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Sample records for blood-derived progenitors generate

  1. Endothelial progenitor cell differentiation using cryopreserved, umbilical cord blood-derived mononuclear cells

    Institute of Scientific and Technical Information of China (English)

    Jun-ho JANG; Hugh C KIM; Sun-kyung KIM; Jeong-eun CHOI; Young-jin KIM; Hyun-woo LEE; Seok-yun KANG; Joon-seong PARK; Jin-hyuk CHOI; Ho-yeong LIM

    2007-01-01

    Aim: To investigate the endothelial differentiation potentiality of umbilical cord blood (UCB), we induced the differentiation of endothelial progenitor cells (EPC)from cryopreserved UCB-derived mononuclear cells (MNC). Methods: MNC from cryopreserved UCB and peripheral blood (PB) were cultured in M199 medium with endothelial cell growth supplements for 14 d. EPC were characterized by RT-PCR,flow cytometry, and immunocytochemistry analysis. The proliferation of differen-tiated EPC was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTI') assay, and vascular endothelial growth factor (VEGF) concentra-tion was measured using an ELISA kit. Characteristics of UCB-derived EPC were compared with those of PB-derived EPC. Results: A number of round-shaped cells were loosely attached to the bottom after 24 h culture, and numerous spindle-shaped cells began to appear from the round-shaped ones on d 7. Those cells expressed endothelial markers such as, Fit-1/VEGFR-1, ecNOS, VE-cadherin, yon Willebrand factor, and secreted VEGF. The patterns of endothelial markers of EPC from PB and UCB did not show striking differences. The results of the prolifera-tion and secretion of VEGF were also similar. Conclusion: We successfully cul-tured UCB cells stored at -196 ℃ into cells with the quality of endothelial cells.Those EPC could be used for angiogenic therapeutics by activating adjacent endothelial cells and enhancing angiogenesis.

  2. Preliminary evaluation of treatment efficacy of umbilical cord blood-derived mesenchymal stem cell-differentiated cardiac pro-genitor cells in a myocardial injury mouse model

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    Truc Le-Buu Pham

    2015-12-01

    Full Text Available Recently, stem cell therapy has been investigated as a strategy to prevent or reverse damage to heart tissue. Although the results of cell transplantation in animal models and patients with myocardial ischemia are promising, the selection of the appropriate cell type remains an issue that requires consideration. In this study, we aimed to evaluate the effect of cardiac progenitor cell transplantation in a mouse model of myocardial ischemia. The cardiac progenitor cells used for transplantation were differentiated from umbilical cord blood mesenchymal stem cells. Animal models injected with phosphate-buffered saline (PBS and healthy mice were used as controls. Cell grafting was assessed by changes in blood pressure and histological evaluation. After 14 days of transplantation, the results demonstrated that the blood pressure of transplanted mice was stable, similar to healthy mice, whereas it fluctuated in PBS-injected mice. Histological analysis showed that heart tissue had regenerated in transplanted mice, but remained damaged in PBS-injected mice. Furthermore, trichrome staining revealed that the transplanted mice did not generate significant amount of scar tissue compared with PBS-injected control mice. In addition, the cardiac progenitor cells managed to survive and integrate with local cells in cell-injected heart tissue 14 days after transplantation. Most importantly, the transplanted cells did not exhibit tumorigenesis. In conclusion, cardiac progenitor cell transplantation produced a positive effect in a mouse model of myocardial ischemia. [Biomed Res Ther 2015; 2(12.000: 435-445

  3. A comparison of umbilical cord blood-derived endothelial progenitor and mononuclear cell transplantation for the treatment of acute hindlimb ischemia

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    Phuc Van Pham

    2014-01-01

    Full Text Available Acute lower limb ischemia is a common peripheral artery disease whose treatment presents many difficulties. Stem cell transplantation is considered a novel and promising method of treating this disease. Umbilical cord blood (UCB is rich in stem cells, including hematopoietic stem cells (HSCs, mesenchymal stem cells (MSCs and endothelial progenitor cells (EPCs. However, historically, banked umbilical cord blood has been used mainly to treat blood-related diseases. Therefore, this study compared the efficacy of umbilical cord bloodderived mononuclear cells (UCB-MNCs with EPC transplantation for the treatment of acute hindlimb ischemia (ALI in mouse models. MNCs were isolated from UCB by Ficoll gradient centrifugation, after which the EPCs were sorted based on CD34+ and CD133+ markers and cultured according to a previously published protocol. To induce ALI, mice were immuno-suppressed using busulfan (BU and cyclophosphamide (CY, after which the femoral arteries were burned. Induction of ALI in the immune suppressed mice was confirmed by the grade of tissue damage, pedal frequency in water, tissue edema, changes in histology, total white blood cell count, and white blood cell composition. Model mice were injected with a dose of MNCs or EPCs and un-treated control mice were injected with phosphate buffered saline. The efficiency of treatment was evaluated by comparing the grade of tissue damage between the three groups of mice. Mice aged 6 and ndash;12 months were suitable for ALI, with 100% of mice exhibiting ischemia from grade I 10%, grade III 50%, grade IV 40%. For all ALI mice, a gradual increase in pedal frequency in water, increased tissue edema, necrosis of muscle tissue, and loss of hindlimb function were observed after 20 days. Transplanted MNCs and EPCs significantly improved hindlimb ischemia compared with control treatment. Moreover, EPC transplantation significantly improved hindlimb ischemia compared with MNC transplantation. Following

  4. A Progenitor Cell Expressing Transcription Factor RORγt Generates All Human Innate Lymphoid Cell Subsets.

    Science.gov (United States)

    Scoville, Steven D; Mundy-Bosse, Bethany L; Zhang, Michael H; Chen, Li; Zhang, Xiaoli; Keller, Karen A; Hughes, Tiffany; Chen, Luxi; Cheng, Stephanie; Bergin, Stephen M; Mao, Hsiaoyin C; McClory, Susan; Yu, Jianhua; Carson, William E; Caligiuri, Michael A; Freud, Aharon G

    2016-05-17

    The current model of murine innate lymphoid cell (ILC) development holds that mouse ILCs are derived downstream of the common lymphoid progenitor through lineage-restricted progenitors. However, corresponding lineage-restricted progenitors in humans have yet to be discovered. Here we identified a progenitor population in human secondary lymphoid tissues (SLTs) that expressed the transcription factor RORγt and was unique in its ability to generate all known ILC subsets, including natural killer (NK) cells, but not other leukocyte populations. In contrast to murine fate-mapping data, which indicate that only ILC3s express Rorγt, these human progenitor cells as well as human peripheral blood NK cells and all mature ILC populations expressed RORγt. Thus, all human ILCs can be generated through an RORγt(+) developmental pathway from a common progenitor in SLTs. These findings help establish the developmental signals and pathways involved in human ILC development.

  5. Genetically engineered blood pharming: generation of HLA-universal platelets derived from CD34+ progenitor cells.

    Science.gov (United States)

    Figueiredo, Constança; Blaszczyk, Rainer

    2014-01-01

    Blood pharming is a recently designed concept to enable in vitro production of blood cells that are safe, effective and readily available. This approach represents an alternative to blood donation and may contribute to overcome the shortage of blood products. However, the high variability of the human leukocyte antigen (HLA) loci remains a major hurdle to the application of off-the-shelf blood products. Refractoriness to platelet (PLT) transfusion caused by alloimmunization against HLA class I antigens constitutes a relevant clinical problem. Thus, it would be desirable to generate PLT units devoid of HLA antigens. To reduce the immunogenicity of cell-based therapeutics, we have permanently reduced HLA class I expression using an RNA interference strategy. Furthermore, we demonstrated that the generation of HLA class I-silenced (HLA-universal) PLTs from CD34+ progenitor cells using an shRNA targeting β2-microglobulin transcripts is feasible. CD34+ progenitor cells derived from G-CSF mobilised donors were transduced with a lentiviral vector encoding for the β2-microglobulin-specific shRNA and differentiated into PLTs using a liquid culture system. The functionality of HLA-silenced PLTs and their ability to escape HLA antibody-mediated cytotoxicity were evaluated in vitro and in vivo. Platelet activation in response to ADP and thrombin were assessed in vitro. The immune-evasion capability of HLA-universal megakaryocytes (MKs) and PLTs was tested in lymphocytotoxicity assays using anti-HLA antibodies. To assess the functionality of HLA-universal PLTs in vivo, HLA-silenced MKs were infused into NOD/SCID/IL-2Rγc(-/-) mice with or without anti-HLA antibodies. PLT generation was evaluated by flow cytometry using anti-CD42a and CD61 antibodies. HLA-universal PLTs demonstrated to be functionally similar to blood-derived PLTs. Lymphocytotoxicity assays showed that HLA-silencing efficiently protects MKs against HLA antibody-mediated complement-dependent cytotoxicity. 80

  6. Genetically engineered blood pharming: generation of HLA-universal platelets derived from CD34+ progenitor cells.

    Science.gov (United States)

    Figueiredo, Constança; Blaszczyk, Rainer

    2014-01-01

    Blood pharming is a recently designed concept to enable in vitro production of blood cells that are safe, effective and readily available. This approach represents an alternative to blood donation and may contribute to overcome the shortage of blood products. However, the high variability of the human leukocyte antigen (HLA) loci remains a major hurdle to the application of off-the-shelf blood products. Refractoriness to platelet (PLT) transfusion caused by alloimmunization against HLA class I antigens constitutes a relevant clinical problem. Thus, it would be desirable to generate PLT units devoid of HLA antigens. To reduce the immunogenicity of cell-based therapeutics, we have permanently reduced HLA class I expression using an RNA interference strategy. Furthermore, we demonstrated that the generation of HLA class I-silenced (HLA-universal) PLTs from CD34+ progenitor cells using an shRNA targeting β2-microglobulin transcripts is feasible. CD34+ progenitor cells derived from G-CSF mobilised donors were transduced with a lentiviral vector encoding for the β2-microglobulin-specific shRNA and differentiated into PLTs using a liquid culture system. The functionality of HLA-silenced PLTs and their ability to escape HLA antibody-mediated cytotoxicity were evaluated in vitro and in vivo. Platelet activation in response to ADP and thrombin were assessed in vitro. The immune-evasion capability of HLA-universal megakaryocytes (MKs) and PLTs was tested in lymphocytotoxicity assays using anti-HLA antibodies. To assess the functionality of HLA-universal PLTs in vivo, HLA-silenced MKs were infused into NOD/SCID/IL-2Rγc(-/-) mice with or without anti-HLA antibodies. PLT generation was evaluated by flow cytometry using anti-CD42a and CD61 antibodies. HLA-universal PLTs demonstrated to be functionally similar to blood-derived PLTs. Lymphocytotoxicity assays showed that HLA-silencing efficiently protects MKs against HLA antibody-mediated complement-dependent cytotoxicity. 80

  7. Enhanced generation of retinal progenitor cells from human retinal pigment epithelial cells induced by amniotic fluid

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    Sanie-Jahromi Fatemeh

    2012-04-01

    Full Text Available Abstract Background Retinal progenitor cells are a convenient source of cell replacement therapy in retinal degenerative disorders. The purpose of this study was to evaluate the expression patterns of the homeobox genes PAX6 and CHX10 (retinal progenitor markers during treatment of human retinal pigment epithelium (RPE cells with amniotic fluid (AF, RPE cells harvested from neonatal cadaver globes were cultured in a mixture of DMEM and Ham's F12 supplemented with 10% FBS. At different passages, cells were trypsinized and co-cultured with 30% AF obtained from normal fetuses of 1416 weeks gestational age. Results Compared to FBS-treated controls, AF-treated cultures exhibited special morphological changes in culture, including appearance of spheroid colonies, improved initial cell adhesion and ordered cell alignment. Cell proliferation assays indicated a remarkable increase in the proliferation rate of RPE cells cultivated in 30% AF-supplemented medium, compared with those grown in the absence of AF. Immunocytochemical analyses exhibited nuclear localization of retinal progenitor markers at a ratio of 33% and 27% for CHX10 and PAX6, respectively. This indicated a 3-fold increase in retinal progenitor markers in AF-treated cultures compared to FBS-treated controls. Real-time PCR data of retinal progenitor genes (PAX6, CHX10 and VSX-1 confirmed these results and demonstrated AF's capacity for promoting retinal progenitor cell generation. Conclusion Taken together, the results suggest that AF significantly promotes the rate of retinal progenitor cell generation, indicating that AF can be used as an enriched supplement for serum-free media used for the in vitro propagation of human progenitor cells.

  8. Nkx2.2+ Progenitors Generate Somatic Motoneurons in the Chick Spinal Cord

    Science.gov (United States)

    Gotoh, Hitoshi; Ono, Katsuhiko; Nomura, Tadashi; Takebayashi, Hirohide; Harada, Hidekiyo; Nakamura, Harukazu; Ikenaka, Kazuhiro

    2012-01-01

    Heterogeneous classes of neurons are present in the spinal cord and are essential for its function. Expression patterns of transcription factors in neural progenitor cells determine neuron subtypes during development. Nkx2.2 is expressed in the progenitor cell pool located just ventrally to the Olig2-positive pool and is indispensable for V3 interneuron generation in the spinal cord and also for visceral motoneuron generation in the hindbrain. However, whether Nkx2.2-positive progenitor cells generate diverse classes of neuron is not fully understood. Using a chick lineage tracing method in a genetically-defined manner, we found that Nkx2.2-expressing progenitor cells differentiate into general visceral motoneurons as well as sim1-positive V3 interneurons. Surprisingly, we further observed that Nkx2.2-expressing progenitors differentiate into somatic motoneuron. Our findings suggest that the different classes of motoneurons are derived from more complex sources than were previously expected in the chick spinal cord. PMID:23284718

  9. Sonic hedgehog promotes generation and maintenance of human forebrain Olig2 progenitors

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    Juan Alberto eOrtega

    2013-12-01

    Full Text Available Function of oligodendrocytes (OLs, myelin forming cells in the CNS, is disrupted in demyelinating diseases such as periventricular leukomalacia or multiple sclerosis. It is, thus, important to better understand factors that can affect generation or differentiation of human OLs. In rodents, Sonic hedgehog (Shh is influencing expression of Olig2, a helix-loop-helix transcription factor required for development of OLs. In humans, Olig2 is present in cortical progenitors at midgestation, however the role of Shh in the specification of human OLs, including Olig2 positive (Olig2+ progenitors, is not fully understood. Here we studied in vitro effects of Shh signaling on proliferation and specification of human cortical Olig2+ progenitors at midgestation. First, we established that the spatiotemporal pattern of Olig2 expression in the human developing CNS, described on cryosections, was preserved in mixed and enriched radial glia cell (RGC cultures. Next, we demonstrated that in vitro treatment with Shh induced an increase in the number of Olig2+ progenitors. Shh treatment increased the density of early oligodendrocyte progenitors (OPCs at the expense of radial glia cells, while the number of late OPCs, did not change. However, inhibition of endogenous Shh with cyclopamine did not reduce the density of Olig2+ cells, implying the presence of an additional Shh-independent mechanism for OLs generation in vitro. These results suggest that the primary role of Shh signaling in the human dorsal oligodendrogenesis is the expansion and specification of multipotent radial glia progenitors into Olig2+ early OPCs. These results obtained in vitro are relevant to understand primary myelination during CNS development, as well as remyelination in demyelinating diseases.

  10. 金黄色葡萄球菌超抗原样蛋白-5抑制人脐血源性内皮祖细胞黏附功能及其机制研究%Staphylococcal superantigen-like protein-5 inhibits adhesion of human umbilical cord blood-derived endothelial progenitor cells to P-selectin-coated surface

    Institute of Scientific and Technical Information of China (English)

    梁华; 曲小龙; 胡厚源; 宋治远; 程彦; 张静

    2011-01-01

    目的 研究金黄色葡萄球菌超抗原样蛋白-5 (staphylococcal superantigen-like protein-5,SSL5)与人脐血源性内皮祖细胞(endothelial progenitor cells,EPCs)表面P-选择素糖蛋白配体-1 (P-selectin glycoprotein ligand-1,PSGL-1) 的结合情况,及其对内皮祖细胞黏附功能的影响.方法 从金黄色葡萄球菌 NCTC 8325菌株的基因组中,扩增ssl5基因,并进行重组SSL5蛋白表达载体的构建.采用密度梯度离心法分离得到脐血中的单个核细胞并进行体外培养,对贴壁细胞在激光共聚焦显微镜下观察其摄取乙酰化低密度脂蛋白(DiI-acLDL)和结合荆豆凝集素(FITC-UEA-1)的情况.以流式细胞仪分析SSL5与EPCs表面PSGL-1的结合情况;以calcein-AM负载EPCs后,定量分析SSL5对EPCs在P-选择素包被表面黏附的抑制作用.结果 DiI-acLDL/ FITC-UEA-1双染阳性的细胞为EPCs.PSGL-1在EPCs表面有较丰富的表达,阳性细胞率为76.6%.SSL5与EPCs的结合随着SSL5浓度的增加而显著升高;并且,SSL5可竞争性抑制抗PSGL-1单克隆抗体(KPL-1)与EPCs的结合.SSL5可显著抑制EPCs在P-选择素表面的黏附,终浓度为30 mg/L的SSL5对EPCs在P-选择素表面黏附的抑制率已接近10 mg/L的KPL-1的效应,两者与空白对照组比较,差异有统计学意义(P<0.01).结论 SSL5可与EPCs表面的PSGL-1结合,而抑制EPCs在P-选择素表面的黏附,提示SSL5可能通过抑制EPCs与损伤内皮或激活的血小板之间的黏附,进而抑制EPCs对损伤内皮的修复作用.%Objective To investigate the binding of staphylococcal superantigen-like protein-5 (SSL5) to P-selectin glycoprotein ligand-1 (PSGL-1) on human umbilical cord blood-derived endothelial progenitor cells (EPCs) and the inhibitive effect of SSL5 on the adhesion of EPCs to P-selectin-coated surface.Methods SSL5 gene was amplified from the genome of Staphylococcus aureus NCTC 8325 and cloned into a vector for expressing recombinant SSL5 protein. Mononuclear cells were

  11. Efficient Generation of NKX6-1+ Pancreatic Progenitors from Multiple Human Pluripotent Stem Cell Lines

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    M. Cristina Nostro

    2015-04-01

    Full Text Available Human pluripotent stem cells (hPSCs represent a renewable source of pancreatic beta cells for both basic research and therapeutic applications. Given this outstanding potential, significant efforts have been made to identify the signaling pathways that regulate pancreatic development in hPSC differentiation cultures. In this study, we demonstrate that the combination of epidermal growth factor (EGF and nicotinamide signaling induces the generation of NKX6-1+ progenitors from all hPSC lines tested. Furthermore, we show that the size of the NKX6-1+ population is regulated by the duration of treatment with retinoic acid, fibroblast growth factor 10 (FGF10, and inhibitors of bone morphogenetic protein (BMP and hedgehog signaling pathways. When transplanted into NOD scid gamma (NSG recipients, these progenitors differentiate to give rise to exocrine and endocrine cells, including monohormonal insulin+ cells. Together, these findings provide an efficient and reproducible strategy for generating highly enriched populations of hPSC-derived beta cell progenitors for studies aimed at further characterizing their developmental potential in vivo and deciphering the pathways that regulate their maturation in vitro.

  12. Treatment with granulocyte colony-stimulating factor decreases the capacity of hematopoietic progenitor cells for generation of lymphocytes in human immunodeficiency virus-infected persons

    DEFF Research Database (Denmark)

    Nielsen, Susanne Dam; Clark, D R; Hutchings, M;

    1999-01-01

    An obstacle to stem cell gene therapy for AIDS is the limited numbers of hematopoietic progenitors available. Granulocyte colony-stimulating factor (G-CSF) is used for mobilization of progenitors, but little is known about the functional characteristics of mobilized progenitors, and immature and T...... cell progenitors may not be mobilized. This study examined the effect of G-CSF on the function of progenitors. Ten human immunodeficiency virus-infected patients received G-CSF (filgrastim, 300 microgram/day) for 5 days. Absolute numbers of immature and T cell progenitors did not increase. The ability...... of CD34+ progenitor cells to generate lymphocytes was examined by use of thymic organ cultures. The mean number of lymphocytes generated per CD34+ cell on day 0 was 0.72 and on day 4 was 0.09 (Pcells generated per CD34+ cell was significantly reduced after G-CSF treatment...

  13. RasGRP1 and RasGRP3 Are Required for Efficient Generation of Early Thymic Progenitors.

    Science.gov (United States)

    Golec, Dominic P; Henao Caviedes, Laura M; Baldwin, Troy A

    2016-09-01

    T cell development is dependent on the migration of progenitor cells from the bone marrow to the thymus. Upon reaching the thymus, progenitors undergo a complex developmental program that requires inputs from various highly conserved signaling pathways including the Notch and Wnt pathways. To date, Ras signaling has not been implicated in the very earliest stages of T cell differentiation, but members of a family of Ras activators called RasGRPs have been shown to be involved at multiple stages of T cell development. We examined early T cell development in mice lacking RasGRP1, RasGRP3, and RasGRPs 1 and 3. We report that RasGRP1- and RasGRP3-deficient thymi show significantly reduced numbers of early thymic progenitors (ETPs) relative to wild type thymi. Furthermore, RasGRP1/3 double-deficient thymi show significant reductions in ETP numbers compared with either RasGRP1 or RasGRP3 single-deficient thymi, suggesting that both RasGRP1 and RasGRP3 regulate the generation of ETPs. In addition, competitive bone marrow chimera experiments reveal that RasGRP1/3 double-deficient progenitors intrinsically generate ETPs less efficiently than wild type progenitors. Finally, RasGRP1/3-deficient progenitors show impaired migration toward the CCR9 ligand, CCL25, suggesting that RasGRP1 and RasGRP3 may regulate progenitor entry into the thymus through a CCR9-dependent mechanism. These data demonstrate that, in addition to Notch and Wnt, the highly conserved Ras pathway is critical for the earliest stages of T cell development and further highlight the importance of Ras signaling during thymocyte maturation. PMID:27465532

  14. Generation of multipotent early lymphoid progenitors from human embryonic stem cells.

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    Larbi, Aniya; Mitjavila-Garcia, Maria Teresa; Flamant, Stéphane; Valogne, Yannick; Clay, Denis; Usunier, Benoît; l'Homme, Bruno; Féraud, Olivier; Casal, Ibrahim; Gobbo, Emilie; Divers, Dominique; Chapel, Alain; Turhan, Ali G; Bennaceur-Griscelli, Annelise; Haddad, Rima

    2014-12-15

    During human embryonic stem cell (ESC) hematopoietic differentiation, the description of the initial steps of lymphopoiesis remains elusive. Using a two-step culture procedure, we identified two original populations of ESC-derived hematopoietic progenitor cells (HPCs) with CD34(+)CD45RA(+)CD7(-) and CD34(+)CD45RA(+)CD7(+) phenotypes. Bulk cultures and limiting dilution assays, culture with MS5 cells in the presence of Notch ligand Delta-like-1 (DL-1), and ex vivo colonization tests using fetal thymic organ cultures showed that although CD34(+)CD45RA(+)CD7(-) HPCs could generate cells of the three lymphoid lineages, their potential was skewed toward the B cell lineages. In contrast, CD34(+)CD45RA(+)CD7(+) HPCs predominantly exhibited a T/natural killer (NK) cell differentiation potential. Furthermore these cells could differentiate equivalently into cells of the granulo-macrophagic lineage and dendritic cells and lacked erythroid potential. Expression profiling of 18 markers by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed that CD34(+)CD45RA(+)CD7(-) and CD34(+)CD45RA(+)CD7(+) HPCs express genes of the lymphoid specification and that CD34(+)CD45RA(+)CD7(-) cells express B-cell-associated genes, while CD34(+)CD45RA(+)CD7(+) HPCs display a T-cell molecular profile. Altogether, these findings indicate that CD34(+)CD45RA(+)CD7(-) and CD34(+)CD45RA(+)CD7(+) HPCs correspond to candidate multipotent early lymphoid progenitors polarized toward either the B or T/NK lineage, respectively. This work should improve our understanding of the early steps of lymphopoiesis from pluripotent stem cells and pave the way for the production of lymphocytes for cell-based immunotherapy and lymphoid development studies.

  15. Generation of Alveolar Epithelial Spheroids via Isolated Progenitor Cells from Human Pluripotent Stem Cells

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    Shimpei Gotoh

    2014-09-01

    Full Text Available No methods for isolating induced alveolar epithelial progenitor cells (AEPCs from human embryonic stem cells (hESCs and induced pluripotent stem cells (hiPSCs have been reported. Based on a study of the stepwise induction of alveolar epithelial cells (AECs, we identified carboxypeptidase M (CPM as a surface marker of NKX2-1+ “ventralized” anterior foregut endoderm cells (VAFECs in vitro and in fetal human and murine lungs. Using SFTPC-GFP reporter hPSCs and a 3D coculture system with fetal human lung fibroblasts, we showed that CPM+ cells isolated from VAFECs differentiate into AECs, demonstrating that CPM is a marker of AEPCs. Moreover, 3D coculture differentiation of CPM+ cells formed spheroids with lamellar-body-like structures and an increased expression of surfactant proteins compared with 2D differentiation. Methods to induce and isolate AEPCs using CPM and consequently generate alveolar epithelial spheroids would aid human pulmonary disease modeling and regenerative medicine.

  16. Generation of Integration-free and Region-Specific Neural Progenitors from Primate Fibroblasts

    Science.gov (United States)

    Lu, Jianfeng; Liu, Huisheng; Huang, Cindy Tzu-Ling; Chen, Hong; Du, Zhongwei; Liu, Yan; Sherafat, Mohammad Amin; Zhang, Su-Chun

    2013-01-01

    SUMMARY Postnatal and adult human and monkey fibroblasts were infected with Sendai virus containing the Yamanaka factors for 24 hr, then they were cultured in a chemically defined medium containing leukemia inhibitory factor (LIF), transforming growth factor (TGF)-β inhibitor SB431542, and glycogen synthase kinase (GSK)-3β inhibitor CHIR99021 at 39°C for inactivation of the virus. Induced neural progenitor (iNP) colonies appeared as early as day 13 and can be expanded for >20 passages. Under the same defined condition, no induced pluripotent stem cell (iPSC) colonies formed at either 37°Cor 39°C. The iNPs predominantly express hindbrain genes and differentiate into hindbrain neurons, and when caudalized, they produced an enriched population of spinal motor neurons. Following transplantation into the forebrain, the iNP-derived cells retained the hindbrain identity. The ability to generate defined, integration-free iNPs from adult primate fibroblasts under a defined condition with predictable fate choices will facilitate disease modeling and therapeutic development. PMID:23643533

  17. Generation of Integration-free and Region-Specific Neural Progenitors from Primate Fibroblasts

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    Jianfeng Lu

    2013-05-01

    Full Text Available Postnatal and adult human and monkey fibroblasts were infected with Sendai virus containing the Yamanaka factors for 24 hr, then they were cultured in a chemically defined medium containing leukemia inhibitory factor (LIF, transforming growth factor (TGF-β inhibitor SB431542, and glycogen synthase kinase (GSK-3β inhibitor CHIR99021 at 39°C for inactivation of the virus. Induced neural progenitor (iNP colonies appeared as early as day 13 and can be expanded for >20 passages. Under the same defined condition, no induced pluripotent stem cell (iPSC colonies formed at either 37°C or 39°C. The iNPs predominantly express hindbrain genes and differentiate into hindbrain neurons, and when caudalized, they produced an enriched population of spinal motor neurons. Following transplantation into the forebrain, the iNP-derived cells retained the hindbrain identity. The ability to generate defined, integration-free iNPs from adult primate fibroblasts under a defined condition with predictable fate choices will facilitate disease modeling and therapeutic development.

  18. Innate lymphoid cell development requires TOX-dependent generation of a common ILC progenitor

    OpenAIRE

    Seehus, Corey R.; Aliahmad, Parinaz; de la Torre, Brian; Iliev, Iliyan D.; Spurka, Lindsay; Funari, Vincent A; Kaye, Jonathan

    2015-01-01

    Diverse innate lymphoid cell (ILC) subtypes have been defined, based on effector function and transcription factor expression. ILCs derive from common lymphoid progenitors, although the transcriptional pathways leading to ILC lineage specification remain poorly characterized. Here we demonstrate that transcriptional regulator TOX is required for the in vivo differentiation of common lymphoid progenitors to ILC lineage-restricted cells. In vitro modeling demonstrates that TOX deficiency result...

  19. Replication of parvovirus B19 in hematopoietic progenitor cells generated in vitro from normal human peripheral blood.

    OpenAIRE

    Schwarz, T F; Serke, S; Hottenträger, B; von Brunn, A; Baurmann, H; Kirsch, A.; Stolz, W.; Huhn, D; Deinhardt, F.; Roggendorf, M

    1992-01-01

    Erythroid progenitor cells generated in vitro from peripheral human blood in the presence of interleukin-3 and erythropoietin were infected with human parvovirus B19. B19 virus DNA replication was highest 48 to 72 h after infection, and maximum levels of B19 virus proteins were detected in culture supernatants at 72 to 96 h after infection. B19 virus propagated in vitro was infectious. This cell culture system with peripheral blood cells facilitates studies in vitro of B19 virus replication.

  20. Hnf1b controls pancreas morphogenesis and the generation of Ngn3+ endocrine progenitors.

    Science.gov (United States)

    De Vas, Matias G; Kopp, Janel L; Heliot, Claire; Sander, Maike; Cereghini, Silvia; Haumaitre, Cécile

    2015-03-01

    Heterozygous mutations in the human HNF1B gene are associated with maturity-onset diabetes of the young type 5 (MODY5) and pancreas hypoplasia. In mouse, Hnf1b heterozygous mutants do not exhibit any phenotype, whereas the homozygous deletion in the entire epiblast leads to pancreas agenesis associated with abnormal gut regionalization. Here, we examine the specific role of Hnf1b during pancreas development, using constitutive and inducible conditional inactivation approaches at key developmental stages. Hnf1b early deletion leads to a reduced pool of pancreatic multipotent progenitor cells (MPCs) due to decreased proliferation and increased apoptosis. Lack of Hnf1b either during the first or the secondary transitions is associated with cystic ducts. Ductal cells exhibit aberrant polarity and decreased expression of several cystic disease genes, some of which we identified as novel Hnf1b targets. Notably, we show that Glis3, a transcription factor involved in duct morphogenesis and endocrine cell development, is downstream Hnf1b. In addition, a loss and abnormal differentiation of acinar cells are observed. Strikingly, inactivation of Hnf1b at different time points results in the absence of Ngn3(+) endocrine precursors throughout embryogenesis. We further show that Hnf1b occupies novel Ngn3 putative regulatory sequences in vivo. Thus, Hnf1b plays a crucial role in the regulatory networks that control pancreatic MPC expansion, acinar cell identity, duct morphogenesis and generation of endocrine precursors. Our results uncover an unappreciated requirement of Hnf1b in endocrine cell specification and suggest a mechanistic explanation of diabetes onset in individuals with MODY5.

