with aplastic anemia but also with MDS. The renal uptake correlated with blood transfusion units, unsaturated iron binding capacity (UIBC), blood pool imaging and bone marrow uptake. The renal uptake correlated with UIBC better than with the blood transfusion units. Following mechanism of the renal uptake is proposed that frequent blood transfusion makes low UIBC, and the low UIBC causes the failure to chelate indium with transferrin. The fast blood clearance of un-chelated indium via kidneys is followed. Hypoplastic bone marrow may also play an important role for the high renal uptake because all patients with the high renal uptake could not be explained by above mentioned mechanism. Caution should be paid to the scans with the high renal uptake because both aplastic anemia and MDS patients show the high renal uptake. (author)

Treatment with at Homeopathic Complex Medication Modulates Mononuclear Bone Marrow Cell Differentiation

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Beatriz Cesar

2011-01-01

Full Text Available A homeopathic complex medication (HCM, with immunomodulatory properties, is recommended for patients with depressed immune systems. Previous studies demonstrated that the medication induces an increase in leukocyte number. The bone marrow microenvironment is composed of growth factors, stromal cells, an extracellular matrix and progenitor cells that differentiate into mature blood cells. Mice were our biological model used in this research. We now report in vivo immunophenotyping of total bone marrow cells and ex vivo effects of the medication on mononuclear cell differentiation at different times. Cells were examined by light microscopy and cytokine levels were measured in vitro. After in vivo treatment with HCM, a pool of cells from the new marrow microenvironment was analyzed by flow cytometry to detect any trend in cell alteration. The results showed decreases, mainly, in CD11b and TER-119 markers compared with controls. Mononuclear cells were used to analyze the effects of ex vivo HCM treatment and the number of cells showing ring nuclei, niche cells and activated macrophages increased in culture, even in the absence of macrophage colony-stimulating factor. Cytokines favoring stromal cell survival and differentiation in culture were induced in vitro. Thus, we observe that HCM is immunomodulatory, either alone or in association with other products.

Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine

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Tomar, Geetanjali B.; Srivastava, Rupesh K.; Gupta, Navita; Barhanpurkar, Amruta P.; Pote, Satish T. [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India); Jhaveri, Hiral M. [Department of Periodontics and Oral Implantology, Dr. D.Y. Patil Dental College and Hospital, Pune (India); Mishra, Gyan C. [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India); Wani, Mohan R., E-mail: mohanwani@nccs.res.in [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India)

2010-03-12

Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into multiple cell lineages. Presently, bone marrow is considered as a prime source of MSCs; however, there are some drawbacks and limitations in use of these MSCs for cell therapy. In this study, we demonstrate that human gingival tissue-derived MSCs have several advantages over bone marrow-derived MSCs. Gingival MSCs are easy to isolate, homogenous and proliferate faster than bone marrow MSCs without any growth factor. Importantly, gingival MSCs display stable morphology and do not loose MSC characteristic at higher passages. In addition, gingival MSCs maintain normal karyotype and telomerase activity in long-term cultures, and are not tumorigenic. Thus, we reveal that human gingiva is a better source of MSCs than bone marrow, and large number of functionally competent clinical grade MSCs can be generated in short duration for cell therapy in regenerative medicine and tissue engineering.

Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine

International Nuclear Information System (INIS)

Tomar, Geetanjali B.; Srivastava, Rupesh K.; Gupta, Navita; Barhanpurkar, Amruta P.; Pote, Satish T.; Jhaveri, Hiral M.; Mishra, Gyan C.; Wani, Mohan R.

2010-01-01

Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into multiple cell lineages. Presently, bone marrow is considered as a prime source of MSCs; however, there are some drawbacks and limitations in use of these MSCs for cell therapy. In this study, we demonstrate that human gingival tissue-derived MSCs have several advantages over bone marrow-derived MSCs. Gingival MSCs are easy to isolate, homogenous and proliferate faster than bone marrow MSCs without any growth factor. Importantly, gingival MSCs display stable morphology and do not loose MSC characteristic at higher passages. In addition, gingival MSCs maintain normal karyotype and telomerase activity in long-term cultures, and are not tumorigenic. Thus, we reveal that human gingiva is a better source of MSCs than bone marrow, and large number of functionally competent clinical grade MSCs can be generated in short duration for cell therapy in regenerative medicine and tissue engineering.

Evaluation of 10 aliphatic halogenated hydrocarbons in the mouse bone marrow micronucleus test.

Science.gov (United States)

Crebelli, R; Carere, A; Leopardi, P; Conti, L; Fassio, F; Raiteri, F; Barone, D; Ciliutti, P; Cinelli, S; Vericat, J A

1999-03-01

Ten halogenated aliphatic hydrocarbons (carbon tetrachloride, 1-chlorohexane, 2,3-dichlorobutane, 1,2-dichloroethane, 1,2-dichloroethylene, 1,3-dichloropropane, hexachloroethane, 1,1,2-trichloroethane, 1,2,3-trichloropropane and 1,1,3-trichloropropene), previously assayed in genetic assays in fungi, were evaluated in the mouse bone marrow micronucleus test in order to assess their genotoxicity in vivo. All chemicals were administered once i.p. at 40 and 70-80% of their respective LD50 to male and female CD-1 mice, 24 and 48 h before killing. All treatments produced evident clinical symptoms, but no marked depression of bone marrow proliferation. No statistically significant increases in the incidence of micronucleated polychromatic erythrocytes over the control values were observed at any sampling time with any of the 10 halogenated hydrocarbons assayed. The comparison of the results obtained in this study with the findings provided by in vitro micronucleus assays on the same chemicals, reported by other authors, indicate that mouse bone marrow is weakly sensitive to the genotoxic effects induced by halogenated hydrocarbons in other test systems. This suggests that the role of such an assay in carcinogen screening may be questionable for this chemical class. An examination of mouse bone marrow micronucleus test results with the halogenated aliphatic hydrocarbons classified as carcinogens by IARC supports this conclusion.

Discrepancy of biologic behavior influenced by bone marrow derived cells in lung cancer.

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Zhang, Jie; Niu, Xiao-Min; Liao, Mei-Lin; Liu, Yun; Sha, Hui-Fang; Zhao, Yi; Yu, Yong-Feng; Tan, Qiang; Xiang, Jia-Qing; Fang, Jing; Lv, Dan-Dan; Li, Xue-Bing; Lu, Shun; Chen, Hai-Quan

2010-11-01

Disseminated cancer cells may initially require local nutrients and growth factors to thrive and survive in bone marrow. However, data on the influence of bone marrow derived cells (BMDC, also called bone stromal cells in some publications) on lung cancer cells is largely unexplored. This study explored the mechanism of how bone stromal factors contribute to the bone tropism in lung cancer. The difference among lung cancer cell lines in their abilities to metastasize to bone was found using the SCID animal model. Supernatant of bone marrow aspiration (BM) and condition medium from human bone stromal cells (BSC) were used to study the activity of bone stromal factors. We found bone stromal factors significantly increased the proliferation, invasion, adhesion and expression of angiogenosis-related factors, and inhibited the apoptosis for high bone metastasis H460 lung cancer cells. These biologic effects were not seen in SPC-A1 or A549 cells, which are low bone metastasis lung cancer cells. Adhesion of H460 cells to surface coated with bone stromal cells can activate some signal transduction pathways, and alter the expression of adhesion associated factors, including integrin β 3 and ADAMTS-1, two potential targets related with bone metastasis. We concluded that bone marrow derived cells had a profound effect on biological behavior of lung cancers, therefore favoring the growth of lung cancer cells in bone.

Patterns of bone-marrow scintigraphy

International Nuclear Information System (INIS)

Touya, J.J.; Lee, G.S.; Narvaez, M.; Marciano, D.

1977-01-01

111 In-transferrin, radiocolloid and bone scans were performed within one week on 105 from more than 250 scanned patients with different haematological disorders. All patients had complete haematological workups and confirmed final diagnoses. From the comparison of the 111 In-transferrin marrow scan with the radiocolloid marrow scan and bone scan, eight basic patterns of localized or generalized disorders in the bone marrow cell production were delineated. The first pattern was called a cold area and two sub-patterns were distinguished in it. A cold area in the erythropoietic and reticuloendothelial scans associated with cold or normal areas in the bone scan corresponded to radiation damage of the marrow or multiple myeloma; a cold area in both marrow scans with a hot area in the bone scan to tumour, infarct and bone trauma. The second pattern was called a hot area. A hot area in the two marrow scans with a normal bone scan was observed in islands of active bone-marrow. Hot areas in both 111 In-transferrin and bone scan associated with a cold area in the radiocolloid scan were observed in tumours growing in bones with or without little active bone marrow. Hot areas on the three scans were observed in osteomyelitis of bones of the extremities. The third pattern was bone-marrow expansion, which was observed in hereditary haemolytic anaemias, in myeloproliferative disorders and in patients with bone-marrow damage following irradiation. The fourth pattern was saturation of the serum iron-binding capacity and it was manifested by increased activity in the kidneys in the 111 In-transferrin scan. The fifth pattern was bone-marrow failure which consists of decreased accumulation in the marrow and increased accumulation in the liver of marrow-seeking agents associated with normal bone scan. The sixth pattern, pure red cell aplasia, was characterized by less accumulation of 111 In-transferrin than radiocolloid in the bone marrow. The seventh pattern, bone-marrow siderosis

Comparison of clinical grade human platelet lysates for cultivation of mesenchymal stromal cells from bone marrow and adipose tissue

DEFF Research Database (Denmark)

Juhl, Morten; Tratwal, Josefine; Follin, Bjarke

2016-01-01

be devoid of any animal derived components. We have evaluated whether human Platelet Lysate (hPL) could be an attractive alternative to animal supplements. METHODS: MSCs from bone marrow (BMSCs) and adipose tissue-derived stromal cells (ASCs) obtained from three donors were culture expanded in three...... culture conditions with 10% fetal bovine serum (FBS). Cell morphology, proliferation, phenotype, genomic stability, and differentiation potential were analyzed. RESULTS: Regardless of manufacturer, BMSCs and ASCs cultured in hPL media showed a significant increase in proliferation capacity compared to FBS...

Studies on the distribution of hematopoietic bone marrow by bone marrow scintigraphy, 2

International Nuclear Information System (INIS)

Fujimori, Katsuhiko

1976-01-01

Distribution of the leukemic marrow was investigated in 42 cases by bone marrow scintigraphy using sup(99m)Tc sulfur colloid in association with clinical findings and ferrokinetics studies in order to clarify hematopoietic function in leukemia. 17 of chronic myelogenous leukemia, 3 of lymphatic leukemia, 2 of monocytic leukemia, 7 of atypical leukemia and one of erythroleukemia. 12 acute myelogenous leukemia were classified into 3 types A, B and C. Type A showed the distribution similar to those obtained with normal controls. Ferrokinetics studies, however, indicated complete absence of erythropoiesis. Type B showed complete lack of sup(99m)Tc activity in usual marrow sites, although ferrokinetics data showed normal erythropoeitic function. Type C showed abnormal concentration of sup(99m)Tc sulfur colloid in the tibiae. 17 chronic myelogenous leukemia showed reduced sup(99m)Tc activity in usual marrow sites and remarkable expanded marrow extending into distal femurs, proximal and distal tibiae and bones of feet. 2 acute lymphotic leukemia patients showed complete absence of sup(99m)Tc activity. The one chronic type showed almost normal distribution. Monocytic leukemia showed decreased marrow distribution in the sternum and vertebrae. Of 6 atypical leukemias one showed almost normal distribution. The others, including a case with hypoplastic luekemia, demonstrated marrow extension similar to that observed in chronic myelogenous leukemia or monocytic leukemia. Erythroleukemia showed increased concentrations of sup(99m)Tc activity in the usual marrow sites and marked marrow expansion throughout all long bones. These results suggest that there is a discrepancy between bone marrow distribution and hematopoietic function in the cases of acute myelogenous leukemia. (J.P.N.)

Prostacyclin Suppresses Twist Expression in the Presence of Indomethacin in Bone Marrow-Derived Mesenchymal Stromal Cells

Science.gov (United States)

Kemper, Oliver; Herten, Monika; Fischer, Johannes; Haversath, Marcel; Beck, Sascha; Classen, Tim; Warwas, Sebastian; Tassemeier, Tjark; Landgraeber, Stefan; Lensing-Höhn, Sabine; Krauspe, Rüdiger; Jäger, Marcus

2014-01-01

Background Iloprost, a stable prostacyclin I2 analogue, seems to have an osteoblast-protective potential, whereas indomethacin suppresses new bone formation. The aim of this study was to investigate human bone marrow stromal cell (BMSC) proliferation and differentiation towards the osteoblastic lineage by administration of indomethacin and/or iloprost. Material/Methods Human bone marrow cells were obtained from 3 different donors (A=26 yrs/m; B=25 yrs/f, C=35 yrs/m) via vacuum aspiration of the iliac crest followed by density gradient centrifugation and flow cytometry with defined antigens (CD105+/73+/45−/14−). The cells were seeded and incubated as follows: without additives (Group 0; donor A/B/C), with 10−7 M iloprost only (Group 0+ilo; A/B), with indomethacin only in concentrations of 10−6 M (Group 1, A), 10−5 M (Group 2, B), 10−4 M (Group 3, A/B), and together with 10−7 M iloprost (Groups 4–6, A/B/C). On Day 10 and 28, UV/Vis spectrometric and immunocytochemical assays (4 samples per group and donor) were performed to investigate cell proliferation (cell count measurement) and differentiation towards the osteoblastic lineage (CD34−, CD45−, CD105+, type 1 collagen (Col1), osteocalcin (OC), alkaline phosphatase (ALP), Runx2, Twist, specific ALP-activity). Results Indomethacin alone suppressed BMSC differentiation towards the osteoblastic lineage by downregulation of Runx2, Col1, and ALP. In combination with indomethacin, iloprost increased cell proliferation and differentiation and it completely suppressed Twist expression at Day 10 and 28. Iloprost alone did not promote cell proliferation, but moderately enhanced Runx2 and Twist expression. However, the proliferative effects and the specific ALP-activity varied donor-dependently. Conclusions Iloprost partially antagonized the suppressing effects of indomethacin on BMSC differentiation towards the osteoblast lineage. It enhanced the expression of Runx2 and, only in the presence of indomethacin

Bone Marrow-Derived Mesenchymal Stromal Cells Enhanced by Platelet-Rich Plasma Maintain Adhesion to Scaffolds in Arthroscopic Simulation.

Science.gov (United States)

Hoberman, Alexander R; Cirino, Carl; McCarthy, Mary Beth; Cote, Mark P; Pauzenberger, Leo; Beitzel, Knut; Mazzocca, Augustus D; Dyrna, Felix

2018-03-01

To assess the response of bone marrow-derived mesenchymal stromal cells (bMSCs) enhanced by platelet-rich plasma (PRP) in the setting of a normal human tendon (NHT), a demineralized bone matrix (DBM), and a fibrin scaffold (FS) with simulated arthroscopic mechanical washout stress. Bone marrow was aspirated from the humeral head and concentrated. BMSCs were counted, plated, and grown to confluence. Cells were seeded onto 3 different scaffolds: (1) NHT, (2) DBM, and (3) FS. Each scaffold was treated with a combination of (+)/(-) PRP and (+)/(-) arthroscopic washout simulation. A period of 60 minutes was allotted before arthroscopic washout. Adhesion, proliferation, and differentiation assays were performed to assess cellular activity in each condition. Significant differences were seen in mesenchymal stromal cell adhesion, proliferation, and differentiation among the scaffolds. DBM and FS showed superior results to NHT for cell adhesion, proliferation, and differentiation. PRP significantly enhanced cellular adhesion, proliferation, and differentiation. Arthroscopic simulation did not significantly decrease bMSC adhesion. We found that the type of scaffold impacts bMSCs' behavior. Both scaffolds (DBM and FS) were superior to NHT. The use of an arthroscopic simulator did not significantly decrease the adhesion of bMSCs to the scaffolds nor did it decrease their biologic differentiation potential. In addition, PRP enhanced cellular adhesion, proliferation, and differentiation. Improved healing after tendon repair can lead to better clinical outcomes. BMSCs are attractive for enhancing healing given their accessibility and regenerative potential. Application of bMSCs using scaffolds as cell carriers relies on arthroscopic feasibility. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions

International Nuclear Information System (INIS)

Ren Hongying; Cao Ying; Zhao, Qinjun; Li Jing; Zhou Cixiang; Liao Lianming; Jia Mingyue; Zhao Qian; Cai Huiguo; Han Zhongchao; Yang Renchi; Chen Guoqiang; Zhao, R.C.

2006-01-01

Low oxygen tension is a potent differentiation inducer of numerous cell types and an effective stimulus of many gene expressions. Here, we described that under 8% O 2 , bone marrow stromal cells (MSCs) exhibited proliferative and morphologic changes. The level of differentiated antigen H-2Dd and the number of G 2 /S/M phase cells increased evidently under 8% O 2 condition. Also, the proportion of wide, flattened, and epithelial-like cells (which were alkaline phosphatase staining positive) in MSCs increased significantly. When cultured in adipogenic medium, there was a 5- to 6-fold increase in the number of lipid droplets under hypoxic conditions compared with that in normoxic culture. We also demonstrated the existence of MSC differentiation under hypoxic conditions by electron microscopy. Expression of Oct4 was inhibited under 8% O 2 condition, but after adipocyte differentiation in normoxic culture and hypoxia-mimicking agents cobalt chloride (CoCl 2 ) and deferoxamine mesylate (DFX) treatments, Oct4 was still expressed in MSCs. These results indicate hypoxia accelerates MSC differentiation and hypoxia and hypoxia-mimicking agents exert different effects on MSC differentiation

Local fibroblast proliferation but not influx is responsible for synovial hyperplasia in a murine model of rheumatoid arthritis

Energy Technology Data Exchange (ETDEWEB)

Matsuo, Yusuke; Mizoguchi, Fumitaka; Saito, Tetsuya [Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519 (Japan); Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST) Program, Sanbancho, Chiyoda-ku, Tokyo, 102-0075 (Japan); Kawahata, Kimito [Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519 (Japan); Ueha, Satoshi; Matsushima, Kouji [Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST) Program, Sanbancho, Chiyoda-ku, Tokyo, 102-0075 (Japan); Department of Molecular Preventive Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033 (Japan); Inagaki, Yutaka [Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST) Program, Sanbancho, Chiyoda-ku, Tokyo, 102-0075 (Japan); Center for Matrix Biology and Medicine, Graduate School of Medicine and the Institute of Medical Sciences, Tokai University, 143 Shimo-kasuya, Isehara, Kanagawa, 259-1193 (Japan); Miyasaka, Nobuyuki [Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519 (Japan); Kohsaka, Hitoshi, E-mail: kohsaka.rheu@tmd.ac.jp [Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519 (Japan); Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST) Program, Sanbancho, Chiyoda-ku, Tokyo, 102-0075 (Japan)

2016-02-12

Synovial fibroblasts play crucial roles in inflammation and joint destruction in rheumatoid arthritis (RA). How they accumulate in the RA joints remains unclear. This study was conducted to discern whether cellular influx from the outside of the joints and local proliferation are responsible for synovial fibroblast accumulation in an animal model of RA. We found that synovial fibroblasts were identified as GFP+ cells using collagen type I alpha 2 (Col1a2)-GFP transgenic reporter mice. Then, bone marrow transplantation and parabiosis techniques were utilized to study the cellular influx. Irradiated wild-type mice were transplanted with bone marrow from Col1a2-GFP mice. Col1a2-GFP and wild-type mice were conjoined for parabiosis. The transplanted mice and the parabionts were subjected to collagen antibody-induced arthritis (CAIA). We found no GFP+ cells in the hyperplastic synovial tissues from the transplanted mice with CAIA and from the wild-type parabionts with CAIA. Furthermore, normal and CAIA synovial tissues from Col1a2-GFP mice and from fluorescent ubiquitination-based cell cycle indicator (Fucci) transgenic mice, in which cells in S/G{sub 2}/M phases of the cell cycle express Azami-Green, were studied for Ki67, a cellular proliferation marker, and vimentin, a fibroblast marker, expression. The percentages of Ki67+/GFP+ and Azami-Green+/vimentin+ cells in the CAIA synovial tissues were higher than those in the untreated synovial tissues (34% vs. 0.40% and 19% vs. 0.26%, respectively). These findings indicate that local fibroblast proliferation but not cellular influx is responsible for the synovial hyperplasia in CAIA. Suppression of proliferation of the local synovial fibroblasts should be a promising treatment for RA. - Highlights: • We studied how synovial fibroblasts accumulate in joints in a murine model of RA. • Bone marrow-derived cells did not accumulate in arthritic joints. • Synovial fibroblasts did not accumulate in arthritic joints via

Effect of fibronectin- and collagen I-coated titanium fiber mesh on proliferation and differentiation of osteogenic cells.

NARCIS (Netherlands)

Dolder, J. van den; Bancroft, G.N.; Sikavitsas, V.I.; Spauwen, P.H.M.; Mikos, A.G.; Jansen, J.A.

2003-01-01

The objective of this study was to evaluate the effects of fibronectin and collagen I coatings on titanium fiber mesh on the proliferation and osteogenic differentiation of rat bone marrow cells. Three main treatment groups were investigated in addition to uncoated titanium fiber meshes: meshes

Intractable Diseases Treated with Intra-Bone Marrow-Bone Marrow Transplantation

Directory of Open Access Journals (Sweden)

Ming eLi

2014-09-01

Full Text Available Bone marrow transplantation (BMT is used to treat hematological disorders, autoimmune diseases and lymphoid cancers. Intra bone marrow-BMT (IBM-BMT has been proven to be a powerful strategy for allogeneic BMT due to the rapid hematopoietic recovery and the complete restoration of T cell functions. IBM-BMT not only replaces hematopoietic stem cells but also mesenchymal stem cells (MSMCs. MSMCs are multi-potent stem cells that can be isolated from bone marrow, umbilical cord blood, and adipose tissue. MSMCs play an important role in the support of hematopoiesis, and modify and influence the innate and adaptive immune systems. MSMCs also differentiate into mesodermal, endodermal and ectodermal lineage cells to repair tissues. This review aims to summarize the functions of bone marrow-derived- MSMCs, and the treatment of intractable diseases such as rheumatoid arthritis and malignant tumors with IBM-BMT.

Bone marrow transplantation immunology

International Nuclear Information System (INIS)

Trentin, J.J.; Kiessling, R.; Wigzell, H.; Gallagher, M.T.; Datta, S.K.; Kulkarni, S.S.

1977-01-01

Tests were made to determine whether genetic resistance (GR) to bone marrow transplantation represents a natural lymphoma-leukemia defense mechanism, as follows: (C57 x AKR) F 1 hybrid mice show GR to C57 parental bone marrow cells, but not to AKR parental bone marrow cells (C3H x AKR) F 1 hybrids show no GR to bone marrow transplantation from either parental strain. However, transplantation of AKR lymphoma cells into lethally irradiated ''resistant'' (C57 x AKR) F 1 and ''nonresistant'' (C3H x AKR) F 1 hybrids produced lymphomatous spleen colonies in ''nonresistant'' hybrids but not in ''resistant'' hybrids. Thus ''resistant'' (C57 x AKR) F 1 hybrids can recognize and reject AKR lymphoma cells, but not normal AKR bone marrow cells. A normal biologic role of leukemia-lymphoma surveillance was postulated for genetic resistance to marrow transplantation, directed at antigens which, like TL, are expressed on normal hemopoietic cells of some strains, but only on leukemic cells of other strains

Patterns of proliferation and differentiation of irradiated haemopoietic stem cells cultured on normal 'stromal' cell colonies in vitro

International Nuclear Information System (INIS)

Mori, K.J.

1981-01-01

Experiments were designed to elucidate whether or not the irradiated bone marrow cells receive any stimulation for the self-replication and differentiation from normal 'stromal' cell colonies in the bone marrow cell culture in vitro. When irradiated or unirradiated bone marrow cells were overlaid on the normal adherent cell colonies, the proliferation of haemopoietic stem cells was supported, the degree of the stimulation depending on the starting cellular concentration. There was, however, no significant changes in the concentration of either CFUs or CFUc regardless of the dose of irradiation on the bone marrow cells overlaid. This was a great contrast to the dose-dependent decrease of CFUs or CFUc within the culture in which both the stem cells and stromal cells were simultaneously irradiated. These results suggest that the balance of self-replication and differentiation of the haemopoietic stem cells is affected only when haemopoietic microenvironment is perturbed. (author)

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

Science.gov (United States)

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

2017-12-01

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

Isolation, culture and intraportal transplantation of rat marrow stromal cell

International Nuclear Information System (INIS)

Wang Ping; Wang Jianhua; Yan Zhiping; Li Wentao; Lin Genlai; Hu Meiyu; Wang Yanhong

2004-01-01

Objective: To observe the tracing and evolution of marrow stromal cell (MSC) after intraportal transplantation into the liver of homogenous rats, and to provide experimental data for MSC differentiation to hepatocyte in vivo. Methods: The MSC was isolated from the leg bone marrow of adult SD rats, and purified by culture-expanded in vitro. Before transplantation, MSC was labeled with DAPI. Then 10 5 MSC were intraportally transplanted into the homogenous rat liver. Rats were killed at 2 hours and 1, 2, 3 and 4 weeks after transplantation. The cryosection samples of liver and lung were observed under fluorescence microscopy. Results: MSC in vitro culture had high ability of proliferation. Except 4 rats were dead because of abdominal bleeding or infection, other recipients were healthy until sacrificed. The implantation cells were detected by identifying the DAPI labeled MSC in the host livers, but not in the host lungs. Conclusion: Intraportal transplanted MSC could immigrate and survive in the host livers at least for 4 weeks. They could immigrate from the small branches of portal veins to hepatic parenchyma

Bone marrow transplantation

International Nuclear Information System (INIS)

Storb, R.; Santos, G.W.

1979-01-01

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

Nicotine-induced chondrogenic differentiation of human bone marrow stromal cells in vitro.

Science.gov (United States)

Ying, Xiaozhou; Zhang, Wei; Cheng, Shaowen; Nie, Pengfei; Cheng, Xiaojie; Shen, Yue; Wang, Wei; Xue, Enxing; Chen, Qingyu; Kou, Dongquan; Peng, Lei; Zhang, Yu; Lu, Chuanzhu

2012-11-01

Nicotine has been reported that it has a dose-dependent effect on matrix mineralization by human bone marrow cells. However, there is no relevant research concerning on chondrogenic differentiation potential of bone marrow stromal stem cells (BMSCs) treated with nicotine in vitro. The aims of the study were to examine the effects of nicotine (0, 10(-7), 10(-6) and 10(-5) M) on the proliferation and chondrogenic differentiation of BMSCs from three healthy donors in vitro. BMSCs proliferation was analyzed by CCK8 assay and real-time polymerase chain reaction was used to assay the expression of type II collagen, aggrecan, type I collagen and type X collagen. The proteoglycan content was stained by Alcian blue, and the sulfated glycosaminoglycan (sGAG) content of BMSCs was quantified spectrofluorometrically using dimethylmethylene blue. The cell viability was not significantly impaired until up to a concentration of 10(-5) M nicotine. Nicotine promoted the proliferation and enhanced the expression of type II collagen at the level up to 10(-6) M (P < 0.05). The expression of aggrecan was reduced at the concentration of 10(-5) M nicotine at day 14 (P < 0.05), and there was no significant difference in aggrecan gene expression at 10(-7) and 10(-6) M nicotine levels compared to control group (n.s.). Also the fibroblastic and hypertrophic gene expressions were down-regulated in the chondrogenic medium with 10(-7)-10(-5) M nicotine (P < 0.05). It was implied that local application of nicotine at an appropriate concentration may be a promising approach for enhancing chondrogenic differentiation capacity of BMSCs in cell-based cartilage tissue engineering. Also these results indicate that nicotine maybe a potentially useful drug for the treatment of Osteoarthritis.

Bone-Marrow Storage and Transplantation

International Nuclear Information System (INIS)

Costăchel, O.; Corneci, I.; Andrian, T.; Kitzulescu, I.; Popescu, N.; Pascu, D.; Buzi, E.; Voiculetz, N.

1969-01-01

The authors present some results from their experiments on bone-marrow storage and transplantation. The main problems with preservation of stored bone marrow are the duration, temperature, adjuvant substances and the significance of viability tests during the conservation processes. The results showed that: • Storage of bone marrow at +4eC produces a progressive decrease in its restoring capacity versus storage time. • While bone marrow stored for 24 h is able to restore 100% of dogs lethally irradiated with 600 rad, after 10 days of storage only 20% of the animals can be restored. • No correlation exists between the actual survival of dogs and that calculated by dye exclusion tests, which indicate a rather high (70%) viability, even after 10 days bone-marrow storage at +4°C. • DNA degradation (depolymerization) measurements of the bone marrow may be used as a supplementary test for checking the viability or restoration potency of bone-marrow cells after storage. • In the freezing process, the optimum contact time between glycerol and the bone-marrow cells is 15 min. Results of experiments regarding certain bone-marrow transplantation problems showed that: • The best time to administer bone marrow is between 24 and 48 h after irradiation. • No survivors were obtained with dogs lethally irradiated with 600 rad by administering autogenic or allogenic DNA extracted from bone marrow, spleen or liver. • Histocompatibility related to sex may play an important role in the bone-marrow graft. The lowest survival of C57BL mice was obtained when the donors were males and the recipients females. • In radioprotection with foetal haemocytopoietic tissues, the donor's age represents one of the main factors. The best results were obtained in experiments on rats, with 19- to 20-day foetal liver (period of complete and maximum haemocytopoietic activity). The tissues mentioned below may be connected with the appearance of certain typical signs of secondary syndrome

Bone-Marrow Storage and Transplantation

Energy Technology Data Exchange (ETDEWEB)

Costachel, O.; Corneci, I.; Andrian, T.; Kitzulescu, I.; Popescu, N.; Pascu, D.; Buzi, E.; Voiculetz, N. [Oncological Institute, Bucharest (Romania)

1969-07-15

The authors present some results from their experiments on bone-marrow storage and transplantation. The main problems with preservation of stored bone marrow are the duration, temperature, adjuvant substances and the significance of viability tests during the conservation processes. The results showed that: Bullet Storage of bone marrow at +4eC produces a progressive decrease in its restoring capacity versus storage time. Bullet While bone marrow stored for 24 h is able to restore 100% of dogs lethally irradiated with 600 rad, after 10 days of storage only 20% of the animals can be restored. Bullet No correlation exists between the actual survival of dogs and that calculated by dye exclusion tests, which indicate a rather high (70%) viability, even after 10 days bone-marrow storage at +4 Degree-Sign C. Bullet DNA degradation (depolymerization) measurements of the bone marrow may be used as a supplementary test for checking the viability or restoration potency of bone-marrow cells after storage. Bullet In the freezing process, the optimum contact time between glycerol and the bone-marrow cells is 15 min. Results of experiments regarding certain bone-marrow transplantation problems showed that: Bullet The best time to administer bone marrow is between 24 and 48 h after irradiation. Bullet No survivors were obtained with dogs lethally irradiated with 600 rad by administering autogenic or allogenic DNA extracted from bone marrow, spleen or liver. Bullet Histocompatibility related to sex may play an important role in the bone-marrow graft. The lowest survival of C57BL mice was obtained when the donors were males and the recipients females. Bullet In radioprotection with foetal haemocytopoietic tissues, the donor's age represents one of the main factors. The best results were obtained in experiments on rats, with 19- to 20-day foetal liver (period of complete and maximum haemocytopoietic activity). The tissues mentioned below may be connected with the appearance of

MR appearances of bone marrow in children following bone marrow transplantation

International Nuclear Information System (INIS)

Boothroyd, A.E.; Sebag, G.; Brunelle, F.

1991-01-01

Two cases are presented of children who demonstrated complete absence of bone marrow signal on MR imaging of the spine following bone marrow transplantation. The possible causes for these appearances are discussed. (orig.)

Onset of apoprotein E secretion during differentiation of mouse bone marrow-derived mononuclear phagocytes

International Nuclear Information System (INIS)

Werb, Z.; Chin, J.R.

1983-01-01

A number of macrophage functions were sequentially expressed when the bone marrow precursors of mononuclear phagocytes differentiated in culture in the presence of a specific growth factor, colony-stimulating factor-1. The authors defined the expression of apoprotein E (ApoE), a major secreted protein of resident peritoneal macrophages, during maturation of adherent bone marrow-derived mononuclear phagocytes into macrophages. By 5 d the bone marrow macrophages were active secretory cells, but few cells contained intracellular immunoreactive ApoE, and little, if any, ApoE was secreted. ApoE secretion was initiated at 9 d, and this correlated with an increase in the percentage of macrophages containing intracellular ApoE. The onset of ApoE secretion was selective, and little change occurred in the other major secreted proteins detected by [ 35 S]methionine incorporation. In parallel, the high rate of plasminogen activator secretion, which peaked at 7 d, decreased markedly. ApoE secretion was not associated with altered expression of the macrophage surface antigen, la, or with secretion of fibronectin. Virtually all cells in independent colonies of bone marrow-derived macrophages eventually expressed ApoE. The proliferating monocyte/macrophage-like cell lines P388D1, J774.2, WHEI-3, RAW 264.1, and MGI.D + secreted little or no ApoE. These data establish that ApoE secretion is developmentally regulated

Osteogenesis of bone marrow mesenchymal stem cells on strontium-substituted nano-hydroxyapatite coated roughened titanium surfaces

OpenAIRE

Yang, Hua-Wei; Lin, Mao-Han; Xu, Yuan-Zhi; Shang, Guang-Wei; Wang, Rao-Rao; Chen, Kai

2015-01-01

Objective: To investigate osteogenesis of bone marrow mesenchymal stem cells (BMSCs) on strontium-substituted nano-hydroxyapatite (Sr-HA) coated roughened titanium surfaces. Methods: Sr-HA coating and HA coating were fabricated on roughened titanium surfaces by electrochemical deposition technique and characterized by field emission scanning electron microscope (FESM). BMSCs were cultured on Sr-HA coating, HA coating and roughened titanium surfaces respectively. Cell proliferation, alkaline p...

Evaluation of renal uptake on [sup 111]InCl[sub 3] bone marrow scintigraphy in patients with aplastic anemia and myelodysplastic syndrome

Energy Technology Data Exchange (ETDEWEB)

Koizumi, Mitsuru; Goto, Masafumi; Nomura, Toshiharu; Watari, Tsutomu; Saito, Kenji (Dokkyo Univ. School of Medicine, Mibu, Tochigi (Japan))

1993-04-01

High renal uptake on bone marrow scan with indium-111 chloride is often shown in patients with bone marrow abnormality. We evaluated the renal uptake on bone marrow scan in 27 cases of aplastic anemia, 20 cases of myelodysplastic syndrome (MDS) and 10 cases of other diseases. The high renal uptake was observed in patients not only with aplastic anemia but also with MDS. The renal uptake correlated with blood transfusion units, unsaturated iron binding capacity (UIBC), blood pool imaging and bone marrow uptake. The renal uptake correlated with UIBC better than with the blood transfusion units. Following mechanism of the renal uptake is proposed that frequent blood transfusion makes low UIBC, and the low UIBC causes the failure to chelate indium with transferrin. The fast blood clearance of un-chelated indium via kidneys is followed. Hypoplastic bone marrow may also play an important role for the high renal uptake because all patients with the high renal uptake could not be explained by above mentioned mechanism. Caution should be paid to the scans with the high renal uptake because both aplastic anemia and MDS patients show the high renal uptake. (author).

Bio-active molecules modified surfaces enhanced mesenchymal stem cell adhesion and proliferation

International Nuclear Information System (INIS)

Mobasseri, Rezvan; Tian, Lingling; Soleimani, Masoud; Ramakrishna, Seeram; Naderi-Manesh, Hossein

2017-01-01

Surface modification of the substrate as a component of in vitro cell culture and tissue engineering, using bio-active molecules including extracellular matrix (ECM) proteins or peptides derived ECM proteins can modulate the surface properties and thereby induce the desired signaling pathways in cells. The aim of this study was to evaluate the behavior of human bone marrow mesenchymal stem cells (hBM-MSCs) on glass substrates modified with fibronectin (Fn), collagen (Coll), RGD peptides (RGD) and designed peptide (R-pept) as bio-active molecules. The glass coverslips were coated with fibronectin, collagen, RGD peptide and R-peptide. Bone marrow mesenchymal stem cells were cultured on different substrates and the adhesion behavior in early incubation times was investigated using scanning electron microscopy (SEM) and confocal microscopy. The MTT assay was performed to evaluate the effect of different bio-active molecules on MSCs proliferation rate during 24 and 72 h. Formation of filopodia and focal adhesion (FA) complexes, two steps of cell adhesion process, were observed in MSCs cultured on bio-active molecules modified coverslips, specifically in Fn coated and R-pept coated groups. SEM image showed well adhesion pattern for MSCs cultured on Fn and R-pept after 2 h incubation, while the shape of cells cultured on Coll and RGD substrates indicated that they might experience stress condition in early hours of culture. Investigation of adhesion behavior, as well as proliferation pattern, suggests R-peptide as a promising bio-active molecule to be used for surface modification of substrate in supporting and inducing cell adhesion and proliferation. - Highlights: • Bioactive molecules modified surface is a strategy to design biomimicry scaffold. • Bi-functional Tat-derived peptide (R-pept) enhanced MSCs adhesion and proliferation. • R-pept showed similar influences to fibronectin on FA formation and attachment.

The Japan Marrow Donor Program, 25 years of experience in achieving 20,000 bone marrow transplantations: organization structure, activity, and financial basis.

Science.gov (United States)

Saito, Hidehiko; Ito, Masaharu; Kato, Shunichi; Kodera, Yoshihisa; Okamoto, Shinichiro; Taniguchi, Shuichi; Takanashi, Minoko; Kanamori, Heiwa; Masaoka, Toru; Takaku, Fumimaro

2018-01-24

The Japan Marrow Donor Program (JMDP), established in 1991, has continued to grow in its capacity to facilitate unrelated bone marrow (BMT) and peripheral blood stem cell transplantation (PBSCT) for the past 25 years in Japan. The current donor pool is 463,465 (as of 31 December 2016) and 20,237 transplants were performed with the help of the Japanese Red Cross, government, and supporters. As JMDP introduced PBSCT in 2010, the vast majority of transplants are BMT. All donors are fully typed for HLA-A, B, C, and DR. The peak age of registered donors is around 40 years. The 8/8 HLA-matched donors are found in our registry for 96% of the patients and 54% of the patients receive a transplant. The median time between the initiation of donor search and the transplantation is approximately 122 days. The median interval between the initiation of donor search and identification of the first potential donor is 40 days. The most common diseases for which unrelated BMT/PBSCT is indicated are acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS), and malignant lymphoma. In recent years we have seen a marked increase in elderly patients who received BMT.

Granulocyte-mobilized bone marrow.

Science.gov (United States)

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

2012-11-01

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

Acute erythroid neoplastic proliferations. A biological study based on 62 patients.

Science.gov (United States)

Domingo-Claros, Alicia; Larriba, Itziar; Rozman, Maruja; Irriguible, Dolors; Vallespí, Teresa; Aventin, Anna; Ayats, Ramon; Millá, Fuensanta; Solé, Francesc; Florensa, Lourdes; Gallart, Miquel; Tuset, Esperanza; Lopez, Carmen; Woessner, Soledad

2002-02-01

The terms acute erythroleukemia and AML-M6 are defined in the FAB classification as proliferations of dysplastic erythroid elements mixed with blasts of myeloid origin, but pure erythroid leukemias are not included. The recent WHO classification has a category of acute myeloid leukemia not otherwise categorized, which includes acute erythroid leukemia (M6) of two subtypes: M6a-erythroleukemia (erythroid/myeloid) and M6b-pure erythroid leukemia. The aims of this co-operative study were to discover the incidences of these different subtypes, and pay special attention to the morphology of these entities. We reviewed a series of 62 patients with erythroid neoplastic proliferations. Previous medical history, age, sex, peripheral blood and bone marrow cell counts, cytochemical stains, immunophenotype, and cytogenetics were evaluated at presentation. We analyzed the incidence of erythrocyte, leukocyte and platelet abnormalities in the peripheral blood. In bone marrow we analyzed dysplastic features of erythroblasts, granulocytic elements and the megakaryocytic lineage. Fifty-three patients met the criteria of M6a subtype of the WHO classification, and 2 were classified as having pure erythremia (M6b); 7 cases could not be classified according to the WHO criteria. Fifty-five patients presented with de novo acute leukemia, and seven patients had secondary acute leukemia. The most frequent dysplastic features in blood smears were: schistocytes, tear-drop and pincered cells in erythrocytes; hypogranulation and hyposegmentation in leukocytes; gigantism and hypogranulation in platelets. In bone marrow, megaloblastic changes, multinuclearity, karyorrhexis and basophilic stippling in erythroblasts; hypogranulation and gigantism in granulocytic series, and micromegakaryocytes and unconnected nuclei in megakarocytes were the most dysplastic features. A positive PAS reaction and increase of bone marrow iron with ring sideroblasts were common features. Trilineage dysplasia was

Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions

Energy Technology Data Exchange (ETDEWEB)

Hongying, Ren; Huiguo, Cai; Zhongchao, Han; Renchi, Yang; Zhao, Qinjun [State Key Lab of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin (China); Ying, Cao; Jing, Li [Institute of Basic Medical Sciences and School of Basic Medicine, Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Cixiang, Zhou [Health Science Center, Shanghai Institutes of Biological Sciences, Chinese Academy of Science-SSMU, Shanghai (China); Lianming, Liao; Mingyue, Jia [Institute of Basic Medical Sciences and School of Basic Medicine, Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Qian, Zhao [Health Science Center, Shanghai Institutes of Biological Sciences, Chinese Academy of Science-SSMU, Shanghai (China); Guoqiang, Chen [Health Science Center, Shanghai Institutes of Biological Sciences, Chinese Academy of Science-SSMU, Shanghai (China); Zhao, R C [State Key Lab of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin (China); [Institute of Basic Medical Sciences and School of Basic Medicine, Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China)]. E-mail: chunhuaz@public.tpt.tj.cn

2006-08-18

Low oxygen tension is a potent differentiation inducer of numerous cell types and an effective stimulus of many gene expressions. Here, we described that under 8% O{sub 2}, bone marrow stromal cells (MSCs) exhibited proliferative and morphologic changes. The level of differentiated antigen H-2Dd and the number of G{sub 2}/S/M phase cells increased evidently under 8% O{sub 2} condition. Also, the proportion of wide, flattened, and epithelial-like cells (which were alkaline phosphatase staining positive) in MSCs increased significantly. When cultured in adipogenic medium, there was a 5- to 6-fold increase in the number of lipid droplets under hypoxic conditions compared with that in normoxic culture. We also demonstrated the existence of MSC differentiation under hypoxic conditions by electron microscopy. Expression of Oct4 was inhibited under 8% O{sub 2} condition, but after adipocyte differentiation in normoxic culture and hypoxia-mimicking agents cobalt chloride (CoCl{sub 2}) and deferoxamine mesylate (DFX) treatments, Oct4 was still expressed in MSCs. These results indicate hypoxia accelerates MSC differentiation and hypoxia and hypoxia-mimicking agents exert different effects on MSC differentiation.

Radiosensitivity of hemopoietic stem cells on cloning in bone marrow and spleen

International Nuclear Information System (INIS)

Shvets, V.N.; Shafirkin, A.V.

1979-01-01

It was shown that population of stem cells from bone marrow of mice is heterogenous by radiosensitivity. A 55%-survival of CFU is exponential function of radiation dose (D 0 -9 rad). A dose-effect curve for radioresistant part of the population (D 0 =180 rad) is sygmoid (Dsub(q)=130 rad). Radiosensitive CFU are suggested to represent a primarily committed fraction of half-semi cells, and radioresistant CFU are referable to a pool of pluripotent stem cells. Heterogenous nature of CFU population is proved with different modifications of radiation effect and interactions of CFU with T-lymphocytes

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 ...

Lin28a regulates germ cell pool size and fertility

Science.gov (United States)

Shinoda, Gen; de Soysa, T. Yvanka; Seligson, Marc T.; Yabuuchi, Akiko; Fujiwara, Yuko; Huang, Pei Yi; Hagan, John P.; Gregory, Richard I.; Moss, Eric G.; Daley, George Q.

2013-01-01

Overexpression of LIN28A is associated with human germ cell tumors and promotes primordial germ cell (PGC) development from embryonic stem cells in vitro and in chimeric mice. Knockdown of Lin28a inhibits PGC development in vitro, but how constitutional Lin28a deficiency affects the mammalian reproductive system in vivo remains unknown. Here, we generated Lin28a knockout (KO) mice and found that Lin28a deficiency compromises the size of the germ cell pool in both males and females by affecting PGC proliferation during embryogenesis. Interestingly however, in Lin28a KO males the germ cell pool partially recovers during postnatal expansion, while fertility remains impaired in both males and females mated to wild type mice. Embryonic overexpression of let-7, a microRNA negatively regulated by Lin28a, reduces the germ cell pool, corroborating the role of the Lin28a/let-7 axis in regulating the germ lineage. PMID:23378032

Central and peripheral distribution of bone marrow on bone marrow scintigraphy with antigranulocytic antibody in hematologic malignancy

Energy Technology Data Exchange (ETDEWEB)

Kang, Do Young [Dong-A University College of Medicne, Busan (Korea, Republic of); Lee, Jae Tae; Sohn, Sang Kyun; Lee, Kyu Bo [Kyungpook National University School of Medicine, Taegu (Korea, Republic of)

2002-10-01

Bone marrow scintigraphy has been used to evaluate the status of bone marrow in various hematologic disorders. We have analyzed the peripheral distribution pattern and central uptake ratio of bone marrow using anti-NCA-95 monoclonal antibody and the their correlation in patients with various hematologic malignancy. Bone marrow immunoscintigraphy was performed using Tc-99m anti-granulocyte monoclonal mouse antibody BW 250/183. Fifty patients were classified into four groups; 11 with acute myelogenous leukemia, 12 with acute lymphocytic leukemia, 15 with lymphoma and 12 with myelodysplastic syndrome. Th extension of peripheral bone marrow was categorized into four grades: I, II, III and IV. The activity of central bone marrow was expressed as sacroiliac uptake ratio. The patient's number was 4 in grade I, 27 in grade II, 15 in grade III and 4 in grade IV according to extension of peripheral bone marrow. The extension of peripheral bone marrow was marked (58% in grade III and IV) in myelodysplastic syndrome and acute lymphocytic leukemia and mild (93% in grade I and II) in lymphoma. Sacroiliac uptake ratio was highest (8.5{+-}4.0) in myelodysplastic syndrome and lowest (5.9{+-}3.6) in acute myelogenous leukemia, but not significantly different among four grades (p=0.003), but there was not correlated between grade of peripheral bone marrow and sacroiliac uptake ratio (r=0.05). Sacroiliac uptake ratio of whole patients was significantly different among four grades (p=0.003), but there was not correlated between grade of peripheral bone marrow and sacroiliac uptake ratio (r=0.05). The pattern of peripheral bone marrow extension and activity of central hemopoietic marrow were not specific to the disease entities. Response of hemopoietic bone marrow may be evaluated on both peripheral and central bone marrow in patients with hematologic malignancy.

Central and peripheral distribution of bone marrow on bone marrow scintigraphy with antigranulocytic antibody in hematologic malignancy

International Nuclear Information System (INIS)

Kang, Do Young; Lee, Jae Tae; Sohn, Sang Kyun; Lee, Kyu Bo

2002-01-01

Bone marrow scintigraphy has been used to evaluate the status of bone marrow in various hematologic disorders. We have analyzed the peripheral distribution pattern and central uptake ratio of bone marrow using anti-NCA-95 monoclonal antibody and the their correlation in patients with various hematologic malignancy. Bone marrow immunoscintigraphy was performed using Tc-99m anti-granulocyte monoclonal mouse antibody BW 250/183. Fifty patients were classified into four groups; 11 with acute myelogenous leukemia, 12 with acute lymphocytic leukemia, 15 with lymphoma and 12 with myelodysplastic syndrome. Th extension of peripheral bone marrow was categorized into four grades: I, II, III and IV. The activity of central bone marrow was expressed as sacroiliac uptake ratio. The patient's number was 4 in grade I, 27 in grade II, 15 in grade III and 4 in grade IV according to extension of peripheral bone marrow. The extension of peripheral bone marrow was marked (58% in grade III and IV) in myelodysplastic syndrome and acute lymphocytic leukemia and mild (93% in grade I and II) in lymphoma. Sacroiliac uptake ratio was highest (8.5±4.0) in myelodysplastic syndrome and lowest (5.9±3.6) in acute myelogenous leukemia, but not significantly different among four grades (p=0.003), but there was not correlated between grade of peripheral bone marrow and sacroiliac uptake ratio (r=0.05). Sacroiliac uptake ratio of whole patients was significantly different among four grades (p=0.003), but there was not correlated between grade of peripheral bone marrow and sacroiliac uptake ratio (r=0.05). The pattern of peripheral bone marrow extension and activity of central hemopoietic marrow were not specific to the disease entities. Response of hemopoietic bone marrow may be evaluated on both peripheral and central bone marrow in patients with hematologic malignancy

Effects of marrow storage at 4 degrees C on the subsequent generation of long-term marrow cultures

International Nuclear Information System (INIS)

Takahashi, M.; Singer, J.W.

1985-01-01

The present study was undertaken to examine the effect of marrow preservation at 4 degrees C on subsequent long-term culture, which evaluates both hematopoietic precursor cells and hematopoietic microenvironmental cells. Storage of unfractionated marrow was superior to storage of buffy-coat cells in tissue culture medium with 20% fetal calf serum. CFU-C recovery in unfractionated marrow was 48.4% at four days and 21.4% at seven days. Long-term marrow cultures from cells stored at 4 degrees C for up to seven days produced CFU-C for up to seven weeks and established confluent marrow stromal cell layers. Suspension cultures of marrow cells preserved at 4 degrees C for seven days cultured with irradiated allogeneic marrow stromal cell layers from normal long-term marrow cultures showed significantly increased CFU-C production from week 2 to week 5 when compared with the control cultures without adherent cell layers. These data suggest that marrow storage at 4 degrees C for up to seven days preserves early hematopoietic precursor cells and microenvironmental cells and may be used for autologous rescue from marrow ablative therapy

Blood and Bone Marrow Transplant?

Science.gov (United States)

... Topics / Blood and Bone Marrow Transplant Blood and Bone Marrow Transplant Also known as Hematopoietic Stem Cell Transplant , Hematopoietic ... person, called a donor, it is an allogeneic transplant. Blood or bone marrow transplants most commonly are used to treat ...

Transforming growth factor-β inhibits CCAAT/enhancer-binding protein expression and PPARγ activity in unloaded bone marrow stromal cells

International Nuclear Information System (INIS)

Ahdjoudj, S.; Kaabeche, K.; Holy, X.; Fromigue, O.; Modrowski, D.; Zerath, E.; Marie, P.J.

2005-01-01

The molecular mechanisms regulating the adipogenic differentiation of bone marrow stromal cells in vivo remain largely unknown. In this study, we investigated the regulatory effects of transforming growth factor beta-2 (TGF-β2) on transcription factors involved in adipogenic differentiation induced by hind limb suspension in rat bone marrow stromal cells in vivo. Time course real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis of gene expression showed that skeletal unloading progressively increases the expression of CCAAT/enhancer-binding protein (C/EBP)α and C/EBPβ α at 5 days in bone marrow stromal cells resulting in increased peroxisome proliferator-activated receptor γ (PPARγ2) transcripts at 7 days. TGF-β2 administration in unloaded rats corrected the rise in C/EBPα and C/EBPβ transcripts induced by unloading in bone marrow stromal cells. This resulted in inhibition of PPARγ2 expression that was associated with increased Runx2 expression. Additionally, the inhibition of C/EBPα and C/EBPβ expression by TGF-β2 was associated with increased PPARγ serine phosphorylation in bone marrow stromal cells, a mechanism that inhibits PPARγ transactivating activity. The sequential inhibitory effect of TGF-β2 on C/EBPα, C/EBPβ, and PPARγ2 resulted in reduced LPL expression and abolition of bone marrow stromal cell adipogenic differentiation, which contributed to prevent bone loss induced by skeletal unloading. We conclude that TGF-β2 inhibits the excessive adipogenic differentiation of bone marrow stromal cells induced by skeletal unloading by inhibiting C/EBPα, C/EBPβ, and PPARγ expression and activity, which provides a sequential mechanism by which TGF-β2 regulates adipogenic differentiation of bone marrow stromal cells in vivo

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

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Magome, Taiki [Department of Radiological Sciences, Faculty of Health Sciences, Komazawa University, Tokyo (Japan); Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota (United States); Department of Radiology, The University of Tokyo Hospital, Tokyo (Japan); Froelich, Jerry [Department of Radiology, University of Minnesota, Minneapolis, Minnesota (United States); Takahashi, Yutaka [Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota (United States); Department of Radiation Oncology, Osaka University, Osaka (Japan); Arentsen, Luke [Department of Therapeutic Radiology, University of Minnesota, Minneapolis, Minnesota (United States); Holtan, Shernan; Verneris, Michael R. [Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota (United States); Brown, Keenan [Mindways Software Inc, Austin, Texas (United States); Haga, Akihiro; Nakagawa, Keiichi [Department of Radiology, The University of Tokyo Hospital, Tokyo (Japan); Holter Chakrabarty, Jennifer L. [College of Medicine, Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Giebel, Sebastian [Department of Bone Marrow Transplantation, Comprehensive Cancer Center M. Curie-Sklodowska Memorial Institute, Gliwice (Poland); Wong, Jeffrey [Department of Radiation Oncology, Beckman Research Institute, City of Hope, Duarte, California (United States); Dusenbery, Kathryn [Department of Therapeutic Radiology, University of Minnesota, Minneapolis, Minnesota (United States); Storme, Guy [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Brussels (Belgium); Hui, Susanta K., E-mail: shui@coh.org [Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota (United States); Department of Therapeutic Radiology, University of Minnesota, Minneapolis, Minnesota (United States); Department of Radiation Oncology, Beckman Research Institute, City of Hope, Duarte, California (United States)

2016-11-01

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

Magnetic resonance imaging of the spinal marrow: Basic understanding of the normal marrow pattern and its variant

Science.gov (United States)

Nouh, Mohamed Ragab; Eid, Ahmed Fathi

2015-01-01

For now, magnetic resonance (MR) is the best noninvasive imaging modality to evaluate vertebral bone marrow thanks to its inherent soft-tissue contrast and non-ionizing nature. A daily challenging scenario for every radiologist interpreting MR of the vertebral column is discerning the diseased from normal marrow. This requires the radiologist to be acquainted with the used MR techniques to judge the spinal marrow as well as its normal MR variants. Conventional sequences used basically to image marrow include T1W, fat-suppressed T2W and short tau inversion recovery (STIR) imaging provides gross morphological data. Interestingly, using non-routine MR sequences; such as opposed phase, diffusion weighted, MR spectroscopy and contrasted-enhanced imaging; may elucidate the nature of bone marrow heterogeneities; by inferring cellular and chemical composition; and adding new functional prospects. Recalling the normal composition of bone marrow elements and the physiologic processes of spinal marrow conversion and reconversion eases basic understanding of spinal marrow imaging. Additionally, orientation with some common variants seen during spinal marrow MR imaging as hemangiomas and bone islands is a must. Moreover, awareness of the age-associated bone marrow changes as well as changes accompanying different variations of the subject’s health state is essential for radiologists to avoid overrating normal MR marrow patterns as pathologic states and metigate unnecessary further work-up. PMID:26753060

Effect of BCNU combined with total body irradiation or cyclophosphamide on survival of dogs after autologous marrow grafts

International Nuclear Information System (INIS)

Paterson, A.H.G.; English, D.

1979-01-01

Dogs were treated with either: (1) 750 rad total body irradiation; (2) BCNU 2 or 4 mg/kg IV 48 hours prior to 750 rad total body irradiation; or (3) BCNU 4 mg/kg IV plus cyclophosphamide 30 mg/kg IV. Results showed that of 11 dogs who received 750 rad total body irradiation and did not receive cryopreserved autologous bone marrow cells, none survived, compared to an 88% survival (31 of 35 dogs) after 750 rad total body irradiation if the dogs received stored autologous bone marrow cells. However, when the dogs were treated with BCNU 2 or 4 mg/kg prior to 750 rad total body irradiation the survival rate, despite infusion of autologous bone marrow cells, dropped to 25% (3 of 12 dogs) for BCNU 2 mg/kg, and 17% (2 of 12 dogs) for BCNU 4 mg/kg. This effect did not seem to be due to direct serum inhibition of hemopoietic cell proliferation since serum obtained at various intervals after BCNU administrations failed to inhibit CFU growth in vitro. The dogs died from hemorrhage and infection; at autopsy there was hemorrhagic pneumonitis and intestinal ulcerations with petechial hemorrhages, suggesting that the combination of BCNU and total body irradiation may have synergistic toxicity on the canine gastro-intestinal tract. When BCNU was combined with cyclophosphamide, reversal of marrow toxicity occurred in 54% (6 of 11 dogs) with stored autologous bone marrow cells compared to no survival (0 of 8 dogs) with stored autologous bone marrow cells. Thus while autologous bone marrow grafts are useful for reversal of marrow toxicity due to many therapeutic protocols, such grafts alone may not provide protection against toxicity due to the combination of high dosage BCNU and total body irradiation

13 CFR 120.611 - Pools backing Pool Certificates.

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Pools backing Pool Certificates. 120.611 Section 120.611 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Secondary Market Certificates § 120.611 Pools backing Pool Certificates. (a) Pool characteristics. As set...

Agar Technique for the Cultivation In Vitro of Bone-Marrow Colonies

Energy Technology Data Exchange (ETDEWEB)

Metcalf, D. [Walter and Eliza Hall Institute, Royal Melbourne Hospital, Melbourne, VIC (Australia)

1969-07-15

In solid-state agar cultures certain haemopoietic cells proliferate and form discrete colonies of 200 - 4000 cells. Colony formation is dependent on stimulation by the colony-stimulating factor, and this is achieved by (1) the use of a cell feeder layer, (2) the addition of conditioned medium, or (3) the addition of human or mouse serum or urine containing the factor. All colonies initially contain granulocytic cells which differentiate from myeloblasts to polymorphs as colony growth proceeds. Later colonies develop a second population of phagocytic mononuclear cells (macrophages). The colony-forming-system is simple, readily quantitated and highly reproducible. Linear dose responses occur between the dose of colony-stimulating factor and the number and size of colonies developing from a standard number of bone-marrow cells. In-vitro colony formation has been achieved with haemopoietic cells of the following species: mouse, rat, hamster, guinea pig, rabbit and human. In the adult mouse, colony-forming cells are located in the bone marrow, spleen and blood and in the embryo, in the yolk sac, liver and spleen. The colony-forming cell appears to be an early member of the granulocytic series. The colony-forming system has been used as a quantitative assay system: (1) to assay levels of colony-stimulating factor in serum and urine and in the chemical- characterization and purification of the factor; and (2) to enumerate the number of colony-forming cells in haemopoietic tissues in response to a variety of experimental procedures and disease states. Since the system is applicable to human bone-marrow cells, it should prove of value in the quantitative assay of (1) survival of human bone marrow on storage, and (2) bone-marrow content of granulocytic precursor cells in various disease states and following various types of therapy. The system is not suitable for the mass production in vitro of haemopoietic cells for therapeutic use. (author)

THE PATHOLOGY OF BONE MARROW FAILURE

OpenAIRE

Leguit , Roos; Van Den Tweel , Jan G

2010-01-01

Abstract An important indication for bone marrow investigation is the presence of bone marrow failure, which manifests itself as (pan)cytopenia. The causes of cytopenia are varied and differ considerable between childhood and adulthood. In the paediatric age group, inherited bone marrow failure syndromes are important causes of bone marrow failure but they play only a minor role in later life. This review gives a comprehensive overview of bone marrow failure disorders in children a...

A simple and efficient method for deriving neurospheres from bone marrow stromal cells

International Nuclear Information System (INIS)

Yang Qin; Mu Jun; Li Qi; Li Ao; Zeng Zhilei; Yang Jun; Zhang Xiaodong; Tang Jin; Xie Peng

2008-01-01

Bone marrow stromal cells (MSCs) can be differentiated into neuronal and glial-like cell types under appropriate experimental conditions. However, previously reported methods are complicated and involve the use of toxic reagents. Here, we present a simplified and nontoxic method for efficient conversion of rat MSCs into neurospheres that express the neuroectodermal marker nestin. These neurospheres can proliferate and differentiate into neuron, astrocyte, and oligodendrocyte phenotypes. We thus propose that MSCs are an emerging model cell for the treatment of a variety of neurological diseases

Mesenchymal Stem Cell Benefits Observed in Bone Marrow Failure and Acquired Aplastic Anemia

Science.gov (United States)

Gonzaga, Vivian Fonseca; Lisboa, Gustavo Sabino; Frare, Eduardo Osório

2017-01-01

Acquired aplastic anemia (AA) is a type of bone marrow failure (BMF) syndrome characterized by partial or total bone marrow (BM) destruction resulting in peripheral blood (PB) pancytopenia, which is the reduction in the number of red blood cells (RBC) and white blood cells (WBC), as well as platelets (PLT). The first-line treatment option of AA is given by hematopoietic stem cell (HSCs) transplant and/or immunosuppressive (IS) drug administration. Some patients did not respond to the treatment and remain pancytopenic following IS drugs. The studies are in progress to test the efficacy of adoptive cellular therapies as mesenchymal stem cells (MSCs), which confer low immunogenicity and are reliable allogeneic transplants in refractory severe aplastic anemia (SAA) cases. Moreover, bone marrow stromal cells (BMSC) constitute an essential component of the hematopoietic niche, responsible for stimulating and enhancing the proliferation of HSCs by secreting regulatory molecules and cytokines, providing stimulus to natural BM microenvironment for hematopoiesis. This review summarizes scientific evidences of the hematopoiesis improvements after MSC transplant, observed in acquired AA/BMF animal models as well as in patients with acquired AA. Additionally, we discuss the direct and indirect contribution of MSCs to the pathogenesis of acquired AA. PMID:29333168

Hedgehog-mediated paracrine interaction between hepatic stellate cells and marrow-derived mesenchymal stem cells

International Nuclear Information System (INIS)

Lin Nan; Tang Zhaofeng; Deng Meihai; Zhong Yuesi; Lin Jizong; Yang Xuhui; Xiang Peng; Xu Ruiyun

2008-01-01

During liver injury, bone marrow-derived mesenchymal stem cells (MSCs) can migrate and differentiate into hepatocytes. Hepatic stellate cell (SC) activation is a pivotal event in the development of liver fibrosis. Therefore, we hypothesized that SCs may play an important role in regulating MSC proliferation and differentiation through the paracrine signaling pathway. We demonstrate that MSCs and SCs both express hedgehog (Hh) pathway components, including its ligands, receptors, and target genes. Transwell co-cultures of SCs and MSCs showed that the SCs produced sonic hedgehog (Shh), which enhanced the proliferation and differentiation of MSCs. These findings demonstrate that SCs indirectly modulate the activity of MSCs in vitro via the Hh pathway, and provide a plausible explanation for the mechanisms of transplanted MSCs in the treatment of liver fibrosis

Comparison of fracture site callus with iliac crest bone marrow as the source of plastic-adherent cells

Directory of Open Access Journals (Sweden)

Achmad Zaki

2013-05-01

Full Text Available Background: Red marrow has been described as the main source of mesenchymal stem cells although its aspiration and isolation from bone marrow was reported to have significant donor site morbidity. Since secondary bone healing occurs through formation of callus as the result of proliferation and differentiation of mesenchymal stem cells, callus may become alternative source for mesenchymal stem cells. In this study, we compared the number of plastic-adherent cells from fracture site callus and bone marrow of iliac crest after two and four weeks of culture.Methods: Sixteen New Zealand rabbits were fracturized at the femoral shaft. Then, these rabbits were taken care. After two weeks of fracturization, 3 mL iliac crest bone marrow aspiration and callus extraction of eight rabbits were cultured (group I. The other eight rabbits were treated equally after four weeks of fracturization (group II. Simultaneously, the cultures were observed after one and two weeks. Four weeks later, they were harvested. Cells were counted using Neubauer hemocytometer. The average number of cells between the sources and groups were statistically analyzed using the unpaired t-test. Results: In group I, there were 2.6 ± 0.1 x 104 cells in the culture of iliac crest bone marrow aspirate and 2.5 ± 0.1 x 104 cells in culture of callus extract from fracture site (p = 0.34. In group II, there were 2.7 ± 0.1 x 104 cells and 2.1 ± 0.1 x 104 cells, respectively (p < 0.001.Conclusion: Fracture site callus at the second week post-fracturization may be potential as source of plastic-adherent cells compared with iliac crest bone marrow. (Med J Indones. 2013;22:70-5Keywords: Bone marrow, fracture site callus, iliac crest, long bone, mesenchymal stem cell, plastic-adherent cells

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

Science.gov (United States)

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

2016-04-01

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

Studies on the distribution of hematopoietic bone marrow by bone marrow scintigraphy, 3. The bone marrow scintigraphy with /sup 111/In-chloride

Energy Technology Data Exchange (ETDEWEB)

Fujimori, K [Kyoto Univ. (Japan). Faculty of Medicine

1976-04-01

A study was made to determine wheter or not bone marrow scintigraphy with /sup 111/In chloride delineates the real distribution of hematopoietic cells. In a patient with acute myelogenous luekemia at the stage of complete remission, there was a significant incorporation of /sup 111/In into bone marrow cells (20 - 28% compared with 6% in the controls). Incorporation of /sup 111/In into peripheral blood cells was 0 at after 10 hours and 5% to 6% after 7 days. The plasma disappearance curve of /sup 111/In consisted of 2 exponential components, one with a half-life of 6.5 to 9.5 hours followed by a slow component with a half-life of 20 to 30 hours. 5 to 7% of the injected dose was excreted in the urine in 24 hours. The distribution of active marrow was investigated with bone marrow scintigraphy in various hematological disorders and the results were compared with those obtained with sup(99m)Tc sulfur colloid. The results obtained in this study suggest that /sup 111/In is incorporated into erythroid precursors, and that this property of /sup 111/In makes in an ideal bone marrow scanning agent for observation of real hematopoietic bone marrow distribution in blood disease.

Delayed erythropoiesis in irradiated rats grafted with syngeneic marrow: effects of cytotoxic drugs and iron-deficiency anemia

International Nuclear Information System (INIS)

Rodday, P.; Bennett, M.; Vitalle, J.J.

1976-01-01

Erythropoiesis in spleens of lethally irradiated Lewis rats grafted with 4-35 x 10 6 syngeneic marrow cells was inhibited or delayed during the test period of 5 days; this was in marked contrast to observations in irradiated mice. The mechanism of this inhibition was the subject of this study. Pretreatment of recipients 9 days prior to irradiation with the cytotoxic drugs cyclophosphamide (CY), busulfan (BUS), or dimethylmyleran (DMM), or the induction of iron deficiency with anemia in recipients reversed this delayed erythropoiesis. However, neither iron-deficiency anemia nor pretreatment with BUS or DMM affected the ability of irradiated recipients to reject 20 to 50 x 10 6 allogeneic marrow cells. The administration of commercial preparations of erythropoietin to hosts stimulated erythropoiesis moderately. However, proliferation of syngeneic marrow cells was not enhanced when infused into lethally irradiated spontaneous hypertensive (SH) inbred-strain rats which have high levels of endogenous erythropoietin. Finally, plasma from irradiated rats treated with phenylhydrazine to produce severe anemia was rich in erythropoietin but failed to stimulate erythropoiesis in the cell transfer system. Two hypotheses are considered

Origanum vulgare leaf extract protects mice bone marrow cells against ionizing radiation

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Reza Ghasemnezhad Targhi

2016-11-01

Full Text Available Objective: Ionizing radiation produces free radicals which induce DNA damage and cell death. Origanum vulgare leaf extract (OVLE is a natural compound and its capability of scavenging free radicals and its antioxidant activity have been demonstrated by many researchers. In this study, using micronucleus assay, radioprotective effect of OVLE against clastogenic and cytotoxic effect of gamma irradiation has been investigated in mice bone marrow cells. Materials and Methods: OVLE was injected intraperitoneally to the BALB/c mice 1hr prior to gamma irradiation (3Gy at the doses of 100 and 200 mg/kg. Twenty four hours after irradiation or treatment, animals were killed and smears were prepared from the bone marrow cells. The slides were stained with May Grunwald–Giemsa method and analyzed microscopically. The frequency of micronucleated polychromatic erythrocytes (MnPCEs, micronucleated normochromatic erythrocyte (MnNCEs and cell proliferation ratio PCE/PCE+NCE (polychromatic erythrocyte/polychromatic erythrocyte + normochromatic erythrocyte were calculated. Results: The results showed that gamma irradiation (3Gy increased the frequency of MnPCEs, MnNCEs and  reduced the PCE/PCE+NCE ratio in mice bone marrow compared to the non-irradiated control group (p< 0.0001. Injection of OVLE significantly reduced the frequency of MnPCEs (p< 0.0001 and MnNCEs (p< 0.05 and increased the PCE/PCE+NCE ratio as compared to the irradiated control group (p< 0.05. Conclusion: It seems that OVLE with its antioxidant properties and its capability of scavenging free radicals and reactive oxygen species can reduce the cytotoxic effects of gamma irradiation in mice bone marrow cells.

Restoration of oligodendrocyte pools in a mouse model of chronic cerebral hypoperfusion.

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Jamie McQueen

Full Text Available Chronic cerebral hypoperfusion, a sustained modest reduction in cerebral blood flow, is associated with damage to myelinated axons and cognitive decline with ageing. Oligodendrocytes (the myelin producing cells and their precursor cells (OPCs may be vulnerable to the effects of hypoperfusion and in some forms of injury OPCs have the potential to respond and repair damage by increased proliferation and differentiation. Using a mouse model of cerebral hypoperfusion we have characterised the acute and long term responses of oligodendrocytes and OPCs to hypoperfusion in the corpus callosum. Following 3 days of hypoperfusion, numbers of OPCs and mature oligodendrocytes were significantly decreased compared to controls. However following 1 month of hypoperfusion, the OPC pool was restored and increased numbers of oligodendrocytes were observed. Assessment of proliferation using PCNA showed no significant differences between groups at either time point but showed reduced numbers of proliferating oligodendroglia at 3 days consistent with the loss of OPCs. Cumulative BrdU labelling experiments revealed higher numbers of proliferating cells in hypoperfused animals compared to controls and showed a proportion of these newly generated cells had differentiated into oligodendrocytes in a subset of animals. Expression of GPR17, a receptor important for the regulation of OPC differentiation following injury, was decreased following short term hypoperfusion. Despite changes to oligodendrocyte numbers there were no changes to the myelin sheath as revealed by ultrastructural assessment and fluoromyelin however axon-glial integrity was disrupted after both 3 days and 1 month hypoperfusion. Taken together, our results demonstrate the initial vulnerability of oligodendroglial pools to modest reductions in blood flow and highlight the regenerative capacity of these cells.

Non-circadian rhythm in proliferation of haematopoietic stem cells

International Nuclear Information System (INIS)

Necas, E.; Znojil, V.

1988-01-01

The proportion of haematopoietic stem cells (CFU-s) engaged in DNA synthesis was determined by means of the [ 3 H]-thymidine ([ 3 H]TdR) suicide technique during recovery of bone marrow from the damage caused by a sublethal total body irradiation. In contrast with previous reports the [ 3 H]TdR suicide rate was not permanently increased. It was observed that CFU-s passed through S phase in synchronous waves, following a dose of irradiation of 1.5 Gy. After a dose of 2.6 Gy, there was only one initial wave of increased CFU-s sensitivity to the action of [ 3 H]TdR. Following the depression occurring 26 hr after the irradiation with 2.6 Gy, the proportion of CFU-s killed by the [ 3 H]TdR was permanently increased until 5-6 days after irradiation. Thereafter large differences in the [ 3 H]TdR suicide data were observed among individual mice. Evidence was obtained that individual mice, which had been irradiated by a dose of 2.6 Gy 8-9 days before, had identical values of the CFU-s [ 3 H]TdR suicide rate in the bone marrow from different bones of the lower extremities. The recurrence of the synchronous waves in CFU-s passage through the cell cycle was recorded when the CFU-s population regenerated to only about 10% of its normal value. It is concluded that the synchronous waves in which CFU-s proliferation occurred reflected the action of the control mechanism on CFU-s proliferation. (author)

Non-circadian rhythm in proliferation of haematopoietic stem cells

Energy Technology Data Exchange (ETDEWEB)

Necas, E; Znojil, V [Charles Univ., Prague (Czechoslovakia). Faculty of Medicine

1988-03-01

The proportion of haematopoietic stem cells (CFU-s) engaged in DNA synthesis was determined by means of the (/sup 3/H)-thymidine ((/sup 3/H)TdR) suicide technique during recovery of bone marrow from the damage caused by a sublethal total body irradiation. In contrast with previous reports the (/sup 3/H)TdR suicide rate was not permanently increased. It was observed that CFU-s passed through S phase in synchronous waves, following a dose of irradiation of 1.5 Gy. After a dose of 2.6 Gy, there was only one initial wave of increased CFU-s sensitivity to the action of (/sup 3/H)TdR. Following the depression occurring 26 hr after the irradiation with 2.6 Gy, the proportion of CFU-s killed by the (/sup 3/H)TdR was permanently increased until 5-6 days after irradiation. Thereafter large differences in the (/sup 3/H)TdR suicide data were observed among individual mice. Evidence was obtained that individual mice, which had been irradiated by a dose of 2.6 Gy 8-9 days before, had identical values of the CFU-s (/sup 3/H)TdR suicide rate in the bone marrow from different bones of the lower extremities. The recurrence of the synchronous waves in CFU-s passage through the cell cycle was recorded when the CFU-s population regenerated to only about 10% of its normal value. It is concluded that the synchronous waves in which CFU-s proliferation occurred reflected the action of the control mechanism on CFU-s proliferation. (author).

Toll-Like Receptor 4 in Bone Marrow-Derived Cells Contributes to the Progression of Diabetic Retinopathy

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Hui Wang

2014-01-01

Full Text Available Diabetic retinopathy (DR is a major microvascular complication in diabetics, and its mechanism is not fully understood. Toll-like receptor 4 (TLR4 plays a pivotal role in the maintenance of the inflammatory state during DR, and the deletion of TLR4 eventually alleviates the diabetic inflammatory state. To further elucidate the mechanism of DR, we used bone marrow transplantation to establish reciprocal chimeric animals of TLR4 mutant mice and TLR4 WT mice combined with diabetes mellitus (DM induction by streptozotocin (STZ treatment to identify the role of TLR4 in different cell types in the development of the proinflammatory state during DR. TLR4 mutation did not block the occurrence of high blood glucose after STZ injection compared with WT mice but did alleviate the progression of DR and alter the expression of the small vessel proliferation-related genes, vascular endothelial growth factor (VEGF, and hypoxia inducible factor-1α (HIF-1α. Grafting bone marrow-derived cells from TLR4 WT mice into TLR4 mutant mice increased the levels of TNF-α, IL-1β, and MIP-2 and increased the damage to the retina. Similarly, VEGF and HIF-1α expression were restored by the bone marrow transplantation. These findings identify an essential role for TLR4 in bone marrow-derived cells contributing to the progression of DR.

Exercise Regulation of Marrow Adipose Tissue

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Gabriel M Pagnotti

2016-07-01

Full Text Available Despite association with low bone density and skeletal fractures, marrow adipose tissue (MAT remains poorly understood. The marrow adipocyte originates from the mesenchymal stem cell pool (MSC that gives rise also to osteoblasts, chondrocytes, and myocytes among other cell types. To date, the presence of MAT has been attributed to preferential biasing of MSC into the adipocyte rather than osteoblast lineage, thus negatively impacting bone formation. Here we focus on understanding the physiology of MAT in the setting of exercise, dietary interventions and pharmacologic agents that alter fat metabolism. The beneficial effect of exercise on musculoskeletal strength is known: exercise induces bone formation, encourages growth of skeletally-supportive tissues, inhibits bone resorption and alters skeletal architecture through direct and indirect effects on a multiplicity of cells involved in skeletal adaptation. MAT is less well studied due to the lack of reproducible quantification techniques. In recent work, osmium-based 3D quantification shows a robust response of MAT to both dietary and exercise intervention in that MAT is elevated in response to high fat diet and can be suppressed following daily exercise. Exercise-induced bone formation correlates with suppression of MAT, such that exercise effects might be due to either calorie expenditure from this depot, or from mechanical biasing of MSC lineage away from fat and toward bone, or a combination thereof. Following treatment with the anti-diabetes drug rosiglitazone - a PPARγ-agonist known to increase MAT and fracture risk - mice demonstrate a 5-fold higher femur MAT volume compared to the controls. In addition to preventing MAT accumulation in control mice, exercise intervention significantly lowers MAT accumulation in rosiglitazone-treated mice. Importantly, exercise induction of trabecular bone volume is unhindered by rosiglitazone. Thus, despite rosiglitazone augmentation of MAT, exercise

MR imaging of normal bone marrow

International Nuclear Information System (INIS)

Stajgis, M.; Paprzycki, W.