  1. Testosterone Enhances the Proliferation of Peripheral-Blood-Derived Endothelial Progenitor Cells by up-regulating Vascular Endothelial Growth Factor Expression%睾酮通过上调血管内皮生长因子表达促进外周血内皮祖细胞增殖

    Institute of Scientific and Technical Information of China (English)

    薛亚威; 任国庆; 王芝; 孙文文; 张浩

    2013-01-01

    目的 探讨雄激素对外周血内皮祖细胞(PB-EPC,)增殖能力的影响及其可能机制.方法 将健康志愿者外周血经密度梯度离心法分离的单个核细胞接种至人纤维连接蛋白包被的培养板中,EGM-2MV培养7天后,多波长激光共聚焦显微镜鉴定FITC标记的荆豆凝集素和Dil标记的乙酰化低密度脂蛋白双染色阳性为PB-EPC.将贴壁细胞分为5组,前4组分别加入0、1、10、100nmol/L睾酮,第5组加入10 nmol/L雄激素受体阻断剂氟他胺干预3h后,再加10 nmol/L睾酮干预.培养48 h后,MTT比色法检测各组PB-EPC的增殖能力.实时定量PCR检测血管内皮生长因子(VEGF) mRNA的表达变化,ELISA检测VEGF分泌量的变化.结果 睾酮呈浓度依赖性促进EPC增殖,雄激素受体阻断剂氟他胺完全阻断睾酮对EPC的促进作用.与空白对照组相比,睾酮在mRNA和蛋白水平上调PB-EPC的VEGF表达,氟他胺可阻断此作用.结论 睾酮通过雄激素受体途径上调VEGF的表达,促进PB-EPC增殖.%Aim To explore the effects and related mechanisms of testosterone on the proliferation of Peripheral-blood endothelial progenitor cells (PB-EPCs). Methods Total mononuclear cells(MNC) were isolated from peripheral blood of healthy volunteers by Ficoll density gradient centrifugation, culturing with EGM-2MV for 7 days in vitro. The adherent cells showed up taking of acetylated low-density ( ac-LDL-Dil) and binding of lectin ( FITC-UEA-I) , observing with confocal laser scanning microscopy. PB-EPC were dealt with four concentrations of testosterone, as 0 nmol/L, 1 nmol/L, 10 nmol/L,and 100 nmol/L respectively, and in another group PB-EPC were pretreated with 10 nmol/L flutamide (androgen receptor antagonist) for 3h and then stimulated with 10 nmol/L testosterone. After 48 h, the ability of cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diph-phenyltetrazolium bromide assay ( MTT). The VEGF expression was tested by quantitative real

  2. 铁过载对脐带血来源的造血干祖细胞及造血支持细胞的作用观察%Effect of iron overload on umbilical cord blood derived hematopoietic stem/progenitor cells and hematopoietic supportive cells

    Institute of Scientific and Technical Information of China (English)

    肖霞; 赵明峰; 卢文艺; 柴笑; 穆娟; 邓琦; 李青; 李玉明

    2013-01-01

    目的 探讨铁过载对脐带血(UCB)来源的造血干祖细胞及造血支持细胞,尤其是间充质干细胞(MSCs)的损伤作用.方法 体外培养脐带血单个核细胞(UCB-MNCs)和脐带血间充质干细胞(UCB-MSCs),向培养液中添加200 μmol/L的枸橼酸铁胺(FAC) 24 h建立铁过载模型.分为MNCs-CTL组、MNCs-FAC组、MSCs-CTL组、MSCs-FAC组,每组设3个复孔,实验重复3次.检测细胞内活性氧物质(ROS)水平变化、细胞增殖、分化、凋亡以及造血支持作用.结果 对UCB-MNCs进行铁过载,MNCs-FAC组造血集落形成单位(CFU-E、CFU-GM、BFU-E、CFU-mix)计数显著低于MNCs-CTL组(P<0.05),MNCs-FAC组造血干细胞(CD+34)、髓系造血细胞(CD+33)、红系造血细胞(GlyA+)比例及计数均显著低于MNCs-CTL组(P均<0.05);MNCs-FAC组的凋亡率高于MNCs-CTL组(P<0.05).MSCs-FAC组的群体倍增时间明显长于MSCs-CTL组,且其凋亡率亦高于MSCs-CTL组(P<0.05).结论 铁过载可抑制造血干祖细胞的增殖、分化,诱导其凋亡,也可抑制MSCs的增殖能力,诱导其凋亡,降低其造血支持能力,且此过程中ROS升高.%Objective To explore the detrimental effect of iron overload on umbilical-cord blood (UCB) derived hematopoietic stem/progenitor cells (HSPCs) and hematopoietic supportive cells,especially mesenchymal stem cells (MSCs).Methods Iron overload model of UCB-MNCs and UCB-MSCs was successfully established by adding 200? mol/L FAC into the culture medium for 12h.Then the reactive oxygen species (ROS) level,cell proliferation,cell differentiation,apoptosis and hematopoietic supportive capability were detected respectively.Results Iron overload was conducted on the UCB-MNCs.The hematopoietic colony forming units (CFU-E,CFU-GM,BFU-E,CFU-mix) counts in the MNCs-FAC group were significantly lower than those of MNCs-CTL group (P < 0.05) ; CD+34,CD3+33,GlyA + cell ratio and counts in the MNCs-FAC group were significantly lower than those in the MNCs-CTL (all P

  3. Generation and Expansion of highly-pure Motor Neuron Progenitors from Human Pluripotent Stem Cells

    OpenAIRE

    Du, Zhong-Wei; Chen, Hong; Liu, Huisheng; Lu, Jianfeng; Qian, Kun; Huang, Cindy Tzu-Ling.; Zhong, Xiaofen; Fan, Frank; Zhang, Su-Chun

    2015-01-01

    SUMMARY Human pluripotent stem cells (hPSCs) have opened new opportunities for understanding human development, modeling disease processes and developing new therapeutics. However, these applications are hindered by low-efficiency and heterogeneity of target cell types differentiated from hPSCs, such as motor neurons (MNs), as well as our inability to maintain the potency of lineage committed progenitors. Here, by using a combination of small molecules that regulate multiple signaling pathway...

  4. Efficient in vitro generation of functional thymic epithelial progenitors from human embryonic stem cells

    OpenAIRE

    Min Su; Rong Hu; Jingjun Jin; Yuan Yan; Yinhong Song; Ryan Sullivan; Laijun Lai

    2015-01-01

    Thymic epithelial cells (TECs) are the major components of the thymic microenvironment for T cell development. TECs are derived from thymic epithelial progenitors (TEPs). It has been reported that human ESCs (hESCs) can be directed to differentiate into TEPs in vitro. However, the efficiency for the differentiation is low. Furthermore, transplantation of hESC-TEPs in mice only resulted in a very low level of human T cell development from co-transplanted human hematopoietic precursors. We show...

  5. Generation of Tripotent Neural Progenitor Cells from Rat Embryonic Stem Cells

    Institute of Scientific and Technical Information of China (English)

    Zhenkun Wang; Xiaoyang Zhao; Zhonghua Liu; Liu Wang; Qi Zhou; Chao Sheng; Tianda Li; Fei Teng; Lisi Sang; Fenglin Cao; Ziwei Wang; Wanwan Zhu; Wei Li

    2012-01-01

    Rat is a valuable model for pharmacological and physiological studies.Germline-competent rat embryonic stem (rES) cell lines have been successfully established and the molecular networks maintaining the self-renewing,undifferentiated state of rES cells have also been well uncovered.However,little is known about the differentiation strategies and the underlying mechanisms of how these authentic rat pluripotent stem cells give rise to specific cell types.The aim of this study is to investigate the neural differentiation capacity of rES cells.By means of a modified procedure based on previous publications - combination of mitogen-activated protein kinase (MAPK) and glycogen synthase kinase 3 (GSK3) inhibitors (two inhibitors,"2i") with feeder-conditioned medium,we successfully obtained high-quality rat embryoid bodies (rEBs) from rES cells and then differentiated them to tripotent neural progenitors.These rES cell-derived neural progenitor cells (rNPCs) were capable of self-renewing and giving rise to all three neural lineages,including astrocytes,oligodendrocytes,and neurons.Besides,these rES cell-derived neurons stained positive for y-aminobutyric acid (GABA) and tyrosine hydroxylase (TH).In summary,we develop an experimental system for differentiating rES cells to tripotent neural progenitors,which may provide a powerful tool for pharmacological test and a valuable platform for studying the pathogenesis of many neurodegenerative disorders such as Parkinson's disease and the development of rat nervous system.

  6. Generation of Integration-free and Region-Specific Neural Progenitors from Primate Fibroblasts

    OpenAIRE

    Jianfeng Lu; Huisheng Liu; Cindy Tzu-Ling Huang; Hong Chen; Zhongwei Du; Yan Liu; Mohammad Amin Sherafat; Su-Chun Zhang

    2013-01-01

    Postnatal and adult human and monkey fibroblasts were infected with Sendai virus containing the Yamanaka factors for 24 hr, then they were cultured in a chemically defined medium containing leukemia inhibitory factor (LIF), transforming growth factor (TGF)-β inhibitor SB431542, and glycogen synthase kinase (GSK)-3β inhibitor CHIR99021 at 39°C for inactivation of the virus. Induced neural progenitor (iNP) colonies appeared as early as day 13 and can be expanded for >20 passages. Under the same...

  7. Efficient non-viral reprogramming of myoblasts to stemness with a single small molecule to generate cardiac progenitor cells.

    Directory of Open Access Journals (Sweden)

    Zeeshan Pasha

    Full Text Available UNLABELLED: The current protocols for generation of induced pluripotent stem (iPS cells involve genome integrating viral vectors which may induce tumorgenesis. The aim of this study was to develop and optimize a non-viral method without genetic manipulation for reprogramming of skeletal myoblasts (SMs using small molecules. METHODS AND RESULTS: SMs from young male Oct3/4-GFP(+ transgenic mouse were treated with DNA methyltransferase (DNMT inhibitor, RG108. Two weeks later, GFP(+ colonies of SM derived iPS cells (SiPS expressing GFP and with morphological similarity of mouse embryonic stem (ESCs were formed and propagated in vitro. SiPS were positive for alkaline phosphatase activity, expressed SSEA1, displayed ES cell specific pluripotency markers and formed teratoma in nude mice. Optimization of culture conditions for embryoid body (EBs formation yielded spontaneously contracting EBs having morphological, molecular, and ultra-structural similarities with cardiomyocytes and expressed early and late cardiac markers. miR profiling showed abrogation of let-7 family and upregulation of ESCs specific miR-290-295 cluster thus indicating that SiPS were similar to ESCs in miR profile. Four weeks after transplantation into the immunocompetent mice model of acute myocardial infarction (n = 12 per group, extensive myogenesis was observed in SiPS transplanted hearts as compared to DMEM controls (n = 6 per group. A significant reduction in fibrosis and improvement in global heart function in the hearts transplanted with SiPS derived cardiac progenitor cells were observed. CONCLUSIONS: Reprogramming of SMs by DNMT inhibitor is a simple, reproducible and efficient technique more likely to generate transgene integration-free iPS cells. Cardiac progenitors derived from iPS cells propagated extensively in the infarcted myocardium without tumorgenesis and improved cardiac function.

  8. A defined, feeder-free, serum-free system to generate in vitro hematopoietic progenitors and differentiated blood cells from hESCs and hiPSCs.

    Directory of Open Access Journals (Sweden)

    Giorgia Salvagiotto

    Full Text Available Human ESC and iPSC are an attractive source of cells of high quantity and purity to be used to elucidate early human development processes, for drug discovery, and in clinical cell therapy applications. To efficiently differentiate pluripotent cells into a pure population of hematopoietic progenitors we have developed a new 2-dimensional, defined and highly efficient protocol that avoids the use of feeder cells, serum or embryoid body formation. Here we showed that a single matrix protein in combination with growth factors and a hypoxic environment is sufficient to generate from pluripotent cells hematopoietic progenitors capable of differentiating further in mature cell types of different lineages of the blood system. We tested the differentiation method using hESCs and 9 iPSC lines generated from different tissues. These data indicate the robustness of the protocol providing a valuable tool for the generation of clinical-grade hematopoietic cells from pluripotent cells.

  9. Embryonic----Fetal Hb switch in humans: studies on erythroid bursts generated by embryonic progenitors from yolk sac and liver.

    Science.gov (United States)

    Peschle, C; Migliaccio, A R; Migliaccio, G; Petrini, M; Calandrini, M; Russo, G; Mastroberardino, G; Presta, M; Gianni, A M; Comi, P

    1984-04-01

    The synthesis of embryonic (zeta, epsilon), fetal (alpha, gamma), and adult (beta) globin was evaluated in human yolk sacs (YS) and livers at different ontogenic stages (i.e., from 6 through 10-12 wk of age) by means of analytical isoelectric focusing. Globin production was comparatively evaluated in vivo (i.e., in directly labeled erythroblasts from YS and liver) and in vitro [i.e., in erythroid bursts generated in culture by erythroid burst-forming units (BFU-E) from the same erythropoietic tissues]. Erythroid bursts generated in vitro by BFU-E from 6-wk livers and YS show essentially a "fetal" globin synthetic pattern: this is in sharp contrast to the "embryonic" pattern in corresponding liver and YS erythroblasts directly labeled in vivo. The invitro phenomenon suggests that (i) 6-wk BFU-E constitute a new generation of progenitors, which have already switched from an embryonic to a fetal program, and/or (ii) expression of their fetal program is induced by unknown in vitro factor(s), which may underlie the in vivo switch at later ontogenic stages. It is emphasized that 6- to 7-wk BFU-E are endowed with the potential for in vitro synthesis of not only epsilon- and gamma-chains but also some beta-globin. In general, we observed an inverse correlation between the levels of epsilon- and beta-chain synthesis. These results, together with previous studies on fetal, perinatal, and adult BFU-E, are compatible with models suggesting that in ontogeny the chromatin configuration is gradually modified at the level of the non-alpha gene cluster, thus leading to a 5'----3' activation of globin genes in a balanced fashion. PMID:6201856

  10. The development of innate lymphoid cells requires TOX-dependent generation of a common innate lymphoid cell progenitor.

    Science.gov (United States)

    Seehus, Corey R; Aliahmad, Parinaz; de la Torre, Brian; Iliev, Iliyan D; Spurka, Lindsay; Funari, Vincent A; Kaye, Jonathan

    2015-06-01

    Diverse innate lymphoid cell (ILC) subtypes have been defined on the basis of effector function and transcription factor expression. ILCs derive from common lymphoid progenitors, although the transcriptional pathways that lead to ILC-lineage specification remain poorly characterized. Here we found that the transcriptional regulator TOX was required for the in vivo differentiation of common lymphoid progenitors into ILC lineage-restricted cells. In vitro modeling demonstrated that TOX deficiency resulted in early defects in the survival or proliferation of progenitor cells, as well as ILC differentiation at a later stage. In addition, comparative transcriptome analysis of bone marrow progenitors revealed that TOX-deficient cells failed to upregulate many genes of the ILC program, including genes that are targets of Notch, which indicated that TOX is a key determinant of early specification to the ILC lineage.

  11. Blood-derived DNA methylation markers of cancer risk.

    Science.gov (United States)

    Marsit, Carmen; Christensen, Brock

    2013-01-01

    The importance of somatic epigenetic alterations in tissues targeted for carcinogenesis is now well recognized and considered a key molecular step in the development of a tumor. Particularly, alteration of gene-specific and genomic DNA methylation has been extensively characterized in tumors, and has become an attractive biomarker of risk due to its specificity and stability in human samples. It also is clear that tumors do not develop as isolated phenomenon in their target tissue, but instead result from altered processes affecting not only the surrounding cells and tissues, but other organ systems, including the immune system. Thus, alterations to DNA methylation profiles detectable in peripheral blood may be useful not only in understanding the carcinogenic process and response to environmental insults, but can also provide critical insights in a systems biological view of tumorigenesis. Research to date has generally focused on how environmental exposures alter genomic DNA methylation content in peripheral blood. More recent work has begun to translate these findings to clinically useful endpoints, by defining the relationship between DNA methylation alterations and cancer risk. This chapter highlights the existing research linking the environment, blood-derived DNA methylation alterations, and cancer risk, and points out how these epigenetic alterations may be contributing fundamentally to carcinogenesis.

  12. MMP2-cleavage of DMP1 generates a bioactive peptide promoting differentiation of dental pulp stem/progenitor cell

    Directory of Open Access Journals (Sweden)

    C Chaussain

    2009-11-01

    Full Text Available Dentin Matrix Protein 1 (DMP1 plays a regulatory role in dentin mineralization and can also function as a signaling molecule. MMP-2 (matrix metalloproteinase-2 is a predominant protease in the dentin matrix that plays a prominent role in tooth formation and a potential role during the carious process. The possibility that MMP-2 can cleave DMP1 to release biologically active peptides was investigated in this study. DMP1, both in the recombinant form and in its native state within the dentin matrix, was shown to be a substrate for MMP-2. Proteolytic processing of DMP1 by MMP-2 produced two major peptides, one that contains the C-terminal region of the protein known to carry both the ASARM (aspartic acid and serine rich domain domain involved in biomineralization and the DNA binding site of DMP1. In vitro experiments with recombinant N- and C-terminal polypeptides mimicking the MMP-2 cleavage products of DMP1 demonstrated an effect of the C-polypeptide on the differentiation of dental pulp stem/progenitor cells to a putative odontoblast phenotype. In vivo implantation of this peptide in a rat injured pulp model induced a rapid formation of a homogeneous dentin bridge covered by a palisade of orientated cells expressing dentin sialoprotein (DSP and DMP1, attesting an efficient repair process. These data suggest that a peptide generated through the proteolytic processing of DMP1 by MMP-2 can regulate the differentiation of mesenchymal cells during dentinogenesis and thus sustain reparative dentin formation in pathological situations such as carious decay. In addition, these data open a new therapeutic possibility of using this peptide to regenerate dentin after an injury.

  13. Generation, Characterization, and Multilineage Potency of Mesenchymal-Like Progenitors Derived from Equine Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Lepage, Sarah I; Nagy, Kristina; Sung, Hoon-Ki; Kandel, Rita A; Nagy, Andras; Koch, Thomas G

    2016-01-01

    Multipotent mesenchymal stromal cells (MSCs) are more and more frequently used to treat orthopedic injuries in horses. However, these cells are limited in their expandability and differentiation capacity. Recently, the first equine-induced pluripotent stem cell (iPSC) lines were reported by us [ 1 ]. In vitro differentiation of iPSCs into MSC-like cells is an attractive alternative to using MSCs derived from other sources, as a much larger quantity of patient-specific cells with broad differentiation potential could be generated. However, the differentiation capacity of iPSCs to MSCs and the potential for use in tissue engineering have yet to be explored. In this study, equine iPSCs were induced to differentiate into an MSC-like population. Upon induction, the iPSCs changed morphology toward spindle-shaped cells similar to MSCs. The ensuing iPSC-MSCs exhibited downregulation of pluripotency-associated genes and an upregulation of MSC-associated genes. In addition, the cells expressed the same surface markers as MSCs derived from equine umbilical cord blood. We then assessed the multilineage differentiation potential of iPSC-MSCs. Although chondrogenesis was not achieved after induction with transforming growth factor-beta 3 (TGFβ3) and/or bone morphogenic protein 4 (BMP-4) in 3D pellet culture, mineralization characteristic of osteogenesis and lipid droplet accumulation characteristic of adipogenesis were observed after chemical induction. We demonstrate a protocol for the derivation of MSC-like progenitor populations from equine iPS cells.

  14. MMP2-cleavage of DMP1 generates a bioactive peptide promoting differentiation of dental pulp stem/progenitor cell.

    Science.gov (United States)

    Chaussain, Catherine; Eapen, Asha Sarah; Huet, Eric; Floris, Caroline; Ravindran, Sriram; Hao, Jianjun; Menashi, Suzanne; George, Anne

    2009-01-01

    Dentin Matrix Protein 1 (DMP1) plays a regulatory role in dentin mineralization and can also function as a signaling molecule. MMP-2 (matrix metalloproteinase-2) is a predominant protease in the dentin matrix that plays a prominent role in tooth formation and a potential role during the carious process. The possibility that MMP-2 can cleave DMP1 to release biologically active peptides was investigated in this study. DMP1, both in the recombinant form and in its native state within the dentin matrix, was shown to be a substrate for MMP-2. Proteolytic processing of DMP1 by MMP-2 produced two major peptides, one that contains the C-terminal region of the protein known to carry both the ASARM (aspartic acid and serine rich domain) domain involved in biomineralization and the DNA binding site of DMP1. In vitro experiments with recombinant N- and C-terminal polypeptides mimicking the MMP-2 cleavage products of DMP1 demonstrated an effect of the C-polypeptide on the differentiation of dental pulp stem/progenitor cells to a putative odontoblast phenotype. In vivo implantation of this peptide in a rat injured pulp model induced a rapid formation of a homogeneous dentin bridge covered by a palisade of orientated cells expressing dentin sialoprotein (DSP) and DMP1, attesting an efficient repair process. These data suggest that a peptide generated through the proteolytic processing of DMP1 by MMP-2 can regulate the differentiation of mesenchymal cells during dentinogenesis and thus sustain reparative dentin formation in pathological situations such as carious decay. In addition, these data open a new therapeutic possibility of using this peptide to regenerate dentin after an injury. PMID:19908197

  15. Histone deacetylase inhibition enhances self renewal and cardioprotection by human cord blood-derived CD34 cells.

    Directory of Open Access Journals (Sweden)

    Ilaria Burba

    Full Text Available BACKGROUND: Use of peripheral blood- or bone marrow-derived progenitors for ischemic heart repair is a feasible option to induce neo-vascularization in ischemic tissues. These cells, named Endothelial Progenitors Cells (EPCs, have been extensively characterized phenotypically and functionally. The clinical efficacy of cardiac repair by EPCs cells remains, however, limited, due to cell autonomous defects as a consequence of risk factors. The devise of "enhancement" strategies has been therefore sought to improve repair ability of these cells and increase the clinical benefit. PRINCIPAL FINDINGS: Pharmacologic inhibition of histone deacetylases (HDACs is known to enhance hematopoietic stem cells engraftment by improvement of self renewal and inhibition of differentiation in the presence of mitogenic stimuli in vitro. In the present study cord blood-derived CD34(+ were pre-conditioned with the HDAC inhibitor Valproic Acid. This treatment affected stem cell growth and gene expression, and improved ischemic myocardium protection in an immunodeficient mouse model of myocardial infarction. CONCLUSIONS: Our results show that HDAC blockade leads to phenotype changes in CD34(+ cells with enhanced self renewal and cardioprotection.

  16. Platelet-Rich Blood Derivatives for Stem Cell-Based Tissue Engineering and Regeneration

    NARCIS (Netherlands)

    Masoudi, E.A.; Ribas, J.; Kaushik, G.; Leijten, J.C.H.; Khademhosseini, A.

    2016-01-01

    Platelet-rich blood derivatives have been widely used in different fields of medicine and stem cell-based tissue engineering. They represent natural cocktails of autologous growth factors, which could provide an alternative for recombinant protein-based approaches. Platelet-rich blood derivatives, s

  17. Development of feeder-free culture systems for generation of ckit+sca1+ progenitors from mouse iPS cells.

    Science.gov (United States)

    Lin, Jian; Fernandez, Irina; Roy, Krishnendu

    2011-09-01

    Patient-specific therapeutic cells derived from induced pluripotent stem (iPS) cells may bypass the ethical issues associated with embryonic stem (ES) cells and avoid potential immunological reactions associated with allogenic transplantation. It is critical, for the ultimate clinical applicability of iPS cell-derived therapies, to establish feeder-free cultures that ensure efficient differentiation of iPS cells into therapeutic progenitors. It is also necessary to understand if iPS cell-derived progenitors differ from those derived from ES cells. In this study, we compared the efficiency of three different feeder-free cultures for differentiating mouse iPS cells into ckit+sca1+ hematopoietic progenitor cells (HPCs) and compared how differentiation and functionality varies between ES and iPS cells. Our results indicated that both iPS and ES cells can be efficiently differentiated into HPCs in suspension cultures supplemented with secretion factors from mouse bone marrow stromal cells (OP9-DL1 conditioned medium). The functionality of these cells was demonstrated by differentiation into CD11c+ dendritic cells (DCs). Both ES and iPS-derived DCs expressed activation molecules (CD86, CD80) in response to LPS stimulation and stimulated T cell proliferation in a mixed lymphocyte reaction (MLR). Extensive quantitative RT-PCR studies were used to study the differences in gene expression profiles of ckit+sca1+ cells generated from the various culture systems as well as differences between ES-derived and iPS-derived cells. We conclude that a feeder-free system using stromal conditioned medium can efficiently generate HPCs as well as functional DCs from iPS cells and the generated cells have similar gene expression profile as those from ES cells. PMID:21188655

  18. TGFβ inhibition enhances the generation of hematopoietic progenitors from human ES cell-derived hemogenic endothelial cells using a stepwise strategy

    Institute of Scientific and Technical Information of China (English)

    Chengyan Wang; Liying Du; Yang Gao; Ming Yin; Mingxiao Ding; Hongkui Deng; Xuming Tang; Xiaomeng Sun; Zhenchuan Miao; Yaxin Lv; Yanlei Yang; Huidan Zhang; Pengbo Zhang; Yang Liu

    2012-01-01

    Embryonic hematopoiesis is a complex process.Elucidating the mechanism regulating hematopoietic differentiation from pluripotent stem cells would allow us to establish a strategy to efficiently generate hematopoietic cells.However,the mechanism governing the generation of hematopoietic progenitors from human embryonic stem cells (hESCs)remains unknown.Here,on the basis of the emergence of CD43+ hematopoietic cells from hemogenic endothelial (HE) cells,we demonstrated that VEGF was essential and sufficient,and that bFGF was synergistic with VEGF to specify the HE cells and the subsequent transition into CD43+ hematopoietic cells.Significantly,we identified TGFβ as a novel signal to regulate hematopoietic development,as the TGFβ inhibitor SB 431542 significantly promoted the transition from HE cells into CD43+ hematopoietic progenitor cells (HPCs) during hESC differentiation.By defining these critical signaling factors during hematopoietic differentiation,we can efficiently generate HPCs from hESCs.Our strategy could offer an in vitro model to study early human hematopoietic development.

  19. The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice

    Science.gov (United States)

    Ju, Xiang-Chun; Hou, Qiong-Qiong; Sheng, Ai-Li; Wu, Kong-Yan; Zhou, Yang; Jin, Ying; Wen, Tieqiao; Yang, Zhengang; Wang, Xiaoqun; Luo, Zhen-Ge

    2016-01-01

    Cortical expansion and folding are often linked to the evolution of higher intelligence, but molecular and cellular mechanisms underlying cortical folding remain poorly understood. The hominoid-specific gene TBC1D3 undergoes segmental duplications during hominoid evolution, but its role in brain development has not been explored. Here, we found that expression of TBC1D3 in ventricular cortical progenitors of mice via in utero electroporation caused delamination of ventricular radial glia cells (vRGs) and promoted generation of self-renewing basal progenitors with typical morphology of outer radial glia (oRG), which are most abundant in primates. Furthermore, down-regulation of TBC1D3 in cultured human brain slices decreased generation of oRGs. Interestingly, localized oRG proliferation resulting from either in utero electroporation or transgenic expression of TBC1D3, was often found to underlie cortical regions exhibiting folding. Thus, we have identified a hominoid gene that is required for oRG generation in regulating the cortical expansion and folding. DOI: http://dx.doi.org/10.7554/eLife.18197.001 PMID:27504805

  20. Treatment with granulocyte colony-stimulating factor decreases the capacity of hematopoietic progenitor cells for generation of lymphocytes in human immunodeficiency virus-infected persons

    DEFF Research Database (Denmark)

    Nielsen, S D; Clark, D R; Hutchings, M;

    1999-01-01

    An obstacle to stem cell gene therapy for AIDS is the limited numbers of hematopoietic progenitors available. Granulocyte colony-stimulating factor (G-CSF) is used for mobilization of progenitors, but little is known about the functional characteristics of mobilized progenitors, and immature and T...... cell progenitors may not be mobilized. This study examined the effect of G-CSF on the function of progenitors. Ten human immunodeficiency virus-infected patients received G-CSF (filgrastim, 300 microgram/day) for 5 days. Absolute numbers of immature and T cell progenitors did not increase. The ability...

  1. Generation of functional platelets from human embryonic stem cells in vitro via ES-sacs, VEGF-promoted structures that concentrate hematopoietic progenitors.

    Science.gov (United States)

    Takayama, Naoya; Nishikii, Hidekazu; Usui, Joichi; Tsukui, Hiroko; Sawaguchi, Akira; Hiroyama, Takashi; Eto, Koji; Nakauchi, Hiromitsu

    2008-06-01

    Human embryonic stem cells (hESCs) could potentially represent an alternative source for blood transfusion therapies and a promising tool for studying the ontogeny of hematopoiesis. When we cultured hESCs on either C3H10T1/2 or OP-9 cells to facilitate hematopoiesis, we found that exogenous administration of vascular endothelial growth factor promoted the emergence of sac-like structures, which we named embryonic stem cell-derived sacs (ES-sacs). These ES-sacs consisted of multiple cysts demarcated by cellular monolayers that retained some of the properties of endothelial cells. The spherical cells inside ES-sacs expressed primarily CD34, along with VE-cadherin, CD31, CD41a, and CD45, and were able to form hematopoietic colonies in semisolid culture and to differentiate into mature megakaryocytes by day 24 in the presence of thrombopoietin. Apparently, ES-sacs provide a suitable environment for hematopoietic progenitors. Relatively large numbers of mature megakaryocytes could be induced from the hematopoietic progenitors within ES-sacs, which were then able to release platelets that displayed integrin alpha IIb beta 3 activation and spreading in response to ADP or thrombin. This novel protocol thus provides a means of generating platelets from hESCs, which could serve as the basis for efficient production of platelets for clinical transfusion and studies of thrombopoiesis.