1994-01-01

Principles of MR bone marrow imaging on the basis of retrospective analysis of MR examinations of bone marrow in different anatomic sites in 200 patients have been discussed. Significance of different physiologic factors and processes such as age, steatosis, osteoporosis, conversion and reconversion, which influence on MR bone marrow images, have been emphasized. T1-weighted images obtained with spin-echo sequences give the most of information about bone marrow structure in MR. Thorough knowledge of bone marrow physiology and clinical status of the patient is indispensable in correct interpretation of hypointensive lesions on T1-weighted images. When presence of disseminated bone marrow disease is suspected, authors propose routine imaging of lumbar vertebral column, pelvis and proximal parts of femoral bones. (author)

Bone marrow edema of the knee joint

International Nuclear Information System (INIS)

Breitenseher, M.J.; Mayerhoefer, M.E.; Hofmann, S.

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.) [de

Effects of smoke and tea on radiation-induced bone marrow cell mutation and marrow inhibition

International Nuclear Information System (INIS)

Gao Yong; Zhang Weiguang

2004-01-01

Objective: To provide scientific information for the prevention and treatment of the radiation damage by analyzing the effects of smoke and tea on radiation-induced bone marrow cell mutation and marrow inhibition. Methods: 7 group mice were exposed to smoke and/or tea and/or radiation respectively. There were also b blank control group and a cyclophosphamide positive control group. The frequencies of micronucleated polychromatic erythrocytes (MPCE), the ratio of polychromatic erythrocytes (PCE) to mature erythrocytes (RBC) in marrow, and the count of peripheral blood hemoleukocyte were observed. Results: The frequencies of MPCE in the groups irradiated with γ-rays were significantly higher than that in the blank control group (P<0.05 or 0.01). The smoke + radiation group's frequency was significantly higher than single radiation group (P<0.05). The ratios of PCE to RBC in the groups irradiated were significantly lower than that in the blank control group (P<0.01). The counts of peripheral blood hemoleukocyte in the groups irradiated were significantly lower than the blank control group (P<0.01). Conclusion: Radiation were able to cause marrow cell mutation and induce marrow inhibition. Smoke increases the effect of radiation-induced marrow cell mutation. Tea and smoke could not affect radiation-induced bone marrow inhibition

Comparison of potentials between stem cells isolated from human anterior cruciate ligament and bone marrow for ligament tissue engineering.

Science.gov (United States)

Cheng, Ming-Te; Liu, Chien-Lin; Chen, Tain-Hsiung; Lee, Oscar K

2010-07-01

We have previously isolated and identified stem cells from human anterior cruciate ligament (ACL). The purpose of this study was to evaluate the differences in proliferation, differentiation, and extracellular matrix (ECM) formation abilities between bone marrow stem cells (BMSCs) and ACL-derived stem cells (LSCs) from the same donors when cultured with different growth factors, including basic fibroblast growth factor (bFGF), epidermal growth factor, and transforming growth factor-beta 1 (TGF-beta1). Ligament tissues and bone marrow aspirate were obtained from patients undergoing total knee arthroplasty and ACL reconstruction surgeries. Proliferation, colony formation, and population doubling capacity as well as multilineage differentiation potentials of LSCs and BMSCs were compared. Gene expression and ECM production for ligament engineering were also evaluated. It was found that BMSCs possessed better osteogenic differentiation potential than LSCs, while similar adipogenic and chondrogenic differentiation abilities were observed. Proliferation rates of both LSCs and BMSCs were enhanced by bFGF and TGF-beta1. TGF-beta1 treatment significantly increased the expression of type I collagen, type III collagen, fibronectin, and alpha-smooth muscle actin in LSCs, but TGF-beta1 only upregulated type I collagen and tenascin-c in BMSCs. Protein quantification further confirmed the results of differential gene expression and suggested that LSCs and BMSCs increase ECM production upon TGF-beta1 treatment. In summary, in comparison with BMSCs, LSCs proliferate faster and maintain an undifferentiated state with bFGF treatment, whereas under TGF-beta1 treatment, LSCs upregulate major tendinous gene expression and produce a robust amount of ligament ECM protein, making LSCs a potential cell source in future applications of ACL tissue engineering.

Sequential growth factor application in bone marrow stromal cell ligament engineering.

Science.gov (United States)

Moreau, Jodie E; Chen, Jingsong; Horan, Rebecca L; Kaplan, David L; Altman, Gregory H

2005-01-01

In vitro bone marrow stromal cell (BMSC) growth may be enhanced through culture medium supplementation, mimicking the biochemical environment in which cells optimally proliferate and differentiate. We hypothesize that the sequential administration of growth factors to first proliferate and then differentiate BMSCs cultured on silk fiber matrices will support the enhanced development of ligament tissue in vitro. Confluent second passage (P2) BMSCs obtained from purified bone marrow aspirates were seeded on RGD-modified silk matrices. Seeded matrices were divided into three groups for 5 days of static culture, with medium supplement of basic fibroblast growth factor (B) (1 ng/mL), epidermal growth factor (E; 1 ng/mL), or growth factor-free control (C). After day 5, medium supplementation was changed to transforming growth factor-beta1 (T; 5 ng/mL) or C for an additional 9 days of culture. Real-time RT-PCR, SEM, MTT, histology, and ELISA for collagen type I of all sample groups were performed. Results indicated that BT supported the greatest cell ingrowth after 14 days of culture in addition to the greatest cumulative collagen type I expression measured by ELISA. Sequential growth factor application promoted significant increases in collagen type I transcript expression from day 5 of culture to day 14, for five of six groups tested. All T-supplemented samples surpassed their respective control samples in both cell ingrowth and collagen deposition. All samples supported spindle-shaped, fibroblast cell morphology, aligning with the direction of silk fibers. These findings indicate significant in vitro ligament development after only 14 days of culture when using a sequential growth factor approach.

Endogenous GAS6 and Mer receptor signaling regulate prostate cancer stem cells in bone marrow.

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Jung, Younghun; Decker, Ann M; Wang, Jingcheng; Lee, Eunsohl; Kana, Lulia A; Yumoto, Kenji; Cackowski, Frank C; Rhee, James; Carmeliet, Peter; Buttitta, Laura; Morgan, Todd M; Taichman, Russell S

2016-05-03

GAS6 and its receptors (Tryo 3, Axl, Mer or "TAM") are known to play a role in regulating tumor progression in a number of settings. Previously we have demonstrated that GAS6 signaling regulates invasion, proliferation, chemotherapy-induced apoptosis of prostate cancer (PCa) cells. We have also demonstrated that GAS6 secreted from osteoblasts in the bone marrow environment plays a critical role in establishing prostate tumor cell dormancy. Here we investigated the role that endogenous GAS6 and Mer receptor signaling plays in establishing prostate cancer stem cells in the bone marrow microenvironment.We first observed that high levels of endogenous GAS6 are expressed by disseminated tumor cells (DTCs) in the bone marrow, whereas relatively low levels of endogenous GAS6 are expressed in PCa tumors grown in a s.c. Interestingly, elevated levels of endogenous GAS6 were identified in putative cancer stem cells (CSCs, CD133+/CD44+) compared to non-CSCs (CD133-/CD44-) isolated from PCa/osteoblast cocultures in vitro and in DTCs isolated from the bone marrow 24 hours after intracardiac injection. Moreover, we found that endogenous GAS6 expression is associated with Mer receptor expression in growth arrested (G1) PCa cells, which correlates with the increase of the CSC populations. Importantly, we found that overexpression of GAS6 activates phosphorylation of Mer receptor signaling and subsequent induction of the CSC phenotype in vitro and in vivo.Together these data suggest that endogenous GAS6 and Mer receptor signaling contribute to the establishment of PCa CSCs in the bone marrow microenvironment, which may have important implications for targeting metastatic disease.

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

International Nuclear Information System (INIS)

Colnot, C.; Huang, S.; Helms, J.

2006-01-01

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

Bone marrow adipocytes promote the regeneration of stem cells and hematopoiesis by secreting SCF

Science.gov (United States)

Zhou, Bo O.; Yu, Hua; Yue, Rui; Zhao, Zhiyu; Rios, Jonathan J.; Naveiras, Olaia; Morrison, Sean J.

2017-01-01

Endothelial cells and Leptin Receptor+ (LepR+) stromal cells are critical sources of haematopoietic stem cell (HSC) niche factors, including Stem Cell Factor (SCF), in bone marrow. After irradiation or chemotherapy, these cells are depleted while adipocytes become abundant. We discovered that bone marrow adipocytes synthesize SCF. They arise from Adipoq-Cre/ER+ progenitors, which represent ~5% of LepR+ cells, and proliferate after irradiation. Scf deletion using Adipoq-Cre/ER inhibited hematopoietic regeneration after irradiation or 5-fluorouracil treatment, depleting HSCs and reducing mouse survival. Scf from LepR+ cells, but not endothelial, hematopoietic, or osteoblastic cells, also promoted regeneration. In non-irradiated mice, Scf deletion using Adipoq-Cre/ER did not affect HSC frequency in long bones, which have few adipocytes, but depleted HSCs in tail vertebrae, which have abundant adipocytes. A-ZIP/F1 ‘fatless” mice exhibited delayed hematopoietic regeneration in long bones but not in tail vertebrae, where adipocytes inhibited vascularization. Adipocytes are a niche component that promotes hematopoietic regeneration. PMID:28714970

Distinct roles of the receptor tyrosine kinases c-ErbB and c-Kit in regulating the balance between erythroid cell proliferation and differentiation

NARCIS (Netherlands)

Wessely, O.; Mellitzer, G.; von Lindern, M.; Levitzki, A.; Gazit, A.; Ischenko, I.; Hayman, M. J.; Beug, H.

1997-01-01

In the bone marrow, multipotent and committed hematopoietic progenitors have to closely regulate their balance between sustained proliferation without differentiation (self renewal) and entering a terminal differentiation pathway. A useful model to analyze this regulation at the molecular level is

Diffusion chamber culture of mouse bone marrow cells, (1)

International Nuclear Information System (INIS)

Sigeta, Chiharu; Tanaka, Kimio; Kawakami, Masahito; Takahashi, Hiroshi; Ohkita, Takeshi

1980-01-01

Mouse bone marrow cells were cultured in diffusion chambers (DC) implanted in the peritoneal cavity of host mice. Host mice were subjected to (1) irradiation ( 60 Co 800 rad) and/or (2) phenylhydrazine induced anemia and then receiving irradiation ( 60 Co 600 rad). After culture periods of 3-7 days, the total number of cells in DC was increased. A marked increase in DC is due to the proliferation of granulocyte series. When host mice were subjected to anemia and irradiation, the start of cell proliferation in DC was delay about two days. On the whole, anemia and irradiation host reduced a little cell growth in DC. The number of immature granulocytes grown in DC in irradiated hosts or anemia and irradiated hosts increased and reached a plateu at day 5. During the plateu period, the proportions between immature and mature granulocytes in DC were kept constantly. The number of macrophages showed a two-phase increasing. Erythroid cells and lymphocytes rapidly disappeared from the chambers during 3 days. The number of erythroid cells was not significantly influenced even in anemia and irradiation hosts. (author)

Effects of marrow grafting on preleukemia cells and thymic nurse cells in C57BL/Ka mice after a leukemogenic split-dose irradiation

International Nuclear Information System (INIS)

Defresne, M.P.; Greimers, R.; Lenaerts, P.; Boniver, J.

1986-01-01

A split-dose regimen of whole-body irradiation (4 X 175 rad at weekly intervals) induced thymic lymphomas in C57BL/Ka mice after a latent period of 3-9 months. Meanwhile, preleukemia cells arose in the thymus and bone marrow and persisted until the onset of lymphomas. Simultaneously, thymic lymphopoiesis was impaired; thymocyte numbers were subnormal and thymic nurse cells disappeared in a progressive but irreversible fashion. The depletion of these lymphoepithelial complexes, which are normally involved in the early steps of thymic lymphopoiesis, was related to altered prothymocyte activity in bone marrow and to damaged thymic microenvironment, perhaps as a consequence of the presence of preleukemia cells. The grafting of normal bone marrow cells after irradiation prevented the development of lymphomas. However, marrow reconstitution did not inhibit the induction of preleukemia cells. They disappeared from the thymus during the second part of the latent period. At the same time, thymic lymphopoiesis was restored; thymocytes and nurse cell numbers returned to normal as a consequence of the proliferation of grafted marrow-derived cells within the thymus. The results thus demonstrated an intimate relationship between preleukemia cells and an alteration of thymic lymphopoiesis, which particularly involved the nurse cell microenvironment. Some preleukemia cells in marrow-reconstituted, irradiated mice derived from the unirradiated marrow inoculate. Thus these cells acquired neoplastic potential through a factor present in the irradiated tissues. The nature of this indirect mechanism was briefly discussed

Autologous bone marrow purging with LAK cells.

Science.gov (United States)

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

1993-12-01

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

Bone marrow-derived mesenchymal stem cells express the pericyte marker 3G5 in culture and show enhanced chondrogenesis in hypoxic conditions.

Science.gov (United States)

Khan, Wasim S; Adesida, Adetola B; Tew, Simon R; Lowe, Emma T; Hardingham, Timothy E

2010-06-01

Bone marrow-derived mesenchymal stem cells are a potential source of cells for the repair of articular cartilage defects. Hypoxia has been shown to improve chondrogenesis in some cells. In this study, bone marrow-derived stem cells were characterized and the effects of hypoxia on chondrogenesis investigated. Adherent bone marrow colony-forming cells were characterized for stem cell surface epitopes, and then cultured as cell aggregates in chondrogenic medium under normoxic (20% oxygen) or hypoxic (5% oxygen) conditions. The cells stained strongly for markers of adult mesenchymal stem cells, and a high number of cells were also positive for the pericyte marker 3G5. The cells showed a chondrogenic response in cell aggregate cultures and, in lowered oxygen, there was increased matrix accumulation of proteoglycan, but less cell proliferation. In hypoxia, there was increased expression of key transcription factor SOX6, and of collagens II and XI, and aggrecan. Pericytes are a candidate stem cell in many tissue, and our results show that bone marrow-derived mesenchymal stem cells express the pericyte marker 3G5. The response to chondrogenic culture in these cells was enhanced by lowered oxygen tension. This has important implications for tissue engineering applications of bone marrow-derived stem cells. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Biodiversity in intertidal rock pools: informing engineering criteria for artificial habitat enhancement in the built environment.

Science.gov (United States)

Firth, Louise B; Schofield, Meredith; White, Freya J; Skov, Martin W; Hawkins, Stephen J

2014-12-01

Coastal defence structures are proliferating to counter rising and stormier seas. With increasing concern about the ecological value of built environments, efforts are being made to create novel habitat to increase biodiversity. Rock pools are infrequent on artificial structures. We compared biodiversity patterns between rock pools and emergent rock and assessed the role of pool depth and substratum incline in determining patterns of biodiversity. Rock pools were more taxon rich than emergent substrata. Patterns varied with depth and incline with algal groups being more positively associated with shallow than deeper habitats. Substratum incline had little influence on colonising epibiota, with the exception of canopy algae in deeper habitats where vertical surfaces supported greater taxon richness than horizontal surfaces. The creation of artificial rock pools in built environments will have a positive effect on biodiversity. Building pools of varying depths and inclines and shore heights will provide a range of habitats, increase environmental heterogeneity, therefore creating more possible ecological niches, promoting local biodiversity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bone-marrow MR imaging before and after autologous marrow transplantation in lymphoma patients without known bone-marrow involvement

International Nuclear Information System (INIS)

Lien, H.H.; Blomlie, V.; Blystad, A.K.; Holte, H.; Kvaloey, S.; Langholm, R.

1997-01-01

Purpose: To study lumbar bone marrow by means of MR imaging before and after bone-marrow transplantation in lymphoma patients. Particular emphasis was paid to heterogeneity and to focal manifestations, i.e. appearances that could simulate tumor. Material and Methods: Twenty-two patients who were disease-free for a minimum of 30 months after transplantation were studied in 107 MR examinations. Two radiologists visually evaluated coronal T1-weighted and short inversion time inversion-recovery (STIR) images. Results: T1-weighted images demonstrated a more heterogeneous marrow after transplantation than before it. Sharply defined focal low signal intensity areas appeared on this sequence in 5 (23%) of the 22 patients at between 21 and 60 weeks after transplantation. The mean age of these 5 patients was 48.4 years (range 42-54 years). The difference in age between these 5 patients and the remaining 17 patients, who had a mean age of 33.4 years (range 14-51 years), was statistically significant (p<0.01, Student's t-test, 2-sided test). Conclusion: Sharply defined focal low signal intensity areas may be seen on T1-weighted images of bone marrow in patients who are in complete remission after transplantation, particularly in those aged over 40-45 years. (orig.)

Neural stem cells induce bone-marrow-derived mesenchymal stem cells to generate neural stem-like cells via juxtacrine and paracrine interactions

International Nuclear Information System (INIS)

Alexanian, Arshak R.

2005-01-01

Several recent reports suggest that there is far more plasticity that previously believed in the developmental potential of bone-marrow-derived cells (BMCs) that can be induced by extracellular developmental signals of other lineages whose nature is still largely unknown. In this study, we demonstrate that bone-marrow-derived mesenchymal stem cells (MSCs) co-cultured with mouse proliferating or fixed (by paraformaldehyde or methanol) neural stem cells (NSCs) generate neural stem cell-like cells with a higher expression of Sox-2 and nestin when grown in NS-A medium supplemented with N2, NSC conditioned medium (NSCcm) and bFGF. These neurally induced MSCs eventually differentiate into β-III-tubulin and GFAP expressing cells with neuronal and glial morphology when grown an additional week in Neurobasal/B27 without bFGF. We conclude that juxtacrine interaction between NSCs and MSCs combined with soluble factors released from NSCs are important for generation of neural-like cells from bone-marrow-derived adherent MSCs

Functional bone marrow scintigraphy in psoriatics

International Nuclear Information System (INIS)

Munz, D.; Altmeyer, P.; Chilf, G.; Schlesinger, G.; Holzmann, H.; Hoer, G.

1982-01-01

24 psoriatics as well as 24 normal healthy adults were studied by functional bone marrow scintigraphy using Tc-99m-labeled human serum albumin millimicrospheres (Tc-99m-HSA-MM). Functional bone marrow scintigraphy is an in vivo test system for the assessment of various functional properties of fixed macrophages. 58% of psoriatics who had no systemic drug treatment demonstrated peripheral extension of the bone marrow space indicating hyperplasia of bone marrow macrophages. This phenomenon could be observed only in one normal subject who was a high-performance sportsman. 83% (n=6) of psoriatics with cirrhosis of liver demonstrated bone marrow extension. The 'capacity' of bone marrow macrophages to engulf Tc-99m-HSA-MM ('uptake ratio') was diminished in 42% of non-treated as well as 66% of psoriatics treated with aromatic retinoid. The phagocytic and proteolytic turnover of Tc-99m-HSA-MM in bone marrow, spleen, and liver was found to be accelerated in 66% of non-treated psoriatics, normal, accelerated or delayed in psoriatics treated with aromatic retinoid as well as considerably delayed in all of the psoriatics with cirrhosis of liver. Functional bone marrow scintigraphy proved to be an appropriate in vivo test system to reveal abnormalities of fixed macrophages in psoriatics. Furthermore, theratpeutic effects as well as influences of pre-existing disorders on different macrophage populations can be assessed. (Author)

The Mitigating Effect of Citrullus colocynthis (L. Fruit Extract against Genotoxicity Induced by Cyclophosphamide in Mice Bone Marrow Cells

Directory of Open Access Journals (Sweden)

Mohammad Shokrzadeh

2013-01-01

Full Text Available Possible genoprotective effect of Citrullus colocynthis (L. (CCT fruits extract against cyclophosphamide- (CP-induced DNA damage in mice bone marrow cells was evaluated using micronucleus assay, as an index of induced chromosomal damage. Mice were preadministered with different doses of CCT via intraperitoneal injection for 7 consecutive days followed by injection with CP (70 mg/kg b.w. 1 hr after the last injection of CCT. After 24 hr, mice were scarified to evaluate the frequency of micronucleated polychromatic erythrocytes (MnPCEs. In addition, the number of polychromatic erythrocytes (PCEs among 1000 normochromatic erythrocytes (NCEs per animal was recorded to evaluate bone marrow. Pretreatment with CCT significantly reduced the number of MnPCEs induced by CP in bone marrow cells (P<0.0001. At 200 mg/kg, CCT had a maximum chemoprotective effect and reduced the number of MnPCEs by 6.37-fold and completely normalized the mitotic activity. CCT also led to marked proliferation and hypercellularity of immature myeloid elements after mice were treated with CP and mitigated the bone marrow suppression. Our study revealed that CCT has an antigenotoxic effect against CP-induced oxidative DNA damage in mice. Therefore, it could be used concomitantly as a supplement to protect people undergoing chemotherapy.

Elevated adipogenesis of marrow mesenchymal stem cells during early steroid-associated osteonecrosis development

Directory of Open Access Journals (Sweden)

Lee Kwong

2007-10-01

Full Text Available Abstract Background Increased bone marrow lipid deposition in steroid-associated osteonecrosis (ON implies that abnormalities in fat metabolism play an important role in ON development. The increase in lipid deposition might be explained by elevated adipogenesis of marrow mesenchymal stem cells (MSCs. However, it remains unclear whether there is a close association between elevated adipogenesis and steroid-associated ON development. Objective The present study was designed to test the hypothesis that there might be a close association between elevated adipogenesis and steroid-associated ON development. Methods ON rabbit model was induced based on our established protocol. Dynamic-MRI was employed for local intra-osseous perfusion evaluation in bilateral femora. Two weeks after induction, bone marrow was harvested for evaluating the ability of adipogenic differentiation of marrow MSCs at both cellular and mRNA level involving adipogenesis-related gene peroxisome proliferator-activated receptor gamma2 (PPARγ2. The bilateral femora were dissected for examining marrow lipid deposition by quantifying fat cell number, fat cell size, lipid deposition area and ON lesions. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON occurrence, the rabbits were divided into ON+ (with at least one ON lesion group and ON- (without ON lesion group. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON extension, the ON+ rabbits were further divided into sub-single-lesion group (SON group: with one ON lesion and sub-multiple-lesion group (MON group: with more than one ON lesion. Results Local intra-osseous perfusion index was found lower in either ON+ or MON group when compared to either ON- or SON group, whereas the marrow fat cells number and area were much larger in either ON+ or MON group as compared with ON- and SON group. The adipogenic differentiation

Bone marrow edema in sports: General concepts

International Nuclear Information System (INIS)

Vanhoenacker, F.M.; Snoeckx, A.

2007-01-01

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

Icariin-Loaded TiO2 Nanotubes for Regulation of the Bioactivity of Bone Marrow Cells

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Yanli Zhang

2018-01-01

Full Text Available To explore the effects of icariin on the biocompatibility of dental implants, icariin- (ICA- loaded TiO2 nanotubes were fabricated on Ti substrates via anodic oxidation and physical absorption. The surface characteristics of the specimens were monitored by field emission scanning electron microscopy (FE-SEM, X-ray diffractometry (XRD, contact angle measurements (CA, and high-pressure liquid chromatography. Additionally, the activities of bone marrow cells, such as cytoskeletal, proliferative activities, mineralization, and osteogenesis-related gene expression on the substrates were investigated in detail. The characterization results demonstrated that ICA-loaded TiO2 nanotubes were successfully fabricated and the hydrophilicity of these TiO2 nanotubes was significantly higher than that of the pure Ti groups. The results also showed that ICA-loaded TiO2 nanotubes might not have enhanced effects on cell proliferation and ALP expression. However, it seemed to significantly promote differentiation of bone marrow cells, demonstrated by enhancing the formation of mineralized nodule and the upregulation of the gene expression such as OC, BSP, OPN, and COL-1. The results indicated that ICA-loaded TiO2 nanotubes can modulate bioactivity of bone marrow cells, which is promising for potential applications in the orthopedics field.

Hawaii ESI: POOLS (Anchialine Pool Points)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for anchialine pools in Hawaii. Anchialine pools are small, relatively shallow coastal ponds that occur...

Magnetic resonance imaging of the bone marrow

International Nuclear Information System (INIS)

Baur-Melnyk, Andrea

2013-01-01

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.

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.

Cash pooling

OpenAIRE

Lozovaya, Karina

2009-01-01

This work makes a mention of cash management. At next chapter describes two most known theoretical models of cash management -- Baumol Model and Miller-Orr Model. Principal part of work is about cash pooling, types of cash pooling, cash pooling at Czech Republic and influence of cash pooling over accounting and taxes.

Human Stromal (Mesenchymal) Stem Cells from Bone Marrow, Adipose Tissue and Skin Exhibit Differences in Molecular Phenotype and Differentiation Potential

DEFF Research Database (Denmark)

Al-Nbaheen, May; Vishnubalaji, Radhakrishnan; Ali, Dalia

2013-01-01

Human stromal (mesenchymal) stem cells (hMSCs) are multipotent stem cells with ability to differentiate into mesoderm-type cells e.g. osteoblasts and adipocytes and thus they are being introduced into clinical trials for tissue regeneration. Traditionally, hMSCs have been isolated from bone marrow......, but the number of cells obtained is limited. Here, we compared the MSC-like cell populations, obtained from alternative sources for MSC: adipose tissue and skin, with the standard phenotype of human bone marrow MSC (BM-MSCs). MSC from human adipose tissue (human adipose stromal cells (hATSCs)) and human skin......, MSC populations obtained from different tissues exhibit significant differences in their proliferation, differentiation and molecular phenotype, which should be taken into consideration when planning their use in clinical protocols....

Effects and Complications of Bone-Marrow Transplantation in Man

Energy Technology Data Exchange (ETDEWEB)

Mathe, G.; Schwarzenberg, L.; Miel, J.L. A; Schneider, M.; Cattan, A.; Schlumberger, J. R. [Institut de cancerologie et immunogenetique, Hopital Paul Brousse, Villejuif (France)

1969-07-15

Full text: Allogenic bone-marrow grafting in 24 human leukaemic subjects is described. The graft failed in 7 cases and took in 17 cases. In the latter group, all 17 cases were complicated by the secondary syndrome which was-fatal in 13 cases and controlled in 4 cases. The immunogenetic and immunological factors determining the establishment and evolution of haematological radiochimeras in man are discussed. The choice of donor is fundamental. Three tests are effective in donor selection, the indirect histocompatibility test, the leucocyte antigen test and the reaction of donor and recipient leucocytes in the dermis of an irradiated hamster. When marrow from several donors is transfused, the recipient spontaneously selects the genetically nearest. It seems likely there is more chance of finding a suitable donor among genetically related subjects than among those who are unrelated. The frequency of graft take seems slightly lower in recipients who have previously received blood transfusions. Total bone-marrow graft is associated with specific tolerance towards donor tissues. This is paralleled by the production in the chimera of immunoglobulins produced by the graft. The secondary syndrome seems, as in animals, to be related essentially to the graft-versus-host reaction. It is convenient to distinguish among its various manifestations, on the one hand, those lesions which are readily controlled such as hepatitis or erythrodermia associated with infiltration and proliferation of immunologically competent cells from the graft and, on the other hand, immune insufficiency with regard to micro-organisms, especially viruses and Candida albicans. This latter group, the mechanism of which is complex, still eludes attempts at preventive and curative control. The use of multiple donors and the administration of cortisone during marrow transfusion and A-methopterin and/or cyclophosphamide in the days following transfusions; seem to have reduced the severity of the secondary

Intravascular Papillary Endothelial Hyperplasia Associated with Venous Pool Arising in the Lower Lip: A Case Report

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Hisanobu Yonezawa

2009-01-01

Full Text Available Intravascular papillary endothelial hyperplasia is a benign nonneoplastic vascular lesion that consists of endothelial cells with abundant vascular tissue with papillary proliferation. An adult female had a painless growing dark red nodule on the left side of the lower lip and often touched and gnawed at it for more than 4 years. The lesion was a tender, smooth mass approximately 1 cm in diameter without discoloration reaction. Magnetic resonance imaging of the lesion showed specific findings. She was diagnosed clinically as having mimicked hemangioma, and the lesion was totally excised under local anesthesia. Histopathological examination revealed that papillary proliferated endothelial cells with venous pool, and the lesion was diagnosed as intravascular papillary endothelial hyperplasia associated with venous pool. There has been no recurrence for more than 1 year. Despite the benign nature of this lesion, it could have been mistaken for a malignant tumor because of its clinical course and radiologic findings.

Anticancer Role of PPARγ Agonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes

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P. J. Simpson-Haidaris

2010-01-01

Full Text Available The use of targeted cancer therapies in combination with conventional chemotherapeutic agents and/or radiation treatment has increased overall survival of cancer patients. However, longer survival is accompanied by increased incidence of comorbidities due, in part, to drug side effects and toxicities. It is well accepted that inflammation and tumorigenesis are linked. Because peroxisome proliferator-activated receptor (PPAR-γ agonists are potent mediators of anti-inflammatory responses, it was a logical extension to examine the role of PPARγ agonists in the treatment and prevention of cancer. This paper has two objectives: first to highlight the potential uses for PPARγ agonists in anticancer therapy with special emphasis on their role when used as adjuvant or combined therapy in the treatment of hematological malignancies found in the vasculature, marrow, and eyes, and second, to review the potential role PPARγ and/or its ligands may have in modulating cancer-associated angiogenesis and tumor-stromal microenvironment crosstalk in bone marrow.

The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment

Science.gov (United States)

Greim, Helmut; Kaden, Debra A.; Larson, Richard A.; Palermo, Christine M.; Rice, Jerry M.; Ross, David; Snyder, Robert

2014-01-01

Hematopoietic stem cells (HSCs) are a unique population of somatic stem cells that can both self-renew for long-term reconstitution of HSCs and differentiate into hematopoietic progenitor cells, which in turn give rise, in a hierarchical manner, to the entire myeloid and lymphoid lineages. The differentiation and maturation of these lineages occurs in the bone marrow niche, a microenvironment that regulates self-renewal, survival, differentiation, and proliferation, with interactions among signaling pathways in the HSCs and the niche required to establish and maintain homeostasis. The accumulation of genetic mutations and cytogenetic abnormalities within cells of the partially differentiated myeloid lineage, particularly as a result of exposure to benzene or cytotoxic anticancer drugs, can give rise to malignancies like acute myeloid leukemia and myelodysplastic syndrome. Better understanding of the mechanisms driving these malignancies and susceptibility factors, both within hematopoietic progenitor cells and cells within the bone marrow niche, may lead to the development of strategies for prevention of occupational and cancer therapy–induced disease. PMID:24495159

Regeneration of hyaline-like cartilage in situ with SOX9 stimulation of bone marrow-derived mesenchymal stem cells

OpenAIRE

Zhang, Xiaowei; Wu, Shili; Naccarato, Ty; Prakash-Damani, Manan; Chou, Yuan; Chu, Cong-Qiu; Zhu, Yong

2017-01-01

Microfracture, a common procedure for treatment of cartilage injury, induces fibrocartilage repair by recruiting bone marrow derived mesenchymal stem cells (MSC) to the site of cartilage injury. However, fibrocartilage is inferior biomechanically to hyaline cartilage. SRY-type high-mobility group box-9 (SOX9) is a master regulator of chondrogenesis by promoting proliferation and differentiation of MSC into chondrocytes. In this study we aimed to test the therapeutic potential of cell penetrat...

MRI in bone marrow lesions

International Nuclear Information System (INIS)

Linden, A.; Theissen, P.; Schauerte, G.; Schicha, H.; Diehl, V.

1989-01-01

MRI has the potential to demonstrate bone marrow pathology due to its good soft tissue contrast. Inflammation and necrosis can be detected very early before there is evidence of radiological changes. In bone tumors intramedullary infiltration can be visualized in addition to soft tissue changes. Metastases of bone and bone marrow, especially in spinal and pelvic regions, are well depicted, often before bone scintigraphy yields pathological findings. In haematological disorders MRI permits follow-up studies due to its good reproducibility. Infiltration by malignant lymphoma and multiple myeloma and its extension in bone marrow can be visualized by MRI, too. However, the most common pathological MRI findings in bone marrow are not very specific, and final diagnosis requires further clinical or histological information. (orig.) [de

Effects of continuous and pulsatile PTH treatments on rat bone marrow stromal cells

International Nuclear Information System (INIS)

Yang Chiming; Frei, Hanspeter; Burt, Helen M.; Rossi, Fabio

2009-01-01

Bone marrow stromal cells (MSCs) differentiation and proliferation are controlled by numerous growth factors and hormones. Continuous parathyroid hormone (PTH) treatment has been shown to decrease osteoblast differentiation, whereas pulsatile PTH increases osteoblast differentiation. However, the effects of PTH treatments on MSCs have not been investigated. This study showed continuous PTH treatment in the presence of dexamethasone (DEX) promoted osteogenic differentiation of rat MSCs in vitro, as demonstrated by increased alkaline phosphatase (ALP) activity, number of ALP expressing cells, and up-regulation of PTH receptor-1, ALP, and osteocalcin mRNA expressions. In contrast, pulsatile PTH treatment was found to suppress osteogenesis of rat MSCs, possibly by promoting the maintenance of undifferentiated cells. Additionally, the observed effects of PTH were strongly dependent on the presence of DEX. MSC proliferation however was not influenced by PTH independent of treatment regimen and presence or absence of DEX. Furthermore, our work raised the possibility that PTH treatment may modulate stem/progenitor cell activity within MSC cultures.

Rotating three-dimensional dynamic culture of adult human bone marrow-derived cells for tissue engineering of hyaline cartilage.

Science.gov (United States)

Sakai, Shinsuke; Mishima, Hajime; Ishii, Tomoo; Akaogi, Hiroshi; Yoshioka, Tomokazu; Ohyabu, Yoshimi; Chang, Fei; Ochiai, Naoyuki; Uemura, Toshimasa

2009-04-01

The method of constructing cartilage tissue from bone marrow-derived cells in vitro is considered a valuable technique for hyaline cartilage regenerative medicine. Using a rotating wall vessel (RWV) bioreactor developed in a NASA space experiment, we attempted to efficiently construct hyaline cartilage tissue from human bone marrow-derived cells without using a scaffold. Bone marrow aspirates were obtained from the iliac crest of nine patients during orthopedic operation. After their proliferation in monolayer culture, the adherent cells were cultured in the RWV bioreactor with chondrogenic medium for 2 weeks. Cells from the same source were cultured in pellet culture as controls. Histological and immunohistological evaluations (collagen type I and II) and quantification of glycosaminoglycan were performed on formed tissues and compared. The engineered constructs obtained using the RWV bioreactor showed strong features of hyaline cartilage in terms of their morphology as determined by histological and immunohistological evaluations. The glycosaminoglycan contents per microg DNA of the tissues were 10.01 +/- 3.49 microg/microg DNA in the case of the RWV bioreactor and 6.27 +/- 3.41 microg/microg DNA in the case of the pellet culture, and their difference was significant. The RWV bioreactor could provide an excellent environment for three-dimensional cartilage tissue architecture that can promote the chondrogenic differentiation of adult human bone marrow-derived cells.

MR imaging of bone marrow disorders

International Nuclear Information System (INIS)

Yoshida, H.; Mano, I.; Yashiro, N.; Asai, S.; Lio, M.

1986-01-01

The author performed MR imaging in 89 patients with bone marrow disorders (29 with aplastic anemia, 20 with leukemia, 9 with postirradiation changes, 8 with hemosiderosis, 6 with primary bone tumors and metastases, and 17 with bone marrow disorders of other etiologies). They selected the thoracic and lumbar vertebral marrow as a target and used both T1-weighted spin-echo images and calculated T1 images. T1 was prolonged in bone marrow hyperplasia but shortened in hypoplasia. Bone marrow T1 values proved to depend on the number of fat cells (pathologic correlation). In aplastic anemia scattered islands of low signal intensity were seen within a background of high signal intensity in some typical cases. MR imaging patterns were used for staging aplastic anemia. T1 was prolonged in leukemia cells

Stimulation of murine stem cell proliferation by circulating activities produced during the recovery of a radiation-induced hematopoietic injury. Estimulacion proliferativa de celulas madre hematopoyeticas de raton por actividades circulantes producidas durante la recuperacion de un dano hematopoyetico radioinducido

Energy Technology Data Exchange (ETDEWEB)

Grande Azanedo, M.T.

1989-02-01

The proliferative activity of CFU-S, low in normal steady state, increases after treatment with different aggressors, i.e., radiation. This stimulation has been attributed in part to a local regulation system of stem cell proliferation, and at least in part to a humoral regulatory system. In the present work it has been investigated the role that circulating activities have in the CFU-S stimulation, by means of in vitro and in vivo incubation assays with diffusion chambers. The results show that bone marrow of mice irradiated with 5 Gy produces in vitro diffusible activities capable of stimulating the CFU-S proliferation. As well with this same dose circulating activities are also produced in vivo. In addition we have observed that these activities are only released during the periods of active hematopoietic regeneration that follow irradiation with moderate doses (1.5 and 5 Gy). In another set of experiments we saw that the stimulating activities are also detected in serum of mice irradiated with 5 Gy. These serum activities modify the proliferative state of very primitive precursors (12 d CFU-S). When the serum activities are added to long term bone marrow cultures the CFU-S are also stimulated to proliferate. Finally, we observed that the radiation-induced serum activities stimulate the proliferation of bone marrow CFU-S when injected into normal mice, suggesting that such activities are involved in the regulation of CFU-S proliferation.

Mastocytosis: magnetic resonance imaging patterns of marrow disease

International Nuclear Information System (INIS)

Avila, N.A.; Ling, A.; Metcalfe, D.D.; Worobec, A.S.

1998-01-01

Objective. To report the bone marrow MRI findings of patients with mastocytosis and correlate them with clinical, pathologic, and radiographic features. Design and patients. Eighteen patients with mastocytosis had T1-weighted spin echo and short tau inversion recovery MRI of the pelvis at 0.5 T. In each patient the MR pattern of marrow disease was classified according to intensity and uniformity and was correlated with the clinical category of mastocytosis, bone marrow biopsy results, and radiographic findings. Results. Two patients had normal MRI scans and normal bone marrow biopsies. One patient had a normal MRI scan and a marrow biopsy consistent with mastocytosis. Fifteen patients had abnormal MRI scans and abnormal marrow biopsies. There were several different MR patterns of marrow involvement; none was specifically associated with any given clinical category of mastocytosis. Fifteen of the 18 patients had radiographs of the pelvis; of those, 13 with abnormal MRI scans and abnormal marrow biopsies had the following radiographic findings: normal (nine); sclerosis (three); diffuse osteopenia (one). Conclusion. While radiographs are very insensitive for the detection of marrow abnormalities in mastocytosis, MRI is very sensitive and may display several different patterns of marrow involvement. (orig.)

EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

International Nuclear Information System (INIS)

Huang, Er-Wen; Xue, Sheng-Jiang; Li, Xiao-Yan; Xu, Suo-Wen; Cheng, Jian-Ding; Zheng, Jin-Xiang; Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong; Li, Jie; Liu, Chao

2014-01-01

Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma

EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

Energy Technology Data Exchange (ETDEWEB)

Huang, Er-Wen [Guangzhou Institute of Forensic Science, Guangzhou (China); Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Xue, Sheng-Jiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Li, Xiao-Yan [Department of Pharmacy, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Xu, Suo-Wen [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Cheng, Jian-Ding; Zheng, Jin-Xiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong [Guangzhou Institute of Forensic Science, Guangzhou (China); Li, Jie, E-mail: mdlijie@sina.com [Department of Anaesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Liu, Chao, E-mail: liuchaogaj@21cn.com [Guangzhou Institute of Forensic Science, Guangzhou (China)

2014-05-02

Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.

miRNA analysis in B-cell chronic lymphocytic leukaemia : proliferation centres characterized by low miR-150 and high BIC/milk-155 expression

NARCIS (Netherlands)

Wang, M.; Tan, L. P.; Dijkstra, M. K.; van Lom, K.; Robertus, J-L; Harms, G.; Blokzijl, T.; Kooistra, K.; van t'Veer, M. B.; Rosati, S.; Visser, L.; Jongen-Lavrencic, M.; Kluin, P. M.; van den Berg, Anke

Several miRNAs have been reported to be associated with immunoglobulin heavy chain (IgH) mutation and ZAP-70 expression status in blood samples of B-cell chronic lymphocytic leukaemia/small lymphocytic lymphoma (B-CLL/SLL). In the bone marrow and lymphoid tissues, proliferation centres (PCs)

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

International Nuclear Information System (INIS)

Peña, Jaime A.; Damm, Timo; Bastgen, Jan; Barkmann, Reinhard; Glüer, Claus C.; Thomsen, Felix; Campbell, Graeme M.

2016-01-01

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

Magnetic resonance imaging of bone marrow disease in children

International Nuclear Information System (INIS)

Cohen, M.D.; Klatte, E.C.; Baehner, R.

1984-01-01

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

Genetics Home Reference: Pearson marrow-pancreas syndrome

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... Health Conditions Pearson marrow-pancreas syndrome Pearson marrow-pancreas syndrome Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Pearson marrow-pancreas syndrome is a severe disorder that usually begins ...

Dominance and persistence of donor marrow in long-lived allogeneic radiation chimeras obtained with unmanipulated bone marrow

International Nuclear Information System (INIS)

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

1983-01-01

Allogeneic, H-2-incompatible irradiation chimeras (H-2sup(d) → H-2sup(b)) constructed with normal, unmanipulated bone marrow and with marrow-derived factors live long and do not manifest a GvH disease. Their response to primary immunization is deficient but their alloreactivity is normal. This chimeric allotolerance cannot be passively transferred from chimeric donors to normal irradiated recipients. Passive transfer of both donor- or recipient-type immuno-competent T-cells into the chimeric mice does not lead to syngeneic reconstitution, rejection of the engrafted marrow or GvH disease, and the mice maintain permanently their chimerism. This new model demonstrates that chimerism is not eradicable in long-lived chimeras reconstituted with unmanipulated bone marrow, and that the bone marrow itself plays a dominant role in maintenance of chimerism. (Auth.)

In vitro proliferation of haemopoietic cells in the presence of adherent cell layers. II. Differential effect of adherent cell layers derived from various organs

NARCIS (Netherlands)

Reimann, J.; Burger, H.

1979-01-01

Mouse bone marrow-derived adherent cell populations promoted proliferation of haemopoietic cells in vitro in a liquid culture system for at least 4 weeks. Adherent cell layers derived from other haemopoietic organs (foetal liver, adult spleen) and fibroblasts from embryonic tissues did not maintain

Developmental and radiobiologic characteristics of canine multinucleated, osteoclast-like cells generated in vitro from canine bone marrow

International Nuclear Information System (INIS)

Seed, T.M.; Kaspar, L.V.; Domann, F.; Niiro, G.K.; LeBuis, D.A.

1988-01-01

We report here our initial observations on the growth and morphology, and developmental radiosensitivity of giant, multinucleated, osteoclast-like cells (MN-OS) generated through in vitro cultivation of hematopoietic progenitor-enriched canine bone marrow samples. Maximum cell densities of 5.5 x 10(3) to 6.5 x 10(3) MN-OS per cm2 of growth area were achieved following 10 to 14 days of culture at 37 degrees C. Acute gamma irradiation of the initial marrow inocula resulted in significant, dose-dependent perturbations of MN-OS formation, growth, and development. Attempts to estimate radiosensitivity of MN-OS progenitors from canine marrow yielded a range of Do values from a low of 212 cGy measured at six days of culture to higher values of 405 to 542 cGy following 10 to 22 days of culture. At the intermediate times of culture (10 to 14 days), the radiation-induced responses were clearly biphasic, reflecting either (a) the presence of multiple subpopulations of MN-OS progenitors with varying degrees of radiosensitivity or (b) the inherent biphasic nature of MN-OS development involving early progenitor cell proliferation followed by maturation and subsequent fusion. Morphologically, MN-OS generated from irradiated marrow inocula appeared only marginally altered, with alterations expressed largely in a biphasic, dose-dependent fashion in terms of smaller cell size, reduced number of nuclei, increased expression of both surface microprojections, and a unique set of crystalloid cytoplasmic inclusions. Functionally, MN-OS appeared to be impaired by irradiation of marrow progenitors, as evidenced by failure to initiate resorptive attachments to devitalized bone spicules in vitro

Bone marrow-derived mesenchymal stem cells propagate immunosuppressive/anti-inflammatory macrophages in cell-to-cell contact-independent and -dependent manners under hypoxic culture.

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Takizawa, Naoki; Okubo, Naoto; Kamo, Masaharu; Chosa, Naoyuki; Mikami, Toshinari; Suzuki, Keita; Yokota, Seiji; Ibi, Miho; Ohtsuka, Masato; Taira, Masayuki; Yaegashi, Takashi; Ishisaki, Akira; Kyakumoto, Seiko

2017-09-15

Immunosuppressive/anti-inflammatory macrophage (Mφ), M2-Mφ that expressed the typical M2-Mφs marker, CD206, and anti-inflammatory cytokine, interleukin (IL)-10, is beneficial and expected tool for the cytotherapy against inflammatory diseases. Here, we demonstrated that bone marrow-derived lineage-positive (Lin+) blood cells proliferated and differentiated into M2-Mφs by cooperation with the bone marrow-derived mesenchymal stem cells (MSCs) under hypoxic condition: MSCs not only promoted proliferation of undifferentiated M2-Mφs, pre-M2-Mφs, in the Lin+ fraction via a proliferative effect of the MSCs-secreted macrophage colony-stimulating factor, but also promoted M2-Mφ polarization of the pre-M2-Mφs through cell-to-cell contact with the pre-M2-Mφs. Intriguingly, an inhibitor for intercellular adhesion molecule (ICAM)-1 receptor/lymphocyte function-associated antigen (LFA)-1, Rwj50271, partially suppressed expression of CD206 in the Lin+ blood cells but an inhibitor for VCAM-1 receptor/VLA-4, BIO5192, did not, suggesting that the cell-to-cell adhesion through LFA-1 on pre-M2-Mφs and ICAM-1 on MSCs was supposed to promoted the M2-Mφ polarization. Thus, the co-culture system consisting of bone marrow-derived Lin+ blood cells and MSCs under hypoxic condition was a beneficial supplier of a number of M2-Mφs, which could be clinically applicable to inflammatory diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Bone Marrow Transplantation: MedlinePlus Health Topic

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... marrow transplant - discharge (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Bone Marrow Transplantation ... transplant - slideshow Graft-versus-host disease Related Health Topics Bone Marrow Diseases Stem Cells National Institutes of ...

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

Science.gov (United States)

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

2018-02-01

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

Studies on the distribution of hematopoietic bone marrow by bone marrow scintigraphy, 1

International Nuclear Information System (INIS)

Fujimori, Katsuhiko

1976-01-01

In 42 patients with hypoplastic anemia, 10 mCi of sup(99m)Tc sulfur colloid was injected intravenously, and scanning was performed one hour later with a Pho/Gamma III scintillation camera. Active bone marrow was usually found in the sternum, vertebrae, pelvis, and the poximal ends of humeri and femurs. These 42 cases were classified into 5 types according to distribution pattern. Type 1 (4 cases) showed complete lack of sup(99m)Tc activity in the usual marrow sites. Ferrokinetic studies indicated remarkable erythropoietic hypofunction. Type 2 (18 cases) showed island-like distribution of marrow in the pelvis or in the heads of humeri and femurs. Type 3 (6 cases) showed approximately normal uptake of sup(99m)Tc sulfur colloid in the sternum and the vertebrae, but no activity in the pelvis; or showed the apposite distribution. Marrow specimens obtained from the sternum and the pelvis showed differences in cellularity in such cases. Type 4 (8 cases) were divided into two groups, A and B. Four patients of group A showed decreased uptake of the colloid in the usual marrow sites, but expanded marrow extending into distal femous, proximal and distal tibiae and bones of the feet. These patients subsequently developed leukemia. The diagnosis was confirmed at autopsy or when leukemic features appeared during the clinical course. The remaining cases, group B, showed island-like sup(99m)Tc activity in the tibia. Until then, there had been no signs of leukemia. Type 5 (6 cases) showed normal distribution with below-normal uptake. It is concluded that the reduction of hematopoietic tissue mass is the main cause of decreased hematopoiesis in hypoplastic anemia. (J.P.N.)

The Effects of Sertoli Cells Condition Medium and Retinoic Acid on the Number of Colonies of Bone Marrow Mesenchymal Stem Cells

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Maryam Salem

2017-04-01

Full Text Available Background & objectives: According to importance of bone marrow mesenchymal stem cells in production of different cell lines, transplantation of these cells are used for treatment of many different diseases during cell therapy. Viability and proliferation of these cells after transplantation are very important. Since infertility is as public health problem in men and women, the scientists attempt to produce germ cells from differentiation of stem cells. It is supposed to use these cells for treatment of different illnesses especially for men with lack of germ cells in testes in future. However, in using stem cells for cell therapy the culture medium should be designed to increase the number of cells and efficiency of transplantation and to guarantee the health of the cells in terms of DNA damage. This study designed a suitable culture medium in order to increase the number of colonies and decrease the cell injuries. Methods: In this study mesenchymal stem cells isolated from bone marrow of mice and exposed to retinoic acid (RA with concentration of 10-6 M and Sertoli cells condition medium. Since mesenchymal stem cells (MSCs produce fibroblastic colonies so the number of colonies was counted every 3 days after culture (days of 2, 5, 8, 11, and 15 under inverted microscope. The staining of ethidium bromide-acridine orange was also done for determination of apoptotic nucleus in days of 10 and 15 after culture. Results: The results showed that the effects of retinoic acid on grow and viability of MSCs is related to the time. It seems that RA increased the proliferation of the cells and the number of colonies increased in low time but the apoptotic cells elevated with increasing the time of culture. Condition medium of Sertoli cells also increased the proliferation of bone marrow stem cells. Conclusion: According to proliferative properties of condition medium, it seems that using condition medium together with RA is better than RA alone for

Bone marrow scintigraphy with 111In-chloride

International Nuclear Information System (INIS)

Kan, Masayasu; Miyamae, Tatsuya

1977-01-01

111 In-chloride as a useful bone marrow-scanning agent has been used for various hematological diseases. We also have studied the distribution of indium-111 by scintigraphy in 28 patients with systemic hematopoietic disorders and other: 4 with aplastic anemia, 8 with leucemia, 3 with iron-deficiency anemia, one with pernicious anemia, 2 with myelofibrosis, 3 with multiple myeloma, one with malignant lymphoma, 3 with liver cirrhosis or Banti-syndrome and 3 with seminoma received post operative irradiation. The results of scintigraphy (the image of bone marrow, liver, spleen, kidney and intestine) were compared with bone marrow biopsies, ferrokinetic data and Se.I./TIBC. The bone marrow image was interpreted on a three-point scale: normal distribution of activity (+), abnormal distribution (+-), body back ground level (-). In the cases of iron-deficiency anemia and pernicious anemia with hyperplastic erythroid marrow, regardless of its severe anemia, the scintigrams showed clearly delineated bone marrow images and normal organ distribution of indium. On the other hand, the scan images revealed severe suppressions of bone marrow activity and markedly increased renal activity in some cases of aplastic anemia, acute leucemia and malignant lymphoma with hypoplastic and/or tumour-cell infiltrative marrows. Thus, it may be said that the bone marrow uptake of indium-111 correlates well with the degree of erythroid elements, no correlation with nucleated cell counts, and there is a strong tendency to increased renal activity in the cases of markedly decreased erythropoietic cell counts. (auth.)

Bone marrow scintigraphy with 111In-chloride

International Nuclear Information System (INIS)

Aburano, Tamio; Ueno, Kyoichi; Sugihara, Masami; Tada, Akira; Tonami, Norihisa

1977-01-01

It is assumed that 111 In-chloride is bound to serum transferrin and then transported into reticulocyte in erythropoietic marrow. However, several biochemical differences between radioiron and 111 In have been reported since these years. In present study, clinical usefulness of 111 In-chloride bone marrow scintigraphy was examined especially by comparing 111 In-chloride image with sup(99m)Tc-colloid. Obtained results are as follows: 1) In most cases, both 111 In-chloride and sup(99m)Tc-colloid images showed similar bone marrow distributions. 2) In three out of 7 cases with hypoplastic anemia and two patients with bone marrow irradiation (700-1,000 rad), the central marrow or irradiated marrow showed marked decreased uptake of 111 In, and showed normal uptake of sup(99m)Tc. 3) In two out of 3 cases with chronic myelogenous leucemia, central marrow showed normal uptake of 111 In, and showed decreased uptake of sup(99m)Tc. From the present study, the same dissociation findings as those between radioiron and radiocolloid could be obtained in hypoplastic anemia and bone marrow irradiation. 111 In-chloride would appear to be a useful erythropoietic imaging agent, although further study of exact comparison with radioiron should be necessary. (auth.)

Bone-marrow transplant - series (image)

Science.gov (United States)

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

The separation of a mixture of bone marrow stem cells from tumor cells: an essential step for autologous bone marrow transplantation

International Nuclear Information System (INIS)

Rubin, P.; Wheeler, K.T.; Keng, P.C.; Gregory, P.K.; Croizat, H.

1981-01-01

KHT tumor cells were mixed with mouse bone marrow to simulate a sample of bone marrow containing metastatic tumor cells. This mixture was separated into a bone marrow fraction and a tumor cell fraction by centrifugal elutriation. Elutriation did not change the transplantability of the bone marrow stem cells as measured by a spleen colony assay and an in vitro erythroid burst forming unit assay. The tumorogenicity of the KHT cells was similarly unaffected by elutriation. The data showed that bone marrow cells could be purified to less than 1 tumor cell in more than 10 6 bone marrow cells. Therefore, purification of bone marrow removed prior to lethal radiation-drug combined therapy for subsequent autologous transplantation appears to be feasible using modifications of this method if similar physical differences between human metastatic tumor cells and human bone marrow cells exist. This possibility is presently being explored

Bone marrow adipocytes promote the regeneration of stem cells and haematopoiesis by secreting SCF.

Science.gov (United States)

Zhou, Bo O; Yu, Hua; Yue, Rui; Zhao, Zhiyu; Rios, Jonathan J; Naveiras, Olaia; Morrison, Sean J

2017-08-01

Endothelial cells and leptin receptor + (LepR + ) stromal cells are critical sources of haematopoietic stem cell (HSC) niche factors, including stem cell factor (SCF), in bone marrow. After irradiation or chemotherapy, these cells are depleted while adipocytes become abundant. We discovered that bone marrow adipocytes synthesize SCF. They arise from Adipoq-Cre/ER + progenitors, which represent ∼5% of LepR + cells, and proliferate after irradiation. Scf deletion using Adipoq-Cre/ER inhibited haematopoietic regeneration after irradiation or 5-fluorouracil treatment, depleting HSCs and reducing mouse survival. Scf from LepR + cells, but not endothelial, haematopoietic or osteoblastic cells, also promoted regeneration. In non-irradiated mice, Scf deletion using Adipoq-Cre/ER did not affect HSC frequency in long bones, which have few adipocytes, but depleted HSCs in tail vertebrae, which have abundant adipocytes. A-ZIP/F1 'fatless' mice exhibited delayed haematopoietic regeneration in long bones but not in tail vertebrae, where adipocytes inhibited vascularization. Adipocytes are a niche component that promotes haematopoietic regeneration.

The inward rectifier potassium channel Kir2.1 is expressed in mouse neutrophils from bone marrow and liver.

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Masia, Ricard; Krause, Daniela S; Yellen, Gary

2015-02-01

Neutrophils are phagocytic cells that play a critical role in innate immunity by destroying bacterial pathogens. Channels belonging to the inward rectifier potassium channel subfamily 2 (Kir2 channels) have been described in other phagocytes (monocytes/macrophages and eosinophils) and in hematopoietic precursors of phagocytes. Their physiological function in these cells remains unclear, but some evidence suggests a role in growth factor-dependent proliferation and development. Expression of functional Kir2 channels has not been definitively demonstrated in mammalian neutrophils. Here, we show by RT-PCR that neutrophils from mouse bone marrow and liver express mRNA for the Kir2 subunit Kir2.1 but not for other subunits (Kir2.2, Kir2.3, and Kir2.4). In electrophysiological experiments, resting (unstimulated) neutrophils from mouse bone marrow and liver exhibit a constitutively active, external K(+)-dependent, strong inwardly rectifying current that constitutes the dominant current. The reversal potential is dependent on the external K(+) concentration in a Nernstian fashion, as expected for a K(+)-selective current. The current is not altered by changes in external or internal pH, and it is blocked by Ba(2+), Cs(+), and the Kir2-selective inhibitor ML133. The single-channel conductance is in agreement with previously reported values for Kir2.1 channels. These properties are characteristic of homomeric Kir2.1 channels. Current density in short-term cultures of bone marrow neutrophils is decreased in the absence of growth factors that are important for neutrophil proliferation [granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF)]. These results demonstrate that mouse neutrophils express functional Kir2.1 channels and suggest that these channels may be important for neutrophil function, possibly in a growth factor-dependent manner. Copyright © 2015 the American Physiological Society.

Differentiation of B and T lymphocytes from precursor cells resident in the bone marrow

Energy Technology Data Exchange (ETDEWEB)

Rosse, C; Press, O W

1978-01-01

A series of experiments in guinea pigs and mice established that proliferating progenitor cells for B and T lymphocytes are a resident population in the bone marrow. It was shown by the combined use of /sup 3/H-TdR radioautography and fluorescent-antibody staining of B and T cells that the majority of bone marrow (BM) lymphocytes are rapidly renewed (RR) B cells and null cells, whereas the thymus (THY) consists overwhelming of RR T lymphocytes; in spleen (SPL) and lymph node (LN) slowly renewed (SR) T and B cells predominate. The rate of B cell turnover in guinea pig bone marrow exceeds that in the SPL or LN, and the appearance of newly generated B cells in the SPL lags behind that in the BM. When systematically administered /sup 3/H-TdR was excluded by tourniquets from tibial and femoral BM no labeled B cells appeared in tibial or femoral marrow over 72 h. When tibial and femoral BM was labeled selectively with /sup 3/H-TdR, labeled B cells appeared in the SPL and LN over 72 h. (It was found in CBA mice that BM cell fractions enriched in lymphocytes (BML) responded to the T cell mitogen PHA in a manner qualitatively different from the response of SPL and LN cells. Experiments with athymic nude mice and with complement-mediated lysis of T and B cells established that PHA responsive cells in SPL and LN were T cells but in BML they were null lymphocytes. Target cells of PHA in BML responded to the mitogen by the generation of T-cell surface markers and blastogenesis; therefore they were identified as pre-T cells. BM pre-T cells are rapidly renewed and, in contrast to PHA responsive cells of SPL and LN, do not recirculate from blood to lymph. Both B and pre-T cells in the BM are division products of transitional cells. Among transitional cells of the marrow are included the progenitors of B and T lmyphhocytes and of all other types of hemopoietic cells.

Local Bone Marrow Renin-Angiotensin System and Atherosclerosis

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Yavuz Beyazit

2011-01-01

Full Text Available Local hematopoietic bone marrow (BM renin-angiotensin system (RAS affects the growth, production, proliferation differentiation, and function of hematopoietic cells. Angiotensin II (Ang II, the dominant effector peptide of the RAS, regulates cellular growth in a wide variety of tissues in pathobiological states. RAS, especially Ang II and Ang II type 1 receptor (AT1R, has considerable proinflammatory and proatherogenic effects on the vessel wall, causing progression of atherosclerosis. Recent investigations, by analyzing several BM chimeric mice whose BM cells were positive or negative for AT1R, disclosed that AT1R in BM cells participates in the pathogenesis of atherosclerosis. Therefore, AT1R blocking not only in vascular cells but also in the BM could be an important therapeutic approach to prevent atherosclerosis. The aim of this paper is to review the function of local BM RAS in the pathogenesis of atherosclerosis.

Attachment, proliferation and differentiation of BMSCs on gas-jet/electrospun nHAP/PHB fibrous scaffolds

International Nuclear Information System (INIS)

Guan Donghua; Chen Zhiqing; Huang Chunpeng; Lin Yinghe

2008-01-01

In this study, poly(3-hydroxybutyrate) (PHB)-based scaffolds containing nanosized hydroxyapatite (nHAP) were manufactured by gas-jet/electrospinning. The morphologies of the scaffolds were characterized. The effect of the scaffolds on attachment, proliferation and differentiation of the bone marrow stroma cells (BMSCs) were accessed by using scanning electron microscopy (SEM), methylthiazol tetrazolium (MTT) assay and alkaline phosphatase (ALP) activity. The results show that the gas-jet/electrospun scaffolds possess an extracellular matrix-like topography. In vitro studies describe that the scaffolds have positive effects on attachment, proliferation and differentiation of BMSCs in vitro. It can be concluded that the scaffolds combing the unique structural features generated by gas-jet/electrospinning with functional factors, have the potential to be used in bone tissue engineering

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

Energy Technology Data Exchange (ETDEWEB)

Peña, Jaime A.; Damm, Timo; Bastgen, Jan; Barkmann, Reinhard; Glüer, Claus C., E-mail: glueer@rad.uni-kiel.de [Sektion Biomedizinische Bildgebung, Klinik für Radiologie und Neuroradiologie, Christian-Albrechts-Universität zu Kiel, Campus Kiel, Kiel 24118 (Germany); Thomsen, Felix [Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional del Sur, Bahía Blanca 8000 (Argentina); Campbell, Graeme M. [Sektion Biomedizinische Bildgebung, Klinik für Radiologie und Neuroradiologie, Christian-Albrechts-Universität zu Kiel, Campus Kiel, Kiel 24118, Germany and Institut für Biomechanik, Technische Universität Hamburg-Harburg (TUHH), Hamburg 21073 (Germany)

2016-07-15

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

Solar swimming pool

Energy Technology Data Exchange (ETDEWEB)

1985-01-01

This report examines the feasibility of using solar collectors to heat the water in a previously unheated outdoor swimming pool. The solar system is used in conjunction with a pool blanket, to conserve heat when the pool is not in use. Energy losses through evaporation can be reduced by as much as 70% by a pool blanket. A total of 130 m{sup 2} of highly durable black synthetic collectors were installed on a support structure at a 30{degree} angle from the horizontal, oriented to the south. Circulation of pool water though the collectors, which is controlled by a differential thermostat, was done with the existing pool pump. Before installation the pool temperature averaged 16{degree}C; after installation it ranged from 20{degree} to 26{degree}C. It was hard to distinguish how much pool heating was due to the solar system and how much heat was retained by the pool blanket. However, the pool season was extended by five weeks and attendance tripled. 2 figs.

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

Science.gov (United States)

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

2015-03-13

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

Inhibition of phosphatidylcholine-specific phospholipase C prevents bone marrow stromal cell senescence in vitro.

Science.gov (United States)

Sun, Chunhui; Wang, Nan; Huang, Jie; Xin, Jie; Peng, Fen; Ren, Yinshi; Zhang, Shangli; Miao, Junying

2009-10-01

Bone marrow stromal cells (BMSCs) can proliferate in vitro and can be transplanted for treating many kinds of diseases. However, BMSCs become senescent with long-term culture, which inhibits their application. To understand the mechanism underlying the senescence, we investigated the activity of phosphatidylcholine-specific phospholipase C (PC-PLC) and levels of integrin beta4, caveolin-1 and ROS with BMSC senescence. The activity of PC-PLC and levels of integrin beta4, caveolin-1 and ROS increased greatly during cell senescence. Selective inhibition of increased PC-PLC activity with D609 significantly decreased the number of senescence-associated beta galactosidase positive cells in BMSCs. Furthermore, D609 restored proliferation of BMSCs and their differentiation into adipocytes. Moreover, D609 suppressed the elevated levels of integrin beta4, caveolin-1 and ROS. The data suggest that PC-PLC is involved in senescence of BMSCs, and its function is associated with integrin beta4, caveolin-1 and ROS. (c) 2009 Wiley-Liss, Inc.

Molecular Mechanisms That Contribute to Bone Marrow Pain

Directory of Open Access Journals (Sweden)

Jason J. Ivanusic

2017-09-01

Full Text Available Pain associated a bony pathology puts a significant burden on individuals, society, and the health-care systems worldwide. Pathology that involves the bone marrow activates sensory nerve terminal endings of peripheral bone marrow nociceptors, and is the likely trigger for pain. This review presents our current understanding of how bone marrow nociceptors are influenced by noxious stimuli presented in pathology associated with bone marrow. A number of ion channels and receptors are emerging as important modulators of the activity of peripheral bone marrow nociceptors. Nerve growth factor (NGF sequestration has been trialed for the management of inflammatory bone pain (osteoarthritis, and there is significant evidence for interaction of NGF with bone marrow nociceptors. Activation of transient receptor potential cation channel subfamily V member 1 sensitizes bone marrow nociceptors and could contribute to increased sensitivity of patients to noxious stimuli in various bony pathologies. Acid-sensing ion channels sense changes to tissue pH in the bone marrow microenvironment and could be targeted to treat pathology that involves acidosis of the bone marrow. Piezo2 is a mechanically gated ion channel that has recently been reported to be expressed by most myelinated bone marrow nociceptors and might be a target for treatments directed against mechanically induced bone pain. These ion channels and receptors could be useful targets for the development of peripherally acting drugs to treat pain of bony origin.

[The process of heme synthesis in bone marrow mesenchymal stem cells cultured under fibroblast growth factor bFGF and hypoxic conditions].

Science.gov (United States)

Poleshko, A G; Lobanok, E S; Mezhevikina, L M; Fesenko, E E; Volotkovskiĭ, I D

2014-01-01

It was demonstrated that fibroblast growth factor bFGF influences the process of heme synthesis, the proliferation activity and viability of bone marrow mesenchymal stem cells in culture under hypoxic conditions. The addition of fibroblast growth factor bFGF (7 ng/ml) to the medium under above conditions led to the accumulation of aminolevulinic acid--an early porphyrin and heme precursor, an increase in CD 71 expression--a transferrin receptor, and also a decrease in porphyrin pigments and heme contents--a late precursor and end products of heme synthesis, respectively. It was found that cultivation of the cells under hypoxic conditions and bFGF is an optimum to maintain high viability and proliferation capacity of the mesenchymal stem cells.

MarCell trademark software for modeling bone marrow radiation cell kinetics

International Nuclear Information System (INIS)

Hasan, J.S.; Jones, T.D.; Morris, M.D.

1997-01-01

Differential equations were used to model cellular injury, repair, and compensatory proliferation in the irradiated bone marrow. Recently, that model was implemented as MarCell trademark, a user-friendly MS-DOS computer program that allows users from a variety of technical disciplines to evaluate complex radiation exposure. The software allows menu selections for different sources of ionizing radiation. Choices for cell lineages include progenitor, stroma, and malignant, and the available species include mouse, rat, dog, sheep, swine, burro, and man. An attractive feature is that any protracted irradiation can be compared with an equivalent prompt dose (EPD) in terms of cell kinetics for either the source used or for a reference such as 250 kVp x rays or 60 Co. EPD is used to mean a dose rate for which no meaningful biological recovery occurs during the period of irradiation. For human as species, output from MarCell trademark includes: risk of 30-day mortality; risk of whole-body cancer and leukemia based either on radiation-induced cytopenia or compensatory cell proliferation; cell survival and repopulation plots as functions of time or dose; and 4-week recovery following treatment. copyright 1997 American Association of Physicists in Medicine

MR imaging of femoral marrow in treated β-thalassemia major

International Nuclear Information System (INIS)

Shen Jun; Liang Biling; Chen Jianyu; Zhao Jiquan; Xu Honggui; Chen Chun

2006-01-01

Objective: To investigate MR imaging features of femoral marrow in treated β-thalassemia major. Methods: MR imaging of the proximal femoral marrow was performed in 35 cases of β-thalassemia major and 45 age- and sex-matched normal children as control. Coronal images of femoral marrow with the techniques of spin echo and fast field echo (FFE) were obtained. On T 1 -weighted imaging the red and yellow femoral marrow were judged and marrow distribution was classified into five groups. The hemosiderosis of marrow was judged on the basis of signal intensity of marrow on FFE imaging. The marrow distribution classification and the hemosiderosis on MR imaging were correlated with clinical features. Results: On FFE, marrow hemosiderosis occurred in 15 patients with a marked hypo-intensity signal and was related to the age (P=0.032). On T 1 -weighted imaging, the femoral marrow in 35 patients was classified as group III and IV, while the marrow distribution was group I or II in all normal children, there was statistically significant difference (P<0.001). The marrow distribution correlated positively with blood transfusion (P=0.049). Conclusion: The red marrow hyperplasia and hemosiderosis could occur in the femoral marrow of the treated β-thalassemia major. The marrow hyperplasia on MR imaging was related to the blood transfusion, and the hemosiderosis related to the age. (authors)

Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells

DEFF Research Database (Denmark)

Simonsen, Janne Lytoft; Rosada, Cecilia; Serakinci, Nedime

2002-01-01

Human bone marrow stromal cells (hMSCs) were stably transduced by a retroviral vector containing the gene for the catalytic subunit of human telomerase (hTERT). Transduced cells (hMSC-TERTs) had telomerase activity, and the mean telomere length was increased as compared with that of control cells....... The transduced cells have now undergone more than 260 population doublings (PD) and continue to proliferate, whereas control cells underwent senescence-associated proliferation arrest after 26 PD. The cells maintained production of osteoblastic markers and differentiation potential during continuous subculturing......, did not form tumors, and had a normal karyotype. When implanted subcutaneously in immunodeficient mice, the transduced cells formed more bone than did normal cells. These results suggest that ectopic expression of telomerase in hMSCs prevents senescence-associated impairment of osteoblast functions....

Using proliferation assessment methodologies for Safeguards-by-Design

International Nuclear Information System (INIS)

Van der Meer, K.; Rossa, R.; Turcanu, C.; Borella, A.

2013-01-01

MYRRHA, an accelerator driven system (ADS) is designed as a proton accelerator coupled to a liquid Pb-Bi spallation target, surrounded by a Pb-Bi cooled sub-critical neutron multiplying medium in a pool type configuration. An assessment based on three methodologies was made of the proliferation risks of the MYRRHA ADS in comparison with the BR2 MTR, an existing research reactor at the Belgian Nuclear Research Centre SCK-CEN. The used methodologies were the TOPS (Technical Opportunities to Increase the Proliferation Resistance of Nuclear Power Systems), the PR-PP and the INPRO methodologies. The various features of the methodologies are described and the results of the assessments are given and discussed. It is concluded that it would be useful to define one single methodology with two options to perform a quick and a more detailed assessment. The paper is followed by the slides of the presentation

Assessment of functional displacement of bone marrow by osteoplastic metastases from prostatic carcinoma with bone marrow scintigraphy

International Nuclear Information System (INIS)

Venz, S.; Cordes, M.; Friedrichs, R.; Hosten, N.; Neumann, K.; Langer, R.; Nagel, R.; Felix, R.

1993-01-01

The detailed examination of the skeleton in prostate cancer has become more critical since surgical treatment requires the non-evidence of bone metastases. The data of 30 patients have been evaluated. All patients had a bone scan and a bone marrow scintigraphy with [ 99m Tc[-anti-NCA95. In this study we compared the degree of bone marrow displacement with the extent of metastatic deposits identified on the bone scan. Six patients showing the criterias of a superscan (maximal avidity of the osteotrope radiatracer) had as a correlate a complete displacement of the hematopoesis in the bone marrow scintigraphy and an increased activity in liver and spleen. The degree of the peripheral extension correlated strongly with the decrease of the haemoglobin in blood samples. The grading was based upon the number of metastatic deposits identified on the scan (0=no metastases; 1≤6 metastases; 2=multiple metastases; 3=superscan). In 28 of 30 patients (93%) we found corresponding results in both the bone scan and the bone marrow scintigraphy. The bone marrow scintigraphy is a sensitive method in the detection of metastatic disease and gives additional information about the extent of bone marrow displacement by osteoplastic metastases. (orig.) [de

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

Science.gov (United States)

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

2007-04-01

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

Can bone marrow differentiate into renal cells?

Science.gov (United States)

Imai, Enyu; Ito, Takahito

2002-10-01

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

Post-irradiation thymocyte regeneration after bone marrow transplantation

International Nuclear Information System (INIS)

Boersma, W.; Betel, I.; Daculsi, R.; Westen, G. van der

1981-01-01

Growth kinetics of the donor-type thymus cell population after transplantation of bone marrow into irradiated syngeneic recipient mice is biphasic. During the first rapid phase of regeneration, lasting until day 19 after transplantation, the rate of development of the donor cells is independent of the number of bone marrow cells inoculated. The second slow phase is observed only when low numbers of bone marrow cells (2.5 x 10 4 ) are transplanted. The decrease in the rate of development is attributed to an efflux of donor cells from the thymus because, at the same time, the first immunologically competent cells are found in spleen. After bone marrow transplantation the regeneration of thymocyte progenitor cells in the marrow is delayed when compared to regeneration of CFUs. Therefore, regenerating marrow has a greatly reduced capacity to restore the thymus cell population. One week after transplantation of 3 x 10 6 cells, 1% of normal capacity of bone marrow is found. It is concluded that the regenerating thymus cells population after bone marrow transplantation is composed of the direct progeny of precursor cells in the inoculum. (author)

Studies on the age-dependent proliferation kinetics of the epithelium of the rat small intestine

International Nuclear Information System (INIS)

Kranz, D.; Dietze, F.; Laue, R.; Fuhrmann, I.

1980-01-01

The small intestine of 244 Wistar rats, aged 6 days, 6 weeks, 6, 12, 23, and 28 months, respectively. were investigated autoradiographically as to their age-dependent cell proliferation kinetics of the mucosal epithelial cells. There were age-dependent differences concerning the hourly regeneration ratio of the crypt cells and the migration velocity of the enterocytes. Both parameters became greater while the existing non growth fraction became smaller with increasing age. The non growth fraction seems to be a reserve being involved into the proliferating pool if required

In vitro analysis of equine, bone marrow-derived mesenchymal stem cells demonstrates differences within age- and gender-matched horses.

Science.gov (United States)

Carter-Arnold, J L; Neilsen, N L; Amelse, L L; Odoi, A; Dhar, M S

2014-09-01

Stem cell therapies are used routinely in equine practice. Most published reports characterise stem cells derived from younger horses; however, middle-aged horses are often in athletic performance, and experience degenerative medical conditions. Thus, mesenchymal stem cells (MSCs) from this group should be investigated. To describe differences in in vitro adherence, proliferation and potential for differentiation of equine bone marrow-derived MSCs (equine BMMSCs) harvested from middle-aged (10-13 years old) female donors. Descriptive study of stem cell characteristics. Equine BMMSCs from 6 horses were cultured in vitro and evaluated for viability, proliferation, osteogenesis, chondrogenesis, adipogenesis, cluster-of-differentiation markers and gene expression. Equine BMMSCs from all 6 donors demonstrated fibroblastic, cellular morphology, adherence to plastic and expression of cluster-of-differentiation markers. They varied in their rate of proliferation and trilineage differentiation. The equine BMMSCs of one of 6 donors demonstrated a higher rate of proliferation, enhanced ability for cell passaging and a more robust in vitro differentiation. Comparatively, equine BMMSCs from 2 donors demonstrated a lower rate of proliferation and lack of osteogenic and chondrogenic differentiation. The results of this study confirm that donor-to-donor variation in equine BMMSCs exists and this variation can be documented using in vitro assays. Subjective assessment suggests that the rate of proliferation tends to correlate with differentiation potential. © 2013 EVJ Ltd.

In vitro evaluation of isolation possibility of stem cells from intra oral soft tissue and comparison of them with bone mar-row stem cells

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P. Torkzaban

2012-01-01

Full Text Available Objective: Stem cells are of great interest for regenerating disturbed tissues and organs. These cells are commonly isolated from the bone marrow, but there has been interest in other tissues in the recent years. In this study, we evaluated the possibility of isolation of stem cells from oral connective tissue and investigated their characteristics.Materials and Methods: In this experimental study, sampling from the bone marrow and oral connective tissue of a beagle dog was performed under general anesthesia. Bone marrow stem cell isolation was performed according to the established protocols. The samples obtained from oral soft tissue were broken to small pieces and after adding collagenase I, the samples were incubated for 45 minutes in 37°C. Other processes were similar to the processes which were carried out on bone marrow cells. Then cell properties were compared to evaluate if the cells from the connective tissue were stem cells.Results: The cells from the bone marrow and connective tissue had the same morphology. The result of colony forming unit assay was relatively similar. Population doubling time was similar too. In addition, both cell groups differentiated to osteoblasts in osteogenic media.Conclusion: The cells isolated from the oral connective tissue had the characteristics of stem cells, including fibroblastoid morphology, self renewal properties, high proliferation rate and differentiation potential.