  2. Efficient generation of human embryonic stem cell-derived cardiac progenitors based on tissue-specific enhanced green fluorescence protein expression.

    Science.gov (United States)

    Szebényi, Kornélia; Péntek, Adrienn; Erdei, Zsuzsa; Várady, György; Orbán, Tamás I; Sarkadi, Balázs; Apáti, Ágota

    2015-01-01

    Cardiac progenitor cells (CPCs) are committed to the cardiac lineage but retain their proliferative capacity before becoming quiescent mature cardiomyocytes (CMs). In medical therapy and research, the use of human pluripotent stem cell-derived CPCs would have several advantages compared with mature CMs, as the progenitors show better engraftment into existing heart tissues, and provide unique potential for cardiovascular developmental as well as for pharmacological studies. Here, we demonstrate that the CAG promoter-driven enhanced green fluorescence protein (EGFP) reporter system enables the identification and isolation of embryonic stem cell-derived CPCs. Tracing of CPCs during differentiation confirmed up-regulation of surface markers, previously described to identify cardiac precursors and early CMs. Isolated CPCs express cardiac lineage-specific transcripts, still have proliferating capacity, and can be re-aggregated into embryoid body-like structures (CAG-EGFP(high) rEBs). Expression of troponin T and NKX2.5 mRNA is up-regulated in long-term cultured CAG-EGFP(high) rEBs, in which more than 90% of the cells become Troponin I positive mature CMs. Moreover, about one third of the CAG-EGFP(high) rEBs show spontaneous contractions. The method described here provides a powerful tool to generate expandable cultures of pure human CPCs that can be used for exploring early markers of the cardiac lineage, as well as for drug screening or tissue engineering applications.

  3. Intermediate Progenitor Cohorts Differentially Generate Cortical Layers and Require Tbr2 for Timely Acquisition of Neuronal Subtype Identity

    Directory of Open Access Journals (Sweden)

    Anca B. Mihalas

    2016-06-01

    Full Text Available Intermediate progenitors (IPs amplify the production of pyramidal neurons, but their role in selective genesis of cortical layers or neuronal subtypes remains unclear. Using genetic lineage tracing in mice, we find that IPs destined to produce upper cortical layers first appear early in corticogenesis, by embryonic day 11.5. During later corticogenesis, IP laminar fates are progressively limited to upper layers. We examined the role of Tbr2, an IP-specific transcription factor, in laminar fate regulation using Tbr2 conditional mutant mice. Upon Tbr2 inactivation, fewer neurons were produced by immediate differentiation and laminar fates were shifted upward. Genesis of subventricular mitoses was, however, not reduced in the context of a Tbr2-null cortex. Instead, neuronal and laminar differentiation were disrupted and delayed. Our findings indicate that upper-layer genesis depends on IPs from many stages of corticogenesis and that Tbr2 regulates the tempo of laminar fate implementation for all cortical layers.

  4. Cord Blood-Derived Hematopoietic Stem/Progenitor Cells: Current Challenges in Engraftment, Infection, and Ex Vivo Expansion

    OpenAIRE

    Katsuhiro Kita; Lee, Jong O; Finnerty, Celeste C.; Herndon, David N

    2011-01-01

    Umbilical cord blood has served as an alternative to bone marrow for hematopoietic transplantation since the late 1980s. Numerous clinical studies have proven the efficacy of umbilical cord blood. Moreover, the possible immaturity of cells in umbilical cord blood gives more options to recipients with HLA mismatch and allows for the use of umbilical cord blood from unrelated donors. However, morbidity and mortality rates associated with hematopoietic malignancies still remain relatively high, ...

  5. Cord Blood-Derived Hematopoietic Stem/Progenitor Cells: Current Challenges in Engraftment, Infection, and Ex Vivo Expansion

    Directory of Open Access Journals (Sweden)

    Katsuhiro Kita

    2011-01-01

    Full Text Available Umbilical cord blood has served as an alternative to bone marrow for hematopoietic transplantation since the late 1980s. Numerous clinical studies have proven the efficacy of umbilical cord blood. Moreover, the possible immaturity of cells in umbilical cord blood gives more options to recipients with HLA mismatch and allows for the use of umbilical cord blood from unrelated donors. However, morbidity and mortality rates associated with hematopoietic malignancies still remain relatively high, even after cord blood transplantation. Infections and relapse are the major causes of death after cord blood transplantation in patients with hematopoietic diseases. Recently, new strategies have been introduced to improve these major problems. Establishing better protocols for simple isolation of primitive cells and ex vivo expansion will also be very important. In this short review, we discuss several recent promising findings related to the technical improvement of cord blood transplantation.

  6. Cord Blood-Derived Hematopoietic Stem/Progenitor Cells: Current Challenges in Engraftment, Infection, and Ex Vivo Expansion

    Science.gov (United States)

    Kita, Katsuhiro; Lee, Jong O.; Finnerty, Celeste C.; Herndon, David N.

    2011-01-01

    Umbilical cord blood has served as an alternative to bone marrow for hematopoietic transplantation since the late 1980s. Numerous clinical studies have proven the efficacy of umbilical cord blood. Moreover, the possible immaturity of cells in umbilical cord blood gives more options to recipients with HLA mismatch and allows for the use of umbilical cord blood from unrelated donors. However, morbidity and mortality rates associated with hematopoietic malignancies still remain relatively high, even after cord blood transplantation. Infections and relapse are the major causes of death after cord blood transplantation in patients with hematopoietic diseases. Recently, new strategies have been introduced to improve these major problems. Establishing better protocols for simple isolation of primitive cells and ex vivo expansion will also be very important. In this short review, we discuss several recent promising findings related to the technical improvement of cord blood transplantation. PMID:21603139

  7. Next generation sequencing and functional analysis of patient urine renal progenitor-derived podocytes to unravel the diagnosis underlying refractory lupus nephritis.

    Science.gov (United States)

    Romagnani, Paola; Giglio, Sabrina; Angelotti, Maria Lucia; Provenzano, Aldesia; Becherucci, Francesca; Mazzinghi, Benedetta; Müller, Susanna; Amann, Kerstin; Weidenbusch, Marc; Romoli, Simone; Lazzeri, Elena; Anders, Hans-Joachim

    2016-09-01

    Often the cause of refractory lupus nephritis (RLN) remains unclear. We performed next-generation sequencing for podocyte genes in an RLN patient and identified compound heterozygosity for APOL1 risk alleles G1 and G2 and a novel homozygous c.[1049C>T]+[1049C>T] NPHS1 gene variant of unknown significance. To test for causality renal progenitor cells isolated from urine of this patient were differentiated into podocytes in vitro. Podocytes revealed aberrant nephrin trafficking, cytoskeletal structure and lysosomal leakage, and increased detachment as compared with podocytes isolated from controls. Thus, lupus podocytopathy can be confirmed as a cause of RLN by functional genetics on patient-derived podocytes. PMID:27325253

  8. The Aryl Hydrocarbon Receptor Antagonist StemRegenin1 Improves In Vitro Generation of Highly Functional Natural Killer Cells from CD34(+) Hematopoietic Stem and Progenitor Cells.

    Science.gov (United States)

    Roeven, Mieke W H; Thordardottir, Soley; Kohela, Arwa; Maas, Frans; Preijers, Frank; Jansen, Joop H; Blijlevens, Nicole M; Cany, Jeannette; Schaap, Nicolaas; Dolstra, Harry

    2015-12-15

    Early natural killer (NK)-cell repopulation after allogeneic stem cell transplantation (allo-SCT) has been associated with reduced relapse rates without an increased risk of graft-versus-host disease, indicating that donor NK cells have specific antileukemic activity. Therefore, adoptive transfer of donor NK cells is an attractive strategy to reduce relapse rates after allo-SCT. Since NK cells of donor origin will not be rejected, multiple NK-cell infusions could be administered in this setting. However, isolation of high numbers of functional NK cells from transplant donors is challenging. Hence, we developed a cytokine-based ex vivo culture protocol to generate high numbers of functional NK cells from granulocyte colony-stimulating factor (G-CSF)-mobilized CD34(+) hematopoietic stem and progenitor cells (HSPCs). In this study, we demonstrate that addition of aryl hydrocarbon receptor antagonist StemRegenin1 (SR1) to our culture protocol potently enhances expansion of CD34(+) HSPCs and induces expression of NK-cell-associated transcription factors promoting NK-cell differentiation. As a result, high numbers of NK cells with an active phenotype can be generated using this culture protocol. These SR1-generated NK cells exert efficient cytolytic activity and interferon-γ production toward acute myeloid leukemia and multiple myeloma cells. Importantly, we observed that NK-cell proliferation and function are not inhibited by cyclosporin A, an immunosuppressive drug often used after allo-SCT. These findings demonstrate that SR1 can be exploited to generate high numbers of functional NK cells from G-CSF-mobilized CD34(+) HSPCs, providing great promise for effective NK-cell-based immunotherapy after allo-SCT.

  9. Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell Therapy Promotes Functional Recovery of Contused Rat Spinal Cord through Enhancement of Endogenous Cell Proliferation and Oligogenesis

    Directory of Open Access Journals (Sweden)

    Sang In Park

    2012-01-01

    Full Text Available Numerous studies have shown the benefits of mesenchymal stem cells (MSCs on the repair of spinal cord injury (SCI model and on behavioral improvement, but the underlying mechanisms remain unclear. In this study, to investigate possible mechanisms by which MSCs contribute to the alleviation of neurologic deficits, we examined the potential effect of human umbilical cord blood-derived MSCs (hUCB-MSCs on the endogenous cell proliferation and oligogenesis after SCI. SCI was injured by contusion using a weight-drop impactor and hUCB-MSCs were transplanted into the boundary zone of the injured site. Animals received a daily injection of bromodeoxyuridine (BrdU for 7 days after treatment to identity newly synthesized cells of ependymal and periependymal cells that immunohistochemically resembled stem/progenitor cells was evident. Behavior analysis revealed that locomotor functions of hUCB-MSCs group were restored significantly and the cavity volume was smaller in the MSCs-transplanted rats compared to the control group. In MSCs-transplanted group, TUNEL-positive cells were decreased and BrdU-positive cells were significantly increased rats compared with control group. In addition, more of BrdU-positive cells expressed neural stem/progenitor cell nestin and oligo-lineage cell such as NG2, CNPase, MBP and glial fibrillary acidic protein typical of astrocytes in the MSC-transplanted rats. Thus, endogenous cell proliferation and oligogenesis contribute to MSC-promoted functional recovery following SCI.

  10. Improved isolation protocol for equine cord blood-derived mesenchymal stromal cells

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Thomsen, Preben Dybdahl; Betts, Dean H.

    2009-01-01

      BACKGROUND AIMS: A robust methodology for the isolation of cord blood-derived multipotent mesenchymal stromal cells (CB-MSCs) from fresh umbilical cord blood has not been reported in any species. The objective of this study was to improve the isolation procedure for equine CB-MSCs. METHODS: Pre......Cyte-EQ medium is superior to Ficoll-Paque PREMIUM density medium for the isolation of putative equine CB MSC and that MSC-qualified FBS may improve the isolation efficiency....

  11. Isolation and characterization of equine peripheral blood-derived multipotent mesenchymal stromal cells

    OpenAIRE

    Armando de M. Carvalho; Ana Lucia M. Yamada; Juliana R.B. Martins; Leandro Maia; Marjorie de A Golim; Elenice Deffune; Carlos A. Hussni; Ana Liz G. Alves

    2013-01-01

    The objective of the study was to isolate, cultivate and characterize equine peripheral blood-derived multipotent mesenchymal stromal cells (PbMSCs). Peripheral blood was collected, followed by the isolation of mononuclear cells using density gradient reagents, and the cultivation of adherent cells. Monoclonal mouse anti-horse CD13, mouse anti-horse CD44, and mouse anti-rat CD90 antibodies were used for the immunophenotypic characterization of the surface of the PbMSCs. These cells were also ...

  12. AR42J-B-13 cell: An expandable progenitor to generate an unlimited supply of functional hepatocytes

    International Nuclear Information System (INIS)

    Hepatocytes are the preparation of choice for Toxicological research in vitro. However, despite the fact that hepatocytes proliferate in vivo during liver regeneration, they are resistant to proliferation in vitro, do not tolerate sub-culture and tend to enter a de-differentiation program that results in a loss of hepatic function. These limitations have resulted in the search for expandable rodent and human cells capable of being directed to differentiate into functional hepatocytes. Research with stem cells suggests that it may be possible to provide the research community with hepatocytes in vitro although to date, significant challenges remain, notably generating a sufficiently pure population of hepatocytes with a quantitative functionality comparable with hepatocytes. This paper reviews work with the AR42J-B-13 (B-13) cell line. The B-13 cell was cloned from the rodent AR42J pancreatic cell line, express genes associated with pancreatic acinar cells and readily proliferates in simple culture media. When exposed to glucocorticoid, 75-85% of the cells trans-differentiate into hepatocyte-like (B-13/H) cells functioning at a level quantitatively similar to freshly isolated rat hepatocytes (with the remaining cells retaining the B-13 phenotype). Trans-differentiation of pancreatic acinar cells also appears to occur in vivo in rats treated with glucocorticoid; in mice with elevated circulating glucocorticoid and in humans treated for long periods with glucocorticoid. The B-13 response to glucocorticoid therefore appears to be related to a real pathophysiological response of a pancreatic cell to glucocorticoid. An understanding of how this process occurs and if it can be generated or engineered in human cells would result in a cell line with the ability to generate an unlimited supply of functional human hepatocytes in a cost effective manner.

  13. Microfluidic generated EGF-gradients induce chemokinesis of transplantable retinal progenitor cells via the JAK/STAT and PI3kinase signaling pathways.

    Directory of Open Access Journals (Sweden)

    Uchenna J Unachukwu

    Full Text Available A growing number of studies are evaluating retinal progenitor cell (RPC transplantation as an approach to repair retinal degeneration and restore visual function. To advance cell-replacement strategies for a practical retinal therapy, it is important to define the molecular and biochemical mechanisms guiding RPC motility. We have analyzed RPC expression of the epidermal growth factor receptor (EGFR and evaluated whether exposure to epidermal growth factor (EGF can coordinate motogenic activity in vitro. Using Boyden chamber analysis as an initial high-throughput screen, we determined that RPC motility was optimally stimulated by EGF concentrations in the range of 20-400 ng/ml, with decreased stimulation at higher concentrations, suggesting concentration-dependence of EGF-induced motility. Using bioinformatics analysis of the EGF ligand in a retina-specific gene network pathway, we predicted a chemotactic function for EGF involving the MAPK and JAK-STAT intracellular signaling pathways. Based on targeted inhibition studies, we show that ligand binding, phosphorylation of EGFR and activation of the intracellular STAT3 and PI3kinase signaling pathways are necessary to drive RPC motility. Using engineered microfluidic devices to generate quantifiable steady-state gradients of EGF coupled with live-cell tracking, we analyzed the dynamics of individual RPC motility. Microfluidic analysis, including center of mass and maximum accumulated distance, revealed that EGF induced motility is chemokinetic with optimal activity observed in response to low concentration gradients. Our combined results show that EGFR expressing RPCs exhibit enhanced chemokinetic motility in the presence of low nanomole levels of EGF. These findings may serve to inform further studies evaluating the extent to which EGFR activity, in response to endogenous ligand, drives motility and migration of RPCs in retinal transplantation paradigms.

  14. Human umbilical cord blood-derived f-macrophages retain pluripotentiality after thrombopoietin expansion

    International Nuclear Information System (INIS)

    We have previously characterized a new type of stem cell from human peripheral blood, termed fibroblast-like macrophage (f-MΦ). Here, using umbilical cord blood as a source, we identified cells with similar characteristics including expression of surface markers (CD14, CD34, CD45, CD117, and CD163), phagocytosis, and proliferative capacity. Further, thrombopoietin (TPO) significantly stimulated the proliferation of cord blood-derived f-MΦ (CB f-MΦ) at low dosage without inducing a megakaryocytic phenotype. Additional experiments demonstrated that TPO-expanded cord blood-derived f-MΦ (TCB f-MΦ) retained their surface markers and differentiation ability. Treatment with vascular endothelial cell growth factor (VEGF) gave rise to endothelial-like cells, expressing Flt-1, Flk-1, von Willebrand Factor (vWF), CD31, acetylated low density lipoprotein internalization, and the ability to form endothelial-like cell chains. In the presence of lipopolyssacharide (LPS) and 25 mM glucose, the TCB f-MΦ differentiated to express insulin mRNA, C-peptide, and insulin. In vitro functional analysis demonstrated that these insulin-positive cells could release insulin in response to glucose and other secretagogues. These findings demonstrate a potential use of CB f-MΦ and may lead to develop new therapeutic strategy for treating dominant disease

  15. Development and bioevaluation of nanofibers with blood-derived growth factors for dermal wound healing.

    Science.gov (United States)

    Bertoncelj, Valentina; Pelipenko, Jan; Kristl, Julijana; Jeras, Matjaž; Cukjati, Marko; Kocbek, Petra

    2014-09-01

    The aim of our work was to produce a modern nanomaterial with incorporated blood-derived growth factors, produced by electrospinning, applicable in treatment of chronic wounds. Platelet-rich plasma was chosen as a natural source of growth factors. Results showed that platelet-rich plasma stimulates keratinocyte and fibroblast cell growth in vitro. Its optimal concentration in growth medium was 2% (v/v) for both types of skin cells, while higher concentrations caused alterations in cell morphology, with reduced cell mobility and proliferation. In the next step hydrophilic nanofibers loaded with platelet-rich plasma were produced from chitosan and poly(ethylene oxide), using electrospinning. The morphology of nanofibers was stable in aqueous conditions for 72 h. It was shown that electrospinning does not adversely affect the biological activity of platelet-rich plasma. The effects of nanofibers with incorporated platelet-rich plasma on cell proliferation, survival, morphology and mobility were examined. Nanofibers limited cell mobility, changed morphology and stimulated cell proliferation. Despite of the small amount of blood-derived growth factors introduced in cell culture via platelet-rich plasma-loaded nanofibers, such nanofibrillar support significantly induced cell proliferation, indicating synergistic effect of nanotopography and incorporated growth factors. The overall results confirm favorable in vitro properties of produced nanofibers, indicating their high potential as a nanomaterial suitable for delivery of platelet-rich plasma in wound healing applications. PMID:24931341

  16. Electrophysiological characterisation of human umbilical cord blood-derived mesenchymal stem cells induced by olfactory ensheathing cell-conditioned medium.

    Science.gov (United States)

    Zeng, Yu; Rong, Mingqiang; Liu, Yunsheng; Liu, Jingfang; Lu, Ming; Tao, Xiaoyu; Li, Zhenyan; Chen, Xin; Yang, Kui; Li, Chuntao; Liu, Zhixiong

    2013-12-01

    Umbilical cord blood-derived marrow stromal cells (UCB-MSCs) with high proliferation capacity and immunomodulatory properties are considered to be a good candidate for cell-based therapies. But until now, little work has been focused on the differentiation of UCB-MSCs. In this work, UCB-MSCs were demonstrated to be negative for CD34 and CD45 expression but positive for CD90 and CD105 expression. The gate values of UCB-MSCs for CD90 and CD105 were 99.3 and 98.6 %, respectively. Two weeks after treatment, the percentage of neuron-like cells differentiated from UCB-MSCs was increased to 84 ± 12 % in the experimental group [treated with olfactory ensheathing cells (OECs)-conditioned medium] and they were neuron-specific enolase positive; few neuron-like cells were found in the control group (without OECs-conditioned medium). Using whole-cell recording, sodium and potassium currents were recorded in UCB-MSCs after differentiation by OECs. Thus, human UCB-MSCs could be differentiated to neural cells by secreted secretion from OECs and exhibited electrophysiological properties similar to mature neurons after 2 weeks post-induction. These results imply that OECs can be used as a new strategy for stem cell differentiation and provide an alternative neurogenesis pathway for generating sufficient numbers of neural cells for cell therapy.

  17. The treatment of neurodegenerative disorders using umbilical cord blood and menstrual blood-derived stem cells.

    Science.gov (United States)

    Sanberg, Paul R; Eve, David J; Willing, Alison E; Garbuzova-Davis, Svitlana; Tan, Jun; Sanberg, Cyndy D; Allickson, Julie G; Cruz, L Eduardo; Borlongan, Cesar V

    2011-01-01

    Stem cell transplantation is a potentially important means of treatment for a number of disorders. Two different stem cell populations of interest are mononuclear umbilical cord blood cells and menstrual blood-derived stem cells. These cells are relatively easy to obtain, appear to be pluripotent, and are immunologically immature. These cells, particularly umbilical cord blood cells, have been studied as either single or multiple injections in a number of animal models of neurodegenerative disorders with some degree of success, including stroke, Alzheimer's disease, amyotrophic lateral sclerosis, and Sanfilippo syndrome type B. Evidence of anti-inflammatory effects and secretion of specific cytokines and growth factors that promote cell survival, rather than cell replacement, have been detected in both transplanted cells.

  18. Effects of hypoxia on proliferation of human cord blood-derived mesenchymal stem cells.

    Science.gov (United States)

    Peng, Longying; Shu, Xiaomei; Lang, Changhui; Yu, Xiaohua

    2016-08-01

    The purpose of our study was to examine the influence of hypoxia on proliferation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). The mononuclear cells were separated by density gradient centrifugation from human umbilical cord blood and then, respectively, cultured under hypoxia (5 % O2) or normoxia (20 % O2). Their cell morphology, cell surface markers, β-galactosidase staining, cell growth curve, DNA cycle, and the expression of hypoxia-inducible factor-1α (HIF-1α) were evaluated. We found that hypoxia, in part via HIF-1α, improved the proliferation efficiency, and prevented senescence of hUCB-MSCs without altering their morphology and surface markers. These results demonstrated that hypoxia provides a favorable culture condition to promote hUCB-MSCs proliferation in vitro, which is a better way to obtain sufficient numbers of hUCB-MSCs for research and certainly clinical application. PMID:25742732

  19. Human umbilical cord blood-derived mesenchymal stem cells promote regeneration of crush-injured rat sciatic nerves

    Institute of Scientific and Technical Information of China (English)

    Mi-Ae Sung; Jong-Ho Lee; Hun Jong Jung; Jung-Woo Lee; Jin-Yong Lee; Kang-Mi Pang; Sang Bae Yoo; Mohammad S. Alrashdan; Soung-Min Kim; Jeong Won Jahng

    2012-01-01

    Several studies have demonstrated that human umbilical cord blood-derived mesenchymal stem cells can promote neural regeneration following brain injury. However, the therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells in guiding peripheral nerve regeneration remain poorly understood. This study was designed to investigate the effects of human umbilical cord blood-derived mesenchymal stem cells on neural regeneration using a rat sciatic nerve crush injury model. Human umbilical cord blood-derived mesenchymal stem cells (1 × 106) or a PBS control were injected into the crush-injured segment of the sciatic nerve. Four weeks after cell injection, brain-derived neurotrophic factor and tyrosine kinase receptor B mRNA expression at the lesion site was increased in comparison to control. Furthermore, sciatic function index, Fluoro Gold-labeled neuron counts and axon density were also significantly increased when compared with control. Our results indicate that human umbilical cord blood-derived mesenchymal stem cells promote the functional recovery of crush-injured sciatic nerves.

  20. Mesenchymal Stem Cell-Derived Microvesicles Support Ex Vivo Expansion of Cord Blood-Derived CD34+ Cells

    Directory of Open Access Journals (Sweden)

    Hui Xie

    2016-01-01

    Full Text Available Mesenchymal stem cells (MSCs are known to support the characteristic properties of hematopoietic stem and progenitor cells (HSPCs in the bone marrow hematopoietic microenvironment. MSCs are used in coculture systems as a feeder layer for the ex vivo expansion of umbilical cord blood (CB to increase the relatively low number of HSPCs in CB. Findings increasingly suggest that MSC-derived microvesicles (MSC-MVs play an important role in the biological functions of their parent cells. We speculate that MSC-MVs may recapitulate the hematopoiesis-supporting effects of their parent cells. In the current study, we found MSC-MVs containing microRNAs that are involved in the regulation of hematopoiesis. We also demonstrated that MSC-MVs could improve the expansion of CB-derived mononuclear cells and CD34+ cells and generate a greater number of primitive progenitor cells in vitro. Additionally, when MSC-MVs were added to the CB-MSC coculture system, they could improve the hematopoiesis-supporting effects of MSCs. These findings highlight the role of MSC-MVs in the ex vivo expansion of CB, which may offer a promising therapeutic approach in CB transplantation.

  1. The therapeutic potential of human umbilical cord blood-derived mesenchymal stem cells in Alzheimer's disease.

    Science.gov (United States)

    Lee, Hyun Ju; Lee, Jong Kil; Lee, Hyun; Shin, Ji-woong; Carter, Janet E; Sakamoto, Toshiro; Jin, Hee Kyung; Bae, Jae-sung

    2010-08-30

    The neuropathological hallmarks of Alzheimer's disease (AD) include the presence of extracellular amyloid-beta peptide (Abeta) in the form of amyloid plaques in the brain parenchyma and neuronal loss. The mechanism associated with neuronal death by amyloid plaques is unclear but oxidative stress and glial activation has been implicated. Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) are being scrutinized as a potential therapeutic tool to prevent various neurodegenerative diseases including AD. However, the therapeutic impact of hUCB-MSCs in AD has not yet been reported. Here we undertook in vitro work to examine the potential impact of hUCB-MSCs treatment on neuronal loss using a paradigm of cultured hippocampal neurons treated with Abeta. We confirmed that hUCB-MSCs co-culture reduced the hippocampal apoptosis induced by Abeta treatment. Moreover, in an acute AD mouse model to directly test the efficacy of hUCB-MSCs treatment on AD-related cognitive and neuropathological outcomes, we demonstrated that markers of glial activation, oxidative stress and apoptosis levels were decreased in AD mouse brain. Interestingly, hUCB-MSCs treated AD mice demonstrated cognitive rescue with restoration of learning/memory function. These data suggest that hUCB-MSCs warrant further investigation as a potential therapeutic agent in AD.

  2. Bioluminescence imaging of cord blood derived mesenchymal stem cell transplanatation into myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Min, Jung Joon; Ahn, Young Keun; Moon, Sung Min; Lim, Sang Yup; Yun, Kyung Ho; Heo, Young Jun; Song, Ho Chun; Jeong, Myung Ho; Bom, Hee Seung [School of Medicine, Chonnam National University, Gwangju (Korea, Republic of)

    2004-07-01

    The conventional method of analyzing myocardial cell transplanation relies on postmortem histology. We sought to demonstrate the feasibility of longitudinal monitoring transplanted cell survival in living animals using optical imaging techniques. Umblical cord blood was collected upon delivery with informed consent. Umblical mononuclear cells were obtained by negative immuno-depletion of CD3, CD14, CD19, CD38, CD66b, and glycophorin- A positive cells, followed by Ficoll- Paque density gradient centrifugation, and plated in non-coated tissue culture flasks in expansion medium. Cells were allowed to adhere overnight, thereafter non-adherent cells were washed out with medium changes. After getting the MSCs, they were transfected [multiplicity of infection (MOl) = 40) with Ad-CMV-Fluc overnight. Rats (n=4) underwent intramyocardial injection of 5 x 10{sup 5} MSCs expressing firefly luciferase (Fluc) reporter gene. Optical bioluminescence imaging was performed using the charged-coupled device camera (Xenogen) from the 1st day of transplantion. Cardiac bioluminescence signals were present from 2nd day of transplantation. Cardiac signals were clearly present at day 2 (9.2x10{sup 3}p/s/cm{sup 2}/sr). The signal reduced from day 3. The locations, magnitude, and survival duration of cord blood derived MSCs were monitored noninvasively. With further development, molecular imaging studies should add critical insights into cardiac cell transplantation.

  3. Bioluminescence imaging of cord blood derived mesenchymal stem cell transplanatation into myocardium

    International Nuclear Information System (INIS)

    The conventional method of analyzing myocardial cell transplanation relies on postmortem histology. We sought to demonstrate the feasibility of longitudinal monitoring transplanted cell survival in living animals using optical imaging techniques. Umblical cord blood was collected upon delivery with informed consent. Umblical mononuclear cells were obtained by negative immuno-depletion of CD3, CD14, CD19, CD38, CD66b, and glycophorin- A positive cells, followed by Ficoll- Paque density gradient centrifugation, and plated in non-coated tissue culture flasks in expansion medium. Cells were allowed to adhere overnight, thereafter non-adherent cells were washed out with medium changes. After getting the MSCs, they were transfected [multiplicity of infection (MOl) = 40) with Ad-CMV-Fluc overnight. Rats (n=4) underwent intramyocardial injection of 5 x 105 MSCs expressing firefly luciferase (Fluc) reporter gene. Optical bioluminescence imaging was performed using the charged-coupled device camera (Xenogen) from the 1st day of transplantion. Cardiac bioluminescence signals were present from 2nd day of transplantation. Cardiac signals were clearly present at day 2 (9.2x103p/s/cm2/sr). The signal reduced from day 3. The locations, magnitude, and survival duration of cord blood derived MSCs were monitored noninvasively. With further development, molecular imaging studies should add critical insights into cardiac cell transplantation

  4. Autologous Endothelial Progenitor Cell-Seeding Technology and Biocompatibility Testing For Cardiovascular Devices in Large Animal Model

    OpenAIRE

    Jantzen, Alexandra E.; Lane, Whitney O.; Gage, Shawn M.; Haseltine, Justin M; Galinat, Lauren J; Jamiolkowski, Ryan M.; Lin, Fu-Hsiung; Truskey, George A.; Achneck, Hardean E.