Forced expression of Sox2 or Nanog in human bone marrow derived mesenchymal stem cells maintains their expansion and differentiation capabilities

International Nuclear Information System (INIS)

Go, Masahiro J.; Takenaka, Chiemi; Ohgushi, Hajime

2008-01-01

Mesenchymal stem cells (MSCs) derived from human bone marrow have capability to differentiate into cells of mesenchymal lineage. The cells have already been applied in various clinical situations because of their expansion and differentiation capabilities. The cells lose their capabilities after several passages, however. With the aim of conferring higher capability on human bone marrow MSCs, we introduced the Sox2 or Nanog gene into the cells. Sox2 and Nanog are not only essential for pluripotency and self-renewal of embryonic stem cells, but also expressed in somatic stem cells that have superior expansion and differentiation potentials. We found that Sox2-expressing MSCs showed consistent proliferation and osteogenic capability in culture media containing basic fibroblast growth factor (bFGF) compared to control cells. Significantly, in the presence of bFGF in culture media, most of the Sox2-expressing cells were small, whereas the control cells were elongated in shape. We also found that Nanog-expressing cells even in the absence of bFGF had much higher capabilities for expansion and osteogenesis than control cells. These results demonstrate not only an effective way to maintain proliferation and differentiation potentials of MSCs but also an important implication about the function of bFGF for self-renewal of stem cells including MSCs

Interleukin-1β modulates endochondral ossification by human adult bone marrow stromal cells

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M Mumme

2012-09-01

Full Text Available Inflammatory cytokines present in the milieu of the fracture site are important modulators of bone healing. Here we investigated the effects of interleukin-1β (IL-1β on the main events of endochondral bone formation by human bone marrow mesenchymal stromal cells (BM-MSC, namely cell proliferation, differentiation and maturation/remodelling of the resulting hypertrophic cartilage. Low doses of IL-1β (50 pg/mL enhanced colony-forming units-fibroblastic (CFU-f and -osteoblastic (CFU-o number (up to 1.5-fold and size (1.2-fold in the absence of further supplements and glycosaminoglycan accumulation (1.4-fold upon BM-MSC chondrogenic induction. In osteogenically cultured BM-MSC, IL-1β enhanced calcium deposition (62.2-fold and BMP-2 mRNA expression by differential activation of NF-κB and ERK signalling. IL-1β-treatment of BM-MSC generated cartilage resulted in higher production of MMP-13 (14.0-fold in vitro, mirrored by an increased accumulation of the cryptic cleaved fragment of aggrecan, and more efficient cartilage remodelling/resorption after 5 weeks in vivo (i.e., more TRAP positive cells and bone marrow, less cartilaginous areas, resulting in the formation of mature bone and bone marrow after 12 weeks. In conclusion, IL-1β finely modulates early and late events of the endochondral bone formation by BM-MSC. Controlling the inflammatory environment could enhance the success of therapeutic approaches for the treatment of fractures by resident MSC and as well as improve the engineering of implantable tissues.

The Bone Marrow Transplantation Center of the National Cancer Institute - its resources to assist patients with bone marrow failure

International Nuclear Information System (INIS)

Tabak, Daniel

1997-01-01

This paper describes the bone marrow transplantation center of the brazilian National Cancer Institute, which is responsible for the cancer control in Brazil. The document also describes the resources available in the Institute for assisting patients presenting bone marrow failures. The Center provides for allogeneic and autologous bone marrow transplants, peripheral stem cell transplants, umbilical cord collections and transplants, and a small experience with unrelated bone marrow transplants. The Center receives patient from all over the country and provides very sophisticated medical care at no direct cost to the patients

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

International Nuclear Information System (INIS)

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

1980-01-01

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

Fractionated total body irradiation and autologous bone marrow transplantation in dogs: Hemopoietic recovery after various marrow cell doses

International Nuclear Information System (INIS)

Bodenburger, U.; Kolb, H.J.; Thierfelder, S.; Netzel, B.; Schaeffer, E.; Kolb, H.

1980-01-01

Hemopoietic recovery was studied in dogs given 2400 R fractionated total body irradiation within one week and graded doses of cryopreserved autologous bone marrow. Complete hemopoietic recovery including histology was observed after this dose and sufficient doses of marrow cells. Doses of more than 5.5 x 10 7 mononuclear marrow cells/kg body weight were sufficient for complete recovery in all dogs, 1.5 to 5.5 x 10 7 cells/kg were effective in some of the dogs and less than 1.5 x 10 7 cells/kg were insufficient for complete recovery. Similarly, more than 30000 CFUsub(c)/kg body weight were required for hemopoietic recovery. The optimal marrow cell dose which has been defined as the minimal dose required for the earliest possible recovery of leukocyte and platelet counts was 7-8 x 10 7 mononuclear marrow cells/kg body weight. It has been concluded that fractionated total body irradiation with 2400 R dose not require greater doses of marrow cells for hemopoietic reconstitution than lower single doses and that the hemopoietic microenvironment is not persistently disturbed after this dose. (author)

Platelet released growth factors boost expansion of bone marrow derived CD34(+) and CD133(+) endothelial progenitor cells for autologous grafting.

Science.gov (United States)

Lippross, Sebastian; Loibl, Markus; Hoppe, Sven; Meury, Thomas; Benneker, Lorin; Alini, Mauro; Verrier, Sophie

2011-01-01

Stem cell based autologous grafting has recently gained mayor interest in various surgical fields for the treatment of extensive tissue defects. CD34(+) and CD133(+) cells that can be isolated from the pool of bone marrow mononuclear cells (BMC) are capable of differentiating into mature endothelial cells in vivo. These endothelial progenitor cells (EPC) are believed to represent a major portion of the angiogenic regenerative cells that are released from bone marrow when tissue injury has occurred. In recent years tissue engineers increasingly looked at the process of vessel neoformation because of its major importance for successful cell grafting to replace damaged tissue. Up to now one of the greatest problems preventing a clinical application is the large scale of expansion that is required for such purpose. We established a method to effectively enhance the expansion of CD34(+) and CD133(+) cells by the use of platelet-released growth factors (PRGF) as a media supplement. PRGF were prepared from thrombocyte concentrates and used as a media supplement to iscove's modified dulbecco's media (IMDM). EPC were immunomagnetically separated from human bone morrow monocyte cells and cultured in IMDM + 10% fetal calf serum (FCS), IMDM + 5%, FCS + 5% PRGF and IMDM + 10% PRGF. We clearly demonstrate a statistically significant higher and faster cell proliferation rate at 7, 14, 21, and 28 days of culture when both PRGF and FCS were added to the medium as opposed to 10% FCS or 10% PRGF alone. The addition of 10% PRGF to IMDM in the absence of FCS leads to a growth arrest from day 14 on. In histochemical, immunocytochemical, and gene-expression analysis we showed that angiogenic and precursor markers of CD34(+) and CD133(+) cells are maintained during long-term culture. In summary, we established a protocol to boost the expansion of CD34(+) and CD133(+) cells. Thereby we provide a technical step towards the clinical application of autologous stem cell

Transplantation of bone marrow derived cells promotes pancreatic islet repair in diabetic mice

International Nuclear Information System (INIS)

Gao Xiaodong; Song Lujun; Shen Kuntang; Wang Hongshan; Niu Weixin; Qin Xinyu

2008-01-01

The transplantation of bone marrow (BM) derived cells to initiate pancreatic regeneration is an attractive but as-yet unrealized strategy. Presently, BM derived cells from green fluorescent protein transgenic mice were transplanted into diabetic mice. Repair of diabetic islets was evidenced by reduction of hyperglycemia, increase in number of islets, and altered pancreatic histology. Cells in the pancreata of recipient mice co-expressed BrdU and insulin. Double staining revealed β cells were in the process of proliferation. BrdU + insulin - PDX-1 + cells, Ngn3 + cells and insulin + glucagon + cells, which showed stem cells, were also found during β-cell regeneration. The majority of transplanted cells were mobilized to the islet and ductal regions. In recipient pancreas, transplanted cells simultaneously expressed CD34 but did not express insulin, PDX-1, Ngn3, Nkx2.2, Nkx6.1, Pax4, Pax6, and CD45. It is concluded that BM derived cells especially CD34 + cells can promote repair of pancreatic islets. Moreover, both proliferation of β cells and differentiation of pancreatic stem cells contribute to the regeneration of β cells

Transcriptome analysis of bone marrow mesenchymal stromal cells from patients with primary myelofibrosis

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Christophe Martinaud

2015-09-01

Full Text Available Primary myelofibrosis (PMF is a clonal myeloproliferative neoplasm whose severity and treatment complexity are attributed to the presence of bone marrow (BM fibrosis and alterations of stroma impairing the production of normal blood cells. Despite the recently discovered mutations including the JAK2V617F mutation in about half of patients, the primitive event responsible for the clonal proliferation is still unknown. In the highly inflammatory context of PMF, the presence of fibrosis associated with a neoangiogenesis and an osteosclerosis concomitant to the myeloproliferation and to the increase number of circulating hematopoietic progenitors suggests that the crosstalk between hematopoietic and stromal cells is deregulated in the PMF BM microenvironmental niches. Within these niches, mesenchymal stromal cells (BM-MSC play a hematopoietic supportive role in the production of growth factors and extracellular matrix which regulate the proliferation, differentiation, adhesion and migration of hematopoietic stem/progenitor cells. A transcriptome analysis of BM-MSC in PMF patients will help to characterize their molecular alterations and to understand their involvement in the hematopoietic stem/progenitor cell deregulation that features PMF.

Effect of poly-A:U, dextran sulfate and yeast RNA on the bone marrow colony-forming ability in irradiated mice

International Nuclear Information System (INIS)

Chernyavskij, V.I.; Lysenko, A.I.; Kulakova, G.S.

1977-01-01

It has been shown, that poly-A:U, dextran sulfate and yeast RNA increased a number of endogenic colonies (COE) in the mouse spleen sublethally irradiated, as a result of, apparently, their mitogenic effect on proliferous COE. The preparations did not affect the number of exogenic colonies when introducting them together with transfer of syngenic cells of bone marrow, taken from the intact donors. Dextran sulfate increased 2.7 times the number of the endogenic colonies in the spleens of nonuniformly irradiated mice mainly due to the COE migration from protected bone marrow areas. The complex of poly-A:U and yest RNA in such experiment type were ineffective. One of the most important factors in the mechanism of the dextran sulfate adjuvant activity possibly is its ability to increase migration potencies of the stem blood-forming cells

Hemopoietic regeneration in murine spleen following transfusion of normal and irradiated marrow: different response of granulocyte/macrophage and erythroid precursors

International Nuclear Information System (INIS)

Wangenheim, K.-H. von; Peterson, H.-P.; Huebner, G.E.; Feinendegen, L.E.

1987-01-01

To investigate cell proliferation in regenerating spleen, bone marrow of normal and gamma-irradiated donor mice (3 weeks after 5 Gy) was transfused into lethally irradiated recipients. In the donors and in the recipient spleens numbers of CFU-S and progenitor cells were determined. In the irradiated donors the progenitors were at control level after 3 weeks of recovery although CFU-S were still at 50% of control. Recipients of the irradiated marrow received therefore an increased proportion of progenitors. CFU-C appeared to be self-renewing and/or increased in number due to enhanced CFU-S differentiation, but not the erythroid progenitors. CFU-S self-renewal was reduced after 5 Gy. The data suggest that cell differentiation and maturation proceed during early splenic regeneration. The quantity of CFU-C does not necessarily mirror the situation in the stem cell compartment. (author)

High-signal T2 changes of the bone marrow of the foot and ankle in children: red marrow or traumatic changes?

International Nuclear Information System (INIS)

Shabshin, Nogah; Schweitzer, Mark E.; Morrison, William B.; Carrino, John A.; Keller, Marc S.; Grissom, Leslie E.

2006-01-01

High-signal T2-weighted bone marrow changes can be found in both bone marrow edema and hematopoietic marrow and are often seen on pediatric MR images of the feet and ankle. To evaluate whether high-signal T2 changes of the bone marrow seen on pediatric MRI of feet and ankles represent residual hematopoietic marrow. A total of 402 bones in 41 pediatric MRI studies of feet and ankles (34 children, 1-18 years) were reviewed by two observers who were blinded to the patients' ages. The studies were reviewed for the presence of high-signal changes of the bone marrow on sagittal fluid-sensitive images. The frequency and location of these foci were correlated with the patients' ages. High-signal T2 changes of the bone marrow were seen in 45/402 bones (11%) and in 24/41 patients younger than 16 years (59%). The changes were most commonly located in the calcaneus (54%), followed by the talus (35%) and navicular bone (35%), invariably at the endosteal surface. In 16 ankles, such foci were seen in the feet but not in the distal tibia/fibula. Symmetric presence (two ankles) or absence (four ankles) of high-signal marrow were seen in six of seven patients with bilateral ankles. High-signal T2 changes of the bone marrow in pediatric feet and ankle MRIs have a symmetric, fairly consistent pattern and disappear after the age of 15 years. We believe that these high-signal areas are normal and represent residual hematopoietic marrow. (orig.)

Radionuclide imaging of bone marrow in hematologic systemic disease

Energy Technology Data Exchange (ETDEWEB)

Kessel, F.; Hahn, K.; Gamm, H.

1987-02-01

Radionuclide imaging studies of the bone marrow were carried out in 164 patients suffering from hematologic systemic disease. One third of 90 patients with Hodgkin lymphoma (HL) or Non Hodgkin lymphoma (NHL) displayed a pathological distribution pattern representing bone marrow expansion. In HL there were 17% accumulation defects caused by metastases in contrast to only 7% in NHL. Among 30 patients with chronic myelocytic leukemia bone marrow expansion was found in 60%, bone marrow displacement and aplasia 10%. Focal bone marrow defects were found in 3 patients. All patients with primary polycythemia rubra vera displayed a pathologic bone marrow distribution pattern as well as splenomegaly. All patients with acute myelocytic leukemia (AML) and one patient with an acute lymphatic leukemia (ALL) had a pathological distribution pattern with bone marrow expansion and displacement. Focal bone marrow defects were not seen. Multiple myeloma with bone marrow expansion was found in 6 of 12 patients and focal accumulation defects were found in 40%, the latter lesions being not visible or equivocal on skeletal imaging studies. Pathological changes in liver and spleen were found in a high percentage of the total collective. The results document the important clinical value of bone marrow scintigraphy among the hematologic diseases studied.

Model of the regulation of the rate of multiplication of the stem cells of the bone marrow. [X radiation, gamma radiation

Energy Technology Data Exchange (ETDEWEB)

Gruzdev, G P; Monichev, A Ya

1975-01-01

A mathematical model of regulation of the rate of multiplication of the stem cells of the bone marrow has been constructed and investigated. Two possible variants of regulation of the proliferative activity of the irradiated stem cells are compared: at the level of tissue and subtissue units. Comparison of the results of modeling with the results of experimental investigations supports the latter mechanism of regulation of the proliferation of the stem cells.

Omega 3 fatty acids reduce myeloid progenitor cell frequency in the bone marrow of mice and promote progenitor cell differentiation

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Sollars Vincent E

2009-03-01

Full Text Available Abstract Background Omega 3 fatty acids have been found to inhibit proliferation, induce apoptosis, and promote differentiation in various cell types. The processes of cell survival, expansion, and differentiation are of key importance in the regulation of hematopoiesis. We investigated the role of omega 3 fatty acids in controlling the frequency of various myeloid progenitor cells in the bone marrow of mice. Increased progenitor cell frequency and blocked differentiation are characteristics of hematopoietic disorders of the myeloid lineage, such as myeloproliferative diseases and myeloid leukemias. Results We found that increasing the proportion of omega 3 fatty acids relative to the proportion of omega 6 fatty acids in the diet caused increased differentiation and reduced the frequency of myeloid progenitor cells in the bone marrow of mice. Furthermore, this had no adverse effect on peripheral white blood cell counts. Conclusion Our results indicate that omega 3 fatty acids impact hematopoietic differentiation by reducing myeloid progenitor cell frequency in the bone marrow and promoting progenitor cell differentiation. Further exploration of this discovery could lead to the use of omega 3 fatty acids as a therapeutic option for patients that have various disorders of hematopoiesis.

Bone marrow dosimetry for monoclonal antibody therapy

International Nuclear Information System (INIS)

Bigler, R.E.; Zanzonico, P.B.; Leonard, R.

1986-01-01

Immunoglobulins must permeate through the basement membrane of capillaries in order to enter the extracellular space (ECS) of tissue. Since the process is quite slow, the blood plasma activity in various organs contributes considerably to the radiation dose of the dose-limiting tissues. In bone marrow the basement membrane is absent and the blood circulation is functionally open. Therefore, blood plasma and marrow ECS maintain equal concentrations of labeled immunoglobulins. A combination of factors including intravenous administration, slow absorption into most tissues, slow breakdown and elimination of labeled immunoglobulin, and rapid entry into bone marrow ECS as well as known radiosensitivity of marrow led the authors to expect this tissue would prove to be the primary tissue at risk for systemic monoclonal antibody therapy. They have developed and applied in a Phase I clinical study of 131 I labeled CEA antibody a procedure for estimation of radiation dose to red bone marrow. Serieal measurements of blood plasma and total body retention are carried out. Binding of labeled antibody to the cellular components of blood is verified to be very low. They have observed bone marrow depression at doses greater than 400 rad. If no special procedures are used to reconstitute marrow after radiation treatment, this level represents a much greater than generally recognized limitation to radiolabeled monoclonal antibody therapy. 25 references, 4 tables

Comparison of immunological properties of bone marrow stromal cells and adipose tissue-derived stem cells before and after osteogenic differentiation in vitro

DEFF Research Database (Denmark)

Niemeyer, Philipp; Kornacker, Martin; Mehlhorn, Alexander

2007-01-01

, the influence of osteogenic differentiation in vitro on the immunological characteristics of BMSCs and ASCs is the subject of this article. Before and after osteogenic induction, the influence of BMSCs and ASCs on the proliferative behavior of resting and activated allogenic peripheral blood mononuclear cells......Mesenchymal stem cells (MSCs) can be isolated from various tissues and represent an attractive cell population for tissue-engineering purposes. MSCs from bone marrow (bone marrow stromal cells [BMSCs]) are negative for immunologically relevant surface markers and inhibit proliferation of allogenic...... T cells in vitro. Therefore, BMSCs are said to be available for allogenic cell therapy. Although the immunological characteristics of BMSCs have been the subject of various investigations, those of stem cells isolated from adipose tissue (ASCs) have not been adequately described. In addition...

Dynamics of bone marrow-derived endothelial progenitor cell/mesenchymal stem cell interaction in co-culture and its implications in angiogenesis

International Nuclear Information System (INIS)

Aguirre, A.; Planell, J.A.; Engel, E.

2010-01-01

Research highlights: → BM-EPCs and MSCs establish complex, self-organizing structures in co-culture. → Co-culture decreases proliferation by cellular self-regulatory mechanisms. → Co-cultured cells present an activated proangiogenic phenotype. → qRT-PCR and cluster analysis identify new target genes playing important roles. -- Abstract: Tissue engineering aims to regenerate tissues and organs by using cell and biomaterial-based approaches. One of the current challenges in the field is to promote proper vascularization in the implant to prevent cell death and promote host integration. Bone marrow endothelial progenitor cells (BM-EPCs) and mesenchymal stem cells (MSCs) are bone marrow resident stem cells widely employed for proangiogenic applications. In vivo, they are likely to interact frequently both in the bone marrow and at sites of injury. In this study, the physical and biochemical interactions between BM-EPCs and MSCs in an in vitro co-culture system were investigated to further clarify their roles in vascularization. BM-EPC/MSC co-cultures established close cell-cell contacts soon after seeding and self-assembled to form elongated structures at 3 days. Besides direct contact, cells also exhibited vesicle transport phenomena. When co-cultured in Matrigel, tube formation was greatly enhanced even in serum-starved, growth factor free medium. Both MSCs and BM-EPCs contributed to these tubes. However, cell proliferation was greatly reduced in co-culture and morphological differences were observed. Gene expression and cluster analysis for wide panel of angiogenesis-related transcripts demonstrated up-regulation of angiogenic markers but down-regulation of many other cytokines. These data suggest that cross-talk occurs in between BM-EPCs and MSCs through paracrine and direct cell contact mechanisms leading to modulation of the angiogenic response.

Marrow donor registry and cord blood bank in Taiwan.

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Lee, Tsung Dao

2002-08-01

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

MR imaging of the bone marrow using short TI IR, 1. Normal and pathological intensity distribution of the bone marrow

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Ishizaka, Hiroshi; Kurihara, Mikiko; Tomioka, Kuniaki; Kobayashi, Kanako; Sato, Noriko; Nagai, Teruo; Heshiki, Atsuko; Amanuma, Makoto; Mizuno, Hitomi.

1989-02-01

Normal vertebral bone marrow intensity distribution and its alteration in various anemias were evaluated on short TI IR sequences. Material consists of 73 individuals, 48 normals and 25 anemic patients excluding neoplastic conditions. All normal and reactive hypercellular bone marrow revealed characteristic intensity distribution; marginal high intensity and central low intensity, corresponding well to normal distribution of red and yellow marrows and their physiological or reactive conversion between red and yellow marrows. Aplastic anemia did not reveal normal intensity distribution, presumably due to autonomous condition.

Aging of bone marrow mesenchymal stromal/stem cells: Implications on autologous regenerative medicine.

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Charif, N; Li, Y Y; Targa, L; Zhang, L; Ye, J S; Li, Y P; Stoltz, J F; Han, H Z; de Isla, N

2017-01-01

With their proliferation, differentiation into specific cell types, and secretion properties, mesenchymal stromal/stem cells (MSC) are very interesting tools to be used in regenerative medicine. Bone marrow (BM) was the first MSC source characterized. In the frame of autologous MSC therapy, it is important to detect donor's parameters affecting MSC potency. Age of the donors appears as one parameter that could greatly affect MSC properties. Moreover, in vitro cell expansion is needed to obtain the number of cells necessary for clinical developments. It will lead to in vitro cell aging that could modify cell properties. This review recapitulates several studies evaluating the effect of in vitro and in vivo MSC aging on cell properties.

Involvement of WNT Signaling in the Regulation of Gestational Age-Dependent Umbilical Cord-Derived Mesenchymal Stem Cell Proliferation

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Sota Iwatani

2017-01-01

Full Text Available Mesenchymal stem cells (MSCs are a heterogeneous cell population that is isolated initially from the bone marrow (BM and subsequently almost all tissues including umbilical cord (UC. UC-derived MSCs (UC-MSCs have attracted an increasing attention as a source for cell therapy against various degenerative diseases due to their vigorous proliferation and differentiation. Although the cell proliferation and differentiation of BM-derived MSCs is known to decline with age, the functional difference between preterm and term UC-MSCs is poorly characterized. In the present study, we isolated UC-MSCs from 23 infants delivered at 22–40 weeks of gestation and analyzed their gene expression and cell proliferation. Microarray analysis revealed that global gene expression in preterm UC-MSCs was distinct from term UC-MSCs. WNT signaling impacts on a variety of tissue stem cell proliferation and differentiation, and its pathway genes were enriched in differentially expressed genes between preterm and term UC-MSCs. Cell proliferation of preterm UC-MSCs was significantly enhanced compared to term UC-MSCs and counteracted by WNT signaling inhibitor XAV939. Furthermore, WNT2B expression in UC-MSCs showed a significant negative correlation with gestational age (GA. These results suggest that WNT signaling is involved in the regulation of GA-dependent UC-MSC proliferation.

Involvement of WNT Signaling in the Regulation of Gestational Age-Dependent Umbilical Cord-Derived Mesenchymal Stem Cell Proliferation

Science.gov (United States)

Shono, Akemi; Yoshida, Makiko; Yamana, Keiji; Thwin, Khin Kyae Mon; Kuroda, Jumpei; Kurokawa, Daisuke; Koda, Tsubasa; Nishida, Kosuke; Ikuta, Toshihiko; Mizobuchi, Masami; Taniguchi-Ikeda, Mariko

2017-01-01

Mesenchymal stem cells (MSCs) are a heterogeneous cell population that is isolated initially from the bone marrow (BM) and subsequently almost all tissues including umbilical cord (UC). UC-derived MSCs (UC-MSCs) have attracted an increasing attention as a source for cell therapy against various degenerative diseases due to their vigorous proliferation and differentiation. Although the cell proliferation and differentiation of BM-derived MSCs is known to decline with age, the functional difference between preterm and term UC-MSCs is poorly characterized. In the present study, we isolated UC-MSCs from 23 infants delivered at 22–40 weeks of gestation and analyzed their gene expression and cell proliferation. Microarray analysis revealed that global gene expression in preterm UC-MSCs was distinct from term UC-MSCs. WNT signaling impacts on a variety of tissue stem cell proliferation and differentiation, and its pathway genes were enriched in differentially expressed genes between preterm and term UC-MSCs. Cell proliferation of preterm UC-MSCs was significantly enhanced compared to term UC-MSCs and counteracted by WNT signaling inhibitor XAV939. Furthermore, WNT2B expression in UC-MSCs showed a significant negative correlation with gestational age (GA). These results suggest that WNT signaling is involved in the regulation of GA-dependent UC-MSC proliferation. PMID:29138639

Magnetic resonance imaging in diffuse malignant bone marrow diseases

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Nyman, R.; Rehn, S.; Glimelius, B.; Hagberg, H.; Hemmingsson, A.; Jung, B.; Simonsson, B.; Sundstroem, C.

Twenty-four patients with malignant bone marrow involvement or polycythemia vera, 8 patients with reactive bone marrow and 7 healthy individuals were examined with spin-echo magnetic resonance imaging at 0.35 T and 0.5 T. Signs of an increased longitudinal relaxation time, T1, were found when normal bone marrow was replaced by malignant cells, polycythemia vera or reactive marrow. A shortened T1 was indicated in 4 patients in bone marrow regions treated by radiation therapy; the marrow was most likely hypocellular in these cases. The estimated T1 relaxation times were highly correlated to the cellularity of the bone marrow as assessed by histology. Among patients with close to 100% cellularity neither T1 nor T2 discriminated between the various malignancies or between malignant and reactive, non-malignant bone marrow. Characterization of tissues in terms of normalized image intensities was also attempted, the motive being to avoid approximations and uncertainties in the assessment of T1 and T2. The normalization was carried out with respect to the image of highest intensity, i.e. the proton density weighted image. The results were in agreement with those for T1 and T2. It was concluded that MRI is valuable for assessing bone marrow cellularity, but not for differentiating between various bone marrow disorders having a similar degree of cellularity.

Maintenance of differentiation potential of human bone marrow mesenchymal stem cells immortalized by human telomerase reverse transcriptase gene despite [corrected] extensive proliferation

DEFF Research Database (Denmark)

Abdallah, Basem M; Haack-Sørensen, Mandana; Burns, Jorge S

2005-01-01

Human bone marrow mesenchymal stem cells (hMSC) represent a population of stem cells that are capable of differentiation into multiple lineages. However, these cells exhibit senescence-associated growth arrest and phenotypic changes during long-term in vitro culture. We have recently demonstrated...

Overview of marrow transplantation

International Nuclear Information System (INIS)

Thomas, E.D.

1985-01-01

Bone marrow transplantation is now an accepted form of therapy for many hematologic disorders including aplastic anemia, genetically determined diseases and malignant diseases, particularly leukemia, and for rescue of patients given intensive chemoradiotherapy for malignant disease. The donor may be a healthy identical twin, a family member or even an unrelated person. Selection is made on the basis of human leukocyte antigen tissue typing. Intensive chemoradiotherapy is used to suppress patients' immune systems to facilitate engraftment and destroy diseased marrow. Transfusion of platelets, erythrocytes and granulocytes (or all of these), antibiotic coverage and protection from infection are necessary during the pancytopenic period. Survival rates vary considerably depending on a patient's disease, clinical state and age. Patients with aplastic anemia transplanted early in the course of their disease have a survival rate of approximately 80%. Patients with acute lymphoblastic leukemia are usually transplanted in a second or subsequent remission and have a survival rate of 25% to 40%. Patients with acute nonlymphoblastic leukemia in remission have survivals ranging from 45% to 70%. More than 200 patients in the chronic phase of chronic granulocytic leukemia have been transplanted with survival ranging from 50% to 70%. Complications of marrow transplantation include marrow graft rejection, graft-versus-host disease, immunologic insufficiency and the possibility of recurrence of the leukemia. 14 references

HSP10 selective preference for myeloid and megakaryocytic precursors in normal human bone marrow

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F Cappello

2009-06-01

Full Text Available Heat shock proteins (HSPs constitute a heterogeneous family of proteins involved in cell homeostasis. During cell life they are involved in harmful insults, as well as in immune and inflammatory reactions. It is known that they regulate gene expression, and cell proliferation, differentiation and death. HSP60 is a mitochondrial chaperonin, highly preserved during evolution, responsible of protein folding. Its function is strictly dependent on HSP10 in both prokaryotic and eukaryotic elements. We investigated the presence and the expression of HSP60 and HSP10 in a series of 20 normal human bone marrow specimens (NHBM by the means of immunohistochemistry. NHBM showed no expression of HSP60, probably due to its being below the detectable threshold, as already demonstrated in other normal human tissues. By contrast, HSP10 showed a selective positivity for myeloid and megakaryocytic lineages. The positivity was restricted to precursor cells, while mature elements were constantly negative.We postulate that HSP10 plays a role in bone marrow cell differentiation other than being a mitochondrial co-chaperonin. The present data emphasize the role of HSP10 during cellular homeostasis and encourage further investigations in this field.

Copper-64 labeled liposomes for imaging bone marrow

International Nuclear Information System (INIS)

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

2016-01-01

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

Effects of cell concentrations on the survival and repopulation of haemopoietic stem cells in irradiated bone marrow cell culture in vitro

International Nuclear Information System (INIS)

Fujitake, Hideki; Okamoto, Yuruko; Okubo, Hiroshi; Miyanomae, Takeshi; Kumagai, Keiko; Mori, K.J.

1981-01-01

Effects of cell concentrations on the survival and repopulation of haemopoietic stem cells after irradiation were studied in the long-term culture of mouse bone marrow cells in vitro. No difference was observed in the survival of the stem cells among cultures in which 0 - 10 7 cells were re-inoculated on the adherent cell colonies in the culture flask. Stem cells showed a significant proliferation within 1 week and the number of the stem cells exceeded the control in 3 weeks after irradiation in the cultures with less than 10 6 re-inoculated cells per flask. In contrast, there was a considerable delay in the onset of stem cell proliferation after irradiation in the culture with 10 7 cells per flask. Based on these results, a possibility that a stimulator of stem cell proliferation, released from irradiated stromal cells, is cancelled by an inhibitory factor produced by irradiated or unirradiated haemopoietic cells is postulated. (author)

Tapak liman (Elephantopus scaber L) extract-induced CD4+ and CD8+ differentiation from hematopoietic stem cells and progenitor cell proliferation in mice (Mus musculus L)

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Djati, Muhammad Sasmito; Habibu, Hindun; Jatiatmaja, Nabilah A.; Rifa'i, Muhaimin

2017-11-01

Tapak Liman (Elephantopus scaber L) is a traditional medicinal plant containing several active compounds that potentially affecting hematopoietic stem cells, such as epifrieelinol, lupeol, stigmasterol, triacontane-1-ol, dotriacontane-1-ol, lupeol acetate, deoxyelephan-topin, isodeoxyelephantopin, polyphenol luteolin-7, as well as various flavonoids and glucosides. The aim of this study was to elucidate the effect of leaf extract of Tapak Liman on hematopoietic stem cells in mice BALB/c, by observation of the relative number of cells expressing CD4/CD8, CD4/CD62L, and TER119/B220 in the spleen, and TER119/B220, TER119/VLA-4 and TER119/CD34 in bone marrow, after being administered leaf extract for 2 weeks. This experiment used 12 female mice, which were divided into three treatment groups, P1= 0.5 g.g bw-1.day-1, P2= 1.0 g.g bw-1.day-1 and P3=2.0 g.g bw-1.day-1 Tapak Liman leaf extract as well as a control. The relative numbers of cells expressing surface molecules were analyzed by flowcytometry and quantitative data were tested using one-way ANOVA. The results showed that the leaf extract of Tapak Liman has no significant effect on erythrocyte proliferation; on the other hand, it had a significant effect on both proliferation and differentiation of B lymphocytes (B220+) in bone marrow (p=0.044) and increased the expression of CD4+, CD8+ molecule in B cells (p=0.026) and erythroid cells in spleen and bone marrow, based on the estimation of cells that expressed TER119+VLA-4+, identified as important in the development pathway of erythrocytes. An increased cell percentage of TER11+VLA-4+ occurred for treatment P2, 12% higher than the control. The increased expression of TER119+VLA-4+ was assumed to be due to the iron content in Tapak Liman, which functioned to stimulate the progenitor hematopoietic cells to proliferate and differentiate into a precursor of erythroid cells (TER119+VLA-4+). There was an increasing number of cells expressing the surface molecules TER119

Role of bone marrow-derived CD11c+ dendritic cells in systolic overload-induced left ventricular inflammation, fibrosis and hypertrophy.

Science.gov (United States)

Wang, Huan; Kwak, Dongmin; Fassett, John; Liu, Xiaohong; Yao, Wu; Weng, Xinyu; Xu, Xin; Xu, Yawei; Bache, Robert J; Mueller, Daniel L; Chen, Yingjie

2017-05-01

Inflammatory responses play an important role in the development of left ventricular (LV) hypertrophy and dysfunction. Recent studies demonstrated that increased T-cell infiltration and T-cell activation contribute to LV hypertrophy and dysfunction. Dendritic cells (DCs) are professional antigen-presenting cells that orchestrate immune responses, especially by modulating T-cell function. In this study, we investigated the role of bone marrow-derived CD11c + DCs in transverse aortic constriction (TAC)-induced LV fibrosis and hypertrophy in mice. We observed that TAC increased the number of CD11c + cells and the percentage of CD11c + MHCII + (major histocompatibility complex class II molecule positive) DCs in the LV, spleen and peripheral blood in mice. Using bone marrow chimeras and an inducible CD11c + DC ablation model, we found that depletion of bone marrow-derived CD11c + DCs significantly attenuated LV fibrosis and hypertrophy in mice exposed to 24 weeks of moderate TAC. CD11c + DC ablation significantly reduced TAC-induced myocardial inflammation as indicated by reduced myocardial CD45 + cells, CD11b + cells, CD8 + T cells and activated effector CD8 + CD44 + T cells in LV tissues. Moreover, pulsing of autologous DCs with LV homogenates from TAC mice promoted T-cell proliferation. These data indicate that bone marrow-derived CD11c + DCs play a maladaptive role in hemodynamic overload-induced cardiac inflammation, hypertrophy and fibrosis through the presentation of cardiac self-antigens to T cells.

BONE MARROW ABONRMALITIES IN HIV INFECTION

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Sharad Antiram Dhurve

2013-06-01

Full Text Available ABSTRACT Introduction; Hematological abnormalities are a common complication of HIV infection.  Bone marrow abnormalities occur in all stages of HIV infection.  Present work was carried out to study the bone marrow abnormalities in patients with HIV/AIDS.  Methods: 160 patients of HIV +ve were included in the study. A complete blood count, relevant biochemical investigations, CD4   counts were done, besides a thorough history and clinical examination. HIV positive patients were classified as those having AIDS and those without AIDS according to NACO criteria.   Bone marrow examination was performed for indication of anemia, leucopenia, pancytopenia and thrombocytopenia. Results: As per CDC criteria 59.81% patients had AIDS in 107 patients. The most common hematological abnormality was anemia, seen in 93.12% patients.  Bone marrow was normocellular in 79.06% of non-AIDS and 79.68% of AIDS, hypocellular in 13.95%.Thrombocytopenia was seen in 4 cases of ART (4.93% and 3 cases (4.68% of AIDS group. Abnormal cells like plasma cell, histocyte and toxic granule found in bone marrow. Conclusions: Myelodysplasia was more common in AIDS than in non AIDS patients. Granulocytic series is most commonly associated with evidence of dysplasia. Anemia in HIV patients can be a good clinical indicator to predict and access the underlying immune status. Thus bone marrow study is imperative to methodically observe and follow clinical and laboratory aberration in such patients in order to improve our diagnostic and therapeutic skills pertinent to HIV/AIDS.

Development of a 3D bone marrow adipose tissue model.

Science.gov (United States)

Fairfield, Heather; Falank, Carolyne; Farrell, Mariah; Vary, Calvin; Boucher, Joshua M; Driscoll, Heather; Liaw, Lucy; Rosen, Clifford J; Reagan, Michaela R

2018-01-26

Over the past twenty years, evidence has accumulated that biochemically and spatially defined networks of extracellular matrix, cellular components, and interactions dictate cellular differentiation, proliferation, and function in a variety of tissue and diseases. Modeling in vivo systems in vitro has been undeniably necessary, but when simplified 2D conditions rather than 3D in vitro models are used, the reliability and usefulness of the data derived from these models decreases. Thus, there is a pressing need to develop and validate reliable in vitro models to reproduce specific tissue-like structures and mimic functions and responses of cells in a more realistic manner for both drug screening/disease modeling and tissue regeneration applications. In adipose biology and cancer research, these models serve as physiologically relevant 3D platforms to bridge the divide between 2D cultures and in vivo models, bringing about more reliable and translationally useful data to accelerate benchtop to bedside research. Currently, no model has been developed for bone marrow adipose tissue (BMAT), a novel adipose depot that has previously been overlooked as "filler tissue" but has more recently been recognized as endocrine-signaling and systemically relevant. Herein we describe the development of the first 3D, BMAT model derived from either human or mouse bone marrow (BM) mesenchymal stromal cells (MSCs). We found that BMAT models can be stably cultured for at least 3 months in vitro, and that myeloma cells (5TGM1, OPM2 and MM1S cells) can be cultured on these for at least 2 weeks. Upon tumor cell co-culture, delipidation occurred in BMAT adipocytes, suggesting a bidirectional relationship between these two important cell types in the malignant BM niche. Overall, our studies suggest that 3D BMAT represents a "healthier," more realistic tissue model that may be useful for elucidating the effects of MAT on tumor cells, and tumor cells on MAT, to identify novel therapeutic

Meeting report of the 2016 bone marrow adiposity meeting.