    2011-01-01

    Implantable cardiovascular devices are manufactured from artificial materials (e.g. titanium (Ti), expanded polytetrafluoroethylene), which pose the risk of thromboemboli formation1,2,3. We have developed a method to line the inside surface of Ti tubes with autologous blood-derived human or porcine endothelial progenitor cells (EPCs)4. By implanting Ti tubes containing a confluent layer of porcine EPCs in the inferior vena cava (IVC) of pigs, we tested the improved biocompatibility of the cel...

  5. Isolation of alveolar epithelial type II progenitor cells from adult human lungs

    OpenAIRE

    Fujino, Naoya; Kubo, Hiroshi; Suzuki, Takaya; Ota, Chiharu; Hegab, Ahmed E.; He, Mei; Suzuki, Satoshi; Suzuki, Takashi; Yamada, Mitsuhiro; Kondo, Takashi; Kato, Hidemasa; Yamaya, Mutsuo

    2010-01-01

    Resident stem/progenitor cells in the lung are important for tissue homeostasis and repair. However, a progenitor population for alveolar type II (ATII) cells in adult human lungs has not been identified. The aim of this study is to isolate progenitor cells from adult human lungs with the ability to differentiate into ATII cells. We isolated colony-forming cells that had the capability for self-renewal and the potential to generate ATII cells in vitro. These undifferentiated progenitor cells ...

  6. Whole blood-derived microRNA signatures in mice exposed to lipopolysaccharides

    Directory of Open Access Journals (Sweden)

    Hsieh Ching-Hua

    2012-07-01

    RNA targets. Conclusions We identified a specific whole blood–derived miRNA signature in mice exposed to LPS, but not to LTA, from different gram-negative bacteria. These whole blood-derived miRNAs are promising as biomarkers for LPS exposure.

  7. GRB Progenitors and Environment

    OpenAIRE

    Lazzati, Davide

    2005-01-01

    The study and knowledge of the environment of Gamma-Ray Bursts is of great interest from many points of view. For high redshift (z>0.5) events, the structure of the ambient medium is one of the best indicators of the nature and properties of the progenitor. It also tells us about the last stages of the pre-explosion evolution of the progenitor. In addition, it is interesting in its own as a sample of the interstellar medium in a high redshift galaxy. Measures of the density and structure of t...

  8. Quantitative analysis by next generation sequencing of hematopoietic stem and progenitor cells (LSK) and of splenic B cells transcriptomes from wild-type and Usp3-knockout mice.

    Science.gov (United States)

    Lancini, Cesare; Gargiulo, Gaetano; van den Berk, Paul C M; Citterio, Elisabetta

    2016-03-01

    The data described here provide genome-wide expression profiles of murine primitive hematopoietic stem and progenitor cells (LSK) and of B cell populations, obtained by high throughput sequencing. Cells are derived from wild-type mice and from mice deficient for the ubiquitin-specific protease 3 (USP3; Usp3Δ/Δ). Modification of histone proteins by ubiquitin plays a crucial role in the cellular response to DNA damage (DDR) (Jackson and Durocher, 2013) [1]. USP3 is a histone H2A deubiquitinating enzyme (DUB) that regulates ubiquitin-dependent DDR in response to DNA double-strand breaks (Nicassio et al., 2007; Doil et al., 2008) [2], [3]. Deletion of USP3 in mice increases the incidence of spontaneous tumors and affects hematopoiesis [4]. In particular, Usp3-knockout mice show progressive loss of B and T cells and decreased functional potential of hematopoietic stem cells (HSCs) during aging. USP3-deficient cells, including HSCs, display enhanced histone ubiquitination, accumulate spontaneous DNA damage and are hypersensitive to ionizing radiation (Lancini et al., 2014) [4]. To address whether USP3 loss leads to deregulation of specific molecular pathways relevant to HSC homeostasis and/or B cell development, we have employed the RNA-sequencing technology and investigated transcriptional differences between wild-type and Usp3Δ/Δ LSK, naïve B cells or in vitro activated B cells. The data relate to the research article "Tight regulation of ubiquitin-mediated DNA damage response by USP3 preserves the functional integrity of hematopoietic stem cells" (Lancini et al., 2014) [4]. The RNA-sequencing and analysis data sets have been deposited in NCBI׳s Gene Expression Omnibus (Edgar et al., 2002) [5] and are accessible through GEO Series accession number GSE58495 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE58495). With this article, we present validation of the RNA-seq data set through quantitative real-time PCR and comparative analysis. PMID:26909367

  9. Quantitative analysis by next generation sequencing of hematopoietic stem and progenitor cells (LSK and of splenic B cells transcriptomes from wild-type and Usp3-knockout mice

    Directory of Open Access Journals (Sweden)

    Cesare Lancini

    2016-03-01

    Full Text Available The data described here provide genome-wide expression profiles of murine primitive hematopoietic stem and progenitor cells (LSK and of B cell populations, obtained by high throughput sequencing. Cells are derived from wild-type mice and from mice deficient for the ubiquitin-specific protease 3 (USP3; Usp3Δ/Δ. Modification of histone proteins by ubiquitin plays a crucial role in the cellular response to DNA damage (DDR (Jackson and Durocher, 2013 [1]. USP3 is a histone H2A deubiquitinating enzyme (DUB that regulates ubiquitin-dependent DDR in response to DNA double-strand breaks (Nicassio et al., 2007; Doil et al., 2008 [2,3]. Deletion of USP3 in mice increases the incidence of spontaneous tumors and affects hematopoiesis [4]. In particular, Usp3-knockout mice show progressive loss of B and T cells and decreased functional potential of hematopoietic stem cells (HSCs during aging. USP3-deficient cells, including HSCs, display enhanced histone ubiquitination, accumulate spontaneous DNA damage and are hypersensitive to ionizing radiation (Lancini et al., 2014 [4]. To address whether USP3 loss leads to deregulation of specific molecular pathways relevant to HSC homeostasis and/or B cell development, we have employed the RNA-sequencing technology and investigated transcriptional differences between wild-type and Usp3Δ/Δ LSK, naïve B cells or in vitro activated B cells. The data relate to the research article “Tight regulation of ubiquitin-mediated DNA damage response by USP3 preserves the functional integrity of hematopoietic stem cells” (Lancini et al., 2014 [4]. The RNA-sequencing and analysis data sets have been deposited in NCBI׳s Gene Expression Omnibus (Edgar et al., 2002 [5] and are accessible through GEO Series accession number GSE58495 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE58495. With this article, we present validation of the RNA-seq data set through quantitative real-time PCR and comparative analysis.

  10. Growth Induction and Low-Oxygen Apoptosis Inhibition of Human CD34+ Progenitors in Collagen Gels

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    Daniele Avitabile

    2013-01-01

    Full Text Available Various reports have indicated low survival of injected progenitors into unfavorable environments such as the ischemic myocardium or lower limb tissues. This represents a major bottleneck in stem-cell-based cardiovascular regenerative medicine. Strategies to enhance survival of these cells in recipient tissues have been therefore sought to improve stem cell survival and ensure long-term engraftment. In the present contribution, we show that embedding human cord blood-derived CD34+ cells into a collagen I-based hydrogel containing cytokines is a suitable strategy to promote stem cell proliferation and protect these cells from anoxia-induced apoptosis.

  11. Production of good manufacturing practice-grade human umbilical cord blood-derived mesenchymal stem cells for therapeutic use.

    Science.gov (United States)

    Van Pham, Phuc; Phan, Ngoc Kim

    2015-01-01

    Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) are multipotent stem cells that can be differentiated into several specific cell types such as adipocytes, osteoblasts, and chondroblasts. They also were demonstrated to trans-differentiate into other cell lineages such as muscle cells and neurons. Thus, they are considered a promising stem cell source for therapeutic use. Here, we describe a method for production of good manufacturing practice-grade human UCB-MSCs for therapeutic use. The obtained UCB-MSCs are free of allogenous or xenogenous proteins. In addition, these MSCs could maintain the MSC phenotype in long-term culture.

  12. Umbilical Cord Blood-Derived Stem Cells Improve Heat Tolerance and Hypothalamic Damage in Heat Stressed Mice

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    Ling-Shu Tseng

    2014-01-01

    Full Text Available Heatstroke is characterized by excessive hyperthermia associated with systemic inflammatory responses, which leads to multiple organ failure, in which brain disorders predominate. This definition can be almost fulfilled by a mouse model of heatstroke used in the present study. Unanesthetized mice were exposed to whole body heating (41.2°C for 1 hour and then returned to room temperature (26°C for recovery. Immediately after termination of whole body heating, heated mice displayed excessive hyperthermia (body core temperature ~42.5°C. Four hours after termination of heat stress, heated mice displayed (i systemic inflammation; (ii ischemic, hypoxic, and oxidative damage to the hypothalamus; (iii hypothalamo-pituitary-adrenocortical axis impairment (reflected by plasma levels of both adrenocorticotrophic-hormone and corticosterone; (iv decreased fractional survival; and (v thermoregulatory deficits (e.g., they became hypothermia when they were exposed to room temperature. These heatstroke reactions can be significantly attenuated by human umbilical cord blood-derived CD34+ cells therapy. Our data suggest that human umbilical cord blood-derived stem cells therapy may improve outcomes of heatstroke in mice by reducing systemic inflammation as well as hypothalamo-pituitary-adrenocortical axis impairment.

  13. Advances in menstrual blood-derived stem cells%宫内膜干细胞研究进展

    Institute of Scientific and Technical Information of China (English)

    张金龙; 张舒琪; 袁立

    2012-01-01

    本文介绍新型间充质干细胞—宫内膜干细胞的来源和特征,简述宫内膜干细胞分离、培养和体外扩增的方法;阐述宫内膜干细胞体外诱导分化心肌细胞和神经细胞的潜能,展望宫内膜干细胞的临床应用价值.%Menstrual blood-derived stem cells (MenSCs) are newly discovered mesenchymal stem cells. They have the potential ability to differentiate into various cell types, including heart and nerve cells. MenSCs provide an alternative source of adult stem cells for research and use in regenerative medicine.

  14. Cord Blood Derived CD4+CD25high T Cells Become Functional Regulatory T Cells upon Antigen Encounter

    Science.gov (United States)

    Mayer, Elisabeth; Bannert, Christina; Gruber, Saskia; Klunker, Sven; Spittler, Andreas; Akdis, Cezmi A.

    2012-01-01

    Background: Upon antigen exposure, cord blood derived T cells respond to ubiquitous environmental antigens by high proliferation. To date it remains unclear whether these “excessive” responses relate to different regulatory properties of the putative T regulatory cell (Treg) compartment or even expansion of the Treg compartment itself. Methods: Cord blood (>37 week of gestation) and peripheral blood (healthy controls) were obtained and different Treg cell subsets were isolated. The suppressive potential of Treg populations after antigen exposure was evaluated via functional inhibition assays ([3H]thymidine incorporation assay and CFSE staining) with or without allergen stimulation. The frequency and markers of CD4+CD25highFoxP3+ T cells were characterized by mRNA analysis and flow cytometry. Results: Cord blood derived CD4+CD25high cells did not show substantial suppressor capacity upon TCR activation, in contrast to CD4+CD25high cells freshly purified from adult blood. This could not be explained by a lower frequency of FoxP3+CD4+CD25highcells or FOXP3 mRNA expression. However, after antigen-specific stimulation in vitro, these cells showed strong proliferation and expansion and gained potent suppressive properties. The efficiency of their suppressive capacity can be enhanced in the presence of endotoxins. If T-cells were sorted according to their CD127 expression, a tiny subset of Treg cells (CD4+CD25+CD127low) is highly suppressive even without prior antigen exposure. Conclusion: Cord blood harbors a very small subset of CD4+CD25high Treg cells that requires antigen-stimulation to show expansion and become functional suppressive Tregs. PMID:22272233

  15. Factors inducing human umbilical cord blood-derived mesenchymal stem cells to differentiate into neuron-like cells

    Institute of Scientific and Technical Information of China (English)

    Nawei Zhang; Fengqing Ji

    2006-01-01

    OBJECTIVE:Human umbilical cord blood-derived mesenchymal stem cells (HUCB-derived MSCs)can differentiate into neuron-like cells,which can be used to treat some central nervous system(CNS)diseases.To investigate the factors,which can induce HUCB-derived MSCs to differentiate into neuron-like cells,so as to find effective methods for future clinical application.DATA SOURCES:Using the key terms"human umbilical cord blood"combined with"mesenchymal stem cells,neuron-like cells,neural cells"respectively,the relevant articles in English published during the period from January 1999 to June 2006 were searched from the Medline database.Meanwhile,relevant Chinese articles published from January 1999 to June 2006 were searched Using the same key terms.STUDY SELECTION: All articles associated with the differentiation from human umbilical cord blood into neuron-like cells were selected firstly.Then the full texts were looked up by searchling Ovid medical Journals full-text database and Elsevier Electrical Journals Full-text Database.Articles with full expeiments,enrolled in inducible factors or involved inducible mechanism were retdeved.DATA EXTRACTION:Among 119 collected correlative articles,29 were involved and 90 were excluded.DATA SYNTHESIS:The inducible factors of HUCB-derived MSCs differentiatling into neuron-like cells included renal endothelial growth factors,fibroblasts,β-mercaptoethanol,dimethyl sulfoxide,butyl hydroxyl anisol,brain-derived neurotrophic factor,Danshen,retinoic acid,sodium ferulate and so on,but its mechanism was unclear.CONCLUSION:Human umbilical cord blood-derived MSCs can differentiate into neuron-like cells,with varied inductors.

  16. The endocannabinoid system drives neural progenitor proliferation.

    Science.gov (United States)

    Aguado, Tania; Monory, Krisztina; Palazuelos, Javier; Stella, Nephi; Cravatt, Benjamin; Lutz, Beat; Marsicano, Giovanni; Kokaia, Zaal; Guzmán, Manuel; Galve-Roperh, Ismael

    2005-10-01

    The discovery of multipotent neural progenitor (NP) cells has provided strong support for the existence of neurogenesis in the adult brain. However, the signals controlling NP proliferation remain elusive. Endocannabinoids, the endogenous counterparts of marijuana-derived cannabinoids, act as neuromodulators via presynaptic CB1 receptors and also control neural cell death and survival. Here we show that progenitor cells express a functional endocannabinoid system that actively regulates cell proliferation both in vitro and in vivo. Specifically, NPs produce endocannabinoids and express the CB1 receptor and the endocannabinoid-inactivating enzyme fatty acid amide hydrolase (FAAH). CB1 receptor activation promotes cell proliferation and neurosphere generation, an action that is abrogated in CB1-deficient NPs. Accordingly, proliferation of hippocampal NPs is increased in FAAH-deficient mice. Our results demonstrate that endocannabinoids constitute a new group of signaling cues that regulate NP proliferation and thus open novel therapeutic avenues for manipulation of NP cell fate in the adult brain.

  17. Isolation and characterisation of peripheral blood-derived feline mesenchymal stem cells.

    Science.gov (United States)

    Sato, Keiichi; Yamawaki-Ogata, Aika; Kanemoto, Isamu; Usui, Akihiko; Narita, Yuji

    2016-10-01

    The aim of this study was to isolate mesenchymal stem cells (MSCs) from feline peripheral blood (fPB-MSCs) and to characterise the cells' in vitro properties. The mononuclear cell fractions were isolated from venous blood of cats by density gradient centrifugation and cultured on plastic dishes under various culture conditions to isolate MSCs. When these cells were cultured with 5% autologous plasma (AP) and 10% foetal bovine serum (FBS), adherent spindle shaped fibroblast-like cells (fPB-MSCs) were obtained from 15/22 (68%) cats. These cells were isolated only from medium containing both AP and FBS. The morphology of these MSCs was similar to those isolated from other species and from other feline tissues. fPB-MSCs expanded steadily up to 5-6 passages, but had increased population doubling time during passaging and almost all cells stopped proliferation at passages 7-9. These cells expressed CD44 and CD90, and were mostly negative for major histocompatibility class II and CD4. The cells could be induced to differentiate into adipogenic, osteogenic and chondrogenic cell lineages. These findings indicate that fPB-MSCs can be generated but appear to require specific culture conditions. PMID:27687950

  18. Coxsackievirus B4 Can Infect Human Peripheral Blood-Derived Macrophages

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    Enagnon Kazali Alidjinou

    2015-11-01

    Full Text Available Beyond acute infections, group B coxsackieviruses (CVB are also reported to play a role in the development of chronic diseases, like type 1 diabetes. The viral pathogenesis mainly relies on the interplay between the viruses and innate immune response in genetically-susceptible individuals. We investigated the interaction between CVB4 and macrophages considered as major players in immune response. Monocyte-derived macrophages (MDM generated with either M-CSF or GM-CSF were inoculated with CVB4, and infection, inflammation, viral replication and persistence were assessed. M-CSF-induced MDM, but not GM-CSF-induced MDM, can be infected by CVB4. In addition, enhancing serum was not needed to infect MDM in contrast with parental monocytes. The expression of viral receptor (CAR mRNA was similar in both M-CSF and GM-CSF MDM. CVB4 induced high levels of pro-inflammatory cytokines (IL-6 and TNFα in both MDM populations. CVB4 effectively replicated and persisted in M-CSF MDM, but IFNα was produced in the early phase of infection only. Our results demonstrate that CVB4 can replicate and persist in MDM. Further investigations are required to determine whether the interaction between the virus and MDM plays a role in the pathogenesis of CVB-induced chronic diseases.

  19. From progenitor to afterlife

    CERN Document Server

    Chevalier, R A

    2006-01-01

    The sequence of massive star supernova types IIP (plateau light curve), IIL (linear light curve), IIb, IIn (narrow line), Ib, and Ic roughly represents a sequence of increasing mass loss during the stellar evolution. The mass loss affects the velocity distribution of the ejecta composition; in particular, only the IIP's typically end up with H moving at low velocity. Radio and X-ray observations of extragalactic supernovae show varying mass loss properties that are in line with expectations for the progenitor stars. For young supernova remnants, pulsar wind nebulae and circumstellar interaction provide probes of the inner ejecta and higher velocity ejecta, respectively. Among the young remnants, there is evidence for supernovae over a range of types, including those that exploded with much of the H envelope present (Crab Nebula, 3C 58, 0540--69) and those that exploded after having lost most of their H envelope (Cas A, G292.0+1.8).

  20. Endothelial progenitor cells in hematologic malignancies.

    Science.gov (United States)

    Testa, Ugo; Saulle, Ernestina; Castelli, Germana; Pelosi, Elvira

    2016-01-01

    Studies carried out in the last years have improved the understanding of the cellular and molecular mechanisms controlling angiogenesis during adult life in normal and pathological conditions. Some of these studies have led to the identification of some progenitor cells that sustain angiogenesis through indirect, paracrine mechanisms (hematopoietic angiogenic cells) and through direct mechanisms, i.e., through their capacity to generate a progeny of phenotypically and functionally competent endothelial cells [endothelial colony forming cells (ECFCs)]. The contribution of these progenitors to angiogenetic processes under physiological and pathological conditions is intensively investigated. Angiogenetic mechanisms are stimulated in various hematological malignancies, including chronic myeloid leukemia (CML), acute myeloid leukemia (AML), myelodysplastic syndromes and multiple myeloma, resulting in an increased angiogenesis that contributes to disease progression. In some of these conditions there is preliminary evidence that some endothelial cells could derive from the malignant clone, thus leading to the speculation that the leukemic cell derives from the malignant transformation of a hemangioblastic progenitor, i.e., of a cell capable of differentiation to the hematopoietic and to the endothelial cell lineages. Our understanding of the mechanisms underlying increased angiogenesis in these malignancies not only contributed to a better knowledge of the mechanisms responsible for tumor progression, but also offered the way for the discovery of new therapeutic targets. PMID:27583252

  1. Identification of bovine material in porcine spray-dried blood derivatives using the Polymerase Chain Reaction technique

    Directory of Open Access Journals (Sweden)

    Sánchez A.

    2004-01-01

    Full Text Available Due to the widely supported theory of bovine spongiform encephalopathy (BSE spread in cattle by contaminated animal feeds, screening of feed products has become essential. For many years, manufacturers have used blood and plasma proteins as high quality ingredients of foods for both pets and farm animals. However, in Europe, the Commission Regulation 1234/2003/EC temporally bans the use of processed animal proteins, including blood-derivative products, in feedstuffs for all farm animals which are fattened or bred for the production of food. This regulation has some exceptions, such as the use of non ruminant blood products into the feed of farm fish. Authorization of the re-introduction of these proteins into animal feed formulations, especially non ruminant proteins into the feed for non ruminant farm animals, is expected when adequate control methods to discriminate ruminant proteins exist. Currently, the number of validated methods to differentiate the species of origin for most of the animal by-products is limited. Here we report the development of a rapid and sensitive polymerase chain reaction (PCR-based assay, which allows detection of bovine or porcine specific mitochondrial DNAfrom spray-dried blood derivate products (plasma, whole blood and red cells, as a marker for bovine contamination in porcine products. Sample extracts, suitable for PCR, were easily and quickly obtained with the commercial PrepManTM Ultra reagent (Applied Biosystems. To confirm the porcine origin of the samples, primers targeting a specific region of 134 bp of the porcine cytochrome b coding sequence were designed (cytbporc1-F and cytbporc2-R. Previously published PCR primers (L8129 and H8357, specific for a 271 bp fragment of the bovine mitochondrial ATPase 8-ATPase 6 genes, were chosen to accomplish amplification of bovine DNA. The limit of detection (LOD of the bovine PCR assay was at least of 0.05% (v/v of bovine inclusion in spray-dried porcine plasma or red

  2. Functional Blood Progenitor Markers in Developing Human Liver Progenitors.

    Science.gov (United States)

    Goldman, Orit; Cohen, Idan; Gouon-Evans, Valerie

    2016-08-01

    In the early fetal liver, hematopoietic progenitors expand and mature together with hepatoblasts, the liver progenitors of hepatocytes and cholangiocytes. Previous analyses of human fetal livers indicated that both progenitors support each other's lineage maturation and curiously share some cell surface markers including CD34 and CD133. Using the human embryonic stem cell (hESC) system, we demonstrate that virtually all hESC-derived hepatoblast-like cells (Hep cells) transition through a progenitor stage expressing CD34 and CD133 as well as GATA2, an additional hematopoietic marker that has not previously been associated with human hepatoblast development. Dynamic expression patterns for CD34, CD133, and GATA2 in hepatoblasts were validated in human fetal livers collected from the first and second trimesters of gestation. Knockdown experiments demonstrate that each gene also functions to regulate hepatic fate mostly in a cell-autonomous fashion, revealing unprecedented roles of fetal hematopoietic progenitor markers in human liver progenitors. PMID:27509132

  3. Progenitors of type Ia supernovae

    CERN Document Server

    Maeda, Keiichi

    2016-01-01

    Natures of progenitors of type Ia Supernovae (SNe Ia) have not yet been clarified. There has been long and intensive discussion on whether the so-called single degenerate (SD) scenario or the double degenerate (DD) scenario, or anything else, could explain a major population of SNe Ia, but the conclusion has not yet been reached. With rapidly increasing observational data and new theoretical ideas, the field of studying the SN Ia progenitors has been quickly developing, and various new insights have been obtained in recent years. This article aims at providing a summary of the current situation regarding the SN Ia progenitors, both in theory and observations. It seems difficult to explain the emerging diversity seen in observations of SNe Ia by a single population, and we emphasize that it is important to clarify links between different progenitor scenarios and different sub-classes of SNe Ia.

  4. Human umbilical cord blood derived mesenchymal stem cells were differentiated into pancreatic endocrine cell by Pdx-1 electrotransfer

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    Phuoc Thi-My Nguyen

    2014-02-01

    Full Text Available Diabetes mellitus type 1 is an autoimmune disease with high incidence in adolescents and young adults. A seductive approach overcomes normally obstacles treatment is cell-replacement therapy to endogenous insulin production. At the present, to get enough pancreatic endocrine cells (PECs in cell transplantation, differentiation of mesenchymal stem cells (MSCs into IPCs is an interesting and promising strategy. This study aimed to orient umbilical cord blood-derived MSCs (UCB-MSCs to PECs by Pdx-1 electrotransfer. UCB-MSCs were isolated from human umbilical cord blood according to published protocol. Pdx-1 was isolated and cloned into a plasmid vector. Optimal voltage of an electrotransfer was investigated to improve the cell viability and gene transfection efficacy. The results showed that 200V of the electrotransfer significantly increased in the efficiency of electrotransfer and survival cells compared with other high voltages (350V and 550V. Pdx-1 successfully transfected UCB-MSCs over-expressed pancreatic related genes as Ngn3, Nkx6.1. These results suggested that Pdx-1 transfected UCB-MSCs were successfully oriented PECs. Different to lentiviral vectors, electrotransfer is a safer method to transfer Pdx-1 to UCB-MSCs and a useful tool in translational research. [Biomed Res Ther 2014; 1(2.000: 50-56

  5. Human Umbilical Cord Blood-Derived Serum for Culturing the Supportive Feeder Cells of Human Pluripotent Stem Cell Lines

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    Ruttachuk Rungsiwiwut

    2016-01-01

    Full Text Available Although human pluripotent stem cells (hPSCs can proliferate robustly on the feeder-free culture system, genetic instability of hPSCs has been reported in such environment. Alternatively, feeder cells enable hPSCs to maintain their pluripotency. The feeder cells are usually grown in a culture medium containing fetal bovine serum (FBS prior to coculture with hPSCs. The use of FBS might limit the clinical application of hPSCs. Recently, human cord blood-derived serum (hUCS showed a positive effect on culture of mesenchymal stem cells. It is interesting to test whether hUCS can be used for culture of feeder cells of hPSCs. This study was aimed to replace FBS with hUCS for culturing the human foreskin fibroblasts (HFFs prior to feeder cell preparation. The results showed that HFFs cultured in hUCS-containing medium (HFF-hUCS displayed fibroblastic features, high proliferation rates, short population doubling times, and normal karyotypes after prolonged culture. Inactivated HFF-hUCS expressed important genes, including Activin A, FGF2, and TGFβ1, which have been implicated in the maintenance of hPSC pluripotency. Moreover, hPSC lines maintained pluripotency, differentiation capacities, and karyotypic stability after being cocultured for extended period with inactivated HFF-hUCS. Therefore, the results demonstrated the benefit of hUCS for hPSCs culture system.

  6. Conditioned Media from Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Inhibits Melanogenesis by Promoting Proteasomal Degradation of MITF.

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    Eun Sung Kim

    Full Text Available Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs secrete various beneficial molecules, which have anti-apoptotic activity and cell proliferation. However, the effect of hUCB-MSCs in melanogenesis is largely unclear. In this study, we show that conditioned media (CM derived from hUCB-MSCs inhibit melanogenesis by regulating microphthalmia-associated transcription factor (MITF expression via the ERK signalling pathway. Treatment of hUCB-MSC-CM strongly inhibited the alpha-melanocyte stimulating hormone-induced hyperpigmentation in melanoma cells as well as melanocytes. Treatment of hUCB-MSC-CM induced ERK1/2 activation in melanocytes. In addition, inhibition of ERK1/2 suppressed the anti-pigmentation activity of the hUCB-MSC-CM in melanocytes and in vitro artificial skin models. We also found that the expression of MITF was appreciably diminished while expression of phosphorylated MITF, which leads to its proteasomal degradation, was increased in cells treated with hUCB-MSC-CM. These results suggested that hUCB-MSC-CM significantly suppresses melanin synthesis via MITF degradation by the ERK pathway activation.

  7. Cartilage repair by human umbilical cord blood-derived mesenchymal stem cells with different hydrogels in a rat model.

    Science.gov (United States)

    Park, Yong-Beom; Song, Minjung; Lee, Choong-Hee; Kim, Jin-A; Ha, Chul-Won

    2015-11-01

    This study was carried out to assess the feasibility of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in articular cartilage repair and to further determine a suitable delivering hydrogel in a rat model. Critical sized full thickness cartilage defects were created. The hUCB-MSCs and three different hydrogel composites (hydrogel A; 4% hyaluronic acid/30% pluronic (1:1, v/v), hydrogel B; 4% hyaluronic acid, and hydrogel C; 4% hyaluronic acid/30% pluronic/chitosan (1:1:2, v/v)) were implanted into the experimental knee (right knee) and hydrogels without hUCB-MSCs were implanted into the control knee (left knee). Defects were evaluated after 8 weeks. The hUCB-MSCs with hydrogels composites resulted in a better repair as seen by gross and histological evaluation compared with hydrogels without hUCB-MSCs. Among the three different hydrogels, the 4% hyaluronic acid hydrogel composite (hydrogel B) showed the best result in cartilage repair as seen by the histological evaluation compared with the other hydrogel composites (hydrogel A and C). The results of this study suggest that hUCB-MSCs may be a promising cell source in combination with 4% hyaluronic acid hydrogels in the in vivo repair of cartilage defects.

  8. Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Miyoung; Jeong, Sang Young; Ha, Jueun; Kim, Miyeon; Jin, Hye Jin; Kwon, Soon-Jae [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of); Chang, Jong Wook [Research Institute for Future Medicine Stem Cell and Regenerative Medicine Center, Samsung Medical Center, Seoul 137-710 (Korea, Republic of); Choi, Soo Jin; Oh, Wonil; Yang, Yoon Sun [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of); Kim, Jae-Sung [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-709 (Korea, Republic of); Jeon, Hong Bae, E-mail: jhb@medi-post.co.kr [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of)

    2014-04-18

    Highlights: • hUCB-MSCs maintained low immunogenicity even after immune challenge in vitro. • Humanized NSG mice were established using human UCB CD34+ cells. • Repeated intravenous hUCB-MSC injection into mice did not lead to immune responses and adverse events. • Allogeneic hUCB-MSCs maintained low immunogenicity in vitro and in vivo. - Abstract: Evaluation of the immunogenicity of human mesenchymal stem cells (MSCs) in an allogeneic setting during therapy has been hampered by lack of suitable models due to technical and ethical limitations. Here, we show that allogeneic human umbilical cord blood derived-MSCs (hUCB-MSCs) maintained low immunogenicity even after immune challenge in vitro. To confirm these properties in vivo, a humanized mouse model was established by injecting isolated hUCB-derived CD34+ cells intravenously into immunocompromised NOD/SCID IL2γnull (NSG) mice. After repeated intravenous injection of human peripheral blood mononuclear cells (hPBMCs) or MRC5 cells into these mice, immunological alterations including T cell proliferation and increased IFN-γ, TNF-α, and human IgG levels, were observed. In contrast, hUCB-MSC injection did not elicit these responses. While lymphocyte infiltration in the lung and small intestine and reduced survival rates were observed after hPBMC or MRC5 transplantation, no adverse events were observed following hUCB-MSC introduction. In conclusion, our data suggest that allogeneic hUCB-MSCs have low immunogenicity in vitro and in vivo, and are therefore “immunologically safe” for use in allogeneic clinical applications.

  9. Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo

    International Nuclear Information System (INIS)

    Highlights: • hUCB-MSCs maintained low immunogenicity even after immune challenge in vitro. • Humanized NSG mice were established using human UCB CD34+ cells. • Repeated intravenous hUCB-MSC injection into mice did not lead to immune responses and adverse events. • Allogeneic hUCB-MSCs maintained low immunogenicity in vitro and in vivo. - Abstract: Evaluation of the immunogenicity of human mesenchymal stem cells (MSCs) in an allogeneic setting during therapy has been hampered by lack of suitable models due to technical and ethical limitations. Here, we show that allogeneic human umbilical cord blood derived-MSCs (hUCB-MSCs) maintained low immunogenicity even after immune challenge in vitro. To confirm these properties in vivo, a humanized mouse model was established by injecting isolated hUCB-derived CD34+ cells intravenously into immunocompromised NOD/SCID IL2γnull (NSG) mice. After repeated intravenous injection of human peripheral blood mononuclear cells (hPBMCs) or MRC5 cells into these mice, immunological alterations including T cell proliferation and increased IFN-γ, TNF-α, and human IgG levels, were observed. In contrast, hUCB-MSC injection did not elicit these responses. While lymphocyte infiltration in the lung and small intestine and reduced survival rates were observed after hPBMC or MRC5 transplantation, no adverse events were observed following hUCB-MSC introduction. In conclusion, our data suggest that allogeneic hUCB-MSCs have low immunogenicity in vitro and in vivo, and are therefore “immunologically safe” for use in allogeneic clinical applications

  10. Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate

    Science.gov (United States)

    Grover, Amit; Mancini, Elena; Moore, Susan; Mead, Adam J.; Atkinson, Deborah; Rasmussen, Kasper D.; O’Carroll, Donal; Jacobsen, Sten Eirik W.

    2014-01-01

    The erythroid stress cytokine erythropoietin (Epo) supports the development of committed erythroid progenitors, but its ability to act on upstream, multipotent cells remains to be established. We observe that high systemic levels of Epo reprogram the transcriptomes of multi- and bipotent hematopoietic stem/progenitor cells in vivo. This induces erythroid lineage bias at all lineage bifurcations known to exist between hematopoietic stem cells (HSCs) and committed erythroid progenitors, leading to increased erythroid and decreased myeloid HSC output. Epo, therefore, has a lineage instructive role in vivo, through suppression of non-erythroid fate options, demonstrating the ability of a cytokine to systematically bias successive lineage choices in favor of the generation of a specific cell type. PMID:24493804

  11. In vitro pancreas organogenesis from dispersed mouse embryonic progenitors

    DEFF Research Database (Denmark)

    Greggio, Chiara; De Franceschi, Filippo; Figueiredo-Larsen, Evan Manuel;

    2014-01-01

    The pancreas is an essential organ that regulates glucose homeostasis and secretes digestive enzymes. Research on pancreas embryogenesis has led to the development of protocols to produce pancreatic cells from stem cells (1). The whole embryonic organ can be cultured at multiple stages...... expanding progenitors and differentiate into endocrine, acinar and ductal cells and which spontaneously self-organize to resemble the embryonic pancreas. We show here that the in vitro process recapitulates many aspects of natural pancreas development. This culture system is suitable to investigate how...... the efficient expansion of dissociated mouse embryonic pancreatic progenitors. By manipulating the composition of the culture medium it is possible to generate either hollow spheres, mainly composed of pancreatic progenitors expanding in their initial state, or, complex organoids which progress to more mature...

  12. Embryonic Heart Progenitors and Cardiogenesis

    Science.gov (United States)

    Brade, Thomas; Pane, Luna S.; Moretti, Alessandra; Chien, Kenneth R.; Laugwitz, Karl-Ludwig

    2013-01-01

    The mammalian heart is a highly specialized organ, comprised of many different cell types arising from distinct embryonic progenitor populations during cardiogenesis. Three precursor populations have been identified to contribute to different myocytic and nonmyocytic cell lineages of the heart: cardiogenic mesoderm cells (CMC), the proepicardium (PE), and cardiac neural crest cells (CNCCs). This review will focus on molecular cues necessary for proper induction, expansion, and lineage-specific differentiation of these progenitor populations during cardiac development in vivo. Moreover, we will briefly discuss how the knowledge gained on embryonic heart progenitor biology can be used to develop novel therapeutic strategies for the management of congenital heart disease as well as for improvement of cardiac function in ischemic heart disease. PMID:24086063

  13. Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve:viscoelasticity characterization

    Institute of Scientific and Technical Information of China (English)

    Xue-man Lv; Yan Liu; Fei Wu; Yi Yuan; Min Luo

    2016-01-01

    The optic nerve is a viscoelastic solid-like biomaterial. Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury. We hypothesized that stress relaxation and creep properties of the optic nerve change after injury. More-over, human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal. To validate this hypothesis, a rabbit model of optic nerve injury was established using a clamp approach. At 7 days after injury, the vitreous body re-ceived a one-time injection of 50 μg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells. At 30 days after injury, stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly, with patho-logical changes in the injured optic nerve also noticeably improved. These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves, and thereby contributes to nerve recovery.

  14. Progenitor Cells and Podocyte Regeneration

    Science.gov (United States)

    Shankland, Stuart J.; Pippin, Jeffrey W.; Duffield, Jeremy S.

    2014-01-01

    The very limited ability of adult podocytes to proliferate in vivo is clinically significant because: podocytes form a vascular barrier which is functionally critical to the nephron; podocyte hypoplasia is a characteristic of disease; and inadequate regeneration of podocytes is a major cause of persistent podocyte hypoplasia. Excessive podocyte loss or inadequate replacement leads to glomerulosclerosis in many progressive kidney diseases. Thus, restoration of podocyte cell density is almost certainly reliant on regeneration by podocyte progenitors. However such putative progenitors have remained elusive until recently. In this review we describe the developmental processes leading to podocyte and parietal epithelial cell (PEC) formation during glomerulogenesis. We compare evidence that in normal human kidneys PECs expressing ‘progenitor’ markers CD133 and CD24 can differentiate into podocytes in vitro and in vivo with evidence from animal models suggesting a more limited role of PEC-capacity to serve as podocyte progenitors in adults. We will highlight tantalizing new evidence that specialized vascular wall cells of afferent arterioles including those which produce renin in healthy kidney, provide a novel local progenitor source of new PECs and podocytes in response to podocyte hypoplasia in the adult, and draw comparisons with glomerulogenesis. PMID:25217270

  15. Hematopoietic stem/progenitor cell commitment to the megakaryocyte lineage.

    Science.gov (United States)

    Woolthuis, Carolien M; Park, Christopher Y

    2016-03-10

    The classical model of hematopoiesis has long held that hematopoietic stem cells (HSCs) sit at the apex of a developmental hierarchy in which HSCs undergo long-term self-renewal while giving rise to cells of all the blood lineages. In this model, self-renewing HSCs progressively lose the capacity for self-renewal as they transit into short-term self-renewing and multipotent progenitor states, with the first major lineage commitment occurring in multipotent progenitors, thus giving rise to progenitors that initiate the myeloid and lymphoid branches of hematopoiesis. Subsequently, within the myeloid lineage, bipotent megakaryocyte-erythrocyte and granulocyte-macrophage progenitors give rise to unipotent progenitors that ultimately give rise to all mature progeny. However, over the past several years, this developmental scheme has been challenged, with the origin of megakaryocyte precursors being one of the most debated subjects. Recent studies have suggested that megakaryocytes can be generated from multiple pathways and that some differentiation pathways do not require transit through a requisite multipotent or bipotent megakaryocyte-erythrocyte progenitor stage. Indeed, some investigators have argued that HSCs contain a subset of cells with biased megakaryocyte potential, with megakaryocytes directly arising from HSCs under steady-state and stress conditions. In this review, we discuss the evidence supporting these nonclassical megakaryocytic differentiation pathways and consider their relative strengths and weaknesses as well as the technical limitations and potential pitfalls in interpreting these studies. Ultimately, such pitfalls will need to be overcome to provide a comprehensive and definitive understanding of megakaryopoiesis. PMID:26787736

  16. Poised Regeneration of Zebrafish Melanocytes Involves Direct Differentiation and Concurrent Replenishment of Tissue-Resident Progenitor Cells.

    Science.gov (United States)

    Iyengar, Sharanya; Kasheta, Melissa; Ceol, Craig J

    2015-06-22

    Efficient regeneration following injury is critical for maintaining tissue function and enabling organismal survival. Cells reconstituting damaged tissue are often generated from resident stem or progenitor cells or from cells that have dedifferentiated and become proliferative. While lineage-tracing studies have defined cellular sources of regeneration in many tissues, the process by which these cells execute the regenerative process is largely obscure. Here, we have identified tissue-resident progenitor cells that mediate regeneration of zebrafish stripe melanocytes and defined how these cells reconstitute pigmentation. Nearly all regeneration melanocytes arise through direct differentiation of progenitor cells. Wnt signaling is activated prior to differentiation, and inhibition of Wnt signaling impairs regeneration. Additional progenitors divide symmetrically to sustain the pool of progenitor cells. Combining direct differentiation with symmetric progenitor divisions may serve as a means to rapidly repair injured tissue while preserving the capacity to regenerate.

  17. Development of the nested polymerase chain reaction (PCR) for detection of hepatitis C virus RNA in blood derivatives. Final report for the period 15 December 1994 - 15 December 1995

    International Nuclear Information System (INIS)

    Testing for the presence of hepatitis C virus (HCV) in blood derivatives used in clinical medicine is important to ensure the safety of such preparations. A reliable and reproducible method is described for the isolation of HCV RNA, subsequent reverse transcription and nested polymerase chain reaction (PCR) from blood derivatives. Of 17 batches of blood derivatives (14 negative for anti-HCV and 3 of unknown anti-HCV status) five were found to be positive in the nested PCR. (author). 4 refs, 3 figs, 1 tab

  18. Multipotent pancreas progenitors: Inconclusive but pivotal topic.

    Science.gov (United States)

    Jiang, Fang-Xu; Morahan, Grant

    2015-12-26

    The establishment of multipotent pancreas progenitors (MPP) should have a significant impact not only on the ontology of the pancreas, but also for the translational research of glucose-responding endocrine β-cells. Deficiency of the latter may lead to the pandemic type 1 or type 2 diabetes mellitus, a metabolic disorder. An ideal treatment of which would potentially be the replacement of destroyed or failed β-cells, by restoring function of endogenous pancreatic endocrine cells or by transplantation of donor islets or in vitro generated insulin-secreting cells. Thus, considerable research efforts have been devoted to identify MPP candidates in the pre- and post-natal pancreas for the endogenous neogenesis or regeneration of endocrine insulin-secreting cells. In order to advance this inconclusive but critical field, we here review the emerging concepts, recent literature and newest developments of potential MPP and propose measures that would assist its forward progression. PMID:26730269

  19. The poster as modernist progenitor

    Directory of Open Access Journals (Sweden)

    Katherine Hauser

    2015-12-01

    Full Text Available Ruth E. Iskin’s The Poster: Art, Advertising. Design, and Collecting, 1860s-1900s positions the late-nineteenth-century advertising poster as the progenitor of valued modernist practices typically attached solely to photography and film. Modernist biases separating high art from mass culture account for scholars ignoring posters, however the poster ushered in an innovative reductive graphic style as well as pioneered the notion of multiple originals.

  20. In vitro pancreas organogenesis from dispersed mouse embryonic progenitors.

    Science.gov (United States)

    Greggio, Chiara; De Franceschi, Filippo; Figueiredo-Larsen, Manuel; Grapin-Botton, Anne

    2014-07-19

    The pancreas is an essential organ that regulates glucose homeostasis and secretes digestive enzymes. Research on pancreas embryogenesis has led to the development of protocols to produce pancreatic cells from stem cells (1). The whole embryonic organ can be cultured at multiple stages of development (2-4). These culture methods have been useful to test drugs and to image developmental processes. However the expansion of the organ is very limited and morphogenesis is not faithfully recapitulated since the organ flattens. We propose three-dimensional (3D) culture conditions that enable the efficient expansion of dissociated mouse embryonic pancreatic progenitors. By manipulating the composition of the culture medium it is possible to generate either hollow spheres, mainly composed of pancreatic progenitors expanding in their initial state, or, complex organoids which progress to more mature expanding progenitors and differentiate into endocrine, acinar and ductal cells and which spontaneously self-organize to resemble the embryonic pancreas. We show here that the in vitro process recapitulates many aspects of natural pancreas development. This culture system is suitable to investigate how cells cooperate to form an organ by reducing its initial complexity to few progenitors. It is a model that reproduces the 3D architecture of the pancreas and that is therefore useful to study morphogenesis, including polarization of epithelial structures and branching. It is also appropriate to assess the response to mechanical cues of the niche such as stiffness and the effects on cell´s tensegrity.

  1. In vitro pancreas organogenesis from dispersed mouse embryonic progenitors.

    Science.gov (United States)

    Greggio, Chiara; De Franceschi, Filippo; Figueiredo-Larsen, Manuel; Grapin-Botton, Anne

    2014-01-01

    The pancreas is an essential organ that regulates glucose homeostasis and secretes digestive enzymes. Research on pancreas embryogenesis has led to the development of protocols to produce pancreatic cells from stem cells (1). The whole embryonic organ can be cultured at multiple stages of development (2-4). These culture methods have been useful to test drugs and to image developmental processes. However the expansion of the organ is very limited and morphogenesis is not faithfully recapitulated since the organ flattens. We propose three-dimensional (3D) culture conditions that enable the efficient expansion of dissociated mouse embryonic pancreatic progenitors. By manipulating the composition of the culture medium it is possible to generate either hollow spheres, mainly composed of pancreatic progenitors expanding in their initial state, or, complex organoids which progress to more mature expanding progenitors and differentiate into endocrine, acinar and ductal cells and which spontaneously self-organize to resemble the embryonic pancreas. We show here that the in vitro process recapitulates many aspects of natural pancreas development. This culture system is suitable to investigate how cells cooperate to form an organ by reducing its initial complexity to few progenitors. It is a model that reproduces the 3D architecture of the pancreas and that is therefore useful to study morphogenesis, including polarization of epithelial structures and branching. It is also appropriate to assess the response to mechanical cues of the niche such as stiffness and the effects on cell´s tensegrity. PMID:25079453

  2. Comparison of articular cartilage repair with different hydrogel-human umbilical cord blood-derived mesenchymal stem cell composites in a rat model

    OpenAIRE

    Chung, Jun Young; Song, Minjung; Ha, Chul-Won; Kim, Jin-A; Lee, Choong-Hee; Park, Yong-Beom

    2014-01-01

    Introduction The present work was designed to explore the feasibility and efficacy of articular cartilage repair using composites of human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) and four different hydrogels in a rat model. Methods Full-thickness articular cartilage defects were created at the trochlear groove of femur in both knees of rats. Composites of hUCB-MSCs and four different hydrogels (group A, 4% hyaluronic acid; group B, 3% alginate:30% pluronic (1:1, v/v); ...

  3. Rosiglitazone promotes development of a novel adipocyte population from bone marrow–derived circulating progenitor cells

    OpenAIRE

    Crossno, Joseph T.; Majka, Susan M.; Grazia, Todd; Gill, Ronald G.; Klemm, Dwight J.

    2006-01-01

    Obesity and weight gain are characterized by increased adipose tissue mass due to an increase in the size of individual adipocytes and the generation of new adipocytes. New adipocytes are believed to arise from resident adipose tissue preadipocytes and mesenchymal progenitor cells. However, it is possible that progenitor cells from other tissues, in particular BM, could also contribute to development of new adipocytes in adipose tissue. We tested this hypothesis by transplanting whole BM cell...

  4. Fluoxetine targets early progenitor cells in the adult brain

    OpenAIRE

    Encinas, Juan M.; Vaahtokari, Anne; Enikolopov, Grigori

    2006-01-01

    Chronic treatment with antidepressants increases neurogenesis in the adult hippocampus. This increase in the production of new neurons may be required for the behavioral effects of antidepressants. However, it is not known which class of cells within the neuronal differentiation cascade is targeted by the drugs. We have generated a reporter mouse line, which allows identification and classification of early neuronal progenitors. It also allows accurate quantitation of changes induced by neuro...

  5. Derivation and characterization of hepatic progenitor cells from human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Dongxin Zhao

    Full Text Available The derivation of hepatic progenitor cells from human embryonic stem (hES cells is of value both in the study of early human liver organogenesis and in the creation of an unlimited source of donor cells for hepatocyte transplantation therapy. Here, we report for the first time the generation of hepatic progenitor cells derived from hES cells. Hepatic endoderm cells were generated by activating FGF and BMP pathways and were then purified by fluorescence activated cell sorting using a newly identified surface marker, N-cadherin. After co-culture with STO feeder cells, these purified hepatic endoderm cells yielded hepatic progenitor colonies, which possessed the proliferation potential to be cultured for an extended period of more than 100 days. With extensive expansion, they co-expressed the hepatic marker AFP and the biliary lineage marker KRT7 and maintained bipotential differentiation capacity. They were able to differentiate into hepatocyte-like cells, which expressed ALB and AAT, and into cholangiocyte-like cells, which formed duct-like cyst structures, expressed KRT19 and KRT7, and acquired epithelial polarity. In conclusion, this is the first report of the generation of proliferative and bipotential hepatic progenitor cells from hES cells. These hES cell-derived hepatic progenitor cells could be effectively used as an in vitro model for studying the mechanisms of hepatic stem/progenitor cell origin, self-renewal and differentiation.

  6. Characterization of Proliferating Neural Progenitors after Spinal Cord Injury in Adult Zebrafish.

    Directory of Open Access Journals (Sweden)

    Subhra Prakash Hui

    Full Text Available Zebrafish can repair their injured brain and spinal cord after injury unlike adult mammalian central nervous system. Any injury to zebrafish spinal cord would lead to increased proliferation and neurogenesis. There are presences of proliferating progenitors from which both neuronal and glial loss can be reversed by appropriately generating new neurons and glia. We have demonstrated the presence of multiple progenitors, which are different types of proliferating populations like Sox2+ neural progenitor, A2B5+ astrocyte/ glial progenitor, NG2+ oligodendrocyte progenitor, radial glia and Schwann cell like progenitor. We analyzed the expression levels of two common markers of dedifferentiation like msx-b and vimentin during regeneration along with some of the pluripotency associated factors to explore the possible role of these two processes. Among the several key factors related to pluripotency, pou5f1 and sox2 are upregulated during regeneration and associated with activation of neural progenitor cells. Uncovering the molecular mechanism for endogenous regeneration of adult zebrafish spinal cord would give us more clues on important targets for future therapeutic approach in mammalian spinal cord repair and regeneration.

  7. Neural Progenitor Cells Derived from Human Embryonic Stem Cells as an Origin of Dopaminergic Neurons

    Directory of Open Access Journals (Sweden)

    Parinya Noisa

    2015-01-01

    Full Text Available Human embryonic stem cells (hESCs are able to proliferate in vitro indefinitely without losing their ability to differentiate into multiple cell types upon exposure to appropriate signals. Particularly, the ability of hESCs to differentiate into neuronal subtypes is fundamental to develop cell-based therapies for several neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease. In this study, we differentiated hESCs to dopaminergic neurons via an intermediate stage, neural progenitor cells (NPCs. hESCs were induced to neural progenitor cells by Dorsomorphin, a small molecule that inhibits BMP signalling. The resulting neural progenitor cells exhibited neural bipolarity with high expression of neural progenitor genes and possessed multipotential differentiation ability. CBF1 and bFGF responsiveness of these hES-NP cells suggested their similarity to embryonic neural progenitor cells. A substantial number of dopaminergic neurons were derived from hES-NP cells upon supplementation of FGF8 and SHH, key dopaminergic neuron inducers. Importantly, multiple markers of midbrain neurons were detected, including NURR1, PITX3, and EN1, suggesting that hESC-derived dopaminergic neurons attained the midbrain identity. Altogether, this work underscored the generation of neural progenitor cells that retain the properties of embryonic neural progenitor cells. These cells will serve as an unlimited source for the derivation of dopaminergic neurons, which might be applicable for treating patients with Parkinson’s disease.

  8. Murine Mueller cells are progenitor cells for neuronal cells and fibrous tissue cells

    International Nuclear Information System (INIS)

    Mammalian Mueller cells have been reported to possess retinal progenitor cell properties and generate new neurons after injury. This study investigates murine Mueller cells under in vitro conditions for their capability of dedifferentiation into retinal progenitor cells. Mueller cells were isolated from mouse retina, and proliferating cells were expanded in serum-containing medium. For dedifferentiation, the cultured cells were transferred to serum-replacement medium (SRM) at different points in time after their isolation. Interestingly, early cell passages produced fibrous tissue in which extracellular matrix proteins and connective tissue markers were differentially expressed. In contrast, aged Mueller cell cultures formed neurospheres in SRM that are characteristic for neuronal progenitor cells. These neurospheres differentiated into neuron-like cells after cultivation on laminin/ornithine cell culture substrate. Here, we report for the first time that murine Mueller cells can be progenitors for both, fibrous tissue cells and neuronal cells, depending on the age of the cell culture

  9. Evolution of progenitor stars of Type Ibc supernovae and long gamma-ray bursts

    CERN Document Server

    Yoon, S -C; Cantiello, M; Woosley, S E; Glatzmaier, G A

    2008-01-01

    We discuss how rotation and binary interactions may be related to the diversity of type Ibc supernovae and long gamma-ray bursts. After presenting recent evolutionary models of massive single and binary stars including rotation, the Tayler-Spruit dynamo and binary interactions, we argue that the nature of SNe Ibc progenitors from binary systems may not significantly differ from that of single star progenitors in terms of rotation, and that most long GRB progenitors may be produced via the quasi-chemically homogeneous evolution at sub-solar metallicity. We also briefly discuss the possible role of magnetic fields generated in the convective core of a massive star for the transport of angular momentum, which is potentially important for future stellar evolution models of supernova and GRB progenitors.

  10. Minor histocompatibility antigens on canine hemopoietic progenitor cells.

    Science.gov (United States)

    Weber, Martin; Lange, Claudia; Günther, Wolfgang; Franz, Monika; Kremmer, Elisabeth; Kolb, Hans-Jochem

    2003-06-15

    Adoptive immunotherapy with CTL against minor histocompatibility Ags (mHA) provides a promising way to treat leukemia relapse in allogeneic chimeras. Here we describe the in vitro generation of CTL against mHA in the dog. We tested their inhibitory effect on the growth of hemopoietic progenitor cells stimulated by hemopoietic growth factors in a 4-day suspension culture. CTL were produced by coculture of donor PBMC with bone marrow-derived dendritic cells (DCs). These DCs were characterized by morphology, high expression of MHC class II and CD1a, and the absence of the monocyte-specific marker CD14. Characteristically these cells stimulated allogeneic lymphocytes (MLR) and, after pulsing with a foreign Ag (keyhole limpet hemocyanin), autologous T cells. CTL were generated either ex vivo by coculture with DCs of DLA-identical littermates or in vivo by immunization of the responder with DCs obtained from a DLA-identical littermate. In suspension culture assays the growth of hemopoietic progenitor cells was inhibited in 53% of DLA-identical littermate combinations. In canine families mHA segregated with DLA as restriction elements. One-way reactivity against mHA was found in five littermate combinations. In two cases mHA might be Y chromosome associated, in three cases autosomally inherited alleles were detected. We conclude that CTL can be produced in vitro and in vivo against mHA on canine hemopoietic progenitor cells using bone marrow-derived DCs. PMID:12794111

  11. Neuromesodermal progenitors and the making of the spinal cord

    Science.gov (United States)

    Henrique, Domingos; Abranches, Elsa; Verrier, Laure; Storey, Kate G.

    2016-01-01

    Neuromesodermal progenitors (NMps) contribute to both the elongating spinal cord and the adjacent paraxial mesoderm. It has been assumed that these cells arise as a result of patterning of the anterior neural plate. However, as the molecular mechanisms that specify NMps in vivo are uncovered, and as protocols for generating these bipotent cells from mouse and human pluripotent stem cells in vitro are established, the emerging data suggest that this view needs to be revised. Here, we review the characteristics, regulation, in vitro derivation and in vivo induction of NMps. We propose that these cells arise within primitive streak-associated epiblast via a mechanism that is separable from that which establishes neural fate in the anterior epiblast. We thus argue for the existence of two distinct routes for making central nervous system progenitors. PMID:26329597

  12. Autophagy Proteins ATG5 and ATG7 Are Essential for the Maintenance of Human CD34(+) Hematopoietic Stem-Progenitor Cells.

    Science.gov (United States)

    Gomez-Puerto, Maria Catalina; Folkerts, Hendrik; Wierenga, Albertus T J; Schepers, Koen; Schuringa, Jan Jacob; Coffer, Paul J; Vellenga, Edo

    2016-06-01

    Autophagy is a highly regulated catabolic process that involves sequestration and lysosomal degradation of cytosolic components such as damaged organelles and misfolded proteins. While autophagy can be considered to be a general cellular housekeeping process, it has become clear that it may also play cell type-dependent functional roles. In this study, we analyzed the functional importance of autophagy in human hematopoietic stem/progenitor cells (HSPCs), and how this is regulated during differentiation. Western blot-based analysis of LC3-II and p62 levels, as well as flow cytometry-based autophagic vesicle quantification, demonstrated that umbilical cord blood-derived CD34(+) /CD38(-) immature hematopoietic progenitors show a higher autophagic flux than CD34(+) /CD38(+) progenitors and more differentiated myeloid and erythroid cells. This high autophagic flux was critical for maintaining stem and progenitor function since knockdown of autophagy genes ATG5 or ATG7 resulted in reduced HSPC frequencies in vitro as well as in vivo. The reduction in HSPCs was not due to impaired differentiation, but at least in part due to reduced cell cycle progression and increased apoptosis. This is accompanied by increased expression of p53, proapoptotic genes BAX and PUMA, and the cell cycle inhibitor p21, as well as increased levels of cleaved caspase-3 and reactive oxygen species. Taken together, our data demonstrate that autophagy is an important regulatory mechanism for human HSCs and their progeny, reducing cellular stress and promoting survival. Stem Cells 2016;34:1651-1663. PMID:26930546

  13. Autophagy Proteins ATG5 and ATG7 Are Essential for the Maintenance of Human CD34(+) Hematopoietic Stem-Progenitor Cells.

    Science.gov (United States)

    Gomez-Puerto, Maria Catalina; Folkerts, Hendrik; Wierenga, Albertus T J; Schepers, Koen; Schuringa, Jan Jacob; Coffer, Paul J; Vellenga, Edo

    2016-06-01

    Autophagy is a highly regulated catabolic process that involves sequestration and lysosomal degradation of cytosolic components such as damaged organelles and misfolded proteins. While autophagy can be considered to be a general cellular housekeeping process, it has become clear that it may also play cell type-dependent functional roles. In this study, we analyzed the functional importance of autophagy in human hematopoietic stem/progenitor cells (HSPCs), and how this is regulated during differentiation. Western blot-based analysis of LC3-II and p62 levels, as well as flow cytometry-based autophagic vesicle quantification, demonstrated that umbilical cord blood-derived CD34(+) /CD38(-) immature hematopoietic progenitors show a higher autophagic flux than CD34(+) /CD38(+) progenitors and more differentiated myeloid and erythroid cells. This high autophagic flux was critical for maintaining stem and progenitor function since knockdown of autophagy genes ATG5 or ATG7 resulted in reduced HSPC frequencies in vitro as well as in vivo. The reduction in HSPCs was not due to impaired differentiation, but at least in part due to reduced cell cycle progression and increased apoptosis. This is accompanied by increased expression of p53, proapoptotic genes BAX and PUMA, and the cell cycle inhibitor p21, as well as increased levels of cleaved caspase-3 and reactive oxygen species. Taken together, our data demonstrate that autophagy is an important regulatory mechanism for human HSCs and their progeny, reducing cellular stress and promoting survival. Stem Cells 2016;34:1651-1663.

  14. Intrathecal injection of human umbilical cord blood-derived mesenchymal stem cells for the treatment of basilar artery dissection: a case report

    Directory of Open Access Journals (Sweden)

    Han Hoon

    2011-12-01

    Full Text Available Abstract Introduction Basilar artery dissection is a rare occurrence, and is significantly associated with morbidity and mortality. To the best of our knowledge, we report the first case of basilar artery dissection treated with mesenchymal stem cells. Case presentation We present the case of a 17-year-old Korean man who was diagnosed with basilar artery dissection. Infarction of the bilateral pons, midbrain and right superior cerebellum due to his basilar artery dissection was partially recanalized by intrathecal injection of human umbilical cord blood-derived mesenchymal stem cells. No immunosuppressants were given to our patient, and human leukocyte antigen alloantibodies were not detected after cell therapy. Conclusions This case indicates that intrathecal injections of mesenchymal stem cells can be used in the treatment of basilar artery dissection.

  15. Identification and expansion of cancer stem cells in tumor tissues and peripheral blood derived from gastric adenocarcinoma patients

    Institute of Scientific and Technical Information of China (English)

    Tie Chen; Xinzu Chen; Fang Wang; Fan Zeng; Hong Xu; Jiankun Hu; Xianming Mo; Kun Yang; Jianhua Yu; Wentong Meng; Dandan Yuan; Feng Bi; Fang Liu; Jie Liu; Bing Dai

    2012-01-01

    Gastric cancer is the fourth most common cancer worldwide,with a high rate of death and low 5-year survival rate.To date,there is a lack of efficient therapeutic protocols for gastric cancer.Recent studies suggest that cancer stem cells (CSCs) are responsible for tumor initiation,invasion,metastasis,and resistance to anticancer therapies.Thus,therapies that target gastric CSCs are attractive.However,CSCs in human gastric adenocarcinoma (GAC)have not been described.Here,we identify CSCs in tumor tissues and peripheral blood from GAC patients.CSCs of human GAC (GCSCs) that are isolated from tumor tissues and peripheral blood of patients carried CD44 and CD54 surface markers,generated tumors that highly resemble the original human tumors when injected into immunodeficient mice,differentiated into gastric epithelial cells in vitro,and self-renewed in vivo and in vitro.Our findings suggest that effective therapeutic protocols must target GCSCs.The capture of GCSCs from the circulation of GAC patients also shows great potential for identification of a critical cell population potentially responsible for tumor metastasis,and provides an effective protocol for early diagnosis and longitudinal monitoring of gastric cancer.