Science.gov (United States)

van der Eerden, Bram; van Wijnen, André

2017-10-02

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

Measurement of MC5 antibody distribution in blood and bone marrow

International Nuclear Information System (INIS)

Johnson, T.K.; Gonzales, R.; Kasliwal, R.; Lear, J.; Feyerabend, A.; Ceriani, R.; Bunn, P.

1990-01-01

PURPOSE: Bone marrow is most often the dose-limiting organ in radioimmunotherapy. Controversy exists over optimal methods of estimating dose exposure to bone marrow. The purpose of this paper is to compare bone marrow activity from serial blood samples versus bone marrow biopsy specimens as measures of dose exposure to bone marrow. Peripheral blood samples and bone marrow biopsy specimens were obtained at 48 and 168 hours after infusion from 12 female patients infused with iodine-131-labeled MC5 antibody. The percentage of bone marrow in each biopsy specimen was assumed to be equivalent to the percentage of active bone marrow estimated to be in the pelvis. Activity present in the bone marrow as calculated with use of the estimated bone marrow mass for an adult female and then compared with the peripheral blood activity

Endogenous Cartilage Repair by Recruitment of Stem Cells.

Science.gov (United States)

Im, Gun-Il

2016-04-01

Articular cartilage has a very limited capacity for repair after injury. The adult body has a pool of stem cells that are mobilized during injury or disease. These cells exist inside niches in bone marrow, muscle, adipose tissue, synovium, and other connective tissues. A method that mobilizes this endogenous pool of stem cells will provide a less costly and less invasive alternative if these cells successfully regenerate defective cartilage. Traditional microfracture procedures employ the concept of bone marrow stimulation to regenerate cartilage. However, the regenerated tissue usually is fibrous cartilage, which has very poor mechanical properties compared to those of normal hyaline cartilage. A method that directs the migration of a large number of autologous mesenchymal stem cells toward injury sites, retains these cells around the defects, and induces chondrogenic differentiation that would enhance success of endogenous cartilage repair. This review briefly summarizes chemokines and growth factors that induce recruitment, proliferation, and differentiation of endogenous progenitor cells, endogenous cell sources for regenerating cartilage, scaffolds for delivery of bioactive factors, and bioadhesive materials that are necessary to bring about endogenous cartilage repair.

Abscopal suppression of bone marrow erythropoiesis

International Nuclear Information System (INIS)

Werts, E.D.; Johnson, M.J.; DeGowin, R.L.

1978-01-01

Abscopal responses of hemopoietic tissue, which we noted in preliminary studies of mice receiving partial-body irradiation, led us to clarify these effects. In studies reported here, one hind leg of CF-1 female mice received 1000, 5000, or 10,000 rad of x radiation. We found a persistent shift from medullary to splenic erythropoiesis preventing anemia in mice receiving 5000 or 10,000 rad. Splenectomy prior to 5000-rad irradiation resulted in anemia, which was not ameliorated by exposure to intermittent hypoxia. Despite evidence for increased levels of erythropoietin in the animals, namely, a reticulocytosis and increased erythrocyte radioiron incorporation, both 59 Fe uptake and erythroblast counts in shielded marrow remained below normal. We found 50 to 90% suppression of the growth of marrow stromal colonies (MSC) from bone marrow aspirates of the shielded and irradiated femoral marrow at 1 month and at least 20% depression of MSC at 1 year, with each dose. We conclude that: (i) high doses of x radiation to one leg of mice caused prolonged suppression of medullary erythropoiesis with splenic compensation to prevent anemia; (ii) splenectomy, anemia, and hypoxia prevented the severe abscopal depression of medullary erythropoiesis; and (iii) suppressed medullary erythropoiesis with decreased growth of MSC suggested a change in the hemopoietic microenvironment of the bone marrow

Detection of bone marrow involvement in patients with cancer

International Nuclear Information System (INIS)

Federico, M.; Silingardi, V.; Wright, R.M.

1989-01-01

Current methods for the study of bone marrow to evaluate possible primary or metastatic cancers are reviewed. Bone marrow biopsy, radionuclide scan, computed tomography and magnetic resonance imaging (MRI) are analyzed with regard to their clinical usefulness at the time of diagnosis and during the course of the disease. Bone marrow biopsy is still the examination of choice not only in hematologic malignancies but also for tumors that metastasize into the marrow. Radionuclide scans are indicated for screening for skeletal metastases, except for those from thyroid carcinoma and multiple myeloma. Computed tomography is useful for cortical bone evaluation. MRI shows a high sensitivity in finding occult sites of disease in the marrow but its use has been restricted by high cost and limited availability. However, the future of MRI in bone marrow evaluation seems assured. MRI is alredy the method of choice for diagnosis of multiple myeloma, when radiography is negative, and for quantitative evaluation of lymphoma when a crucial therapeutic decision (i.e. bone marrow transplantation) must be made. Finally, methods are being developed that will enhance the sensitivity and specificity of MRI studies of bone marrow

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.

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

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

2016-01-01

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

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

International Nuclear Information System (INIS)

Waksman, Ron; Baffour, Richard

2003-01-01

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

Proton MR spectroscopy of hyperplastic hematopoietic marrow in aplastic anemia

Energy Technology Data Exchange (ETDEWEB)

Amano, Yasuo; Kumazaki, Tatsuo [Nippon Medical School, Tokyo (Japan); Arai, Nobuyuki

1997-04-01

The purpose of this study was to compare the findings of magnetic resonance (MR) spectroscopy of hyperplastic hematopoietic marrow with those of normal bone marrow. Twenty-four samples of normal marrow from eight control subjects and 19 samples of hyperplastic marrow in aplastic anemia were examined with a 1.5 T MR unit. The former showed low intensity on opposed-phase T1-weighted images, while the latter showed high intensity on both fast STIR and opposed-phase T1-weighted images. MR spectroscopy quantitatively confirmed that the water; fat ratio was increased and the transverse relaxation time of water was changed in hyperplastic bone marrow, compared with normal bone marrow. In summary, MR imaging is able to detect hematopoietic regions among a wide range of bone marrow of aplastic anemia, while MR spectroscopy allowed us to quantitatively analyze the cell population of hyperplastic hematopoietic marrow in aplastic anemia. (author)

Proton MR spectroscopy of hyperplastic hematopoietic marrow in aplastic anemia

International Nuclear Information System (INIS)

Amano, Yasuo; Kumazaki, Tatsuo; Arai, Nobuyuki.

1997-01-01

The purpose of this study was to compare the findings of magnetic resonance (MR) spectroscopy of hyperplastic hematopoietic marrow with those of normal bone marrow. Twenty-four samples of normal marrow from eight control subjects and 19 samples of hyperplastic marrow in aplastic anemia were examined with a 1.5 T MR unit. The former showed low intensity on opposed-phase T1-weighted images, while the latter showed high intensity on both fast STIR and opposed-phase T1-weighted images. MR spectroscopy quantitatively confirmed that the water; fat ratio was increased and the transverse relaxation time of water was changed in hyperplastic bone marrow, compared with normal bone marrow. In summary, MR imaging is able to detect hematopoietic regions among a wide range of bone marrow of aplastic anemia, while MR spectroscopy allowed us to quantitatively analyze the cell population of hyperplastic hematopoietic marrow in aplastic anemia. (author)

Late taste disorders in bone marrow transplantation: clinical evaluation with taste solutions in autologous and allogeneic bone marrow recipients.

Science.gov (United States)

Marinone, M G; Rizzoni, D; Ferremi, P; Rossi, G; Izzi, T; Brusotti, C

1991-01-01

The aim of this work was to determine the type and the significance of taste disorders in allogeneic bone marrow transplanted patients. In a retrospective study the taste threshold of a cohort of 15 allogeneic bone marrow transplanted patients, 4-51 months after transplantation (mean: 30.6 +/- 15.8), was compared to the taste threshold of 8 autologous bone marrow recipients, 4-48 months after transplantation (mean: 24.12 +/- 12.18), and to the taste threshold of a group of 20 consecutive normal subjects. Allogeneic bone marrow transplanted patients showed a significant hypogeusia for salt (Pearson's chi square p = 0.0002; Yates' correction p = 0.0007) and sour (Pearson's chi square p = 0.001; Yates' correction p = 0.008). No significant variations were observed for sweet and bitter. Autologous bone marrow recipients did not show any significant variation of taste acuity for sweet, salt or sour; a constant reduction of the taste threshold for bitter was observed, but the values were not significantly different from normal (Pearson's chi square p = 0.47; Yates' correction p = 0.83). So, late and selective taste disorders are observed in allogeneic bone marrow transplanted patients. Since the severity of the disorders is not strictly related to the severity of chronic oral G.V.H.D., taste analysis could discover the slightest, clinically undetectable cases of chronic oral G.V.H.D. The mechanism of immune aggression on the sensorial taste cells is poorly understood. Further trials are needed to define variations of taste acuity not only after allogeneic bone marrow transplantation, but also in systemic immune diseases.

Exciting Pools

Science.gov (United States)

Wright, Bradford L.

1975-01-01

Advocates the creation of swimming pool oscillations as part of a general investigation of mechanical oscillations. Presents the equations, procedure for deriving the slosh modes, and methods of period estimation for exciting swimming pool oscillations. (GS)

Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell Fate.

Science.gov (United States)

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

2017-03-07

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

Intra-osseous injection of donor mesenchymal stem cell (MSC) into the bone marrow in living donor kidney transplantation; a pilot study.

Science.gov (United States)

Lee, Hyunah; Park, Jae Berm; Lee, Sanghoon; Baek, Soyoung; Kim, HyunSoo; Kim, Sung Joo

2013-04-11

Mesenchymal stem cells (MSCs) are multi-potent non-hematopoietic progenitor cells possessing an immune-regulatory function, with suppression of proliferation of activated lymphocytes. In this study, adult living donor kidney transplantation (LDKT) recipients were given MSCs derived from the donor bone marrow to evaluate the safety and the feasibility of immunological changes related to the intra-osseous injection of MSC into the bone marrow. MSCs were derived from negative HLA cross-match donors. Donor bone marrow was harvested 5 weeks prior to KT. At the time of transplantation, 1 x 106 cell/kg of donor MSC was directly injected into the bone marrow of the recipient's right iliac bone. Patients' clinical outcomes, presence of mixed chimerism by short tandem repeat polymerase chain reaction, analysis of plasma FoxP3 mRNA and cytokine level, and mixed lymphocyte reaction (MLR) were performed. Seven patients enrolled in this study and received donor MSC injections simultaneously with LDKT. The median age of recipients was 36 years (32 ~ 48). The number of HLA mismatches was 3 or less in 5 and more than 3 in 2. No local complications or adverse events such as hypersensitivity occurred during or after the injection of donor MSC. There was no graft failure, but the biopsy-proven acute rejections were observed in 3 recipients during the follow-up period controlled well with steroid pulse therapy (SPT). The last serum creatinine was a median of 1.23 mg/dL (0.83 ~ 2.07). Mixed chimerism was not detected in the peripheral blood of the recipients at 1 and 8 week of post-transplantation. Donor-specific lymphocyte or T cell proliferation and Treg priming responses were observed in some patients. Plasma level of IL-10, a known mediator of MSC-induced immune suppression, increased in the patients with Treg induction. Donor MSC injection into the iliac bone at the time of KT was feasible and safe. A possible correlation was observed between the induction of inhibitory

Depletion of NAD pool contributes to impairment of endothelial progenitor cell mobilization in diabetes.

Science.gov (United States)

Wang, Pei; Yang, Xi; Zhang, Zheng; Song, Jie; Guan, Yun-Feng; Zou, Da-Jin; Miao, Chao-Yu

2016-06-01

The impaired mobilization of endothelial progenitor cells (EPCs) from bone marrow (BM) critically contributes to the diabetes-associated vascular complications. Here, we investigated the relationship between the nicotinamide phosphoribosyltransferase (NAMPT)-controlled nicotinamide adenine dinucleotide (NAD) metabolism and the impaired mobilization of BM-derived EPCs in diabetic condition. The NAMPT-NAD pool in BM and BM-derived EPCs in wild-type (WT) and diabetic db/db mice was determined. Nicotinamide, a natural substrate for NAD biosynthesis, was administrated for 2weeks in db/db mice to examine the influence of enhancing NAD pool on BM and blood EPCs number. The modulations of stromal cell-derived factor-1α (SDF-1α) and endothelial nitric oxide synthase (eNOS) protein in BM were measured using immunoblotting. The EPCs intracellular NAMPT level and NAD concentration, as well as the blood EPCs number, were compared between 9 healthy people and 16 patients with type 2 diabetes mellitus (T2DM). The T2DM patients were treated with nicotinamide for two weeks and then the blood EPCs number was determined. Moreover, the association between blood EPCs numbers and EPCs intracellular NAD(+)/NAMPT protein levels in 21 healthy individuals was determined. We found that NAD concentration and NAMPT expression in BM and BM-derived EPCs of db/db mice were significantly lower than those in WT mice BM. Enhancing NAD pool not only increased the EPCs intracellular NAD concentration and blood EPCs number, but also improved post-ischemic wound healing and blood reperfusion in db/db mice with hind-limb ischemia model. Enhancing NAD pool rescued the impaired modulations of stromal cell-derived factor-1α (SDF-1α) and endothelial nitric oxide synthase (eNOS) protein levels in db/db mice BM upon hind-limb ischemia. In addition, enhancing NAD pool significantly inhibited PARP and caspase-3 activates in db/db mice BM. The intracellular NAMPT-NAD pool was positively associated with blood

Mesenchymal Stromal Cells from Osteoarthritic Synovium Are a Distinct Population Compared to Their Bone-Marrow Counterparts regarding Surface Marker Distribution and Immunomodulation of Allogeneic CD4+ T-Cell Cultures

Directory of Open Access Journals (Sweden)

Sebastien Hagmann

2016-01-01

Full Text Available Introduction. The participation of an inflammatory joint milieu has been described in osteoarthritis (OA pathogenesis. Mesenchymal stromal cells (MSCs play an important role in modulating inflammatory processes. Based on previous studies in an allogeneic T-cell coculture model, we aimed at further determining the role of synovial MSCs in OA pathogenesis. Methods. Bone-marrow (BM and synovial membrane (SM MSCs from hip joints of late stage OA patients and CD4+ T-cells from healthy donors were analysed regarding surface marker expression before and after coculture. Proliferation upon CD3/CD28 stimulation and cytokine analyses were compared between MSCs. Results. SM-MSCs differed from BM-MSCs in several surface markers and their osteogenic differentiation potential. Cocultures of both MSCs with CD4+ T-cells resulted in recruitment of CD45RA+ FoxP3+ regulatory T-cells. Upon stimulation, only SM-MSCs suppressed CD4+ T-cell proliferation, while both SM-MSCs and BM-MSCs modified cytokine profiles through suppressing IL-2 and TNF-α as well as increasing IL-6 secretion. Conclusions. Synovial MSCs from OA joints are a unique fraction that can be distinguished from their bone-marrow derived counterparts. Their unique ability to suppress CD3/CD28 induced CD4+ T-cell proliferation makes them a potential target for future therapeutic approaches.

Clinical aspects of bone marrow transplantation

International Nuclear Information System (INIS)

Shmitts, N.; Gassmann, V.; Leffler, G.

1986-01-01

Experience of bone marrow transplantation into patients with myeloproliferative syndromes, myelodysplasias and highly malignant lymphomas is presented. Side early and late effects of transplantation are described. The frequency and severity of complications of bone marrow transplantation depend sufficiently on the disease as well as on patient's age and general condition

Effect of boron on osteogenic differentiation of human bone marrow stromal cells.

Science.gov (United States)

Ying, Xiaozhou; Cheng, Shaowen; Wang, Wei; Lin, Zhongqin; Chen, Qingyu; Zhang, Wei; Kou, Dongquan; Shen, Yue; Cheng, Xiaojie; Rompis, Ferdinand An; Peng, Lei; Zhu Lu, Chuan

2011-12-01

Bone marrow stromal cells (BMSCs) have been well established as an ideal source of cell-based therapy for bone tissue engineering applications. Boron (B) is a notable trace element in humans; so far, the effects of boron on the osteogenic differentiation of BMSCs have not been reported. The aim of this study was to evaluate the effects of boron (0, 1, 10,100, and 1,000 ng/ml) on osteogenic differentiation of human BMSCs. In this study, BMSCs proliferation was analyzed by cell counting kit-8 (CCK8) assay, and cell osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity assay, Von Kossa staining, and real-time PCR. The results indicated that the proliferation of BMSCs was no different from the control group when added with B at the concentration of 1, 10, and 100 ng/ml respectively (P > 0.05); in contrast, 1,000 ng/ml B inhibited the proliferation of BMSCs at days 4, 7, and 14 (P < 0.05). By ALP staining, we discovered that BMSCs treated with 10 and 100 ng/ml B presented a higher ALP activity compared with control (P < 0.05). By real-time PCR, we detected the messenger RNA expression of ALP, osteocalcin, collagen type I, and bone morphogenetic proteins 7 were also increased in 10 and 100 ng/ml B treatment groups (P < 0.05). The calcium depositions were increased in 1 and 10 ng/ml B treatment groups (P < 0.05). Taken all together, it was the first time to report that B could increase osteogenic effect by stimulating osteogenic differentiation-related marker gene synthesis during the proliferation and differentiation phase in human BMSCs and could be a promising approach for enhancing osteogenic capacity of cell-based construction in bone tissue engineering.

Effect of bone marrow depletion on prostaglandin E-producing suppressor macrophages in mouse spleen

International Nuclear Information System (INIS)

Shibata, Y.; Volkman, A.

1985-01-01

The i.p. injection of Corynebacterium parvum (CP) into CBA/J mice effected increases in macrophage colony-forming cells (M-CFC) when spleen cells were cultured with L cell culture filtrate as a source of colony-stimulating factor. Significant increases in phagocytic macrophages (M phi) with Fc receptors for IgG2a and IgG2b immune complexes were additionally noted among the spleen cells in these mice. These M phi effectively inhibited Con A-induced lymphocyte proliferation, probably reflecting a 10-fold increase above normal controls in prostaglandin E to 47 ng/3 X 10(6) spleen cells/ml. To determine whether the suppressor M phi are immediate derivatives of splenic M-CFC, we tried to induce suppressor M phi by the injection of CP into mice depleted of bone marrow M-CFC by the earlier administration of the bone-seeking isotope, 89Sr. This procedure reduced M-CFC in the bone marrow to less than 1% of normal for more than 30 days. Monocytes in the blood fell to 5% of normal by day 10 and were 30% on day 30. Levels of resident peritoneal M phi showed relatively little change in this period. By contrast, splenic M-CFC increased to 20-fold higher than the cold 88Sr controls. CP-induced suppressor M phi activity, however, was sharply reduced in 89Sr marrow-depleted mice on day 10, despite the striking increase in M-CFC. There was a threefold increase in the number of phagocytic M phi binding IgG2a immune complexes, with no significant increase in IgG2b binding M phi. The kinetics of recovery of suppressor M phi activity showed that on days 20, 30, and 50 after 89Sr injection the activities reached 20%, 30%, and 70% of the cold control, respectively, and correlated with the recovery of significant levels of M-CFC in the bone marrow. Taken together, these observations suggest that splenic M-CFC are not an immediate source of PGE-suppressor M phi in vivo

Bone Marrow and Peripheral Blood Leptin Levels in Lymphoproliferative Diseases - Relation to the Bone Marrow Fat and Infiltration

Czech Academy of Sciences Publication Activity Database

Gaja, A.; Churý, Z.; Pecen, Ladislav; Fraňková, H.; Jandáková, H.; Hejlová, N.

2000-01-01

Roč. 47, č. 5 (2000), s. 307-312 ISSN 0028-2685 Institutional research plan: AV0Z1030915 Keywords : leptin * bone marrow fat * bone marrow infiltration * lymphoproliferative disease Subject RIV: BA - General Mathematics Impact factor: 0.579, year: 2000

Bone and marrow dose modeling

International Nuclear Information System (INIS)

Stabin, Michael G.

2004-01-01

Nuclear medicine therapy is being used increasingly in the treatment of cancer (thyroid, leukemia/lymphoma with RIT, primary and secondary bone malignancies, and neuroblastomas). In all cases it is marrow toxicity that limits the amount of treatment that can be administered safely. Marrow dose calculations are more difficult than for many major organs because of the intricate association of bone and soft tissue elements. In RIT, there appears to be no consensus on how to calculate that dose accurately, or of individual patients ability to tolerate planned therapy. Available dose models are designed after an idealized average, healthy individual. Patient-specific methods are applied in evaluation of biokinetic data, and need to be developed for treatment of the physical data (dose conversion factors) as well: age, prior patient therapy, disease status. Contributors to marrow dose: electrons and photons

Increased extracellular and intracellular Ca{sup 2+} lead to adipocyte accumulation in bone marrow stromal cells by different mechanisms

Energy Technology Data Exchange (ETDEWEB)

Hashimoto, Ryota, E-mail: hryota@juntendo.ac.jp [Department of Physiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Katoh, Youichi, E-mail: katoyo@juntendo-urayasu.jp [Juntendo University Faculty of International Liberal Arts, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Department of Cardiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Miyamoto, Yuki [Juntendo University Faculty of Health Care and Nursing, Takasu 2-5-1, Urayasu-shi, Chiba 279-0023 (Japan); Itoh, Seigo; Daida, Hiroyuki [Department of Cardiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Nakazato, Yuji [Center for Environmental Research, Department of Cardiology, Juntendo University Faculty of Medicine Urayasu Hospital, Tomioka 2-1-1, Urayasu-shi, Chiba 279-0022 (Japan); Okada, Takao [Department of Physiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan)

2015-02-20

Mesenchymal stem cells found in bone marrow stromal cells (BMSCs) are the common progenitors for both adipocyte and osteoblast. An increase in marrow adipogenesis is associated with age-related osteopenia and anemia. Both extracellular and intracellular Ca{sup 2+} ([Ca{sup 2+}]{sub o} and [Ca{sup 2+}]{sub i}) are versatile signaling molecules that are involved in the regulation of cell functions, including proliferation and differentiation. We have recently reported that upon treatment of BMSCs with insulin and dexamethasone, both high [Ca{sup 2+}]{sub o} and high [Ca{sup 2+}]{sub i} enhanced adipocyte accumulation, which suggested that increases in [Ca{sup 2+}]{sub o} caused by bone resorption may accelerate adipocyte accumulation in aging and diabetic patients. In this study, we used primary mouse BMSCs to investigate the mechanisms by which high [Ca{sup 2+}]{sub o} and high [Ca{sup 2+}]{sub i} may enhance adipocyte accumulation. In the process of adipocyte accumulation, two important keys are adipocyte differentiation and the proliferation of BMSCs, which have the potential to differentiate into adipocytes. Use of MTT assay and real-time RT-PCR revealed that high [Ca{sup 2+}]{sub i} (ionomycin)-dependent adipocyte accumulation is caused by enhanced proliferation of BMSCs but not enhanced differentiation into adipocytes. Using fura-2 fluorescence-based approaches, we showed that high [Ca{sup 2+}]{sub o} (addition of CaCl{sub 2}) leads to increases in [Ca{sup 2+}]{sub i}. Flow cytometric methods revealed that high [Ca{sup 2+}]{sub o} suppressed the phosphorylation of ERK independently of intracellular Ca{sup 2+}. The inhibition of ERK by U0126 and PD0325901 enhanced the differentiation of BMSCs into adipocytes. These data suggest that increased extracellular Ca{sup 2+} provides the differentiation of BMSCs into adipocytes by the suppression of ERK activity independently of increased intracellular Ca{sup 2+}, which results in BMSC proliferation. - Highlights: �

Irradiation of the red bone marrow and the health implications ...

African Journals Online (AJOL)

The physiology and function of the bone is looked at as to the role in housing bone marrow. The bone marrow and particularly the red bone marrow is discussed. Sources of radiation are discussed and the health implications highlighted for caution and for study or evaluation. Key Words: Bone marrow, Irradiation, Radiation, ...

Bone marrow transplantation - a field in continuous development

International Nuclear Information System (INIS)

Pfeffer, P.F.

1975-01-01

The symptoms of the radiation syndrome are described briefly and the Vinca accident in 1958 is used as an illustration of the application of bone marrow transplantation as a treatment in radiation accidents. Thereafter the immunological problems arising when a permanent substitution of donor marrow is required are discussed. Greatest experience in bone marrow transplantation has been had in the treatment of aplastic anemia and acute leukemia. In these cases the recipient's bone marrow cells must be killed by whole body irradiation or by cyclophosphamide to preclude graft-host reaction. The removal of marrow from the donor and transplanting in the recipient are described, as is the progress of the patient in a typical case. The graft-host reaction is then discussed, as is the danger of secondary infections. In conclusion the long term results are evaluated and the future developments of the treatment discussed. (JIW)

How to exhaust your bone marrow

DEFF Research Database (Denmark)

Salomo, Louise; Salomo, Morten; Andersen, Steven A W

2013-01-01

at work and in his spare time, and kept a very thorough training and weight diary. Owing to a high intake of energy and protein drinks he tried to optimise his physical performance and kept a normal body mass index  at 23.7. A bone marrow biopsy showed gelatinous bone marrow transformation, normally seen...

Inherited Bone Marrow Failure Syndromes (IBMFS)

Science.gov (United States)

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

MR imaging of marrow heterotopia in the hemoglobinopathies

International Nuclear Information System (INIS)

Trakadas, S.; Papavasiliou, C.; Gouliamos, A.D.; Vlahos, L.

1987-01-01

The MR imaging findings of marrow heterotopia in the costovertebral angles in patients with various hemoglobinopathies are presented. There was good correlation between the MR imaging findings and the appearance of the masses on conventional radiography or CT. The masses were of low signal intensity, similar to the signal intensity of the adjacent marrow of the thoracic spine, and surrounded by a high-intensity rim attributed to a layer of fat surrounding the masses. The latter finding is thought to be characteristic of marrow heterotopia masses. MR imaging may also reveal potential intrusion of marrow heterotopia into the spinal canal, thus eliminating the need for myelography

Adhesion and growth of human bone marrow mesenchymal stem cells on precise-geometry 3D organic–inorganic composite scaffolds for bone repair

International Nuclear Information System (INIS)

Chatzinikolaidou, Maria; Rekstyte, Sima; Danilevicius, Paulius; Pontikoglou, Charalampos; Papadaki, Helen; Farsari, Maria; Vamvakaki, Maria

2015-01-01

Engineering biomaterial scaffolds that promote attachment and growth of mesenchymal stem cells in three dimensions is a crucial parameter for successful bone tissue engineering. Towards this direction, a lot of research effort has focused recently into the development of three-dimensional porous scaffolds, aiming to elicit positive cellular behavior. However, the fabrication of three-dimensional tissue scaffolds with a precise geometry and complex micro- and nano-features, supporting cell in-growth remains a challenge. In this study we report on a positive cellular response of human bone marrow-derived (BM) mesenchymal stem cells (MSCs) onto hybrid material scaffolds consisting of methacryloxypropyl trimethoxysilane, zirconium propoxide, and 2-(dimethylamino)ethyl methacrylate (DMAEMA). First, we use Direct fs Laser Writing, a 3D scaffolding technology to fabricate the complex structures. Subsequently, we investigate the morphology, viability and proliferation of BM-MSCs onto the hybrid scaffolds and examine the cellular response from different donors. Finally, we explore the effect of the materials' chemical composition on cell proliferation, employing three different material surfaces: (i) a hybrid consisting of methacryloxypropyl trimethoxysilane, zirconium propoxide and 50 mol% DMAEMA, (ii) a hybrid material comprising methacryloxypropyl trimethoxysilane and zirconium propoxide, and (iii) a purely organic polyDMAEMA. Our results show a strong adhesion of BM-MSCs onto the hybrid material containing 50% DMAEMA from the first 2 h after seeding, and up to several days, and a proliferation increase after 14 and 21 days, similar to the polystyrene control, independent of cell donor. These findings support the potential use of our proposed cell–material combination in bone tissue engineering. - Graphical abstract: Scanning electron microscopy image depicting cell adhesion of bone marrow mesenchymal stem cells into a pore of a hybrid Direct Laser Writing

Adhesion and growth of human bone marrow mesenchymal stem cells on precise-geometry 3D organic–inorganic composite scaffolds for bone repair

Energy Technology Data Exchange (ETDEWEB)

Chatzinikolaidou, Maria, E-mail: mchatzin@materials.uoc.gr [Department of Materials Science and Technology, University of Crete (Greece); Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology Hellas (FORTH) (Greece); Rekstyte, Sima; Danilevicius, Paulius [Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology Hellas (FORTH) (Greece); Pontikoglou, Charalampos; Papadaki, Helen [Hematology Laboratory, School of Medicine, University of Crete (Greece); Farsari, Maria [Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology Hellas (FORTH) (Greece); Vamvakaki, Maria [Department of Materials Science and Technology, University of Crete (Greece); Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology Hellas (FORTH) (Greece)

2015-03-01

Engineering biomaterial scaffolds that promote attachment and growth of mesenchymal stem cells in three dimensions is a crucial parameter for successful bone tissue engineering. Towards this direction, a lot of research effort has focused recently into the development of three-dimensional porous scaffolds, aiming to elicit positive cellular behavior. However, the fabrication of three-dimensional tissue scaffolds with a precise geometry and complex micro- and nano-features, supporting cell in-growth remains a challenge. In this study we report on a positive cellular response of human bone marrow-derived (BM) mesenchymal stem cells (MSCs) onto hybrid material scaffolds consisting of methacryloxypropyl trimethoxysilane, zirconium propoxide, and 2-(dimethylamino)ethyl methacrylate (DMAEMA). First, we use Direct fs Laser Writing, a 3D scaffolding technology to fabricate the complex structures. Subsequently, we investigate the morphology, viability and proliferation of BM-MSCs onto the hybrid scaffolds and examine the cellular response from different donors. Finally, we explore the effect of the materials' chemical composition on cell proliferation, employing three different material surfaces: (i) a hybrid consisting of methacryloxypropyl trimethoxysilane, zirconium propoxide and 50 mol% DMAEMA, (ii) a hybrid material comprising methacryloxypropyl trimethoxysilane and zirconium propoxide, and (iii) a purely organic polyDMAEMA. Our results show a strong adhesion of BM-MSCs onto the hybrid material containing 50% DMAEMA from the first 2 h after seeding, and up to several days, and a proliferation increase after 14 and 21 days, similar to the polystyrene control, independent of cell donor. These findings support the potential use of our proposed cell–material combination in bone tissue engineering. - Graphical abstract: Scanning electron microscopy image depicting cell adhesion of bone marrow mesenchymal stem cells into a pore of a hybrid Direct Laser Writing

Swimming-pool piles

International Nuclear Information System (INIS)

Trioulaire, M.

1959-01-01

In France two swimming-pool piles, Melusine and Triton, have just been set in operation. The swimming-pool pile is the ideal research tool for neutron fluxes of the order of 10 13 . This type of pile can be of immediate interest to many research centres, but its cost must be reduced and a break with tradition should be observed in its design. It would be an advantage: - to bury the swimming-pool; - to reject the experimental channel; - to concentrate the cooling circuit in the swimming-pool; - to carry out all manipulations in the water; - to double the core. (author) [fr

Shifting bone marrow edema of the knee

International Nuclear Information System (INIS)

Moosikasuwan, Josh B.; Schultz, Elizabeth; Miller, Theodore T.; Math, Kevin

2004-01-01

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.)

Bone marrow scintigraphy in hemopoietic depletion states

International Nuclear Information System (INIS)

Fortynova, J.; Bakos, K.; Pradacova, J.

1981-01-01

Bone marrow scintigraphy was performed in 29 patients with hemopoietic depletion states of various etiology. Two tracers were used for visualization, viz., sup(99m)Tc-sulfur-colloid and 111 InCl 3 ;some patients were examined using both indicators. 111 InCl 3 is bound to transferrin and is adsorbed on the surface of reticulocytes and erythroblasts. A scintillation camera PHO GAMMA SEARLE IV fitted with a moving table and computer CLINCOM were used to obtain whole-body images. The comparison of all scans and marrow puncture smears was done. In patients with aplastic anemia with both hyperplastic or hypoplastic marrow good correlation of bone marrow scans and sternal puncture smears was found. In several cases the scintigraphic examination helped to establish the diagnosis of marrow depletion. A peculiar disadvantage of the imaging method with either sup(99m)Tc-sulfur-colloid or 111 InCl 3 is that it shows the disorders in erythropoietic and reticuloendothelial cells whereas the defects in myelopoietic cell series and platelet precursors are not provable. According to literature data, great attention is paid to the prognostic value of scintigraphic examination in aplastic anemia. (author)

Bone marrow scintigraphy in hemopoietic depletion states

Energy Technology Data Exchange (ETDEWEB)

Fortynova, J. (Ustav Hematologie a Krevni Transfuze, Prague (Czechoslovakia)); Bakos, K.; Pradacova, J. (Karlova Univ., Prague (Czechoslovakia). Biofyzikalni Ustav)

1981-01-01

Bone marrow scintigraphy was performed in 29 patients with hemopoietic depletion states of various etiology. Two tracers were used for visualization, viz., sup(99m)Tc-sulfur-colloid and /sup 111/InCl/sub 3/; some patients were examined using both indicators. /sup 111/InCl/sub 3/ is bound to transferrin and is adsorbed on the surface of reticulocytes and erythroblasts. A scintillation camera PHO GAMMA SEARLE IV fitted with a moving table and computer CLINCOM were used to obtain whole-body images. The comparison of all scans and marrow puncture smears was done. In patients with aplastic anemia with both hyperplastic or hypoplastic marrow good correlation of bone marrow scans and sternal puncture smears was found. In several cases the scintigraphic examination helped to establish the diagnosis of marrow depletion. A peculiar disadvantage of the imaging method with either sup(99m)Tc-sulfur-colloid or /sup 111/InCl/sub 3/ is that it shows the disorders in erythropoietic and reticuloendothelial cells whereas the defects in myelopoietic cell series and platelet precursors are not provable. According to literature data, great attention is paid to the prognostic value of scintigraphic examination in aplastic anemia.

Bone marrow transplantation and other treatment after radiation injury

International Nuclear Information System (INIS)

Balner, H.

1977-01-01

This review deals mainly with current concepts about bone marrow transplantation as therapy for serious radiation injury. Such injury can be classified according to the following broadly defined dose ranges: (1) the supralethal range, leading mainly to the cerebral and intestinal syndromes; (2) the potentially lethal or therapeutic range which causes the bone marrow syndrome, and (3) the sublethal range which rarely leads to injury requiring therapy. The bone marrow syndrome of man and animals is discussed in detail. The optimal therapy for this syndrome is bone marrow transplantation in conjunction with conventional supportive treatment. The principal complications of such therapy are Graft versus Host Disease and a slow recovery of the recipient's immune system. Concerted research activities in a number of institutions have led to considerable progress in the field of bone marrow transplantation. Improved donor selection, new techniques for stem-cell separation and preservation, as well as effective barrier-nursing and antibiotic decontamination, have made bone marrow transplantation an accepted therapy for marrow depression, including the aplasia caused by excessive exposure to radiation. The review also contains a number of guidelines for the handling of serious radiation accidents. (Auth.)

Evaluation of bone marrow in patients with pancytopenia

Directory of Open Access Journals (Sweden)

R Pathak

2012-09-01

Full Text Available Background: Pancytopenia is a common hematological finding resulting from varieties of disease processes that require evaluation of bone marrow. This study was carried out to evaluate bone marrow findings in patients presenting with pancytopenia.Materials and Method: This was a prospective cross sectional study carried out to identify the causes of pancytopenia based on bone marrow examination. Bone marrow examinations were performed in 503 cases for different indications over a period of one year.Results: One hundred and two (20.27% cases fulfilled the criteria of pancytopenia. Trephine biopsy was possible only in 48 cases. In 75% cases aspiration findings were similar to biopsy. Mean age of patients was 38.8 years. Maximum number of cases was seen in age group of 15-30 years. Hypoplastic anemia was the commonest cause followed by hematological malignancies, megaloblastic anemia, leishmaniasis and Gaucher disease. Bone marrow examination alone was able to establish the diagnosis in 76.5% cases. In rest marrow findings were nonspecific and in 4.9% cases findings were normal.Conclusion: Bone marrow aspiration coupled with trephine biopsy can diagnose majority but not all the cases of pancytopenia. Hypoplastic anemia, hematological malignancies and megaloblastic anemia are the commonest causes of pancytopenia. Maximum diagnostic yield can be achieved by correlation with clinical findings, peripheral blood findings and with other laboratory and radiological parameters.Journal of Pathology of Nepal (2012 Vol. 2, 265-271DOI: http://dx.doi.org/10.3126/jpn.v2i4.6875

HLA in bone marrow transplantation

International Nuclear Information System (INIS)

Tsuji, Kimiyoshi

1989-01-01

It has been well understood that human major histocompatibility antigen system, HLA is the most important role in the allo transplantation. Therefore, the structure of HLA genes was presented by the recent information (1987). Moreover, their functions in vitro and in vivo also were described. Finally, bone marrow transplantation and HLA network system in Japan against HLA mismatched case was proposed. It is eagerly expected that functional and clinical bone marrow transplantation in Japan could be succeeded. (author)

In vitro formation of osteoclasts from long-term cultures of bone marrow mononuclear phagocytes

International Nuclear Information System (INIS)

Burger, E.H.; Van der Meer, J.W.; van de Gevel, J.S.; Gribnau, J.C.; Thesingh, G.W.; van Furth, R.

1982-01-01

The origin of osteoclasts was studied in an in vitro model using organ cultures of periosteum-free embryonic mouse long-bone primordia, which were co-cultured with various cell populations. The bone rudiments were freed of their periosteum-perichondrium by collagenase treatment in a stage before cartilage erosion and osteoclast formation, and co-cultured for 7 d with either embryonic liver or mononuclear phagocytes from various sources. Light and electron microscopic examination of the cultures showed that mineralized matrix-resorbing osteoclasts developed only in bones co-cultured with embryonic liver or with cultured bone marrow mononuclear phagocytes but not when co-cultured with blood monocytes or resident or exudate peritoneal macrophages. Osteoclasts developed from the weakly adherent, but not from the strongly adherent cells of bone marrow cultures, whereas 1,000 rad irradiation destroyed the capacity of such cultures to form osteoclasts. In bone cultures to which no other cells were added, osteoclasts were virtually absent. Bone-resorbing activity of in vitro formed osteoclasts was demonstrated by 45 Ca release studies. These studies demonstrate that osteoclasts develop from cells present in cultures of proliferating mononuclear phagocytes and that, at least in our system, monocytes and macrophages are unable to form osteoclasts. The most likely candidates for osteoclast precursor cells seem to be monoblasts and promonocytes

Bone marrow transplant

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... Arrange medical leave from work Take care of bank or financial statements Arrange care of pets Arrange ... Bleeding during cancer treatment Bone marrow transplant - discharge Central venous catheter - dressing change Central venous catheter - flushing ...