  16. The progenitors of stripped-envelope supernovae

    Science.gov (United States)

    Elias-Rosa, N.

    2013-05-01

    The type Ib/c SNe are those explosions which come from massive star populations, but lack hydrogen and helium. These have been proposed to originate in the explosions of massive Wolf-Rayet stars, and we should easily be able to detect the very luminous, young progenitors if they exist. However, there has not been any detection of progenitors so far. I present the study of two extinguished Type Ic SNe 2003jg and 2004cc. In both cases there is no clear evidence of a direct detection of their progenitors in deep pre-explosion images. Upper limits derived by inserting artificial stars of known brightness at random positions around the progenitor positions (M_v>-8.8 and M_v>-9 magnitudes for the progenitors of SN 2003jg and SN 2004cc, respectively) are brighter than those expected for a massive WC (Wolf-Rayet, carbon-rich) or WO (Wolf-Rayet, oxygen-rich) (e.g., approximately between -3 and -6 in the LMC). Therefore, this is perhaps further evidence that the most massive stars may give rise to black-holes forming SNe, or it is an undetected, compact massive star hidden by a thick dust lane. However the extinction toward these SNe is currently one of the largest known. Even if these results do not directly reveal the nature of the type Ic SN progenitors, they can help to characterize the dusty environment which surrounded the progenitor of the stripped-envelope CC-SNe.

  17. Functional analysis of retinal microglia and their effects on progenitors.

    Science.gov (United States)

    Carter, Debra A; Balasubramaniam, Balini; Dick, Andrew D

    2013-01-01

    The identification of stem/progenitor cells within the retinal neural environment has opened up the possibility of therapy via cellular replacement and/or reprogramming of resident cell populations. Within the neuro-retinal niche, following injury or in disease states (including inflammation and degeneration), cellular responses affect tissue homeostasis, reduce cell density, disrupt tissue architecture, and produce scar formation. Microglia (resident retinal immune cell tissue macrophage) are key to the maintenance of retinal homeostasis and are implicated in responses that may influence the control and behavior of retinal progenitors. Factors to consider in the generation of a transplantable cell resource with good migratory and integrative capacity include their yield, purity, and functional viability. Utilizing human postmortem retina, we have created a research platform to isolate, culture, and characterize adult retinal microglia as well as analyze their effect on retinal progenitors. Here, we describe techniques using magnetic labeled bead cell separation to isolate pure populations of retinal CD133(+) precursor cells and CD11b(+) microglia from primary adult retinal cell suspensions (RCSs), enabling flow cytometric cell phenotypic and qPCR genotypic analysis, as well as functional analysis by real-time ratiometric calcium imaging.

  18. Neutronization During Carbon Simmering In Type Ia Supernova Progenitors

    Science.gov (United States)

    Martínez-Rodríguez, Héctor; Piro, Anthony L.; Schwab, Josiah; Badenes, Carles

    2016-07-01

    When a Type Ia supernova (SN Ia) progenitor first ignites carbon in its core, it undergoes ∼103–104 years of convective burning prior to the onset of thermonuclear runaway. This carbon simmering phase is important for setting the thermal profile and composition of the white dwarf. Using the MESA stellar evolution code, we follow this convective burning and examine the production of neutron-rich isotopes. The neutron content of the SN fuel has important consequences for the ensuing nucleosynthesis, and in particular, for the production of secondary Fe-peak nuclei like Mn and stable Ni. These elements have been observed in the X-ray spectra of SN remnants like Tycho, Kepler, and 3C 397, and their yields can provide valuable insights into the physics of SNe Ia and the properties of their progenitors. We find that weak reactions during simmering can at most generate a neutron excess of ≈ 3 × 10‑4. This is ≈ 70% lower than that found in previous studies that do not take the full density and temperature profile of the simmering region into account. Our results imply that the progenitor metallicity is the main contributor to the neutron excess in SN Ia fuel for Z ≳ 1/3 Z ⊙. Alternatively, at lower metallicities, this neutron excess provides a floor that should be present in any centrally-ignited SN Ia scenario.

  19. Endothelin-1 supports clonal derivation and expansion of cardiovascular progenitors derived from human embryonic stem cells.

    Science.gov (United States)

    Soh, Boon-Seng; Ng, Shi-Yan; Wu, Hao; Buac, Kristina; Park, Joo-Hye C; Lian, Xiaojun; Xu, Jiejia; Foo, Kylie S; Felldin, Ulrika; He, Xiaobing; Nichane, Massimo; Yang, Henry; Bu, Lei; Li, Ronald A; Lim, Bing; Chien, Kenneth R

    2016-03-08

    Coronary arteriogenesis is a central step in cardiogenesis, requiring coordinated generation and integration of endothelial cell and vascular smooth muscle cells. At present, it is unclear whether the cell fate programme of cardiac progenitors to generate complex muscular or vascular structures is entirely cell autonomous. Here we demonstrate the intrinsic ability of vascular progenitors to develop and self-organize into cardiac tissues by clonally isolating and expanding second heart field cardiovascular progenitors using WNT3A and endothelin-1 (EDN1) human recombinant proteins. Progenitor clones undergo long-term expansion and differentiate primarily into endothelial and smooth muscle cell lineages in vitro, and contribute extensively to coronary-like vessels in vivo, forming a functional human-mouse chimeric circulatory system. Our study identifies EDN1 as a key factor towards the generation and clonal derivation of ISL1(+) vascular intermediates, and demonstrates the intrinsic cell-autonomous nature of these progenitors to differentiate and self-organize into functional vasculatures in vivo.

  20. Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins.

    Science.gov (United States)

    Fukusumi, Hayato; Shofuda, Tomoko; Bamba, Yohei; Yamamoto, Atsuyo; Kanematsu, Daisuke; Handa, Yukako; Okita, Keisuke; Nakamura, Masaya; Yamanaka, Shinya; Okano, Hideyuki; Kanemura, Yonehiro

    2016-01-01

    Human neural progenitor cells (hNPCs) have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC) clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB) formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi). Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes.

  1. [Single-donor (apheresis) platelets and pooled whole-blood-derived platelets--significance and assessment of both blood products].

    Science.gov (United States)

    Hitzler, Walter E

    2014-01-01

    The transfusion efficacy of ATK, which contain fully functional platelets, is beyond all doubt. The equivalence of ATK and PTK has been subject of many studies. Some of those studies show the superiority of ATK's, while others do not, but there have been no studies that demonstrated a superiority of PTK's. The superiority of platelets stored in plasma and in third generation additive solution was demonstrated in clinical studies; therefore, it cannot be said that all the platelet concentrates on the German market are equivalent in efficacy. Of decisive importance, above all, is the risk of transfusion-transmitted infections with known pathogens, or those not yet discovered. This risk is different for ATK compared to PTK. Taking this difference in risk and the difference in donor exposure of transfused patients into account, it can definitely be said that ATK and PTK are not equivalent. In 2012, the Robert-Koch-Institute (RKI) published a mathematical risk model for different platelet concentrates and assessed the risk of transmitting known pathogens such as HIV, HCV, and HBV. The risk was higher for PTK compared to ATK. The relative risks for PTK derived from 4BCs were 2.2 (95%--CI: 2.1-2.4) for HIV, 2.7 (95%--CI: 2.5-3.0) for HCV, and 2.2 (95%--CI: 2.8-3.7) for HBV. At the present time, these are the relative risks of transfusion-transmitted infections with the traditional pathogens for PTK compared to ATK. In addition to the RKI assessed risks, there is the theoretical risk of a new, unknown agent, transmitted through blood exposure. The magnitude of this risk is hardly predictable for PTK. The experience gathered so far, especially in the last three decades, with the emergence of HIV, prions, and West Nil virus, shows that the biological nature of a next transfusion-transmissible infectious agent cannot be predictable. This agent, if we think at a conventional sexually transmissible agent with nucleic acid and long latent period, would spread first in areas with

  2. [Single-donor (apheresis) platelets and pooled whole-blood-derived platelets--significance and assessment of both blood products].

    Science.gov (United States)

    Hitzler, Walter E

    2014-01-01

    The transfusion efficacy of ATK, which contain fully functional platelets, is beyond all doubt. The equivalence of ATK and PTK has been subject of many studies. Some of those studies show the superiority of ATK's, while others do not, but there have been no studies that demonstrated a superiority of PTK's. The superiority of platelets stored in plasma and in third generation additive solution was demonstrated in clinical studies; therefore, it cannot be said that all the platelet concentrates on the German market are equivalent in efficacy. Of decisive importance, above all, is the risk of transfusion-transmitted infections with known pathogens, or those not yet discovered. This risk is different for ATK compared to PTK. Taking this difference in risk and the difference in donor exposure of transfused patients into account, it can definitely be said that ATK and PTK are not equivalent. In 2012, the Robert-Koch-Institute (RKI) published a mathematical risk model for different platelet concentrates and assessed the risk of transmitting known pathogens such as HIV, HCV, and HBV. The risk was higher for PTK compared to ATK. The relative risks for PTK derived from 4BCs were 2.2 (95%--CI: 2.1-2.4) for HIV, 2.7 (95%--CI: 2.5-3.0) for HCV, and 2.2 (95%--CI: 2.8-3.7) for HBV. At the present time, these are the relative risks of transfusion-transmitted infections with the traditional pathogens for PTK compared to ATK. In addition to the RKI assessed risks, there is the theoretical risk of a new, unknown agent, transmitted through blood exposure. The magnitude of this risk is hardly predictable for PTK. The experience gathered so far, especially in the last three decades, with the emergence of HIV, prions, and West Nil virus, shows that the biological nature of a next transfusion-transmissible infectious agent cannot be predictable. This agent, if we think at a conventional sexually transmissible agent with nucleic acid and long latent period, would spread first in areas with

  3. A Multipotent Progenitor Domain Guides Pancreatic Organogenesis

    OpenAIRE

    Zhou, Qiao; Law, Anica Chi-Ying; Rajagopal, Jayaraj; Anderson, William J.; Gray, Paul A.; Douglas A Melton

    2007-01-01

    The mammalian pancreas is constructed during embryogenesis by multipotent progenitors, the identity and function of which remain poorly understood. We performed genome-wide transcription factor expression analysis of the developing pancreas to identify gene expression domains that may represent distinct progenitor cell populations. Five discrete domains were discovered. Genetic lineage-tracing experiments demonstrate that one specific domain, located at the tip of the branching pancreatic tre...

  4. Ascl3 marks adult progenitor cells of the mouse salivary gland.

    Science.gov (United States)

    Rugel-Stahl, Anastasia; Elliott, Marilyn E; Ovitt, Catherine E

    2012-05-01

    The Ascl3 transcription factor marks a subset of salivary gland duct cells present in the three major salivary glands of the mouse. In vivo, these cells generate both duct and secretory acinar cell descendants. Here, we have analyzed whether Ascl3-expressing cells retain this multipotent lineage potential in adult glands. Cells isolated from mouse salivary glands were cultured in vitro as non-adherent spheres. Lineage tracing of the Ascl3-expressing cells within the spheres demonstrates that Ascl3+ cells isolated from adult glands remain multipotent, generating both duct and acinar cell types in vitro. Furthermore, we demonstrate that the progenitor cells characterized by Keratin 5 expression are an independent population from Ascl3+ progenitor cells. We conclude that the Ascl3+ cells are intermediate lineage-restricted progenitor cells of the adult salivary glands.

  5. Supernova Remnant Progenitor Masses in M31

    CERN Document Server

    Jennings, Zachary G; Murphy, Jeremiah W; Dalcanton, Julianne J; Gilbert, Karoline M; Dolphin, Andrew E; Fouesneau, Morgan; Weisz, Daniel R

    2012-01-01

    Using HST photometry, we age-date 59 supernova remnants (SNRs) in the spiral galaxy M31 and use these ages to estimate zero-age main sequence masses (MZAMS) for their progenitors. To accomplish this, we create color-magnitude diagrams (CMDs) and use CMD fitting to measure the recent star formation history (SFH) of the regions surrounding cataloged SNR sites. We identify any young coeval population that likely produced the progenitor star and assign an age and uncertainty to that population. Application of stellar evolution models allows us to infer the MZAMS from this age. Because our technique is not contingent on precise location of the progenitor star, it can be applied to the location of any known SNR. We identify significant young SF around 53 of the 59 SNRs and assign progenitor masses to these, representing a factor of 2 increase over currently measured progenitor masses. We consider the remaining 6 SNRs as either probable Type Ia candidates or the result of core-collapse progenitors that have escaped ...

  6. Directed Differentiation of Human Embryonic Stem Cells into Neural Progenitors.

    Science.gov (United States)

    Banda, Erin; Grabel, Laura

    2016-01-01

    A variety of protocols have been used to produce neural progenitors from human embryonic stem cells. We have focused on a monolayer culture approach that generates neural rosettes. To initiate differentiation, cells are plated in a serum-free nutrient-poor medium in the presence of a BMP inhibitor. Depending on the cell line used, additional growth factor inhibitors may be required to promote neural differentiation. Long-term culture and addition of the Notch inhibitor DAPT can promote terminal neuronal differentiation. Extent of differentiation is monitored using immunocytochemistry for cell type-specific markers.

  7. Human umbilical cord blood-derived mesenchymal stem cells improve neuropathology and cognitive impairment in an Alzheimer's disease mouse model through modulation of neuroinflammation.

    Science.gov (United States)

    Lee, Hyun Ju; Lee, Jong Kil; Lee, Hyun; Carter, Janet E; Chang, Jong Wook; Oh, Wonil; Yang, Yoon Sun; Suh, Jun-Gyo; Lee, Byoung-Hee; Jin, Hee Kyung; Bae, Jae-Sung

    2012-03-01

    Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) have a potential therapeutic role in the treatment of neurological disorders, but their current clinical usage and mechanism of action has yet to be ascertained in Alzheimer's disease (AD). Here we report that hUCB-MSC transplantation into amyloid precursor protein (APP) and presenilin1 (PS1) double-transgenic mice significantly improved spatial learning and memory decline. Furthermore, amyloid-β peptide (Aβ) deposition, β-secretase 1 (BACE-1) levels, and tau hyperphosphorylation were dramatically reduced in hUCB-MSC transplanted APP/PS1 mice. Interestingly, these effects were associated with reversal of disease-associated microglial neuroinflammation, as evidenced by decreased microglia-induced proinflammatory cytokines, elevated alternatively activated microglia, and increased anti-inflammatory cytokines. These findings lead us to suggest that hUCB-MSC produced their sustained neuroprotective effect by inducing a feed-forward loop involving alternative activation of microglial neuroinflammation, thereby ameliorating disease pathophysiology and reversing the cognitive decline associated with Aβ deposition in AD mice.

  8. Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Z.H. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Li, X.L. [Department of Dermatology, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); He, X.J. [Department of Orthopedics, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Wu, B.J.; Xu, M. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Chang, H.M. [Department of Otolaryngology - Head and Neck Surgery, Affiliated Hospital of Xi' an Medical University, Xi' an (China); Zhang, X.H. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Xing, Z. [Department of Clinical Dentistry, Faculty of Dentistry, Center for Clinical Dental Research, University of Bergen, Bergen (Norway); Jing, X.H.; Kong, D.M.; Kou, X.H.; Yang, Y.Y. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China)

    2014-03-18

    SRY-related high-mobility-group box 9 (Sox9) gene is a cartilage-specific transcription factor that plays essential roles in chondrocyte differentiation and cartilage formation. The aim of this study was to investigate the feasibility of genetic delivery of Sox9 to enhance chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells (hUC-MSCs). After they were isolated from human umbilical cord blood within 24 h after delivery of neonates, hUC-MSCs were untreated or transfected with a human Sox9-expressing plasmid or an empty vector. The cells were assessed for morphology and chondrogenic differentiation. The isolated cells with a fibroblast-like morphology in monolayer culture were positive for the MSC markers CD44, CD105, CD73, and CD90, but negative for the differentiation markers CD34, CD45, CD19, CD14, or major histocompatibility complex class II. Sox9 overexpression induced accumulation of sulfated proteoglycans, without altering the cellular morphology. Immunocytochemistry demonstrated that genetic delivery of Sox9 markedly enhanced the expression of aggrecan and type II collagen in hUC-MSCs compared with empty vector-transfected counterparts. Reverse transcription-polymerase chain reaction analysis further confirmed the elevation of aggrecan and type II collagen at the mRNA level in Sox9-transfected cells. Taken together, short-term Sox9 overexpression facilitates chondrogenesis of hUC-MSCs and may thus have potential implications in cartilage tissue engineering.

  9. Transplantation of progenitor cells after reperfused acute myocardial infarction: evaluation of perfusion and myocardial viability with FDG-PET and thallium SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Doebert, Natascha; Berner, Uwe; Menzel, Christian; Hamscho, Nadja; Gruenwald, Frank [Department of Nuclear Medicine, University of Frankfurt (Germany); Britten, Martina; Assmus, Birgit; Lehmann, Ralf; Schaechinger, Volker; Zeiher, Andreas M. [Department of Cardiology, University of Frankfurt (Germany); Dimmeler, Stefanie [Department of Molecular Cardiology, University of Frankfurt (Germany)

    2004-08-01

    Clinical outcome after myocardial infarction depends on the extent of irreversibly damaged myocardium. Implantation of bone marrow-/circulating blood-derived progenitor cells has been shown to improve contractile cardiac function after myocardial infarction in both experimental and initial clinical studies. In the present study, first observations of the effect of local intracoronary progenitor cell infusion on the regeneration of infarcted cardiac tissue after acute myocardial infarction was evaluated by means of {sup 18}F-fluorodeoxyglucose positron emission tomography (PET) and {sup 201}Tl single-photon emission computed tomography (SPECT). Twenty-six patients underwent intracoronary infusion of bone marrow-derived (BMCs) (15 patients) or circulating blood-derived endothelial progenitor cells (EPCs) (11 patients) 4{+-}2 days after acute myocardial infarction. Based on a left ventricular segmentation model (17 segments), mean signal intensities as a parameter of viability and perfusion in the infarct zone and non-infarct areas were calculated quantitatively by PET and SPECT at baseline and at 4 months of follow-up. Transplantation of progenitor cells was associated with a significant increase in the mean signal intensity (MSI) in the infarct zone from 54.5% (25th and 75th percentiles: 47.7%, 60.0%) to 58.0% (52.7%, 66.7%) on PET (P=0.013) and from 58.0% (49.5%, 63.0%) to 61.5% (52.5%, 70.2%) on SPECT (P=0.005). Global left ventricular ejection fraction (LVEF) increased from 53.5% (42.6%, 60.0%) to 58.0% (53.0%, 65.8%) (P<0.001). In the five patients without an increase in MSI on PET, LVEF changed from 60.0% (50.0%, 64.0%) to 72.0% (64.0%, 75.5%) at follow-up. PET and SPECT did not show any significant changes in MSI in the non-infarct areas [from 73% (68.5%, 76.2%) to 73% (69.7%, 78.0%) for PET and from 72.0% (66.5%, 77.6%) to 73.0% (67.5%, 78.2%) for SPECT]. There were no significant differences in myocardial viability and perfusion between BMC and EPC infusion

  10. Progenitors of core-collapse supernovae

    CERN Document Server

    Smartt, Stephen J

    2009-01-01

    Knowledge of the progenitors of core-collapse supernovae is a fundamental component in understanding the explosions. The recent progress in finding such stars is reviewed. The minimum initial mass that can produce a supernova has converged to 8 +/- 1 solar masses, from direct detections of red supergiant progenitors of II-P SNe and the most massive white dwarf progenitors, although this value is model dependent. It appears that most type Ibc supernovae arise from moderate mass interacting binaries. The highly energetic, broad-lined Ic supernovae are likely produced by massive, Wolf-Rayet progenitors. There is some evidence to suggest that the majority of massive stars above ~20 solar masses may collapse quietly to black-holes and that the explosions remain undetected. The recent discovery of a class of ultra-bright type II supernovae and the direct detection of some progenitor stars bearing luminous blue variable characteristics suggests some very massive stars do produce highly energetic explosions. The phys...

  11. Transplantable progenitors of natural killer cells are distinct from those of T and B lymphocytes.

    OpenAIRE

    Hackett, J; Bosma, G C; Bosma, M J; Bennett, M.; Kumar, V

    1986-01-01

    We have utilized a mouse mutant (C.B-17 scid) that lacks functional T and B lymphocytes to examine the relationship among transplantable progenitors of natural killer (NK) cells, T cells, and B cells. The NK-progenitor cells contained in the bone marrow were detected by their ability to generate mature NK cells, following transfer of bone marrow cells into NK cell-depleted and lethally irradiated mice. Regeneration of NK activity in the recipient mice was monitored by two different assays: th...

  12. It Is All in the Blood: The Multifaceted Contribution of Circulating Progenitor Cells in Diabetic Complications

    Directory of Open Access Journals (Sweden)

    Gian Paolo Fadini

    2012-01-01

    Full Text Available Diabetes mellitus (DM is a worldwide growing disease and represents a huge social and healthcare problem owing to the burden of its complications. Micro- and macrovascular diabetic complications arise from excess damage through well-known biochemical pathways. Interestingly, microangiopathy hits the bone marrow (BM microenvironment with features similar to retinopathy, nephropathy and neuropathy. The BM represents a reservoir of progenitor cells for multiple lineages, not limited to the hematopoietic system and including endothelial cells, smooth muscle cells, cardiomyocytes, and osteogenic cells. All these multiple progenitor cell lineages are profoundly altered in the setting of diabetes in humans and animal models. Reduction of endothelial progenitor cells (EPCs along with excess smooth muscle progenitor (SMP and osteoprogenitor cells creates an imbalance that promote the development of micro- and macroangiopathy. Finally, an excess generation of BM-derived fusogenic cells has been found to contribute to diabetic complications in animal models. Taken together, a growing amount of literature attributes to circulating progenitor cells a multi-faceted role in the pathophysiology of DM, setting a novel scenario that puts BM and the blood at the centre of the stage.

  13. Production of human glucocerebrosidase in mice after retroviral gene transfer into multipotential hematopoietic progenitor cells

    International Nuclear Information System (INIS)

    The human glucocerebrosidase (GC) gene has been transferred efficiently into spleen colony-forming unit (CFU-S) multipotential hematopoietic progenitor cells, and production of human GC RNA and protein has been achieved in transduced CFU-S colonies. High-titer retroviral vectors containing the human GC cDNA were constructed. Four vectors were compared with respect to gene-transfer efficiency into CFU-S progenitors. One vector (G vector) required high concentrations of interleukins 3 and 6 during stimulation and coculture for efficient transduction of CFU-S progenitors. The remaining three vectors (NTG, GTN, and GI vectors) transduced these progenitors at infection frequencies approaching 100% using low concentrations of hematopoietic growth factors to simulate cell division prior to and during the infection. Vectors using the viral long terminal repeat enhancer/promoter to drive the human GC cDNA produced high levels of human GC RNA in the progeny of CFU-S progenitors after gene transfer. All three vectors producing human GC RNA in CFU-S colonies can generate human GC as detected by immunochemical analysis of CFU-S colonies. The capacity of the viral long terminal repeat and the internal thymidine kinase promoter to direct synthesis of RNA in transduced bone marrow and spleen cells 5 months after bone marrow transplantation reflected the performance of these promoters in NTG-transduced CFU-S colonies

  14. Brief Azacytidine Step Allows The Conversion of Suspension Human Fibroblasts into Neural Progenitor-Like Cells

    Directory of Open Access Journals (Sweden)

    Fahimeh Mirakhori

    2015-04-01

    Full Text Available In recent years transdifferentiation technology has enabled direct conversion of human fibroblasts to become a valuable, abundant and accessible cell source for patient-specific induced cell generation in biomedical research. The majority of transdifferentiation approaches rely upon viral gene delivery which due to random integration with the host genome can cause genome instability and tumorigenesis upon transplantation. Here, we provide a simple way to induce neural progenitor-like cells from human fibroblasts without genetic manipulation by changing physicochemical culture properties from monolayer culture into a suspension in the presence of a chemical DNA methyltransferase inhibitor agent, Azacytidine. We have demonstrated the expression of neural progenitor-like markers, morphology and the ability to spontaneously differentiate into neural-like cells. This approach is simple, inexpensive, lacks genetic manipulation and could be a foundation for future chemical neural transdifferentiation and a safe induction of neural progenitor cells from human fibroblasts for clinical applications.

  15. Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion

    DEFF Research Database (Denmark)

    Santoni-Rugiu, Eric; Jelnes, Peter; Thorgeirsson, Snorri S;

    2005-01-01

    biliary cells to restore liver homeostasis. In recent years, hepatic progenitor cells have been the subject of increasing interest due to their therapeutic potential in numerous liver diseases as alternative or supportive/complementary tools to liver transplantation. While the first investigations on......Although normally quiescent, the adult mammalian liver possesses a great capacity to regenerate after different types of injuries in order to restore the lost liver mass and ensure maintenance of the multiple liver functions. Major players in the regeneration process are mature residual cells......, including hepatocytes, cholangiocytes and stromal cells. However, if the regenerative capacity of mature cells is impaired by liver-damaging agents, hepatic progenitor cells are activated and expand into the liver parenchyma. Upon transit amplification, the progenitor cells may generate new hepatocytes and...

  16. Endothelial progenitor cells in cardiovascular diseases

    Institute of Scientific and Technical Information of China (English)

    Poay; Sian; Sabrina; Lee; Kian; Keong; Poh

    2014-01-01

    Endothelial dysfunction has been associated with the development of atherosclerosis and cardiovascular diseases. Adult endothelial progenitor cells(EPCs) are derived from hematopoietic stem cells and are capable of forming new blood vessels through a process of vas-culogenesis. There are studies which report correlations between circulating EPCs and cardiovascular risk fac-tors. There are also studies on how pharmacotherapies may influence levels of circulating EPCs. In this review, we discuss the potential role of endothelial progenitor cells as both diagnostic and prognostic biomarkers. In addition, we look at the interaction between cardio-vascular pharmacotherapies and endothelial progenitor cells. We also discuss how EPCs can be used directly and indirectly as a therapeutic agent. Finally, we evalu-ate the challenges facing EPC research and how these may be overcome.

  17. Haemopoietic progenitor cells in human peripheral blood

    International Nuclear Information System (INIS)

    The purpose of the investigation reported is to purify haemopoietic progenitor cells from human peripheral blood using density gradient centrifugation in order to isolate a progenitor cell fraction without immunocompetent cells. The purification technique of peripheral blood flow colony forming unit culture (CFU-c) by means of density gradient centrifugation and a combined depletion of various rosettes is described. The results of several 'in vitro' characteristics of purified CFU-c suspensions and of the plasma clot diffusion chamber culture technique are presented. Irradiation studies revealed that for both human bone marrow and peripheral blood the CFU-c were less radioresistant than clusters. Elimination of monocytes (and granulocytes) from the test suspensions induced an alteration in radiosensitivity pararmeters. The results obtained with the different techniques are described by analysing peripheral progenitor cell activity in myeloproliferative disorders. (Auth.)

  18. Transplantation of human umbilical cord blood-derived mononuclear cells induces recovery of motor dysfunction in a rat model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Chen C

    2016-04-01

    Full Text Available Chao Chen,1,* Jing Duan,1,* Aifang Shen,2,* Wei Wang,1 Hao Song,1 Yanming Liu,1 Xianjie Lu,1 Xiaobing Wang,2 Zhiqing You,1 Zhongchao Han,3,4 Fabin Han1 1Center for Stem Cells and Regenerative Medicine, The Liaocheng People's Hospital, Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of China; 2Department of Gynecology and Obstetrics, The Liaocheng People's Hospital, Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of China; 3The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences, Peking Union of Medical College, Tianjin, People's Republic of China; 4National Engineering Research Center of Cell Products, AmCellGene Co. Ltd., TEDA, Tianjin, People's Republic of China*These authors contributed equally to this workAbstract: Human umbilical cord blood-derived mononuclear cells (hUCB-MNCs were reported to have neurorestorative capacity for neurological disorders such as stroke and traumatic brain injury. This study was performed to explore if hUCB-MNC transplantation plays any therapeutic effects for Parkinson's disease (PD in a 6-OHDA-lesioned rat model of PD. hUCB-MNCs were isolated from umbilical cord blood and administered to the striatum of the 6-OHDA-lesioned rats. The apomorphine-induced locomotive turning-overs were measured to evaluate the improvement of motor dysfunctions of the rats after administration of hUCB-MNCs. We observed that transplanted hUCB-MNCs significantly improve the motor deficits of the PD rats and that grafted hUCB-MNCs integrated to the host brains and differentiated to neurons and dopamine neurons in vivo after 16 weeks of transplantation. Our study provided evidence that transplanted hUCB-MNCs play therapeutic effects in a rat PD model by differentiating to neurons and dopamine neurons. Keywords: hUCB-MNCs, Parkinson's disease, transplantation

  19. Generalized Liver- and Blood-Derived CD8+ T-Cell Impairment in Response to Cytokines in Chronic Hepatitis C Virus Infection.

    Directory of Open Access Journals (Sweden)

    Stephanie C Burke Schinkel

    Full Text Available Generalized CD8+ T-cell impairment in chronic hepatitis C virus (HCV infection and the contribution of liver-infiltrating CD8+ T-cells to the immunopathogenesis of this infection remain poorly understood. It is hypothesized that this impairment is partially due to reduced CD8+ T-cell activity in response to cytokines such as IL-7, particularly within the liver. To investigate this, the phenotype and cytokine responsiveness of blood- and liver-derived CD8+ T-cells from healthy controls and individuals with HCV infection were compared. In blood, IL-7 receptor α (CD127 expression on bulk CD8+ T-cells in HCV infection was no different than controls yet was lower on central memory T-cells, and there were fewer naïve cells. IL-7-induced signalling through phosphorylated STAT5 was lower in HCV infection than in controls, and differed between CD8+ T-cell subsets. Production of Bcl-2 following IL-7 stimulation was also lower in HCV infection and inversely related to the degree of liver fibrosis. In liver-derived CD8+ T-cells, STAT5 activation could not be increased with cytokine stimulation and basal Bcl-2 levels of liver-derived CD8+ T-cells were lower than blood-derived counterparts in HCV infection. Therefore, generalized CD8+ T-cell impairment in HCV infection is characterized, in part, by impaired IL-7-mediated signalling and survival, independent of CD127 expression. This impairment is more pronounced in the liver and may be associated with an increased potential for apoptosis. This generalized CD8+ T-cell impairment represents an important immune dysfunction in chronic HCV infection that may alter patient health.