Platelet lysate as a novel serum-free media supplement for the culture of equine bone marrow-derived mesenchymal stem cells.

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Naskou, Maria C; Sumner, Scarlett M; Chocallo, Anna; Kemelmakher, Hannah; Thoresen, Merrilee; Copland, Ian; Galipeau, Jacques; Peroni, John F

2018-03-22

Mesenchymal stem cells (MSCs) produced for clinical purposes rely on culture media containing fetal bovine serum (FBS) which is xenogeneic and has the potential to significantly alter the MSC phenotype, rendering these cells immunogenic. As a result of bovine-derived exogenous proteins expressed on the cell surface, MSCs may be recognized by the host immune system as non-self and be rejected. Platelet lysate (PL) may obviate some of these concerns and shows promising results in human medicine as a possible alternative to FBS. Our goal was to evaluate the use of equine platelet lysate (ePL) pooled from donor horses in place of FBS to culture equine MSCs. We hypothesized that ePL, produced following apheresis, will function as the sole media supplement to accelerate the expansion of equine bone marrow-derived MSCs without altering their phenotype and their immunomodulatory capacity. Platelet concentrate was obtained via plateletpheresis and ePL were produced via freeze-thaw and centrifugation cycles. Population doublings (PD) and doubling time (DT) of bone marrow-derived MSCs (n = 3) cultured with FBS or ePL media were calculated. Cell viability, immunophenotypic analysis, and trilineage differentiation capacity of MSCs were assessed accordingly. To assess the ability of MSCs to modulate inflammatory responses, E. coli lipopolysaccharide (LPS)-stimulated monocytes were cocultured with MSCs cultured in the two different media formulations, and cell culture supernatants were assayed for the production of tumor necrosis factor (TNF)-α. Our results showed that MSCs cultured in ePL media exhibited similar proliferation rates (PD and DT) compared with those cultured in FBS at individual time points. MSCs cultured in ePL showed a statistically significant increased viability following a single washing step, expressed similar levels of MSC markers compared to FBS, and were able to differentiate towards the three lineages. Finally, MSCs cultured in ePL efficiently suppressed

Bone marrow in pediatric patients with Hodgkin's disease.

Science.gov (United States)

Khan, Fauzia Shafi; Hasan, Rabiya Fayyaz

2012-01-01

Hodgkin's disease is a malignant process of lymphoreticular system that constitutes 6% of childhood cancers Accurate staging of lymphoma is the basis for rational therapeutic planning and assessment of the presence or absence of marrow involvement is a basic part of the staging evaluation. The objective of this study was to determine the incidence of marrow infiltration in paediatric patients with Hodgkin's disease and to ascertain its morphological spectrum in the marrow. The study included 85 paediatric patients with diagnosed Hodgkin's disease seen at The Children's Hospital/Institute of Child Health, Lahore, from January 2010 to December 2011, referred to haematology department for bone marrow biopsies. Ages ranged between two years to fourteen years with an average age of seven years, the male female ratio being 13:1. Mixed cellularity was the commonest histological type present in 66 (78%) cases. The presenting feature common in all cases was superficial lymphadenopathy followed by hepatomegaly in 17 (20%) cases and splenomegaly in 16 (19%). All the marrow aspirates were negative for infiltration. Trephine biopsies revealed marrow infiltration in 9 (10.5%). Five (56%) cases had bilateral while 4 (44%) had unilateral involvement. Pattern of infiltration was diffuse in 8 (89%) and focal in one (11%) trephines. Increased marrow fibrosis was present in eight (89%) cases. Diagnostic Reed Sternberg cells were identified in only one case and the mononuclear variants were present in six cases and atypical cells were present in two cases in these immunohistochemistry for CD15 and CD30 was performed which was positive. Granulomas in one and lymphoid aggregates were present in two trephine biopsies otherwise negative for Hodgkin's infiltration. Bone marrow infiltration was present in 10.5% cases, immunohistochemistry was used to confirm infiltration in two cases, the pattern of infiltration being diffuse in majority (89%).

Increased bone marrow blood flow in polycythemia vera

International Nuclear Information System (INIS)

Lathinen, R.; Lathinen, T.; Hyoedynmaa, S.

1983-01-01

Bone marrow blood flow was measured in polycythemia vera, in compensatory and in relative polycythemia with a 133 Xe washout method. In the treated polycythemia vera bone marrow blood flow was significantly increased compared with the age-matched controls. The fraction of blood flow entering the bone and flowing through the hematopoietic marrow was markedly increased in both the untreated and the treated polycythemia vera. Although the number of observations in compensatory and relative polycythemia was small, the results suggest that bone marrow blood flow is not markedly increased in these diseases. The results also suggest that in older patients the simple 133 Xe method may support the diagnosis of polycythemia vera. (orig.)

Increased bone marrow blood flow in polycythemia vera

Energy Technology Data Exchange (ETDEWEB)

Lathinen, R.; Lathinen, T.; Hyoedynmaa, S.

1983-01-01

Bone marrow blood flow was measured in polycythemia vera, in compensatory and in relative polycythemia with a /sup 133/Xe washout method. In the treated polycythemia vera bone marrow blood flow was significantly increased compared with the age-matched controls. The fraction of blood flow entering the bone and flowing through the hematopoietic marrow was markedly increased in both the untreated and the treated polycythemia vera. Although the number of observations in compensatory and relative polycythemia was small, the results suggest that bone marrow blood flow is not markedly increased in these diseases. The results also suggest that in older patients the simple /sup 133/Xe method may support the diagnosis of polycythemia vera.

Effect of molecular weight and concentration of hyaluronan on cell proliferation and osteogenic differentiation in vitro

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Zhao, Ningbo, E-mail: curl-zhao@163.com; Wang, Xin, E-mail: 394041230@qq.com; Qin, Lei, E-mail: qinlei30@126.com; Guo, Zhengze, E-mail: zhzeguo@163.com; Li, Dehua, E-mail: lidehuafmmu@163.com

2015-09-25

Hyaluronan (HA), the simplest glycosaminoglycan and a major component of the extracellular matrix, exists in various tissues. It is involved in some critical biological procedures, including cellular signaling, cell adhesion and proliferation, and cell differentiation. The effect of molecular weight (MW) and concentration of HA on cell proliferation and differentiation was controversial. In this study, we investigated the effect of MW and concentration of HA on the proliferation and osteogenic differentiation of rabbit bone marrow-derived stem cells in vitro. Results showed that high MW HA decreased the cell adhesion rate in a concentration-dependant manner. The cell adhesion rate was decreased by increasing MW of HA. Cell proliferation was significantly enhanced by low MW HA (P < 0.05). The factorial analysis indicated that MW and concentration had an interactive effect on the cell adhesion rate and cell proliferation (P < 0.05). High MW HA increased the mRNA expressions of ALP, RUNX-2 and OCN. The higher the MW was, the higher the mRNA expressions were. The factorial analysis indicated that MW and concentration had an interactive effect on ALP mRNA expression (P < 0.05). HA of higher MW and higher concentration promoted bone formation. These findings provide some useful information in understanding the mechanism underlying the effect of MW and concentration of HA on cell proliferation and differentiation. - Highlights: • Effect of hyaluronan on cell proliferation and differentiation is evaluated in vitro. • Hyaluronan of low molecular weight increases cell proliferation. • Hyaluronan of high molecular weight promotes cell osteogenic differentiation. • Molecular weight and concentration of hyaluronan show interactive effect.

In vitro induction of alkaline phosphatase levels predicts in vivo bone forming capacity of human bone marrow stromal cells

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Henk-Jan Prins

2014-03-01

Full Text Available One of the applications of bone marrow stromal cells (BMSCs that are produced by ex vivo expansion is for use in in vivo bone tissue engineering. Cultured stromal cells are a mixture of cells at different stages of commitment and expansion capability, leading to a heterogeneous cell population that each time can differ in the potential to form in vivo bone. A parameter that predicts for in vivo bone forming capacity is thus far lacking. We employed single colony-derived BMSC cultures to identify such predictive parameters. Using limiting dilution, we have produced sixteen single CFU-F derived BMSC cultures from human bone marrow and found that only five of these formed bone in vivo. The single colony-derived BMSC strains were tested for proliferation, osteogenic-, adipogenic- and chondrogenic differentiation capacity and the expression of a variety of associated markers. The only robust predictors of in vivo bone forming capacity were the induction of alkaline phosphatase, (ALP mRNA levels and ALP activity during in vitro osteogenic differentiation. The predictive value of in vitro ALP induction was confirmed by analyzing “bulk-cultured” BMSCs from various bone marrow biopsies. Our findings show that in BMSCs, the additional increase in ALP levels over basal levels during in vitro osteogenic differentiation is predictive of in vivo performance.

Spent fuel storage pool

International Nuclear Information System (INIS)

Murakami, Naoshi.

1996-01-01

Fences are disposed to a fuel exchange floor surrounding the upper surface of a fuel pool for preventing overflow of pool water. The fences comprise a plurality of flat boards arranged in parallel with each other in the longitudinal direction while being vertically inclined, and slits are disposed between the boards for looking down the pool. Further, the fences comprise wide boards and are constituted so as to be laid horizontally on the fuel exchange floor in a normal state and uprisen by means of the signals from an earthquake sensing device. Even if pool water is overflow from the fuel pool by the vibrations occurred upon earthquake and flown out to the floor of the fuel exchange floor, the overflow from the fuel exchange floor is prevented by the fences. An operator who monitors the fuel pool can observe the inside of the fuel pool through the slits formed to the fences during normal operation. The fences act as resistance against overflowing water upon occurrence of an earthquake thereby capable of reducing the overflowing amount of water due to the vibrations of pool water. The effect of preventing overflowing water can be enhanced. (N.H.)

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

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Katia Mareschi

2012-01-01

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

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

Science.gov (United States)

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

2012-01-01

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

Changes in compartments of hemospoietic and stromal marrow progenitor cells after continuous low dose gamma-irradiation

Science.gov (United States)

Domaratskaya, E.; Starostin, V.

The low dose continuous gamma-irradiation chosen corresponded with that affected the organisms onboard a spacecraft (Mitrikas, Tsetlin, 2000). F1 (CBAxC57Bl/6) male and female mice were used at 3 4 months of age. Experimental mice were- irradiated during 10 days to a total dose of 15 mGy (Co60 gamma-sources, mean dose rate of 1.5-2.0 mGy/day). Another group of intact mice served as control. Younger and advanced hemopoietic progenitors measured at day 11 (i.e. CFU -S-11) and day 7 (i.e. CFU-S-7), respectively, after transplantation of test donor cells were assayed by the method of Till and McCulloch (1961). Stromal changes were evaluated by estimation of in vitro fibroblastic colony-forming units (CFU -F ) content and by the ability of ectopically grafted (under renal capsule) stroma to regenerate the new bone marrow organ. CFU-S-11 number increased of 40% as compared with control and almost 2-fold higher than that of CFU-S-7. The CFU-F content increased almost of 3-fold. Size of ectopic marrow transplants was estimated at day 70 following grafting by counting myelokariocyte and CFU -S number that repopulated the newly formed bone marrow organ. It was found more than 2-fold increase of myelokariocytes in transplants produced by marrow stroma of irradiated donors. CFU -S contents in transplants increased strikingly in comparison to control level. CFU-S-7 and CFU-S-11 increased of 7.5- and of 3.7-fold, respectively, i.e. the rate of advanced CFU - S predominated. It should be noted a good correlation between number of stromal progenitor cells (CFU-F) and ectopic transplant sizes evaluated as myelokaryocyte counts when irradiated donors used. In the same time, if sizes of transplants was measured as CFU-S-7 and CFU - S-11 numbers, their increases were more pronounced. Therefore, continuous low dose gamma- irradiation augments significantly both hemopoietic and stromal progenitor cell number in bone marrow. Additionally, the ratio of distinct CFU -S subpopulations

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

Science.gov (United States)

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

2018-04-01

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

The role of growth factors in maintenance of stemness in bone marrow-derived mesenchymal stem cells

Energy Technology Data Exchange (ETDEWEB)

Eom, Young Woo; Oh, Ji-Eun [Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Lee, Jong In [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Baik, Soon Koo [Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Department of Internal Medicine, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Rhee, Ki-Jong [Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei Univ., Wonju (Korea, Republic of); Shin, Ha Cheol; Kim, Yong Man [Pharmicell Co., Ltd., Sungnam (Korea, Republic of); Ahn, Chan Mug [Department of Basic Science, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Kong, Jee Hyun [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Kim, Hyun Soo, E-mail: khsmd@pharmicell.com [Pharmicell Co., Ltd., Sungnam (Korea, Republic of); Shim, Kwang Yong, E-mail: kyshim@yonsei.ac.kr [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of)

2014-02-28

Highlights: • Expression of FGF-2, FGF-4, EGF, and HGF decreased during long-term culture of BMSCs. • Loss of growth factors induced autophagy, senescence and decrease of stemness. • FGF-2 increased proliferation potential via AKT and ERK activation in BMSCs. • FGF-2 suppressed LC3-II expression and down-regulated senescence of BMSCs. • HGF was important in maintenance of the differentiation potential of BMSCs. - Abstract: Mesenchymal stem cells (MSCs) are an active topic of research in regenerative medicine due to their ability to secrete a variety of growth factors and cytokines that promote healing of damaged tissues and organs. In addition, these secreted growth factors and cytokines have been shown to exert an autocrine effect by regulating MSC proliferation and differentiation. We found that expression of EGF, FGF-4 and HGF were down-regulated during serial passage of bone marrow-derived mesenchymal stem cells (BMSCs). Proliferation and differentiation potentials of BMSCs treated with these growth factors for 2 months were evaluated and compared to BMSCs treated with FGF-2, which increased proliferation of BMSCs. FGF-2 and -4 increased proliferation potentials at high levels, about 76- and 26-fold, respectively, for 2 months, while EGF and HGF increased proliferation of BMSCs by less than 2.8-fold. Interestingly, differentiation potential, especially adipogenesis, was maintained only by HGF treatment. Treatment with FGF-2 rapidly induced activation of AKT and later induced ERK activation. The basal level of phosphorylated ERK increased during serial passage of BMSCs treated with FGF-2. The expression of LC3-II, an autophagy marker, was gradually increased and the population of senescent cells was increased dramatically at passage 7 in non-treated controls. But FGF-2 and FGF-4 suppressed LC3-II expression and down-regulated senescent cells during long-term (i.e. 2 month) cultures. Taken together, depletion of growth factors during serial passage

The role of growth factors in maintenance of stemness in bone marrow-derived mesenchymal stem cells

International Nuclear Information System (INIS)

Eom, Young Woo; Oh, Ji-Eun; Lee, Jong In; Baik, Soon Koo; Rhee, Ki-Jong; Shin, Ha Cheol; Kim, Yong Man; Ahn, Chan Mug; Kong, Jee Hyun; Kim, Hyun Soo; Shim, Kwang Yong

2014-01-01

Highlights: • Expression of FGF-2, FGF-4, EGF, and HGF decreased during long-term culture of BMSCs. • Loss of growth factors induced autophagy, senescence and decrease of stemness. • FGF-2 increased proliferation potential via AKT and ERK activation in BMSCs. • FGF-2 suppressed LC3-II expression and down-regulated senescence of BMSCs. • HGF was important in maintenance of the differentiation potential of BMSCs. - Abstract: Mesenchymal stem cells (MSCs) are an active topic of research in regenerative medicine due to their ability to secrete a variety of growth factors and cytokines that promote healing of damaged tissues and organs. In addition, these secreted growth factors and cytokines have been shown to exert an autocrine effect by regulating MSC proliferation and differentiation. We found that expression of EGF, FGF-4 and HGF were down-regulated during serial passage of bone marrow-derived mesenchymal stem cells (BMSCs). Proliferation and differentiation potentials of BMSCs treated with these growth factors for 2 months were evaluated and compared to BMSCs treated with FGF-2, which increased proliferation of BMSCs. FGF-2 and -4 increased proliferation potentials at high levels, about 76- and 26-fold, respectively, for 2 months, while EGF and HGF increased proliferation of BMSCs by less than 2.8-fold. Interestingly, differentiation potential, especially adipogenesis, was maintained only by HGF treatment. Treatment with FGF-2 rapidly induced activation of AKT and later induced ERK activation. The basal level of phosphorylated ERK increased during serial passage of BMSCs treated with FGF-2. The expression of LC3-II, an autophagy marker, was gradually increased and the population of senescent cells was increased dramatically at passage 7 in non-treated controls. But FGF-2 and FGF-4 suppressed LC3-II expression and down-regulated senescent cells during long-term (i.e. 2 month) cultures. Taken together, depletion of growth factors during serial passage

Nódulos linfóides medulares Bone marrow lymphoid nodules

Directory of Open Access Journals (Sweden)

Silvia M. M. Magalhães

2003-06-01

haemolysis, myeloproliferative disorders and autoimmune diseases. They are usually considered to be a reactional feature. As bone marrow is the most common site of extranodal involvement of follicular lymphoma, the most important differential diagnosis is represented by bone marrow involvement by malignant lymphoma. From a practical point of view bone marrow lymphoid infiltrates are easy to diagnose on a histological basis. Benign aggregates are typically smaller, well distinguishable, contain a mixed population of cells and are nonparatrabecular. Neoplastic aggregates involving bone marrow as a paratrabecular infiltrate composed of cleaved cells. Immunophenotyping using a panel of monoclonal antibodies is capable of determining the lineage, subset and stage of differentiation of neoplastic lymphoid cells and may therefore contribute to confirm diagnosis. Especially in controversial cases, immunogenotypic analysis of the lymphoid proliferation may be helpful. Monoclonality may be detected by monotypic expressions of immunoglobulins or clonal rearrangements in the immunoglobulin heavy chain or T cell receptor genes. Ideally, the results of immunogenotypic analysis should be interpreted only in conjunction with the results of morphologic evaluation and immunophenotypic analysis. Morphology is still the gold standard in evaluating bone marrow infiltration by follicular lymphoma and immunophenotypic and immunogenotypic analysis should be considered as useful complementary investigations.

Lipocalin-2 inhibits osteoclast formation by suppressing the proliferation and differentiation of osteoclast lineage cells

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyun-Ju, E-mail: biohjk@knu.ac.kr [Department of Molecular Medicine, Cell and Matrix Research Institute, Clinical Trial Center, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Yoon, Hye-Jin [Department of Molecular Medicine, Cell and Matrix Research Institute, Clinical Trial Center, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Yoon, Kyung-Ae [Department of Orthopedic Surgery, Skeletal Diseases Genome Research Center, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Gwon, Mi-Ri; Jin Seong, Sook [Department of Molecular Medicine, Cell and Matrix Research Institute, Clinical Trial Center, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Suk, Kyoungho [Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Kim, Shin-Yoon [Department of Orthopedic Surgery, Skeletal Diseases Genome Research Center, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Yoon, Young-Ran, E-mail: yry@knu.ac.kr [Department of Molecular Medicine, Cell and Matrix Research Institute, Clinical Trial Center, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of)

2015-06-10

Lipocalin-2 (LCN2) is a member of the lipocalin superfamily and plays a critical role in the regulation of various physiological processes, such as inflammation and obesity. In this study, we report that LCN2 negatively modulates the proliferation and differentiation of osteoclast precursors, resulting in impaired osteoclast formation. The overexpression of LCN2 in bone marrow-derived macrophages or the addition of recombinant LCN2 protein inhibits the formation of multinuclear osteoclasts. LCN2 suppresses macrophage colony-stimulating factor (M-CSF)-induced proliferation of osteoclast precursor cells without affecting their apoptotic cell death. Interestingly, LCN2 decreases the expression of the M-CSF receptor, c-Fms, and subsequently blocks its downstream signaling cascades. In addition, LCN2 inhibits RANKL-induced osteoclast differentiation and attenuates the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1), which are important modulators in osteoclastogenesis. Mechanistically, LCN2 inhibits NF-κB signaling pathways, as demonstrated by the suppression of IκBα phosphorylation, nuclear translocation of p65, and NF-κB transcriptional activity. Thus, LCN2 is an anti-osteoclastogenic molecule that exerts its effects by retarding the proliferation and differentiation of osteoclast lineage cells. - Highlights: • LCN2 expression is regulated during osteoclast development. • LCN2 suppresses M-CSF-mediated osteoclast precursor proliferation. • LCN2 inhibits RANKL-induced osteoclast differentiation.

Red-yellow marrow conversion: Its effect on the location of some solitary bone lesions

International Nuclear Information System (INIS)

Kricun, M.E.

1985-01-01

The location of red marrow related bone lesions is dependent upon the distribution of red marrow. It is altered by the normal conversion of red marrow to yellow (fat) marrow and by the reconversion of yellow marrow to red marrow caused by marrow infiltrating disorders or marrow stress disorders. (orig.)

Hemopoiesis in bone marrow of lethally irradiated mice

International Nuclear Information System (INIS)

Viktora, L.; Zoubkova, M.; Urbankova, J.

1976-01-01

A percentual representation of individual types of cells and their share of the restoration of hemopoiesis in bone marrow was observed on the 9th, 12th, 16th and 20th days following transplantation of bone marrow cells to letally irradiated mice. Myelopoiesis was ascertained which on the 20th day after transplantation became the dominant constituent and reached peak level around the 16th day after transplantation. The examination further showed that with regard to the period of irradiation and transplantation the erythropoiesis in bone marrow culminates on the 9th day after the transplantation and that normal values are quickly restored. On the 2ath day myelopoiesis and lymphopoiesis come close to values in normal bone marrow

Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment

Science.gov (United States)

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

2009-01-01

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

Meta-analysis of dual-energy computed tomography virtual non-calcium imaging to detect bone marrow edema.

Science.gov (United States)

Li, Mou; Qu, Yali; Song, Bin

2017-10-01

This meta-analysis aimed to evaluate the accuracy of dual-energy CT (DECT) virtual non-calcium (VNC) imaging for the detection of bone marrow edema (BME). A systematic literature search up to March 2017 was performed to find relevant original studies. Two reviewers independently selected studies, assessed literature quality, and extracted data. Pooled sensitivity, specificity, area under receiver operating characteristic (AUROC) curve, and other measures of DECT accuracy for detecting BME were calculated using random effects models. Risk of heterogeneity was assessed for the appropriateness of meta-analysis. Fourteen studies involving 2205 regions of vertebrae, hips, knees, and ankles were included. To evaluate the accuracy of BME detection using DECT, calculations were performed to obtain a pooled sensitivity of 0.812 (95% confidence interval [CI], 0.780-0.841) and specificity of 0.951 (95% CI, 0.940-0.960). The AUROC value was 0.9635. The major potential cause of heterogeneity was bone position. No significant publication bias was present. DECT VNC imaging gives very good diagnostic performance for BME detection and will likely be an important and common modality for acute assessment in the future. Copyright © 2017. Published by Elsevier B.V.

The production of IL-1, IL-3, CSA by bone marrow nuclears during bone marrow haemopoiesis after lethal irradiation and syngenic bone marrow transplantation

International Nuclear Information System (INIS)

Dygaj, A.M.; Buznik, D.V.; Bogdashin, I.V.; Agafonov, V.I.

1994-01-01

The production of haemopoietic factors (IL-1, IL-3, CSA) by adherent and unadherent cells of lethally irradiate CBA mice bone marrow and after syngenic myelokaryocyte transplantation was studied. Radioresistant myelokaryocytes capable to produce haemopoetic factors IL-1, CSA as early as 24 hr after irradiation were found in adherent cell fraction. The synthesis of humoral factors (IL-3, CSA) by unadherent bone marrow elements was realised in a late of experiment (3-6 days) that was connected with forming of functionally valuable cell forms from transplanted or viable stem cells

Magnetic resonance imaging of the bone marrow in hematological malignancies

International Nuclear Information System (INIS)

Berg, B.C. vande; Lecouvet, F.E.; Maldague, B.; Malghem, J.; Michaux, L.; Ferrant, A.

1998-01-01

Despite its lack of specificity, magnetic resonance imaging (MRI) of the bone marrow has the potential to play a role in the management of patients with primary neoplastic disorders of the hematopoietic system, including lymphomas, leukemias and multiple myeloma. In addition to its use in the assessment of suspected spinal cord compression, bone marrow MRI could be used as a prognostic method or as a technique to assess the response to treatment. The current review addresses the common patterns of bone marrow involvement observed in primary neoplasms of the bone marrow, basic technical principles of bone marrow MRI, and several applications of MRI in selected clinical situations. (orig.) (orig.)

Bone marrow examination: Indications and diagnostic value

International Nuclear Information System (INIS)

Bashawri, Layla A.

2002-01-01

Objective was to identify the main indications for bone marrow examination in a University hospital setup and the most common diagnoses encountered. To also identify the extent of correlation, if any, between the preliminary diagnosis and the result of the final bone marrow diagnosis. The requests and reports of all bone marrow biopsies and aspirations carried out during a 12-year period from January 1988 through to December 1999, in King Fahd Hospital of the University, Al Khobar, Kingdom of Saudi Arabia were retrospectively reviewed. The information extracted included the main indications for performing this procedure, age groups involved, and the most common diagnoses encountered. A specially designed form was used for this purpose and the data was analyzed using the statistical package for social sciences. Randomly selected slides of the most common diagnoses were reviewed to concur with the diagnosis. There was a total of 1813 bone marrow biopsies or aspirations, or both, performed. The main indications for bone marrow examination in a descending order of frequency were the following: The diagnosis and management of acute leukemia 403 (22.2%), staging for lymphoma 276 (15.2%), evaluation of pancytopenia 215 (11.9%), thrombocytopenia 173 (9.5%), investigation of anemia 151 (8.3%), fever (pyrexia of unknown origin) 130 (7.2%), lymphadenopathy 120 (6.6%), and hepatosplenomegaly 80 (4.4%). The most common diagnoses encountered were: acute lymphoblastic leukemia 242 (13.3%), immune thrombocytopenia 123 (6.8%), acute myeloblastic leukemia 80 (4.4%), hypersplenism 79 (4.4%), chronic granulocytic leukemia 73 (4.0%), megaloblastic anemia 66 (3.6%), bone marrow positive for lymphomatous infiltration 63 (3.5%), chronic lymphocytic leukemia 40 (2.2%), and multiple myeloma 32 (1.8%). This study confirms that bone marrow examination is a very important investigation for establishing the diagnosis in many conditions, especially hematological neoplasms. The most common

[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.

Biochemical markers predictive for bone marrow involvement in systemic mastocytosis

NARCIS (Netherlands)

Donker, Marjolein L.; van Doormaal, Jasper J.; van Doormaal, Frederiek F.; Kluin, Philip M.; van der Veer, Eveline; de Monchy, Jan G. R.; Kema, Ido P.; Kluin-Nelemans, Hanneke C.

Systemic mastocytosis is characterized by bone marrow involvement, which requires a bone marrow biopsy for diagnostic work-up. We questioned whether bone marrow involvement could be predicted using biochemical markers. We selected patients with various symptoms suggestive of indolent systemic

Hemopoietic stem cell niches, recovery from radiation and bone marrow transfusions

International Nuclear Information System (INIS)

Cronkite, E.P.; Carsten, A.L.; Brecher, G.; Feinendegen, L.

1979-01-01

Studies were conducted on the appearance of cells in recipient bone marrow with chromosome markers after bone marrow transfusion to recipients that had different treatments. Investigators tried to replete the bone marrow CFV spleen at various times after recovery from maximal sublethal doses of x radiation or during continuous exposure to tritiated water. Studies were made on the effect of diverse treatments on the acceptance of bone marrow transfusions as shown by chromosomal markers. Results showed that the bone marrow of animals rescued by transfusion of 4 x 10 6 bone marrow cells will accept from 0 to 25% of the second transfusion of bone marrow cells given one to 4 months after the first transfusion and examined 2 to 3 weeks after the second transfusion. This may be due to the second transfusion filling up empty niches

Magnetic resonance imaging of clival marrow in patients with anorexia nervosa

Energy Technology Data Exchange (ETDEWEB)

Kuwashima, Shigeko; Nishimura, Gen; Yamato, Minoru; Fujioka, Mutsuhisa [Dokkyo Univ. School of Medicine, Mibu, Tochigi (Japan)

1996-04-01

Hematological abnormalities, commonly associated with anorexia nervosa (AN) patients, are thought to be the results of serous atrophy in the bone marrow. Magnetic resonance imaging (MRI) has been utilized to ascertain T1 and T2 prolongation of marrow intensity in the lumbar spine, pelvis and proximal femora. The results correlate well with the severity of hematological abnormalities and body mass index. More importantly, the propensity for peripheral marrow involvement of T2 prolongation contrasts with the axial involvement in other marrow disorders. MRI undertaken in patients with AN to exclude hypothalamic tumor showed that the clival marrow was equivalent to the peripheral marrow. The signal pattern of clival marrow on sagittal T1 weighted MR images was evaluated in four teen-age female patients with AN complicated by hematological abnormalities. Although the clival marrow intensity should be uniformly high in teen-agers, three patients, two with pancytopenia and one with leukopenia and anemia, exhibited homogenous low intensity. One patient who had leukopenia only and the highest body mass index, showed inhomogeneous low intensity. The signal changes returned to normal in all patients but one, who died before examination after 6-11 months, at which time the others had almost recovered their original weight and normal hemogram. T1 prolongation in the clival marrow represents bone marrow dysfunction and the inhomogeneity of the signal change may imply relative preservation of hematopoiesis and body fat composition. Lack of knowledge of this phenomenon may lead to diagnostic confusion with other marrow disorders on cranial MRI. (author).

Magnetic resonance imaging of clival marrow in patients with anorexia nervosa

International Nuclear Information System (INIS)

Kuwashima, Shigeko; Nishimura, Gen; Yamato, Minoru; Fujioka, Mutsuhisa

1996-01-01

Hematological abnormalities, commonly associated with anorexia nervosa (AN) patients, are thought to be the results of serous atrophy in the bone marrow. Magnetic resonance imaging (MRI) has been utilized to ascertain T1 and T2 prolongation of marrow intensity in the lumbar spine, pelvis and proximal femora. The results correlate well with the severity of hematological abnormalities and body mass index. More importantly, the propensity for peripheral marrow involvement of T2 prolongation contrasts with the axial involvement in other marrow disorders. MRI undertaken in patients with AN to exclude hypothalamic tumor showed that the clival marrow was equivalent to the peripheral marrow. The signal pattern of clival marrow on sagittal T1 weighted MR images was evaluated in four teen-age female patients with AN complicated by hematological abnormalities. Although the clival marrow intensity should be uniformly high in teen-agers, three patients, two with pancytopenia and one with leukopenia and anemia, exhibited homogenous low intensity. One patient who had leukopenia only and the highest body mass index, showed inhomogeneous low intensity. The signal changes returned to normal in all patients but one, who died before examination after 6-11 months, at which time the others had almost recovered their original weight and normal hemogram. T1 prolongation in the clival marrow represents bone marrow dysfunction and the inhomogeneity of the signal change may imply relative preservation of hematopoiesis and body fat composition. Lack of knowledge of this phenomenon may lead to diagnostic confusion with other marrow disorders on cranial MRI. (author)

Operation and maintenance techniques of pool and pool water purification system in IMEF

Energy Technology Data Exchange (ETDEWEB)

Soong, Woong Sup

1999-03-01

IMEF pool is used pass way between pool and hot cell in order to inlet and outlet of fuel pin in cask. All operation is performed conforming with naked eyes. Therefore floating matter is filtered so as to easy under water handling. Also radioactivity in pool water is controlled according to the nuclear law, radioactivity ration maintained less than 15mR/hr on pool side. Perfect operation and maintenance can be achieved well trained operator. Result obtained from the perfection can give more influence over restrain, spreading contamination of radioactivity materials. This report describes operation and maintenance technique of pool water purification system in IMEF. (Author). 7 refs., 13 figs.

Operation and maintenance techniques of pool and pool water purification system in IMEF

International Nuclear Information System (INIS)

Soong, Woong Sup

1999-03-01

IMEF pool is used pass way between pool and hot cell in order to inlet and outlet of fuel pin in cask. All operation is performed conforming with naked eyes. Therefore floating matter is filtered so as to easy under water handling. Also radioactivity in pool water is controlled according to the nuclear law, radioactivity ration maintained less than 15mR/hr on pool side. Perfect operation and maintenance can be achieved well trained operator. Result obtained from the perfection can give more influence over restrain, spreading contamination of radioactivity materials. This report describes operation and maintenance technique of pool water purification system in IMEF. (Author). 7 refs., 13 figs

Micro/Nano Structural Tantalum Coating for Enhanced Osteogenic Differentiation of Human Bone Marrow Stem Cells.

Science.gov (United States)

Ding, Ding; Xie, Youtao; Li, Kai; Huang, Liping; Zheng, Xuebin

2018-04-03

Recently, tantalum has been attracting much attention for its anticorrosion resistance and biocompatibility, and it has been widely used in surface modification for implant applications. To improve its osteogenic differentiation of human bone marrow stem cells (hBMSCs), a micro/nano structure has been fabricated on the tantalum coating surface through the combination of anodic oxidation and plasma spraying method. The morphology, composition, and microstructure of the modified coating were comprehensively studied by employing scanning electron microscopy (SEM), X-ray diffraction (XRD) as well as transmission electron microscopy (TEM). The effects of hierarchical structures as well as micro-porous structure of tantalum coating on the behavior for human bone marrow stem cells (hBMSCs) were evaluated and compared at both cellular and molecular levels in vitro. The experimental results show that a hierarchical micro/nano structure with Ta₂O₅ nanotubes spread onto a micro-scale tantalum coating has been fabricated successfully, which is confirmed to promote cell adhesion and spreading. Besides, the hierarchical micro/nano tantalum coating can provide 1.5~2.1 times improvement in gene expression, compared with the micro-porous tantalum coating. It demonstrates that it can effectively enhance the proliferation and differentiation of hBMSCs in vitro.

Micro/Nano Structural Tantalum Coating for Enhanced Osteogenic Differentiation of Human Bone Marrow Stem Cells

Directory of Open Access Journals (Sweden)

Ding Ding

2018-04-01

Full Text Available Recently, tantalum has been attracting much attention for its anticorrosion resistance and biocompatibility, and it has been widely used in surface modification for implant applications. To improve its osteogenic differentiation of human bone marrow stem cells (hBMSCs, a micro/nano structure has been fabricated on the tantalum coating surface through the combination of anodic oxidation and plasma spraying method. The morphology, composition, and microstructure of the modified coating were comprehensively studied by employing scanning electron microscopy (SEM, X-ray diffraction (XRD as well as transmission electron microscopy (TEM. The effects of hierarchical structures as well as micro-porous structure of tantalum coating on the behavior for human bone marrow stem cells (hBMSCs were evaluated and compared at both cellular and molecular levels in vitro. The experimental results show that a hierarchical micro/nano structure with Ta2O5 nanotubes spread onto a micro-scale tantalum coating has been fabricated successfully, which is confirmed to promote cell adhesion and spreading. Besides, the hierarchical micro/nano tantalum coating can provide 1.5~2.1 times improvement in gene expression, compared with the micro-porous tantalum coating. It demonstrates that it can effectively enhance the proliferation and differentiation of hBMSCs in vitro.

The Role od Bone Marrow Aspirate and Trephine Samples in ...

African Journals Online (AJOL)

Other disorders diagnosed after bone marrow examination include myelodysplastic syndrome (MDS), aplastic anaemia, megaloblastic anaemia and myelofibrosis. Only 8.75% of these patients had a normal bone marrow. Conclusions: This study has demonstrated the complexity of using bone marrow examination in ...

The effect of stem cell from human exfoliated deciduous teeth on T lymphocyte proliferation.

Science.gov (United States)

Alipour, Razieh; Adib, Minoo; Hashemi-Beni, Batool; Sadeghi, Farzaneh

2014-01-01

Mesenchymal stem cells (MSC), a specific type of adult tissue stem cell; have the immunosuppressive effects that make them valuable targets for regenerative medicine and treatment of many human illnesses. Hence, MSC have been the subject of numerous studies. The classical source of MSC is adult bone marrow (BM). Due to many shortcomings of harvesting MSC from BM, finding the alternative sources for MSC is an urgent. Stem cells from human exfoliated deciduous teeth (SHED) are relative new MSC populations that fulfill these criteria but their potential immunosuppressive effect has not been studied enough yet. Thus, in this work the effect of SHED on the proliferation of in vitro activated T lymphocytes were explored. In this study, both mitogen and alloantigen activated T cells were cultured in the presence of different numbers of SHED. In some co-cultures, activated T cells were in direct contact to MSCs and in other co-cultures; they were separated from SHED by a permeable membrane. In all co-cultures, the proliferation of T cells was measured by ELISA Bromodeoxyuridine proliferation assay. In general, our results showed that SHED significantly suppress the proliferation of activated T cells in a dose-dependent manner. Moreover, the suppression was slightly stronger when MSCs were in physical contact to activated T cells. This study showed that SHED likewise other MSC populations can suppress the activation of T lymphocytes, which can be used instead of BM derived MSCs in many investigational and clinical applications.

Widespread marrow necrosis during pregnancy

International Nuclear Information System (INIS)

Knickerbocker, W.J.; Quenville, N.F.

1982-01-01

Recently, a 22-year-old Caucasian female was referred to our Hospital two days post-partum. She had been feeling unwell during the last few days of her pregnancy and complained of multiple aches and pains, worst in the abdomen and lower back. Her admission platelet count was severely depressed and a bone biopsy showed extensive marrow necrosis with viable bony trabeculae. There was no evidence of vasculitis, vascular thrombosis, or malignancy. Widespread marrow necrosis in pregnancy followed by recovery, to our knowledge, has not been previously reported. (orig.)

18F-FDG PET-CT imaging versus bone marrow biopsy in pediatric Hodgkin's lymphoma: a quantitative assessment of marrow uptake and novel insights into clinical implications of marrow involvement

International Nuclear Information System (INIS)

Hassan, Aamna; Siddique, Maimoona; Bashir, Humayun; Riaz, Saima; Nawaz, M.K.; Wali, Rabia; Mahreen, Asma

2017-01-01

To evaluate whether positron emission tomography/computed tomography using fluorine-18 fluoro-deoxyglucose ( 18 F-FDG PET-CT) predicts bone marrow involvement (BMI) in pediatric Hodgkin's lymphoma (pHL) with sufficient accuracy to supplant routine staging bone marrow biopsy (BMB), and to assess the clinical importance of marrow disease by comparing the prognosis of stage IV HL with BMI versus that without BMI. Data were retrospectively analyzed for all cases of pHL between July 2010 and June 2015 referred for staging 18 F-FDG PET-CT scan and BMB. The reference standard was BMB. Stage IV patients were divided into three groups to compare their progression-free and overall survival: PET+ BMB-, PET+ BMB+, and PET- BMB-. Of the 784 patients, 83.3% were male and 16.7% female, with age ranging from 2 to 18 years (mean 10.3 years). Among the total cases, 104 (13.3%) had BMI; of these, 100 were detected by PET imaging and 58 by BMB. BMB and 18 F-FDG PET/CT scans were concordant for BMI detection in 728 patients (93%): positive concordance in 54 and negative in 674. Of the 56 discordant cases, four had a false-negative PET scans and were upstaged by BMB, 46 with focal uptake were PET/CT-positive and BMB-negative (not obtained from active sites), and six with diffuse uptake were false-positive on PET due to paraneoplastic marrow activation. The sensitivity, specificity, PPV, and NPV of PET for identifying BMI was 93.6, 94, 53, and 99.4% respectively. On quantitative assessment, mean iBM-SUV max of bilateral iliac crests was significantly higher in those with BMI versus those without (p < 0.05). 18 F-FDG PET-CT imaging is more sensitive than BMB for BMI detection in pHL staging. BMB should be limited to those with normal marrow uptake in the presence of poor risk factors or those with diffusely increased uptake to exclude marrow involvement in the background of reactive marrow. (orig.)

Pediatric cervical spine marrow T2 hyperintensity: a systematic analysis

Energy Technology Data Exchange (ETDEWEB)

Gefen, Ron [Cooper University Hospital, Department of Diagnostic Radiology, Candem, NJ (United States); Schweitzer, Mark E. [The Ottawa Hospital and University of Ottawa, Department of Diagnostic Imaging, Ottawa (Canada); Shabshin, Nogah [Department of Diagnostic Imaging, Chaim Sheba Medical Center, Tel-HaShomer (Israel); Hospital of University of Pennsylvania, Department of Diagnostic Imaging, Philadelphia, PA (United States)

2011-08-15

Hyperintense areas of vertebral bone marrow on fluid-sensitive sequences are at times seen on pediatric MRI of the cervical spine in children without suspicious clinical conditions to explain marrow pathology. Although these likely have no clinical significance they may be mistaken for pathology. The purpose of this study is to systematically evaluate the locations and patterns of marrow T2 hyperintensity in the pediatric cervical spine, with respect to age. At 1.5 T, the C2 through T3 vertebrae of 82 children aged 0-17 years without clinically suspicious marrow abnormality were retrospectively reviewed by two musculoskeletal radiologists, who were blinded to patients' age. The frequency, intensity, and location of the foci of marrow T2 hyperintensity were recorded for each vertebra on a 12-point scoring system and were correlated with the patients' age. Foci of marrow hyperintensity were seen in 46/82 (56.1%) patients and in 241/734 (32.8%) vertebrae. Foci were most common in C4 (42% of patients), C5 (45.7%), and C6 (37.8%). The foci of T2 hyperintensity were more common inferiorly (188 foci) and adjacent to the anterior cortex (123). Analysis revealed no significant correlation between age and marrow score (Spearman = -0.147, P = 0.19), but did find a trend towards increased presence of marrow T2 hyperintensity in the ages of most rapid growth, 8-14 years (81.5% of patients). Vertebral body marrow T2 hyperintensity was most common endosteally and in the mid-cervical spine with a slight peak in adolescence. We therefore believe that these pediatric cervical marrow changes may be related to rapid bone growth at the point of maximal kyphotic stress. (orig.)

Radiation-induced aneusomic clones in bone marrow of rats

International Nuclear Information System (INIS)

Kohno, Sei-Ichi; Ishihara, Takaaki

1976-01-01

Wistar rats 3 months old were given a single whole-body X-irradiation with 700 R. They were killed 9.3 months, on average, after irradiation. From the bone marrows of the 23 irradiated rats, 54 clones of cells with radiation-induced chromosome abnormalities ranging from 3.3 to 78.3% in size were obtained. Karyotype analysis at the banding level showed that 43 out of the 54 clones had balanced chromosome constitutions and that the remaining 11 clones were unbalanced. The 43 balanced clones consisted of 33 clones with reciprocal translocations, 6 with inversions and 4 with both translocations and inversions. The 11 unbalanced clones were made up of 7 aneuploid clones and 4 pseudo-diploid clones. Of the 54 clones, 15 were large with frequencies of more than 25%. Contrary to general belief that cells with unbalanced chromosome constitutions have less capacity to proliferate than those with balanced ones, 8 of the 15 large clones, especially all, except 1, of the largest 6 clones were unbalanced, either aneuploid or pseudo-diploid

The evaluation of the bone marrow accumulation of Ga-67 citrate

Energy Technology Data Exchange (ETDEWEB)

Ohnishi, Takashi; Jinnouchi, Seishi; Hoshi, Hiroaki; Yoshimura, Hiroshi; Nagamachi, Shigeki; Watanabe, Katsushi (Miyazaki Medical Coll., Kiyotake (Japan))

1989-11-01

The bone marrow distribution of Ga-67 citrate may be influenced by various elements in serum. In order to make these points clear, 1,955 whole body images were reviewed on the relationship between the accumulation of bone marrow and laboratory examination data of each patients. Increasing accumulation in the bone marrow was determined as positive when the bones of lower extremities were deposited on the images, because these bones was not visualized in normal gallium image. Laboratory data of 20 patients without having bone marrow accumulation was used as control. The positive findings of bone marrow accumulation was observed in 38 patients (2%) including 23 malignancies and 15 benign disease. The malignant tumor infiltration to the bone marrow was demonstrated by bone marrow aspiration biopsy in 2 out of 7 patients with bone marrow accumulation of Ga-67. Seven out of 15 patients with benign disease were collagen disease such as aortitis syndrome or SLE. The values of hemoglobin, hematocrit, serum iron and creatinine clearance were significantly lower in the patients with positive findings in comparison with control. These results suggest that the lower level of serum iron and anemia may cause increasing bone marrow accumulation of Ga-67 citrate. (author).

The evaluation of the bone marrow accumulation of Ga-67 citrate

International Nuclear Information System (INIS)

Ohnishi, Takashi; Jinnouchi, Seishi; Hoshi, Hiroaki; Yoshimura, Hiroshi; Nagamachi, Shigeki; Watanabe, Katsushi

1989-01-01

The bone marrow distribution of Ga-67 citrate may be influenced by various elements in serum. In order to make these points clear, 1,955 whole body images were reviewed on the relationship between the accumulation of bone marrow and laboratory examination data of each patients. Increasing accumulation in the bone marrow was determined as positive when the bones of lower extremities were deposited on the images, because these bones was not visualized in normal gallium image. Laboratory data of 20 patients without having bone marrow accumulation was used as control. The positive findings of bone marrow accumulation was observed in 38 patients (2%) including 23 malignancies and 15 benign disease. The malignant tumor infiltration to the bone marrow was demonstrated by bone marrow aspiration biopsy in 2 out of 7 patients with bone marrow accumulation of Ga-67. Seven out of 15 patients with benign disease were collagen disease such as aortitis syndrome or SLE. The values of hemoglobin, hematocrit, serum iron and creatinine clearance were significantly lower in the patients with positive findings in comparison with control. These results suggest that the lower level of serum iron and anemia may cause increasing bone marrow accumulation of Ga-67 citrate. (author)

Biodegradable Thermogel as Culture Matrix of Bone Marrow Mesenchymal Stem Cells for Potential Cartilage Tissue Engineering

Institute of Scientific and Technical Information of China (English)

Yan-bo Zhang; Jian-xun Ding; Wei-guo Xu; Jie Wu; Fei Chang; Xiu-li Zhuang; Xue-si Chen

2014-01-01

Poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer was synthesized through the ring-opening polymerization of LA and GA with PEG as macroinitiator and stannous octoate as catalyst.The amphiphilic copolymer self-assembled into micelles in aqueous solutions,and formed hydrogels as the increase of temperature at relatively high concentrations (＞ 15 wt％).The favorable degradability of the hydrogel was confirmed by in vitro and in vivo degradation experiments.The good cellular and tissular compatibilities of the thermogel were demonstrated.The excellent adhesion and proliferation of bone marrow mesenchymal stem cells endowed PLGA-PEG-PLGA thermogelling hydrogel with fascinating prospect for cartilage tissue engineering.

Swimming pool granuloma

Science.gov (United States)

... this page: //medlineplus.gov/ency/article/001357.htm Swimming pool granuloma To use the sharing features on this page, please enable JavaScript. A swimming pool granuloma is a long-term (chronic) skin ...

T1 value of hyperplastic and hypoplastic bone marrow

International Nuclear Information System (INIS)

Asai, Sae; Yoshida, Hideo; Yoshikawa, Hiroki; Yashiro, Naofumi; Iio, Masahiro; Takaku, Fumimaro

1985-01-01

Magnetic resonance (MR) images of the bone marrow of 18 patients (11 normal control, 4 aplastic anemia, 2 chronic myelocytic leukemia, 1 polycythemia vera) were discussed. MR imager had 0.15T registive system. Sagittal section of the body was obtained with inversion recovery (TR1,000, 1,600/TI 350, 450/TE 13, 40 msec) and saturation recovery (TR 1,000, 2,000/TE 13,40 msec) sequences. T 1 relaxation time was calculated from those images. T 1 value of the thoracic and lumbar vertebral bone marrow which contains red marrow even in elderly patients was measured. The results were as follows: 1) T 1 values of chronic myelocytic leukemia (CML) and polycythemia vera were longer than that of normal. 2) T 1 values of four aplastic anemia were all shorter than normal. CML and polycythemia vera can be called myeloproliferative disease and their bone marrows are hyperplastic, which may explain elongated T 1 . The bone marrow of aplasticanemia is hypoplastic and shows fatty change which may have decreased T 1 . Our results suggest T 1 value of bone marrow is useful to evaluate hematological disorders. (author)

Reconstitution of the myeloid and lymphoid compartments after the transplantation of autologous and genetically modified CD34+ bone marrow cells, following gamma irradiation in cynomolgus macaques

Directory of Open Access Journals (Sweden)

Auregan Gwenaelle

2008-06-01

Full Text Available Abstract Background Prolonged, altered hematopoietic reconstitution is commonly observed in patients undergoing myeloablative conditioning and bone marrow and/or mobilized peripheral blood-derived stem cell transplantation. We studied the reconstitution of myeloid and lymphoid compartments after the transplantation of autologous CD34+ bone marrow cells following gamma irradiation in cynomolgus macaques. Results The bone marrow cells were first transduced ex vivo with a lentiviral vector encoding eGFP, with a mean efficiency of 72% ± 4%. The vector used was derived from the simian immunodeficiency lentivirus SIVmac251, VSV-g pseudotyped and encoded eGFP under the control of the phosphoglycerate kinase promoter. After myeloid differentiation, GFP was detected in colony-forming cells (37% ± 10%. A previous study showed that transduction rates did not differ significantly between colony-forming cells and immature cells capable of initiating long-term cultures, indicating that progenitor cells and highly immature hematopoietic cells were transduced with similar efficiency. Blood cells producingeGFP were detected as early as three days after transplantation, and eGFP-producing granulocyte and mononuclear cells persisted for more than one year in the periphery. Conclusion The transplantation of CD34+ bone marrow cells had beneficial effects for the ex vivo proliferation and differentiation of hematopoietic progenitors, favoring reconstitution of the T- and B-lymphocyte, thrombocyte and red blood cell compartments.

Curcumin-functionalized silk materials for enhancing adipogenic differentiation of bone marrow-derived human mesenchymal stem cells

Science.gov (United States)

Li, Chunmei; Luo, Tingting; Zheng, Zhaozhu; Murphy, Amanda R.; Wang, Xiaoqin; Kaplan, David L.

2014-01-01

Curcumin, a natural phenolic compound derived from the plant Curcuma longa, was physically entrapped and stabilized in silk hydrogel films and its influence on human bone marrow-derived mesenchymal stem cells (hBMSCs) was assessed related to adipogenic differentiation. The presence of curcumin significantly reduced silk gelation time and changed the porous morphology of gel matrix, but did not change the formation of silk beta-sheet structure. Based on spectrofluorimetric analysis, curcumin likely interacted with hydrophobic residues in silk, interacting with the beta-sheet domains formed in the hydrogels. The antioxidant activity of silk film-associated curcumin remained functional over at least one month in both the dry and hydrated state. Negligible curcumin was released from silk hydrogel films over 48 hours incubation in aqueous solution. For hBMSCs cultured on silk films containing more than 0.25 mg/mL curcumin, cell proliferation was inhibited while adipogenesis was significantly promoted based on transcripts as well as oil red O staining. When hBMSCs were cultured in media containing free curcumin, both proliferation and adipogenesis of hBMSCs were inhibited when curcumin concentrations exceeded 5 μM, which is more than 1,000-times higher than the level of curcumin released from the films in aqueous solution. Thus, silk film-associated curcumin exhibited different effects on hBMSC proliferation and differentiation when compared to curcumin in solution. PMID:25132274

Swimming pool hydraulics and their significance for public pools. Bedeutung der Beckenhydraulik in oeffentlichen Schwimmbaedern

Energy Technology Data Exchange (ETDEWEB)

Gansloser, G

1989-11-01

The term of swimming pool hydraulics means the process of letting in and drawing off water to and from the pool while ensuring that no inadmissible water-borne contaminant concentrations will occur anywhere within the pool. Measurements were performed on a pool to study the significance of correct pool hydraulics. The author points out that a wrong water recirculation design will bring to nought the effects of an elaborate water treatment system; by contrast, poor pool water quality can be greatly improved by redesigning the pool water hydraulics approach. In principle, systems with with water inlet at one side and water outlet at the far side will fall short of hygienic requirements. (BWI).

MRI of the marrow in the paediatric skeleton

International Nuclear Information System (INIS)

Foster, K.; Chapman, S.; Johnson, K.

2004-01-01

Magnetic resonance imaging (MRI) has greatly advanced evaluation of marrow diseases of the paediatric skeleton. As with many other aspects of paediatric radiology it is important to recognize the normal variations in the appearance of the marrow that occur in the growing child. These normal variations need to be differentiated from diseases and conditions that affect the marrow. This review describes the normal changes that occur in children with age, and the appearances of the pathological changes seen in infection, infiltration, haematological disorders, transplantation and radiation therapy

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.

Karyotype of cryopreserved bone marrow cells.

Science.gov (United States)

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

2003-07-01

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

MR imaging of normal bone marrow; Obraz MR prawidlowego szpiku kostnego

Energy Technology Data Exchange (ETDEWEB)

Stajgis, M.; Paprzycki, W. [Osrodek Diagnostyki Obrazowej IR, Akademia Medyczna, Poznan (Poland)

1994-12-31

Principles of MR bone marrow imaging on the basis of retrospective analysis of MR examinations of bone marrow in different anatomic sites in 200 patients have been discussed. Significance of different physiologic factors and processes such as age, steatosis, osteoporosis, conversion and reconversion, which influence on MR bone marrow images, have been emphasized. T1-weighted images obtained with spin-echo sequences give the most of information about bone marrow structure in MR. Thorough knowledge of bone marrow physiology and clinical status of the patient is indispensable in correct interpretation of hypointensive lesions on T1-weighted images. When presence of disseminated bone marrow disease is suspected, authors propose routine imaging of lumbar vertebral column, pelvis and proximal parts of femoral bones. (author) 7 refs, 7 figs

PDA: Pooled DNA analyzer

Directory of Open Access Journals (Sweden)

Lin Chin-Yu

2006-04-01

Full Text Available Abstract Background Association mapping using abundant single nucleotide polymorphisms is a powerful tool for identifying disease susceptibility genes for complex traits and exploring possible genetic diversity. Genotyping large numbers of SNPs individually is performed routinely but is cost prohibitive for large-scale genetic studies. DNA pooling is a reliable and cost-saving alternative genotyping method. However, no software has been developed for complete pooled-DNA analyses, including data standardization, allele frequency estimation, and single/multipoint DNA pooling association tests. This motivated the development of the software, 'PDA' (Pooled DNA Analyzer, to analyze pooled DNA data. Results We develop the software, PDA, for the analysis of pooled-DNA data. PDA is originally implemented with the MATLAB® language, but it can also be executed on a Windows system without installing the MATLAB®. PDA provides estimates of the coefficient of preferential amplification and allele frequency. PDA considers an extended single-point association test, which can compare allele frequencies between two DNA pools constructed under different experimental conditions. Moreover, PDA also provides novel chromosome-wide multipoint association tests based on p-value combinations and a sliding-window concept. This new multipoint testing procedure overcomes a computational bottleneck of conventional haplotype-oriented multipoint methods in DNA pooling analyses and can handle data sets having a large pool size and/or large numbers of polymorphic markers. All of the PDA functions are illustrated in the four bona fide examples. Conclusion PDA is simple to operate and does not require that users have a strong statistical background. The software is available at http://www.ibms.sinica.edu.tw/%7Ecsjfann/first%20flow/pda.htm.

Antibody formation in mouse bone marrow. IV. The influence of splenectomy on the bone marrow plaque-forming cell response to sheep red blood cells

International Nuclear Information System (INIS)

Benner, R.; Oudenaren, A. van

1975-01-01

Mouse bone marrow is barely capable of plaque-forming cell (PFC) activity during the primary response to sheep red blood cells (SRBC). However, during the secondary response, it becomes the major center of activity containing IgM-, IgG- and IgA-PFC. In the present paper the influence of splenectomy was studied on primary and secondary PFC activity in the bone marrow. Differences in primary and secondary bone marrow PFC responses are probably related to the presence of B and T memory cells in situ. Therefore the effect of splenectomy on the appearance of B and T memory cells in the bone marrow was also investigated. iv.plenectomy before intravenous (iv) immunization with 4 x 10 8 SRBC prevented any primary PFC activity in the bone marrow. The influence of splenectomy before priming on secondary PFC activity in the bone marrow depended on the priming dose of SRBC. Splenectomy before priming with 10 7 SRBC iv completely prevented IgM-, IgG-, and IgA-PFC activity in the bone marrow upon subsequent boosting with 4 x 10 8 SRBC iv. By means of cell transfer experiments it was shown that after splenectomy no B or T memory cells appeared in the bone marrow after priming with 10 7 SRBC iv. Cell transfer experiments showed that splenectomy before priming with 10 7 SRBC iv not only interfered with the appearance of B and T memory cells in the bone marrow, but also with the appearance of B memory cells in peripheral lymph nodes, mesenteric lymph node, Peyer's patches, thymus, and blood. Immunization of spenectomized mice with 4 x 10 8 SRBC iv induced the appearance of B memory cells in peripheral lymph nodes, mesenteric lymph node, Peyer's patches, thymus, and blood

Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia.

Directory of Open Access Journals (Sweden)

Antonella Conforti

Full Text Available Alterations in hematopoietic microenvironment of acute lymphoblastic leukemia patients have been claimed to occur, but little is known about the components of marrow stroma in these patients. In this study, we characterized mesenchymal stromal cells (MSCs isolated from bone marrow (BM of 45 pediatric patients with acute lymphoblastic leukemia (ALL-MSCs at diagnosis (day+0 and during chemotherapy treatment (days: +15; +33; +78, the time points being chosen according to the schedule of BM aspirates required by the AIEOP-BFM ALL 2009 treatment protocol. Morphology, proliferative capacity, immunophenotype, differentiation potential, immunomodulatory properties and ability to support long-term hematopoiesis of ALL-MSCs were analysed and compared with those from 41 healthy donors (HD-MSCs. ALL-MSCs were also genetically characterized through array-CGH, conventional karyotyping and FISH analysis. Moreover, we compared ALL-MSCs generated at day+0 with those isolated during chemotherapy. Morphology, immunophenotype, differentiation potential and in vitro life-span did not differ between ALL-MSCs and HD-MSCs. ALL-MSCs showed significantly lower proliferative capacity (p<0.001 and ability to support in vitro hematopoiesis (p = 0.04 as compared with HD-MSCs, while they had similar capacity to inhibit in vitro mitogen-induced T-cell proliferation (p = N.S.. ALL-MSCs showed neither the typical translocations carried by the leukemic clone (when present, nor other genetic abnormalities acquired during ex vivo culture. Our findings indicate that ALL-MSCs display reduced ability to proliferate and to support long-term hematopoiesis in vitro. ALL-MSCs isolated at diagnosis do not differ from those obtained during treatment.

13 CFR 120.1706 - Pool Originator's retained interest in Pool.

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Pool Originator's retained interest in Pool. 120.1706 Section 120.1706 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Establishment of SBA Secondary Market Guarantee Program for First Lien Position 504 Loan...

Silk fibroin/gelatin–chondroitin sulfate–hyaluronic acid effectively enhances in vitro chondrogenesis of bone marrow mesenchymal stem cells

International Nuclear Information System (INIS)

Sawatjui, Nopporn; Damrongrungruang, Teerasak; Leeanansaksiri, Wilairat; Jearanaikoon, Patcharee; Hongeng, Suradej; Limpaiboon, Temduang

2015-01-01

Tissue engineering is becoming promising for cartilage repair due to the limited self-repair capacity of cartilage tissue. We previously fabricated and characterized a three-dimensional silk fibroin/gelatin–chondroitin sulfate–hyaluronic acid (SF–GCH) scaffold and showed that it could promote proliferation of human bone marrow mesenchymal stem cells (BM-MSCs). This study aimed to evaluate its biological performance as a new biomimetic material for chondrogenic induction of BM-MSCs in comparison to an SF scaffold and conventional pellet culture. We found that the SF–GCH scaffold significantly enhanced the proliferation and chondrogenic differentiation of BM-MSCs compared to the SF scaffold and pellet culture in which the production of sulfated glycoaminoglycan was increased in concordance with the up-regulation of chondrogenic-specific gene markers. Our findings indicate the significant role of SF–GCH by providing a supportive structure and the mimetic cartilage environment for chondrogenesis which enables cartilage regeneration. Thus, our fabricated SF–GCH scaffold may serve as a potential biomimetic material for cartilage tissue engineering. - Highlights: • SF–GCH scaffold enhances proliferation and chondrogenic differentiation of BM-MSCs. • SF–GCH acts as a supportive and biomimetic material for BM-MSC chondrogenesis. • SF–GCH is a potential biomimetic scaffold suitable for cartilage tissue engineering

Silk fibroin/gelatin–chondroitin sulfate–hyaluronic acid effectively enhances in vitro chondrogenesis of bone marrow mesenchymal stem cells

Energy Technology Data Exchange (ETDEWEB)

Sawatjui, Nopporn [Biomedical Sciences, Graduate School, Khon Kaen University, Khon Kaen 40002 (Thailand); Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002 (Thailand); Damrongrungruang, Teerasak [Department of Oral Diagnosis, Faculty of Dentistry, Khon Kaen University, Khon Kaen 40002 (Thailand); Leeanansaksiri, Wilairat [Stem Cell Therapy and Transplantation Research Group, Suranaree University of Technology, Nakhon Ratchasima 30000 (Thailand); School of Microbiology, Suranaree University of Technology, Nakhon Ratchasima 30000 (Thailand); Jearanaikoon, Patcharee [Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002 (Thailand); Hongeng, Suradej [Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400 (Thailand); Limpaiboon, Temduang, E-mail: temduang@kku.ac.th [Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002 (Thailand)

2015-07-01

Tissue engineering is becoming promising for cartilage repair due to the limited self-repair capacity of cartilage tissue. We previously fabricated and characterized a three-dimensional silk fibroin/gelatin–chondroitin sulfate–hyaluronic acid (SF–GCH) scaffold and showed that it could promote proliferation of human bone marrow mesenchymal stem cells (BM-MSCs). This study aimed to evaluate its biological performance as a new biomimetic material for chondrogenic induction of BM-MSCs in comparison to an SF scaffold and conventional pellet culture. We found that the SF–GCH scaffold significantly enhanced the proliferation and chondrogenic differentiation of BM-MSCs compared to the SF scaffold and pellet culture in which the production of sulfated glycoaminoglycan was increased in concordance with the up-regulation of chondrogenic-specific gene markers. Our findings indicate the significant role of SF–GCH by providing a supportive structure and the mimetic cartilage environment for chondrogenesis which enables cartilage regeneration. Thus, our fabricated SF–GCH scaffold may serve as a potential biomimetic material for cartilage tissue engineering. - Highlights: • SF–GCH scaffold enhances proliferation and chondrogenic differentiation of BM-MSCs. • SF–GCH acts as a supportive and biomimetic material for BM-MSC chondrogenesis. • SF–GCH is a potential biomimetic scaffold suitable for cartilage tissue engineering.

BONE MARROW ABONRMALITIES IN HIV INFECTION

OpenAIRE

Sharad Antiram Dhurve

2013-01-01

Introduction Hematological abnormalities are a common complication of HIV infection. Bone marrow abnormalities occur in all stages of HIV infection. Present work was carried out to study the bone marrow abnormalities in patients with HIV/AIDS. Methods 160 patients of HIV +ve were included in the study. A complete blood count, relevant biochemical investigations, CD4 counts were done, besides a thorough history and clinical examination. HIV positive patients were classified as those having AID...

Post-irradiation thymocyte regeneration after bone marrow transplantation

International Nuclear Information System (INIS)

Boersma, W.J.A.

1981-01-01

Bone marrow cells were separated according to buoyant density, velocity sedimentation and cell surface charge. Fractionated (C3H x AKR)F 1 bone marrow cells were transplanted into lethally-irradiated C3H recipients. In all fractions, the CFUs content and the capacity to restore the thymus cell population were determined. For all the physical parameters tested, thymocyte progenitor cells show the same distribution as CFUs. The relationship between number of thymocyte progenitor cells and number of CFUs is dependent on density. Bone marrow progenitors of PHA responsive cells are of low buoyant density and show a distribution which resembles the distribution of the progenitors of Thy 1 positive cells. After transplantation of large numbers of bone marrow cells into irradiated mice, no significant change in the CFUs content of the thymus was observed. (author)

Intrathymic lymphopoiesis: stromal cell-associated proliferation of T cells is independent of lymphocyte genotype.

Science.gov (United States)

Kyewski, B A; Travis, M; Kaplan, H S

1984-09-01

We analyzed the genetic restriction of direct cell-cell interactions between thymocytes and a) cortical epithelial cells, b) macrophages, and c) medullary dendritic cells in the mouse thymus. Thymectomized (C3H X C57BL/Ka)F1 hybrid mice were doubly grafted with P1 and P2 neonatal thymus grafts, were lethally irradiated, and were reconstituted with a mixture of P1 and P2 bone marrow cells which differed in the Thy-1 locus. The contributions of both parental inocula to the composition of the free and stromal cell-associated T cell compartments were analyzed separately in thymic grafts of each parental strain. The lymphoid composition in both compartments essentially reflected the peripheral T cell-chimerism in the host. The development of lymphostromal complexes was not restricted by the genotype of the partner cells. Statistical analysis of the distributions of P1 and P2 T cells among free thymocytes and within individual lymphostromal complexes, however, suggests that the T cells of an individual complex are the progeny of oligoclonal proliferation. Thus, both epithelial cells and bone marrow-derived stromal cells seem to be involved in different stages of intrathymic lymphopoiesis.

Capacidade da matriz extracelular da medula óssea de induzir proliferação de células mielóides in vitro no modelo de desnutrição protéica em camundongos Capacity of the extracellular matrix of the bone marrow to induce proliferation of myeloid cells in vitro in model of protein malnutrition in mice

Directory of Open Access Journals (Sweden)

Cidônia de Lourdes Vituri

2008-09-01

Full Text Available Este trabalho tem por objetivo verificar se a matriz extracelular (MEC obtida da medula óssea de camundongos com desnutrição protéica energética sustenta a sobrevivência, se induz proliferação de células mielóides, bem como avaliar a capacidade desta MEC de interagir com citocinas hematopoiéticas in vitro. Camundongos machos "Swiss" foram submetidos à desnutrição protéica (4% de caseína até que perdessem 20% do peso inicial e o grupo-controle foi mantido com uma dieta contendo 14% de caseína. A medula óssea foi extraída com tampão PBS suplementado com 1 mg de aprotinina/mL. Os ensaios de proliferação foram realizados com a linhagem mielóide FDC-P1, pelo método colorimétrico de redução do MTT. A MEC obtida tanto do grupo-controle como do desnutrido induziu proliferação celular in vitro. Os ensaios de interação foram realizados com IL-3 e GM-CSF na concentração de 10 ρg e 500 ρg/mL, que demonstraram efeito sinérgico e efeito regulatório, respectivamente. A MEC obtida de animais do grupo desnutrido quando submetida ao ensaio de ligação ao GM-CSF mostrou maior proliferação celular do que a MEC obtida de animais do grupo-controle (pThe aim of this study was to verify the capacity of the extracellular matrix (ECM obtained from bone marrow of malnourished mice to sustain survival and to induce the proliferation of myeloid cells. We also verified the capacity of the tests to interact with in vitro hematopoietic cytokines. Male "Swiss" mice were submitted to protein malnutrition with a diet content of '4% casein until they lost 20% of the original weight, while the group-control was kept with a diet content of 14% of casein. The bone marrow was extracted with 1.0 mg of aprotinin/mL in PBS. The proliferation tests were carried out with myeloid cell line FDCP-1, by the colorimetric method of reduction of the MTT. The obtained ECM from nourished and undernourished mice induced cellular proliferation invitro. Tests

Bone marrow transplantation for an infant with neutrophil dysfunction

Energy Technology Data Exchange (ETDEWEB)

Camitta, B M; Quesenberry, P J; Parkman, R; Boxer, L A; Stossel, T P; Cassady, J R; Rappeport, J M; Nathan, D G [Harvard Medical School, Boston, Mass. (USA); Tufts Univ., Boston, Mass. (USA). School of Medicine)

1977-01-01

A child with severe neutrophil dysfunction and intractable infections received bone marrow transplants from histocompatible siblings. After a first transplant preceded by cyclophosphamide (CY), antithymocyte serum (ATS) and procarbazine (PCB) preconditioning, there was no evidence for engraftment and autologous marrow function rapidly returned. Cell mediated lysis showed no evidence of patient sensitization against the marrow donor suggesting that graft rejection did not cause the transplant failure. A second transplant was performed utilizing another matched sibling donor. Total body irradiation was added to CY, ATS, and PCB for preconditioning after in vitro studies of the colony forming capacity (CFUsub(c)) of the patient's marrow cells showed normal sensitivity to radiation. Full engraftment ensued with correction of granulocyte function abnormalities. The patient eventually died of intractable pulmonary disease. Experience with this child suggests that cyclophosphamide alone may be insufficient preparation for marrow transplantation in some patients with non-neoplastic hematologic disorders. Experimental and clinical data supporting this contention are reviewed.

{sup 18}F-FDG PET-CT imaging versus bone marrow biopsy in pediatric Hodgkin's lymphoma: a quantitative assessment of marrow uptake and novel insights into clinical implications of marrow involvement

Energy Technology Data Exchange (ETDEWEB)

Hassan, Aamna; Siddique, Maimoona; Bashir, Humayun; Riaz, Saima; Nawaz, M.K. [Shaukat Khanum Memorial Cancer Hospital and Research Centre, Department of Nuclear Medicine, Lahore (Pakistan); Wali, Rabia; Mahreen, Asma [Shaukat Khanum Memorial Cancer Hospital and Research Centre, Paediatric Oncology, Lahore (Pakistan)

2017-07-15

To evaluate whether positron emission tomography/computed tomography using fluorine-18 fluoro-deoxyglucose ({sup 18}F-FDG PET-CT) predicts bone marrow involvement (BMI) in pediatric Hodgkin's lymphoma (pHL) with sufficient accuracy to supplant routine staging bone marrow biopsy (BMB), and to assess the clinical importance of marrow disease by comparing the prognosis of stage IV HL with BMI versus that without BMI. Data were retrospectively analyzed for all cases of pHL between July 2010 and June 2015 referred for staging {sup 18}F-FDG PET-CT scan and BMB. The reference standard was BMB. Stage IV patients were divided into three groups to compare their progression-free and overall survival: PET+ BMB-, PET+ BMB+, and PET- BMB-. Of the 784 patients, 83.3% were male and 16.7% female, with age ranging from 2 to 18 years (mean 10.3 years). Among the total cases, 104 (13.3%) had BMI; of these, 100 were detected by PET imaging and 58 by BMB. BMB and {sup 18}F-FDG PET/CT scans were concordant for BMI detection in 728 patients (93%): positive concordance in 54 and negative in 674. Of the 56 discordant cases, four had a false-negative PET scans and were upstaged by BMB, 46 with focal uptake were PET/CT-positive and BMB-negative (not obtained from active sites), and six with diffuse uptake were false-positive on PET due to paraneoplastic marrow activation. The sensitivity, specificity, PPV, and NPV of PET for identifying BMI was 93.6, 94, 53, and 99.4% respectively. On quantitative assessment, mean iBM-SUV{sub max} of bilateral iliac crests was significantly higher in those with BMI versus those without (p < 0.05). {sup 18}F-FDG PET-CT imaging is more sensitive than BMB for BMI detection in pHL staging. BMB should be limited to those with normal marrow uptake in the presence of poor risk factors or those with diffusely increased uptake to exclude marrow involvement in the background of reactive marrow. (orig.)

Loss of C/EBP alpha cell cycle control increases myeloid progenitor proliferation and transforms the neutrophil granulocyte lineage

DEFF Research Database (Denmark)

Porse, Bo T; Bryder, David; Theilgaard-Mönch, Kim

2005-01-01

dissociate the ability of C/EBP alpha to block cell cycle progression through E2F inhibition from its function as a transcriptional activator impair the in vivo development of the neutrophil granulocyte and adipose lineages. We now show that such mutations increase the capacity of bone marrow (BM) myeloid...... progenitors to proliferate, and predispose mice to a granulocytic myeloproliferative disorder and transformation of the myeloid compartment of the BM. Both of these phenotypes were transplantable into lethally irradiated recipients. BM transformation was characterized by a block in granulocyte differentiation...

Transplantation of bone marrow cells into lethally irradiated mice

International Nuclear Information System (INIS)

Viktora, L.; Hermanova, E.

1978-01-01

Morphological changes were studied of megakaryocytes in the bone marrow and spleen of lethally irradiated mice (0.2 C/kg) after transplantation of living bone marrow cells. It was observed that functional trombopoietic megakaryocytes occur from day 15 after transplantation and that functional active megakaryocytes predominate in bone marrow and spleen from day 20. In addition, other types of cells, primarily granulocytes, were detected in some megakaryocytes. (author)

Interplay of thymus and bone marrow regeneration in x-irradiated mice

International Nuclear Information System (INIS)

Hiesche, K.-D.

1975-01-01

aim of the prepresent investigation was to study the modifying effects of bone marrow cells on regeneration, after X-irradiation, of thymus and bone marrow cell populations. Data are presented which indicate that the cellular composition of the thymus and, in particular, the frequency of the stem cells in the organ at the time of radiation exposure determines thymic regeneration for about two weeks after irradiation. After this period, regeneration depends on new precursors from the bone marrow which have previously seeded the thymus. In contrast to the thymus, cellular restoration of the bone marrow is already initially dependent on the number of protected or transplanted marrow cells. Two phases in the recovery of thymic PHA-reactivity after irradiation were observed: one initial phase which is independent on the number of the available bone marrow cells, and a subsequent phase during which PHA-reactivity is slightly increased in mice irradiated with partly protected bone marrow in comparison to in total body irradiated animals. During the entire observation period, PHA-reactivity remains at a low level not exeeding 50 % of that in untreated mice. In contrast the thymus is fully repopulated with regard to the number of nonreactive cells. Alternative pathways of thymocyte development within the thymus are discussed. Bone marrow X cells were shown to be as sensitive to in vitro treatment with a specific H-2 antiserum as were lymphocytes from normal bone marrow. This finding was teken to indicate that the X cells represent a particular lymphoid cell type. A xenogeneic rabbit-anti-mouse embryo antiserum was more toxic to pre-irradiated bone marrow, with high proportion of X cells, than to bone marrow from untreated mice, using in vitro cytotoxicity test. A possible embryonic character of the X cells is discussed. (author)

Interplay of thymus and bone marrow regeneration in x-irradiated mice

Energy Technology Data Exchange (ETDEWEB)

Hiesche, K D

1975-01-01

The aim of the present investigation was to study the modifying effects of bone marrow cells on regeneration, after X-irradiation, of thymus and bone marrow cell populations. Data are presented which indicate that the cellular composition of the thymus and, in particular, the frequency of the stem cells in the organ at the time of radiation exposure determines thymic regeneration for about two weeks after irradiation. After this period, regeneration depends on new precursors from the bone marrow which have previously seeded the thymus. In contrast to the thymus, cellular restoration of the bone marrow is already initially dependent on the number of protected or transplanted marrow cells. Two phases in the recovery of thymic PHA-reactivity after irradiation were observed: one initial phase which is independent on the number of the available bone marrow cells, and a subsequent phase during which PHA-reactivity is slightly increased in mice irradiated with partly protected bone marrow in comparison to in total body irradiated animals. During the entire observation period, PHA-reactivity remains at a low level not exeeding 50 % of that in untreated mice. In contrast the thymus is fully repopulated with regard to the number of nonreactive cells. Alternative pathways of thymocyte development within the thymus are discussed. Bone marrow X cells were shown to be as sensitive to in vitro treatment with a specific H-2 antiserum as were lymphocytes from normal bone marrow. This finding was teken to indicate that the X cells represent a particular lymphoid cell type. A xenogeneic rabbit-anti-mouse embryo antiserum was more toxic to pre-irradiated bone marrow, with high proportion of X cells, than to bone marrow from untreated mice, using in vitro cytotoxicity test. A possible embryonic character of the X cells is discussed.

Intraoperative bone and bone marrow sampling: a simple method for accurate measurement of uptake of radiopharmaceuticals in bone and bone marrow