  20. Immunoregulation and human umbilical cord blood-derived mesenchymal stem cells transplantation%脐血间充质干细胞移植与免疫调节

    Institute of Scientific and Technical Information of China (English)

    焦保良; 王景川; 高炳华; 王新生

    2012-01-01

    BACKGROUND: Research in recent years suggests that the self-renewal and multi-directional differentiation potency of human umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) offer basic condition to cell transplantation treatment. Moreover, their immunoloregulation function enormously expands the direction and limits cell transplantation treatment. OBJECTIVE: To retrospectively analyze the immunoloregulation and human UCB-MSCs transplantation. METHODS: The key word "umbilical cord blood-derived mesenchymal stem cells" was used to search in Pubmed database and CNKI database from January 2008 to June 2011 in English and Chinese using computer. The preliminary screening was made through reading the title and abstract. The articles with unrelated contents, repetitive and Meta analysis were excluded. 30 papers of pertinent literature to be published in the near future or published in the authority magazine were selected to review. RESULTS AND CONCLUSION: Human UCB-MSCs have the similar self-renewal and multi-directional differentiation potency with the bone marrow derived mesenchymal stem cells. Through cell transplantation technique, human UCB-MSCs show powerful potentiality in diabetes mellitus treatment, neural degeneration disease like Alzheimer's disease and Parkinson's disease and injury of nerve retreatment. Meanwhile, human UCB-MSCs have immunoregulatory ettects, they can lower immune reaction through down regulation of T-cells. We also get some advancements on several immunological diseases such as cell therapy of graft versus host disease and lupus nephritis.%背景:近年研究显示,脐血间充质干细胞的自我更新和多向分化潜能为细胞移植治疗提供了基础条件,而其免疫调节功能也极大地拓展了细胞治疗的方向和范围. 目的:就近期脐血间充质干细胞的免疫调节和细胞移植研究进行回顾分析. 摘要进行初筛,排除研究内容与此文无关的文献、重复性研究及Meta分析,

  1. The effects of X-irradiation on ex vivo expansion of cryopreserved human hematopoietic stem/progenitor cells

    International Nuclear Information System (INIS)

    In our previous study (Life Sciences 84: 598, 2009), we demonstrated that placental/umbilical cord blood-derived mesenchymal stem cell-like stromal cells have the effect to support the regeneration of freshly prepared X-irradiated hematopoietic stem/progenitor cells (HSPCs). Generally, HSPCs are supplied from companies, institutions, and cell banks that cryopreserve them for clinical and experimental use. In this study, the influence of cryopreservation on the responses of HSPCs to irradiation and co-culture with stromal cells is assessed. After cryopreservation with the optimal procedure, 2 Gy-irradiated HSPCs were cultured with or without stromal cells supplemented with combination of interleukin-3, stem cell factor, and thrombopoietin. The population of relatively immature CD34+/CD38- cells in cryopreserved cells was significantly higher than in fresh cells prior to cryopreservation; furthermore, the hematopoietic progenitor populations of CD34+/CD45RA+ cells and CD34+/CD117+ cells in cryopreserved cells were significantly lower than that in fresh cells. However, the rate of expansion in the cryopreserved HSPCs was lower than in the fresh HSPCs. In the culture of cryopreserved cells irradiated with 2 Gy, the growth rates of CD34+ cells, CD34+/CD38- cells, and hematopoietic progenitors were greater than growth rates of their counter parts in the culture of fresh cells. Surprisingly, the effect to support the hematopoiesis in co-culture with stromal cells was never observed in the X-irradiated HSPCs after cryopreservation. The present results demonstrated that cryopreserving process increased the rate of immature and radio-resistant HSPCs but decreased the effects to support the hematopoiesis by stromal cells, thus suggesting that cryopreservation changes the character of HSPCs. (author)

  2. X Inactivation and Progenitor Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ruben Agrelo

    2011-04-01

    Full Text Available In mammals, silencing of one of the two X chromosomes is necessary to achieve dosage compensation. The 17 kb non-coding RNA called Xist triggers X inactivation. Gene silencing by Xist can only be achieved in certain contexts such as in cells of the early embryo and in certain hematopoietic progenitors where silencing factors are present. Moreover, these epigenetic contexts are maintained in cancer progenitors in which SATB1 has been identified as a factor related to Xist-mediated chromosome silencing.

  3. Pigment Cell Progenitors in Zebrafish Remain Multipotent through Metamorphosis.

    Science.gov (United States)

    Singh, Ajeet Pratap; Dinwiddie, April; Mahalwar, Prateek; Schach, Ursula; Linker, Claudia; Irion, Uwe; Nüsslein-Volhard, Christiane

    2016-08-01

    The neural crest is a transient, multipotent embryonic cell population in vertebrates giving rise to diverse cell types in adults via intermediate progenitors. The in vivo cell-fate potential and lineage segregation of these postembryonic progenitors is poorly understood, and it is unknown if and when the progenitors become fate restricted. We investigate the fate restriction in the neural crest-derived stem cells and intermediate progenitors in zebrafish, which give rise to three distinct adult pigment cell types: melanophores, iridophores, and xanthophores. By inducing clones in sox10-expressing cells, we trace and quantitatively compare the pigment cell progenitors at four stages, from embryogenesis to metamorphosis. At all stages, a large fraction of the progenitors are multipotent. These multipotent progenitors have a high proliferation ability, which diminishes with fate restriction. We suggest that multipotency of the nerve-associated progenitors lasting into metamorphosis may have facilitated the evolution of adult-specific traits in vertebrates. PMID:27453500

  4. Regulation of human umbilical cord blood-derived multi-potent stem cells by autogenic osteoclast-based niche-like structure

    International Nuclear Information System (INIS)

    Stem cell niches provide the micro-environment for the development of stem cells. Under our culturing regimen, a kind of osteoclast-centralized structure supports the proliferation of MSCs, derived from human cord blood, once they reside on osteoclasts. MSCs in this structure expressed Oct4 which is a marker of embryonic stem cells. Floating daughter cells of MSCs colony showed abilities to differentiate into osteocyte, adipocyte, and neuronal progenitor cells. Compared with the easy senescence of MSCs without this niche-like structure in vitro, these results suggested that osteoclasts might play an important role the development and maintenance of Umbilical cord blood (UCB)-derived MSCs and might provide a means to expand UCB-MSCs in vitro, more easily, through a stem cell niche-like structure

  5. Sonic hedgehog lineage in the mouse hypothalamus: from progenitor domains to hypothalamic regions

    Directory of Open Access Journals (Sweden)

    Alvarez-Bolado Gonzalo

    2012-01-01

    Full Text Available Abstract Background The hypothalamus is a brain region with essential functions for homeostasis and energy metabolism, and alterations of its development can contribute to pathological conditions in the adult, like hypertension, diabetes or obesity. However, due to the anatomical complexity of the hypothalamus, its development is not well understood. Sonic hedgehog (Shh is a key developmental regulator gene expressed in a dynamic pattern in hypothalamic progenitor cells. To obtain insight into hypothalamic organization, we used genetic inducible fate mapping (GIFM to map the lineages derived from Shh-expressing progenitor domains onto the four rostrocaudally arranged hypothalamic regions: preoptic, anterior, tuberal and mammillary. Results Shh-expressing progenitors labeled at an early stage (before embryonic day (E9.5 contribute neurons and astrocytes to a large caudal area including the mammillary and posterior tuberal regions as well as tanycytes (specialized median eminence glia. Progenitors labeled at later stages (after E9.5 give rise to neurons and astrocytes of the entire tuberal region and in particular the ventromedial nucleus, but not to cells in the mammillary region and median eminence. At this stage, an additional Shh-expressing domain appears in the preoptic area and contributes mostly astrocytes to the hypothalamus. Shh-expressing progenitors do not contribute to the anterior region at any stage. Finally, we show a gradual shift from neurogenesis to gliogenesis, so that progenitors expressing Shh after E12.5 generate almost exclusively hypothalamic astrocytes. Conclusions We define a fate map of the hypothalamus, based on the dynamic expression of Shh in the hypothalamic progenitor zones. We provide evidence that the large neurogenic Shh-expressing progenitor domains of the ventral diencephalon are continuous with those of the midbrain. We demonstrate that the four classical transverse zones of the hypothalamus have clearly

  6. In vivo identification of periodontal progenitor cells.

    Science.gov (United States)

    Roguljic, H; Matthews, B G; Yang, W; Cvija, H; Mina, M; Kalajzic, I

    2013-08-01

    The periodontal ligament contains progenitor cells; however, their identity and differentiation potential in vivo remain poorly characterized. Previous results have suggested that periodontal tissue progenitors reside in perivascular areas. Therefore, we utilized a lineage-tracing approach to identify and track periodontal progenitor cells from the perivascular region in vivo. We used an alpha-smooth muscle actin (αSMA) promoter-driven and tamoxifen-inducible Cre system (αSMACreERT2) that, in combination with a reporter mouse line (Ai9), permanently labels a cell population, termed 'SMA9'. To trace the differentiation of SMA9-labeled cells into osteoblasts/cementoblasts, we utilized a Col2.3GFP transgene, while expression of Scleraxis-GFP was used to follow differentiation into periodontal ligament fibroblasts during normal tissue formation and remodeling following injury. In uninjured three-week-old SMA9 mice, tamoxifen labeled a small population of cells in the periodontal ligament that expanded over time, particularly in the apical region of the root. By 17 days and 7 weeks after labeling, some SMA9-labeled cells expressed markers indicating differentiation into mature lineages, including cementocytes. Following injury, SMA9 cells expanded, and differentiated into cementoblasts, osteoblasts, and periodontal ligament fibroblasts. SMA9-labeled cells represent a source of progenitors that can give rise to mature osteoblasts, cementoblasts, and fibroblasts within the periodontium. PMID:23735585

  7. Binary progenitor models of type IIb supernovae

    NARCIS (Netherlands)

    Claeys, J.S.W.A.; de Mink, S.E.; Pols, O.R.; Eldridge, J.J.; Baes, M.

    2011-01-01

    Massive stars that lose their hydrogen-rich envelope down to a few tenths of a solar mass explode as extended type IIb supernovae, an intriguing subtype that links the hydrogen-rich type II supernovae with the hydrogen-poor type Ib and Ic. The progenitors may be very massive single stars that lose t

  8. GRB 011121 A Massive Star Progenitor

    CERN Document Server

    Price, P A; Reichart, D E; Kulkarni, S R; Subramanian, R; Wark, R M; Wieringa, M H; Frail, D A; Bailey, J; Boyle, B; Corbett, E A; Gunn, K; Ryder, S D; Seymour, N; Koviak, K; McCarthy, P; Phillips, M; Axelrod, T S; Bloom, J S; Djorgovski, S G; Fox, D W; Galama, T J; Harrison, F A; Hurley, K; Sari, R; Schmidt, B P; Yost, S A; Brown, M J I; Cline, T; Frontera, F; Guidorzi, C; Montanari, E

    2002-01-01

    Of the cosmological gamma-ray bursts, GRB 011121 has the lowest redshift, z=0.36. More importantly, the multi-color excess in the afterglow detected in the Hubble Space Telescope (HST) light curves is compelling observational evidence for an underlying supernova. Here we present near-infrared and radio observations of the afterglow. We undertake a comprehensive modeling of these observations and those reported in the literature and find good evidence favoring a wind-fed circumburst medium. In detail, we infer the progenitor had a mass loss rate of Mdot ~ 10^-7 / v_w3 Mo/yr where v_w3 is the speed of the wind from the progenitor in units of 10^3 km/s. This mass loss rate is similar to that inferred for the progenitor of SN 1998bw which has been associated with GRB 980425. Our data, taken in conjunction with the HST results of Bloom et al. (2002), provide a consistent picture: the long duration GRB 011121 had a massive star progenitor which exploded as a supernova at about the same time as the GRB event.

  9. Periodontal Bioengineering: A Discourse in Surface Topographies, Progenitor Cells and Molecular Profiles

    Science.gov (United States)

    Dangaria, Smit J.

    2011-12-01

    Stem/progenitor cells are a population of cells capable of providing replacement cells for a given differentiated cell type. We have applied progenitor cell-based technologies to generate novel tissue-engineered implants that use biomimetic strategies with the ultimate goal of achieving full regeneration of lost periodontal tissues. Mesenchymal periodontal tissues such as cementum, alveolar bone (AB), and periodontal ligament (PDL) are neural crest-derived entities that emerge from the dental follicle (DF) at the onset of tooth root formation. Using a systems biology approach we have identified key differences between these periodontal progenitors on the basis of global gene expression profiles, gene cohort expression levels, and epigenetic modifications, in addition to differences in cellular morphologies. On an epigenetic level, DF progenitors featured high levels of the euchromatin marker H3K4me3, whereas PDL cells, AB osteoblasts, and cementoblasts contained high levels of the transcriptional repressor H3K9me3. Secondly, we have tested the influence of natural extracellular hydroxyapatite matrices on periodontal progenitor differentiation. Dimension and structure of extracellular matrix surfaces have powerful influences on cell shape, adhesion, and gene expression. Here we show that natural tooth root topographies induce integrin-mediated extracellular matrix signaling cascades in tandem with cell elongation and polarization to generate physiological periodontium-like tissues. In this study we replanted surface topography instructed periodontal ligament progenitors (PDLPs) into rat alveolar bone sockets for 8 and 16 weeks, resulting in complete attachment of tooth roots to the surrounding alveolar bone with a periodontal ligament fiber apparatus closely matching physiological controls along the entire root surface. Displacement studies and biochemical analyses confirmed that progenitor-based engineered periodontal tissues were similar to control teeth and

  10. SUPERNOVA REMNANT PROGENITOR MASSES IN M31

    Energy Technology Data Exchange (ETDEWEB)

    Jennings, Zachary G.; Williams, Benjamin F.; Dalcanton, Julianne J.; Gilbert, Karoline M.; Fouesneau, Morgan; Weisz, Daniel R. [Department of Astronomy, University of Washington Seattle, Box 351580, WA 98195 (United States); Murphy, Jeremiah W. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Dolphin, Andrew E., E-mail: zachjenn@uw.edu, E-mail: adolphin@raytheon.com [Raytheon, 1151 East Hermans Road, Tucson, AZ 85706 (United States)

    2012-12-10

    Using Hubble Space Telescope photometry, we age-date 59 supernova remnants (SNRs) in the spiral galaxy M31 and use these ages to estimate zero-age main-sequence masses (M{sub ZAMS}) for their progenitors. To accomplish this, we create color-magnitude diagrams (CMDs) and employ CMD fitting to measure the recent star formation history of the regions surrounding cataloged SNR sites. We identify any young coeval population that likely produced the progenitor star, then assign an age and uncertainty to that population. Application of stellar evolution models allows us to infer the M{sub ZAMS} from this age. Because our technique is not contingent on identification or precise location of the progenitor star, it can be applied to the location of any known SNRs. We identify significant young star formation around 53 of the 59 SNRs and assign progenitor masses to these, representing a factor of {approx}2 increase over currently measured progenitor masses. We consider the remaining six SNRs as either probable Type Ia candidates or the result of core-collapse progenitors that have escaped their birth sites. In general, the distribution of recovered progenitor masses is bottom-heavy, showing a paucity of the most massive stars. If we assume a single power-law distribution, dN/dM{proportional_to}M{sup {alpha}}, then we find a distribution that is steeper than a Salpeter initial mass function (IMF) ({alpha} = -2.35). In particular, we find values of {alpha} outside the range -2.7 {>=} {alpha} {>=} -4.4 to be inconsistent with our measured distribution at 95% confidence. If instead we assume a distribution that follows a Salpeter IMF up to some maximum mass, then we find that values of M{sub Max} > 26 are inconsistent with the measured distribution at 95% confidence. In either scenario, the data suggest that some fraction of massive stars may not explode. The result is preliminary and requires more SNRs and further analysis. In addition, we use our distribution to estimate a

  11. Response to intravenous allogeneic equine cord-blood-derived mesenchymal stromal cells administered from chilled or frozen state in serum and protein free media

    Directory of Open Access Journals (Sweden)

    Lynn Brandon Williams

    2016-07-01

    Full Text Available Equine Mesenchymal stromal cells (MSC are commonly transported, chilled or frozen, to veterinary clinics. These MSC must remain viable and minimally affected by culture, transport, or injection processes. The safety of two carrier solutions developed for optimal viability and excipient use were evaluated in ponies, with and without allogeneic cord blood-derived (CB MSC. We hypothesized that neither the carrier solutions nor CB-MSC would elicit measurable changes in clinical, hematological, or biochemical parameters. In 9 ponies (study 1 a bolus of HypoThermosol® FRS (HTS-FRS, CryoStor® CS10 (CS10 or saline was injected IV (n=3/treatment. Study 2, following a one week washout period 5x107 pooled allogeneic CB-MSC were administered IV in HTS-FRS following 24h simulated chilled transport. Study 3, following another one week washout period 5x107 pooled allogeneic CB-MSC were administered IV in CS10 immediately after thawing. Nine ponies received CB-MSCs in study 2 and 3 and three ponies received the cell carrier media without cells. CB-MSCs were pooled in equal numbers from five unrelated donors. In all studies ponies were monitored with physical examination, and blood collection for 7 days following injection. CD4 and CD8 lymphocyte populations were also evaluated in each blood sample.In all three studies, physical exam, complete blood cell count, serum biochemistry, and coagulation panel did not deviate from established normal ranges. Proportions of CD4+ and CD8+ lymphocytes increased at 168h post injection in CB-MSC treatment groups regardless of the carrier solution. Decreases in CD4+/CD8+ double positive populations were observed at 24 h and 72 h in CB-MSC treated animals. There was no difference in viability between CB-MSC suspended in HTS-FRS or CS10.HTS-FRS and CS10 used for low volume excipient injection of MSC suspensions was not associated with short-term adverse reactions. HTS-FRS and CS10 both adequately maintain CB-MSC viability

  12. Reversal of type 1 diabetes via islet β cell regeneration following immune modulation by cord blood-derived multipotent stem cells

    Directory of Open Access Journals (Sweden)

    Zhao Yong

    2012-01-01

    Full Text Available Abstract Background Inability to control autoimmunity is the primary barrier to developing a cure for type 1 diabetes (T1D. Evidence that human cord blood-derived multipotent stem cells (CB-SCs can control autoimmune responses by altering regulatory T cells (Tregs and human islet β cell-specific T cell clones offers promise for a new approach to overcome the autoimmunity underlying T1D. Methods We developed a procedure for Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates lymphocytes from the whole blood and briefly co-cultures them with adherent CB-SCs before returning them to the patient's circulation. In an open-label, phase1/phase 2 study, patients (n = 15 with T1D received one treatment with the Stem Cell Educator. Median age was 29 years (range: 15 to 41, and median diabetic history was 8 years (range: 1 to 21. Results Stem Cell Educator therapy was well tolerated in all participants with minimal pain from two venipunctures and no adverse events. Stem Cell Educator therapy can markedly improve C-peptide levels, reduce the median glycated hemoglobin A1C (HbA1C values, and decrease the median daily dose of insulin in patients with some residual β cell function (n = 6 and patients with no residual pancreatic islet β cell function (n = 6. Treatment also produced an increase in basal and glucose-stimulated C-peptide levels through 40 weeks. However, participants in the Control Group (n = 3 did not exhibit significant change at any follow-up. Individuals who received Stem Cell Educator therapy exhibited increased expression of co-stimulating molecules (specifically, CD28 and ICOS, increases in the number of CD4+CD25+Foxp3+ Tregs, and restoration of Th1/Th2/Th3 cytokine balance. Conclusions Stem Cell Educator therapy is safe, and in individuals with moderate or severe T1D, a single treatment produces lasting improvement in metabolic control. Initial results indicate Stem Cell

  13. Notch signaling: a novel regulating differentiation mechanism of human umbilical cord blood-derived mesenchymal stem cells into insulin-producing cells in vitro

    Institute of Scientific and Technical Information of China (English)

    HU Yan-hua; WU De-quan; GAO Feng; LI Guo-dong; ZHANG Xin-chen

    2010-01-01

    Background Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) could be induced to differentiate into insulin producing cells (IPCs) in vitro, which have good application potential in the cell replacement treatment of type-1 diabetes. However, the mechanisms regulating this differentiation have remained largely unknown. Notch signaling is critical in cell differentiation. This study investigated whether Notch signaling could regulate the IPCs differentiation of human UCB-MSCs. Methods Using an interfering Notch signaling protocol in vitro, we studied the role of Notch signaling in differentiation of human UCB-MSCs into IPCs. In a control group the induction took place without interfering Notch signaling. Results Human UCB-MSCs expressed the genes of Notch receptors (Notch 1 and Notch 2) and ligands (Jagged 1 and Deltalike 1). Human UCB-MSCs with over-expressing Notch signaling in differentiation resulted in the down-regulation of insulin gene level, proinsulin protein expression, and insulin-positive cells percentage compared with the control group. These results showed that over-expressing Notch signaling inhibited IPCs differentiation. Conversely, when Notch signaling was attenuated by receptor inhibitor, the induced cells increased on average by 3.06-fold (n=4, P<0.001) in insulin gene level, 2.60-fold (n=3, P <0.02) in proinsulin protein expression, and 1.62-fold (n=6, P <0.001) in the rate of IPCs compared with the control group. Notch signaling inhibition significantly promoted IPCs differentiation with about 40% of human UCB-MSCs that converted to IPCs, but these IPCs were not responsive to glucose challenge very well both in vitro and in vivo. Hence, further research has to be carried out in the future. Conclusions Notch signaling may be an important mechanism regulating IPCs differentiation of human UCB-MSCs in vitro and Notch signaling inhibition may be an efficient way to increase the number of IPCs, which may resolve the shortage of

  14. Neutronization During Carbon Simmering In Type Ia Supernova Progenitors

    CERN Document Server

    Martínez-Rodríguez, Héctor; Schwab, Josiah; Badenes, Carles

    2016-01-01

    When a Type Ia supernova (SN Ia) progenitor first ignites carbon in its core, it undergoes ${\\sim} \\,10^{3}-10^{4} \\,$yr of convective burning prior to the onset of thermonuclear runaway. This carbon simmering phase is important for setting the thermal profile and composition of the white dwarf. Using the \\texttt{MESA} stellar evolution code, we follow this convective burning and examine the production of neutron-rich isotopes. The neutron content of the SN fuel has important consequences for the ensuing nucleosynthesis, and, in particular, for the production of secondary Fe-peak nuclei like Mn and stable Ni. These elements have been observed in the X-ray spectra of SN remnants like Tycho, Kepler, and 3C 397, and their yields can provide valuable insights into the physics of SNe Ia and the properties of their progenitors. We find that weak reactions during simmering can at most generate a neutron excess of ${\\approx} \\, 3 \\times 10^{-4}$. This is ${\\approx} \\, 8 \\times 10^{-4}$ lower than that found in previo...

  15. Identification of a Bipotent Epithelial Progenitor Population in the Adult Thymus

    Directory of Open Access Journals (Sweden)

    Svetlana Ulyanchenko

    2016-03-01

    Full Text Available Thymic epithelial cells (TECs are critically required for T cell development, but the cellular mechanisms that maintain adult TECs are poorly understood. Here, we show that a previously unidentified subpopulation, EpCam+UEA1−Ly-51+PLET1+MHC class IIhi, which comprises <0.5% of adult TECs, contains bipotent TEC progenitors that can efficiently generate both cortical (c TECs and medullary (m TECs. No other adult TEC population tested in this study contains this activity. We demonstrate persistence of PLET1+Ly-51+ TEC-derived cells for 9 months in vivo, suggesting the presence of thymic epithelial stem cells. Additionally, we identify cTEC-restricted short-term progenitor activity but fail to detect high efficiency mTEC-restricted progenitors in the adult thymus. Our data provide a phenotypically defined adult thymic epithelial progenitor/stem cell that is able to generate both cTECs and mTECs, opening avenues for improving thymus function in patients.

  16. Resident microglia, rather than blood-derived macrophages, contribute to the earlier and more pronounced inflammatory reaction in the immature compared with the adult hippocampus after hypoxia-ischemia.

    Science.gov (United States)

    Umekawa, Takashi; Osman, Ahmed M; Han, Wei; Ikeda, Tomoaki; Blomgren, Klas

    2015-12-01

    The mechanisms of neuronal injury after hypoxia-ischemia (HI) are different in the immature and the adult brain, but microglia activation has not been compared. The purpose of this study was to phenotype resident microglia and blood-derived macrophages in the hippocampus after HI in neonatal (postnatal day 9, P9) or adult (3 months of age, 3mo) mice. Unilateral brain injury after HI was induced in Cx3cr1(GFP/+) Ccr2(RFP/+) male mice on P9 (n = 34) or at 3mo (n = 53) using the Vannucci model. Resident microglia (Cx3cr1-GFP+) proliferated and were activated earlier after HI in the P9 (1-3 days) than that in the 3mo hippocampus, but remained longer in the adult brain (3-7 days). Blood-derived macrophages (Ccr2-RFP+) peaked 3 days after HI in both immature (P9) and adult (3mo) hippocampi but were twice as frequent in adult brains, 41% vs. 21% of all microglia/macrophages. CCL2 expression was three times higher in the P9 hippocampi, indicating that the proinflammatory response was more pronounced in the immature brain after HI. This corresponded well with the higher numbers of galectin-3-positive resident microglia in the P9 hippocampi, but did not correlate with CD16/32- or CD206-positive resident microglia or blood-derived macrophages. In conclusion, resident microglia, rather than infiltrating blood-derived macrophages, proliferate and are activated earlier in the immature than in the adult brain, but remain increased longer in the adult brain. The inflammatory response is more pronounced in the immature brain, and this correlate well with galectin-3 expression in resident microglia.

  17. Origin of hemopoietic stromal progenitor cells in chimeras

    International Nuclear Information System (INIS)

    Intravenously injected bone marrow cells do not participate in the regeneration of hemopoietic stromal progenitors in irradiated mice, nor in the curetted parts of the recipient's marrow. The hemopoietic stromal progenitors in allogeneic chimeras are of recipient origin. The adherent cell layer (ACL) of long-term cultures of allogeneic chimera bone marrow contains only recipient hemopoietic stromal progenitors. However, in ectopic hemopoietic foci produced by marrow implantation under the renal capsule and repopulated by the recipient hemopoietic cells after irradiation and reconstitution by syngeneic hemopoietic cells, the stromal progenitors were of implant donor origin, as were stromal progenitors of the ACL in long-term cultures of hemopoietic cells from ectopic foci. Our results confirm that the stromal and hemopoietic progenitors differ in origin and that hemopoietic stromal progenitors are not transplantable by the intravenous route in mice

  18. Adult Olfactory Bulb Interneuron Phenotypes Identified by Targeting Embryonic and Postnatal Neural Progenitors.

    Science.gov (United States)

    Figueres-Oñate, Maria; López-Mascaraque, Laura

    2016-01-01

    Neurons are generated during embryonic development and in adulthood, although adult neurogenesis is restricted to two main brain regions, the hippocampus and olfactory bulb. The subventricular zone (SVZ) of the lateral ventricles generates neural stem/progenitor cells that continually provide the olfactory bulb (OB) with new granule or periglomerular neurons, cells that arrive from the SVZ via the rostral migratory stream. The continued neurogenesis and the adequate integration of these newly generated interneurons is essential to maintain homeostasis in the olfactory bulb, where the differentiation of these cells into specific neural cell types is strongly influenced by temporal cues. Therefore, identifying the critical features that control the generation of adult OB interneurons at either pre- or post-natal stages is important to understand the dynamic contribution of neural stem cells. Here, we used in utero and neonatal SVZ electroporation along with a transposase-mediated stable integration plasmid, in order to track interneurons and glial lineages in the OB. These plasmids are valuable tools to study the development of OB interneurons from embryonic and post-natal SVZ progenitors. Accordingly, we examined the location and identity of the adult progeny of embryonic and post-natally transfected progenitors by examining neurochemical markers in the adult OB. These data reveal the different cell types in the olfactory bulb that are generated in function of age and different electroporation conditions. PMID:27242400

  19. Interneuron progenitor transplantation to treat CNS dysfunction

    Directory of Open Access Journals (Sweden)

    Muhammad O Chohan

    2016-08-01

    Full Text Available Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field.

  20. Noninvasive Imaging of Administered Progenitor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Steven R Bergmann, M.D., Ph.D.

    2012-12-03

    The objective of this research grant was to develop an approach for labeling progenitor cells, specifically those that we had identified as being able to replace ischemic heart cells, so that the distribution could be followed non-invasively. In addition, the research was aimed at determining whether administration of progenitor cells resulted in improved myocardial perfusion and function. The efficiency and toxicity of radiolabeling of progenitor cells was to be evaluated. For the proposed clinical protocol, subjects with end-stage ischemic coronary artery disease were to undergo a screening cardiac positron emission tomography (PET) scan using N-13 ammonia to delineate myocardial perfusion and function. If they qualified based on their PET scan, they would undergo an in-hospital protocol whereby CD34+ cells were stimulated by the administration of granulocytes-colony stimulating factor (G-CSF). CD34+ cells would then be isolated by apharesis, and labeled with indium-111 oxine. Cells were to be re-infused and subjects were to undergo single photon emission computed tomography (SPECT) scanning to evaluate uptake and distribution of labeled progenitor cells. Three months after administration of progenitor cells, a cardiac PET scan was to be repeated to evaluate changes in myocardial perfusion and/or function. Indium oxine is a radiopharmaceutical for labeling of autologous lymphocytes. Indium-111 (In-111) decays by electron capture with a t{sub ½} of 67.2 hours (2.8 days). Indium forms a saturated complex that is neutral, lipid soluble, and permeates the cell membrane. Within the cell, the indium-oxyquinolone complex labels via indium intracellular chelation. Following leukocyte labeling, ~77% of the In-111 is incorporated in the cell pellet. The presence of red cells and /or plasma reduces the labeling efficacy. Therefore, the product needed to be washed to eliminate plasma proteins. This repeated washing can damage cells. The CD34 selected product was a 90

  1. FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage

    Energy Technology Data Exchange (ETDEWEB)

    Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki, E-mail: yasukiishizaki@gunma-u.ac.jp

    2015-08-07

    The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytes and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture.

  2. BMP signaling in the nephron progenitor niche

    OpenAIRE

    Oxburgh, Leif; Brown, Aaron C.; Fetting, Jennifer; Hill, Beth

    2011-01-01

    Bone morphogenic proteins (BMPs) play diverse roles in embryonic kidney development, regulating essential aspects of both ureteric bud and nephron development. In this review, we provide an overview of reported expression patterns and functions of BMP signaling components within the nephrogenic zone or nephron progenitor niche of the developing kidney. Reported in situ hybridization results are relatively challenging to interpret and sometimes conflicting. Comparing these with high-resolution...

  3. Human Fetal Progenitor Tenocytes for Regenerative Medicine.

    OpenAIRE

    Grognuz A.; Scaletta C.; Farron A.; Raffoul W.; Applegate L.A.

    2016-01-01

    Tendon injuries are very frequent and affect a wide and heterogeneous population. Unfortunately, the healing process is long with outcomes that are not often satisfactory due to fibrotic tissue appearance, which leads to scar and adhesion development. Tissue engineering and cell therapies emerge as interesting alternatives to classical treatments. In this study, we evaluated human fetal progenitor tenocytes (hFPTs) as a potential cell source for treatment of tendon afflictions, as fetal cells...

  4. TOX3 regulates neural progenitor identity.

    Science.gov (United States)

    Sahu, Sanjeeb Kumar; Fritz, Alina; Tiwari, Neha; Kovacs, Zsuzsa; Pouya, Alireza; Wüllner, Verena; Bora, Pablo; Schacht, Teresa; Baumgart, Jan; Peron, Sophie; Berninger, Benedikt; Tiwari, Vijay K; Methner, Axel

    2016-07-01

    The human genomic locus for the transcription factor TOX3 has been implicated in susceptibility to restless legs syndrome and breast cancer in genome-wide association studies, but the physiological role of TOX3 remains largely unknown. We found Tox3 to be predominantly expressed in the developing mouse brain with a peak at embryonic day E14 where it co-localizes with the neural stem and progenitor markers Nestin and Sox2 in radial glia of the ventricular zone and intermediate progenitors of the subventricular zone. Tox3 is also expressed in neural progenitor cells obtained from the ganglionic eminence of E15 mice that express Nestin, and it specifically binds the Nestin promoter in chromatin immunoprecipitation assays. In line with this, over-expression of Tox3 increased Nestin promoter activity, which was cooperatively enhanced by treatment with the stem cell self-renewal promoting Notch ligand Jagged and repressed by pharmacological inhibition of Notch signaling. Knockdown of Tox3 in the subventricular zone of E12.5 mouse embryos by in utero electroporation of Tox3 shRNA revealed a reduced Nestin expression and decreased proliferation at E14 and a reduced migration to the cortical plate in E16 embryos in electroporated cells. Together, these results argue for a role of Tox3 in the development of the nervous system. PMID:27080130

  5. Constraints for the progenitor masses of 17 historic core-collapse supernovae

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Benjamin F.; Peterson, Skyler; Gilbert, Karoline; Dalcanton, Julianne J. [Department of Astronomy, Box 351580, University of Washington, Seattle, WA 98195 (United States); Murphy, Jeremiah [Department of Physics, Florida State University, Tallahassee, FL 32306 (United States); Dolphin, Andrew E. [Raytheon, 1151 E. Hermans Road, Tucson, AZ 85706 (United States); Jennings, Zachary G., E-mail: ben@astro.washington.edu, E-mail: peters8@uw.edu, E-mail: jd@astro.washington.edu, E-mail: jeremiah@physics.fsu.edu, E-mail: kgilbert@stsci.edu, E-mail: dolphin@raytheon.com, E-mail: zgjennin@ucsc.edu [University of California Observatories, Santa Cruz, CA 95064 (United States)

    2014-08-20

    Using resolved stellar photometry measured from archival Hubble Space Telescope imaging, we generate color-magnitude diagrams of the stars within 50 pc of the locations of historic core-collapse supernovae (SNe) that took place in galaxies within 8 Mpc. We fit these color-magnitude distributions with stellar evolution models to determine the best-fit age distribution of the young population. We then translate these age distributions into probability distributions for the progenitor mass of each SN. The measurements are anchored by the main-sequence stars surrounding the event, making them less sensitive to assumptions about binarity, post-main-sequence evolution, or circumstellar dust. We demonstrate that, in cases where the literature contains masses that have been measured from direct imaging, our measurements are consistent with (but less precise than) these measurements. Using this technique, we constrain the progenitor masses of 17 historic SNe, 11 of which have no previous estimates from direct imaging. Our measurements still allow the possibility that all SN progenitor masses are <20 M {sub ☉}. However, the large uncertainties for the highest-mass progenitors also allow the possibility of no upper-mass cutoff.

  6. Double-peaked Supernovae and the Signature of Progenitors with Low-mass Extended Envelopes

    CERN Document Server

    Nakar, Ehud

    2014-01-01

    Early observations of supernova light curves are powerful tools for shedding light on the pre-explosion structures of their progenitors and their mass-loss histories just prior to explosion. Some core-collapse supernovae that are detected during the first days after the explosion prominently show two peaks in the optical bands, where the first is presumably powered by the cooling of shocked surface material and the second peak is clearly powered by radioactive decay. Here we explore, first, whether this type of light curve can be generated by a progenitor with a "standard" density profile, such as a red supergiant or a Wolf-Rayet star. We find that such a progenitor: (i) cannot produce a double-peaked light curve in the $R$ and $I$ bands, and (ii) cannot exhibit a fast drop in the bolometric luminosity as is seen after the first peak. We then explore the signature of a progenitor with a massive, compact core surrounded by extended, low-mass material. This may be a hydrostatic low-mass envelope or material eje...

  7. Global transcriptome analysis of T-competent progenitors in the bone marrow

    Directory of Open Access Journals (Sweden)

    Vionnie W.C. Yu

    2015-09-01

    Full Text Available T cells are known to develop in the thymus. However, molecular events that control the transition from hematopoietic progenitor cells in the bone marrow to T precursor cells seeded in the thymus remained poorly defined. Our recent report showed that osteocalcin (Ocn-expressing bone cells in the bone marrow have major impact on T cell immunity by regulating T progenitor development in the bone marrow (Yu et al., 2015 [1]. Selective endogenous depletion of Ocn+ cells by inducible diphtheria toxin receptor expression (OcnCre;iDTR led to reduction of T-competent common lymphoid progenitors (Ly6D− CLPs in the bone marrow and loss of T cells in the thymus. Expression of the Notch ligand DLL4 by Ocn+ cells in the bone marrow ensures the production of Ly6D− CLPs, and expression of chemotactic molecules CCR7 and PSGL1 to enable subsequent thymic seeding. These data indicate that specific mesenchymal cells in bone marrow provide key molecular drivers enforcing thymus-seeding progenitor generation and thereby directly link skeletal biology to the production of T cell based adaptive immunity. Here we present the transcriptome profiles of Ly6D− CLPs derived from Ocn+ cells deleted mice (OcnCre+;iDTR compared to those derived from control littermates (OcnCre−;iDTR. These data are publically available from NCBI Gene Expression Omnibus (GEO with the accession number GSE66102.

  8. Constraints for the progenitor masses of 17 historic core-collapse supernovae

    International Nuclear Information System (INIS)

    Using resolved stellar photometry measured from archival Hubble Space Telescope imaging, we generate color-magnitude diagrams of the stars within 50 pc of the locations of historic core-collapse supernovae (SNe) that took place in galaxies within 8 Mpc. We fit these color-magnitude distributions with stellar evolution models to determine the best-fit age distribution of the young population. We then translate these age distributions into probability distributions for the progenitor mass of each SN. The measurements are anchored by the main-sequence stars surrounding the event, making them less sensitive to assumptions about binarity, post-main-sequence evolution, or circumstellar dust. We demonstrate that, in cases where the literature contains masses that have been measured from direct imaging, our measurements are consistent with (but less precise than) these measurements. Using this technique, we constrain the progenitor masses of 17 historic SNe, 11 of which have no previous estimates from direct imaging. Our measurements still allow the possibility that all SN progenitor masses are <20 M ☉. However, the large uncertainties for the highest-mass progenitors also allow the possibility of no upper-mass cutoff.

  9. 血管内皮生长因子和雌二醇促进血管内皮祖细胞分化生成血管的对比研究%Comparative study of vascular endothelial growth factor and estradiol in promoting endothelial progenitor cells differentiation and generation blood vessels

    Institute of Scientific and Technical Information of China (English)

    董勇; 李文志; 辛毅; 孙智

    2013-01-01

    Objective To compare the ability of vascular endothelial growth factor (VEGF) and estradiol in promoting endothelial progenitor cells differentiation and generation blood vessels under common doses. Methods To isolate and culture human peripheral blood EPCs first, then to mixe with the matrigel and transplante to the lower abdomens of nine nude mice.to divide the nine nude mice into three groups according to a random grouping, to inject VEGF.estradiol and saline at a regular time,to observe and record the growing status of vascular tissue regularly.to draw the vascular tissue after six weeks, to observe the organizational structure by HE staining, then contrast with the groups. Results The vascular tissue volume groups injected of drugs have significant difference with the groups injected of saline.they have bigger volume to contrast the groups injected of saline, but he vascular tissue volume between the groups injected of drugs is no significant difference. By drawning HE staining, the vascular tissues have proliferational mussy blood vessels.The vascular density of the groups injected of drugs is significantly greater than the groups injected of saline, but he vascular density between the groups injected of drugs is small. Conclusion VEGF and estradiol can promote EPCs differentiation and generation blood vessels.their respective promoting EPCs differentiation and generation blood vessels potency is no significant difference under common doses.%目的:对比研究常规剂量下血管内皮生长因子(VEGF)和雌二醇对血管内皮祖细胞(EPCs)分化生成血管的促进作用.方法:分离培养人外周血EPCs,与基质胶混匀后注射到9只裸鼠双侧下腹部,另设2只注射等体积培养液与基质胶的混合液.将9只注射细胞的裸鼠随机分为3组,每组分别定期局部注射VEGF、雌二醇,生理盐水,定期观察记录血管组织块的生长状况.移植6周后取材,测量计算血管组织块的体积、HE染色观察血管

  10. Targeting pancreatic progenitor cells in human embryonic stem cell differentiation for the identification of novel cell surface markers.

    Science.gov (United States)

    Fishman, Bettina; Segev, Hanna; Kopper, Oded; Nissenbaum, Jonathan; Schulman, Margarita; Benvenisty, Nissim; Itskovitz-Eldor, Joseph; Kitsberg, Danny

    2012-09-01

    New sources of beta cells are needed in order to develop cell therapies for patients with diabetes. An alternative to forced expansion of post-mitotic beta cells is the induction of differentiation of stem-cell derived progenitor cells that have a natural self-expansion capacity into insulin-producing cells. In order to learn more about these progenitor cells at different stages along the differentiation process in which they become progressively more committed to the final beta cell fate, we took the approach of identifying, isolating and characterizing stage specific progenitor cells. We generated human embryonic stem cell (HESC) clones harboring BAC GFP reporter constructs of SOX17, a definitive endoderm marker, and PDX1, a pancreatic marker, and identified subpopulations of GFP expressing cells. Using this approach, we isolated a highly enriched population of pancreatic progenitor cells from hESCs and examined their gene expression with an emphasis on the expression of stage-specific cell surface markers. We were able to identify novel molecules that are involved in the pancreatic differentiation process, as well as stage-specific cell markers that may serve to define (alone or in combination with other markers) a specific pancreatic progenitor cell. These findings may help in optimizing conditions for ultimately generating and isolating beta cells for transplantation therapy.

  11. In Vitro Differentiation and Expansion of Human Pluripotent Stem Cell-Derived Pancreatic Progenitors

    OpenAIRE

    Chmielowiec, Jolanta; Borowiak, Malgorzata

    2014-01-01

    Recent progress in understanding stem cell biology has been remarkable, especially in deciphering signals that support differentiation towards tissue-specific lineages. This achievement positions us firmly at the beginning of an era of patient-specific regenerative medicine and human disease modeling. It will be necessary to equip the progress in this era with a reliable source of self-renewing progenitor cells that differentiate into functional target cells. The generation of pancreatic prog...

  12. Asymmetric centrosome inheritance maintains neural progenitors in neocortex

    OpenAIRE

    Wang, Xiaoqun; Tsai, Jin-Wu; Imai, Janice H.; Lian, Wei-Nan; Vallee, Richard B.; Shi, Song-Hai

    2009-01-01

    Asymmetric divisions of radial glial progenitors produce self-renewing radial glia and differentiating cells simultaneously in the ventricular zone (VZ) of the developing neocortex. While differentiating cells leave the VZ to constitute the future neocortex, renewing radial glial progenitors stay in the VZ for subsequent divisions. The differential behaviour of progenitors and their differentiating progeny is essential for neocortical development; however, the mechanisms that ensure these beh...

  13. Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Ursula; M; Gehling; Marc; Willems; Kathleen; Schlagner; Ralf; A; Benndorf; Maura; Dandri; Jrg; Petersen; Martina; Sterneck; Joerg-Matthias; Pollok; Dieter; K; Hossfeld; Xavier; Rogiers

    2010-01-01

    AIM:To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells. METHODS:Peripheral blood samples from 72 patients with liver cirrhosis of varying etiology were analyzed by flow cytometry.Identified progenitor cell subsets were immunoselected and used for functional assays in vitro. Plasma levels of stromal cell-derived factor-1(SDF-1) were measured using an enzyme linked immunosorbent assay.RESULTS:Progenitor cells with a CD133 + /CD45 + CD14 + phenotype we...

  14. Impaired function of bone marrow-derived endothelial progenitor cells in murine liver fibrosis.

    Science.gov (United States)

    Shirakura, Katsuya; Masuda, Haruchika; Kwon, Sang-Mo; Obi, Syotaro; Ito, Rie; Shizuno, Tomoko; Kurihara, Yusuke; Mine, Tetsuya; Asahara, Takayuki

    2011-01-01

    Liver fibrosis (LF) caused by chronic liver damage has been considered as an irreversible disease. As alternative therapy for liver transplantation, there are high expectations for regenerative medicine of the liver. Bone marrow (BM)- or peripheral blood-derived stem cells, including endothelial progenitor cells (EPCs), have recently been used to treat liver cirrhosis. We investigated the biology of BM-derived EPC in a mouse model of LF. C57BL/6J mice were subcutaneously injected with carbon tetrachloride (CCl(4)) every 3 days for 90 days. Sacrificed 2 days after final injection, whole blood (WB) was collected for isolation of mononuclear cells (MNCs) and biochemical examination. Assessments of EPC in the peripheral blood and BM were performed by flow cytometry and EPC colony-forming assay, respectively, using purified MNCs and BM c-KIT(+), Sca-1(+), and Lin(-) (KSL) cells. Liver tissues underwent histological analysis with hematoxylin/eosin/Azan staining, and spleens were excised and weighed. CCl(4)-treated mice exhibited histologically bridging fibrosis, pseudolobular formation, and splenomegaly, indicating successful induction of LF. The frequency of definitive EPC-colony-forming-units (CFU) as well as total EPC-CFU at the equivalent cell number of 500 BM-KSL cells decreased significantly (p changes in primitive EPC-CFU occurred in LF mice. The frequency of WB-MNCs of definitive EPC-CFU decreased significantly (p < 0.01) in LF mice compared with control mice. Together, these findings indicated the existence of impaired EPC function and differentiation in BM-derived EPCs in LF mice and might be related to clinical LF.

  15. Molecular analysis of endothelial progenitor cell (EPC subtypes reveals two distinct cell populations with different identities

    Directory of Open Access Journals (Sweden)

    Simpson David A

    2010-05-01

    Full Text Available Abstract Background The term endothelial progenitor cells (EPCs is currently used to refer to cell populations which are quite dissimilar in terms of biological properties. This study provides a detailed molecular fingerprint for two EPC subtypes: early EPCs (eEPCs and outgrowth endothelial cells (OECs. Methods Human blood-derived eEPCs and OECs were characterised by using genome-wide transcriptional profiling, 2D protein electrophoresis, and electron microscopy. Comparative analysis at the transcript and protein level included monocytes and mature endothelial cells as reference cell types. Results Our data show that eEPCs and OECs have strikingly different gene expression signatures. Many highly expressed transcripts in eEPCs are haematopoietic specific (RUNX1, WAS, LYN with links to immunity and inflammation (TLRs, CD14, HLAs, whereas many transcripts involved in vascular development and angiogenesis-related signalling pathways (Tie2, eNOS, Ephrins are highly expressed in OECs. Comparative analysis with monocytes and mature endothelial cells clusters eEPCs with monocytes, while OECs segment with endothelial cells. Similarly, proteomic analysis revealed that 90% of spots identified by 2-D gel analysis are common between OECs and endothelial cells while eEPCs share 77% with monocytes. In line with the expression pattern of caveolins and cadherins identified by microarray analysis, ultrastructural evaluation highlighted the presence of caveolae and adherens junctions only in OECs. Conclusions This study provides evidence that eEPCs are haematopoietic cells with a molecular phenotype linked to monocytes; whereas OECs exhibit commitment to the endothelial lineage. These findings indicate that OECs might be an attractive cell candidate for inducing therapeutic angiogenesis, while eEPC should be used with caution because of their monocytic nature.

  16. Sonic hedgehog signaling regulates mode of cell division of early cerebral cortex progenitors and increases astrogliogenesis

    Directory of Open Access Journals (Sweden)

    Geissy LL Araújo

    2014-03-01

    Full Text Available The morphogen Sonic Hedgehog (SHH plays a critical role in the development of different tissues. In the central nervous system, SHH is well known to contribute to the patterning of the spinal cord and separation of the brain hemispheres. In addition, it has recently been shown that SHH signaling also contributes to the patterning of the telencephalon and establishment of adult neurogenic niches. In this work, we investigated whether SHH signaling influences the behavior of neural progenitors isolated from the dorsal telencephalon, which generate excitatory neurons and macroglial cells in vitro. We observed that SHH increases proliferation of cortical progenitors and generation of astrocytes, whereas blocking SHH signaling with cyclopamine has opposite effects. In both cases, generation of neurons did not seem to be affected. However, cell survival was broadly affected by blockade of SHH signaling. SHH effects were related to three different cell phenomena: mode of cell division, cell cycle length and cell growth. Together, our data in vitro demonstrate that SHH signaling controls cell behaviors that are important for proliferation of cerebral cortex progenitors, as well as differentiation and survival of neurons and astroglial cells.

  17. Adult mouse subventricular zone stem and progenitor cells are sessile and epidermal growth factor receptor negatively regulates neuroblast migration.

    Directory of Open Access Journals (Sweden)

    Yongsoo Kim

    Full Text Available BACKGROUND: The adult subventricular zone (SVZ contains stem and progenitor cells that generate neuroblasts throughout life. Although it is well accepted that SVZ neuroblasts are migratory, recent evidence suggests their progenitor cells may also exhibit motility. Since stem and progenitor cells are proliferative and multipotential, if they were also able to move would have important implications for SVZ neurogenesis and its potential for repair. METHODOLOGY/PRINCIPAL FINDINGS: We studied whether SVZ stem and/or progenitor cells are motile in transgenic GFP+ slices with two photon time lapse microscopy and post hoc immunohistochemistry. We found that stem and progenitor cells; mGFAP-GFP+ cells, bright nestin-GFP+ cells and Mash1+ cells were stationary in the SVZ and rostral migratory stream (RMS. In our search for motile progenitor cells, we uncovered a population of motile betaIII-tubulin+ neuroblasts that expressed low levels of epidermal growth factor receptor (EGFr. This was intriguing since EGFr drives proliferation in the SVZ and affects migration in other systems. Thus we examined the potential role of EGFr in modulating SVZ migration. Interestingly, EGFr(low neuroblasts moved slower and in more tortuous patterns than EGFr-negative neuroblasts. We next questioned whether EGFr stimulation affects SVZ cell migration by imaging Gad65-GFP+ neuroblasts in the presence of transforming growth factor alpha (TGF-alpha, an EGFr-selective agonist. Indeed, acute exposure to TGF-alpha decreased the percentage of motile cells by approximately 40%. CONCLUSIONS/SIGNIFICANCE: In summary, the present study directly shows that SVZ stem and progenitor cells are static, that EGFr is retained on some neuroblasts, and that EGFr stimulation negatively regulates migration. This result suggests an additional role for EGFr signaling in the SVZ.

  18. How do I perform hematopoietic progenitor cell selection?

    Science.gov (United States)

    Avecilla, Scott T; Goss, Cheryl; Bleau, Sharon; Tonon, Jo-Ann; Meagher, Richard C

    2016-05-01

    Graft-versus-host disease remains the most important source of morbidity and mortality associated with allogeneic stem cell transplantation. The implementation of hematopoietic progenitor cell (HPC) selection is employed by some stem cell processing facilities to mitigate this complication. Current cell selection methods include reducing the number of unwanted T cells (negative selection) and/or enriching CD34+ hematopoietic stem/progenitors (positive selection) using immunomagnetic beads subjected to magnetic fields within columns to separate out targeted cells. Unwanted side effects of cell selection as a result of T-cell reduction are primary graft failure, increased infection rates, delayed immune reconstitution, possible disease relapse, and posttransplant lymphoproliferative disease. The Miltenyi CliniMACS cell isolation system is the only device currently approved for clinical use by the Food and Drug Administration. It uses magnetic microbeads conjugated with a high-affinity anti-CD34 monoclonal antibody capable of binding to HPCs in marrow, peripheral blood, or umbilical cord blood products. The system results in significantly improved CD34+ cell recoveries (50%-100%) and consistent 3-log CD3+ T-cell reductions compared to previous generations of CD34+ cell selection procedures. In this article, the CliniMACS procedure is described in greater detail and the authors provide useful insight into modifications of the system. Successful implementation of cell selection procedures can have a significant positive clinical effect by greatly increasing the pool of donors for recipients requiring transplants. However, before a program implements cell selection techniques, it is important to consider the time and financial resources required to properly and safely perform these procedures. PMID:26919388

  19. Bone Marrow Stress Decreases Osteogenic Progenitors.

    Science.gov (United States)

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

    2015-11-01

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

  20. Enhancing endothelial progenitor cell for clinical use

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Circulating endothelial progenitor cells (EPCs) havebeen demonstrated to correlate negatively with vascularendothelial dysfunction and cardiovascular risk factors.However, translation of basic research into the clinicalpractice has been limited by the lack of unambiguousand consistent definitions of EPCs and reduced EPCcell number and function in subjects requiring them forclinical use. This article critically reviews the definitionof EPCs based on commonly used protocols, their valueas a biomarker of cardiovascular risk factor in subjectswith cardiovascular disease, and strategies to enhanceEPCs for treatment of ischemic diseases.

  1. The effect of Heparin-VEGF multilayer on the biocompatibility of decellularized aortic valve with platelet and endothelial progenitor cells.

    Directory of Open Access Journals (Sweden)

    Xiaofeng Ye

    Full Text Available The application of polyelectrolyte multilayer films is a new, versatile approach to surface modification of decellularized tissue, which has the potential to greatly enhance the functionality of engineered tissue constructs derived from decellularized organs. In the present study, we test the hypothesis that Heparin- vascular endothelial growth factor (VEGF multilayer film can not only act as an antithrombotic coating reagent, but also induce proliferation of endothelial progenitor cells (EPCs on the decellularized aortic heart valve. SEM demonstrated the adhesion and geometric deformation of platelets. The quantitative assay of platelet activation was determined by measuring the production of soluble P-selectin. Binding and subsequent release of heparin and VEGF from valve leaflets were assessed qualitatively by laser confocal scanning microscopy and quantitatively by ELISA methods. Human blood derived EPCs were cultured and the adhesion and growth of EPCs on the surface modified valvular scaffolds were assessed. The results showed that Heparin-VEGF multilayer film improved decellularized valve haemocompatibility with respect to a substantial reduction of platelet adhesion. Release of VEGF from the decellularized heart valve leaflets at physiological conditions was sustained over 5 days. In vitro biological tests demonstrated that EPCs achieved better adhesion, proliferation and migration on the coatings with Heparin-VEGF multilayer film. Combined, these results indicate that Heparin-VEGF multilayer film could be used to cover the decellularized porcine aortic valve to decrease platelet adhesion while exhibiting excellent EPCs biocompatibility.

  2. Inhibition of Progenitor Dendritic Cell Maturation by Plasma from Patients with Peripartum Cardiomyopathy: Role in Pregnancy-associated Heart Disease

    Directory of Open Access Journals (Sweden)

    Jane E. Ellis

    2005-01-01

    Full Text Available Dendritic cells (DCs play dual roles in innate and adaptive immunity based on their functional maturity, and both innate and adaptive immune responses have been implicated in myocardial tissue remodeling associated with cardiomyopathies. Peripartum cardiomyopathy (PPCM is a rare disorder which affects women within one month antepartum to five months postpartum. A high occurrence of PPCM in central Haiti (1 in 300 live births provided the unique opportunity to study the relationship of immune activation and DC maturation to the etiology of this disorder. Plasma samples from two groups (n = 12 of age- and parity-matched Haitian women with or without evidence of PPCM were tested for levels of biomarkers of cardiac tissue remodeling and immune activation. Significantly elevated levels of GM-CSF, endothelin-1, proBNP and CRP and decreased levels of TGF- were measured in PPCM subjects relative to controls. Yet despite these findings, in vitro maturation of normal human cord blood derived progenitor dendritic cells (CBDCs was significantly reduced (p < 0.001 in the presence of plasma from PPCM patients relative to plasma from post-partum control subjects as determined by expression of CD80, CD86, CD83, CCR7, MHC class II and the ability of these matured CBDCs to induce allo-responses in PBMCs. These results represent the first findings linking inhibition of DC maturation to the dysregulation of normal physiologic cardiac tissue remodeling during pregnancy and the pathogenesis of PPCM.

  3. Alcohol Increases Liver Progenitor Populations and Induces Disease Phenotypes in Human IPSC-Derived Mature Stage Hepatic Cells.

    Science.gov (United States)

    Tian, Lipeng; Deshmukh, Abhijeet; Prasad, Neha; Jang, Yoon-Young

    2016-01-01

    Alcohol consumption has long been a global problem affecting human health, and has been found to influence both fetal and adult liver functions. However, how alcohol affects human liver development and liver progenitor cells remains largely unknown. Here, we used human induced pluripotent stem cells (iPSCs) as a model to examine the effects of alcohol, on multi-stage hepatic cells including hepatic progenitors, early and mature hepatocyte-like cells derived from human iPSCs. While alcohol has little effect on endoderm development from iPSCs, it reduces formation of hepatic progenitor cells during early hepatic specification. The proliferative activities of early and mature hepatocyte-like cells are significantly decreased after alcohol exposure. Importantly, at a mature stage of hepatocyte-like cells, alcohol treatment increases two liver progenitor subsets, causes oxidative mitochondrial injury and results in liver disease phenotypes (i.e., steatosis and hepatocellular carcinoma associated markers) in a dose dependent manner. Some of the phenotypes were significantly improved by antioxidant treatment. This report suggests that fetal alcohol exposure may impair generation of hepatic progenitors at early stage of hepatic specification and decrease proliferation of fetal hepatocytes; meanwhile alcohol injury in post-natal or mature stage human liver may contribute to disease phenotypes. This human iPSC model of alcohol-induced liver injury can be highly valuable for investigating alcoholic injury in the fetus as well as understanding the pathogenesis and ultimately developing effective treatment for alcoholic liver disease in adults. PMID:27570479

  4. Galactic Constraints on Supernova Progenitor Models

    CERN Document Server

    Acharova, I; Mishurov, Yu; Kovtyukh, V

    2013-01-01

    We undertake a statistical analysis of the radial abundance distributions in the Galactic disk within a theoretical framework for Galactic chemical evolution which incorporates the influence of spiral arms. 1) The mean mass of oxygen ejected per core-collapse SNe (CC SNe) event (which are concentrated within spiral arms) is $\\sim$0.27 M$_{\\odot}$; 2) the mean mass of iron ejected by `tardy' Type Ia SNe (SNeIa; progenitors of whom are older/longer-lived stars with ages $\\simgt$100 Myr and up to several Gyr, which do not concentrate within spiral arms) is $\\sim$0.58 M$_{\\odot}$; 3) the upper mass of iron ejected by prompt SNeIa (SNe whose progenitors are younger/shorter-lived stars with ages $\\simlt$100 Myr, which are concentrated within spiral arms) is $\\leq$0.23 M$_{\\odot}$ per event; 4) the corresponding mean mass of iron produced by CC SNe is $\\leq$0.04 M$_{\\odot}$ per event; (v) short-lived SNe (core-collapse or prompt SNeIa) supply $\\sim$85% of the Galactic disk's iron. The inferred low mean mass of oxyge...

  5. Endothelial Progenitor Cells Enter the Aging Arena.

    Directory of Open Access Journals (Sweden)

    Kate eWilliamson

    2012-02-01

    Full Text Available Age is a significant risk factor for the development of vascular diseases, such as atherosclerosis. Although pharmacological treatments, including statins and anti-hypertensive drugs, have improved the prognosis for patients with cardiovascular disease, it remains a leading cause of mortality in those aged 65 years and over. Furthermore, given the increased life expectancy of the population in developed countries, there is a clear need for alternative treatment strategies. Consequently, the relationship between aging and progenitor cell-mediated repair is of great interest. Endothelial progenitor cells (EPCs play an integral role in the cellular repair mechanisms for endothelial regeneration and maintenance. However, EPCs are subject to age-associated changes that diminish their number in circulation and function, thereby enhancing vascular disease risk. A great deal of research is aimed at developing strategies to harness the regenerative capacity of these cells.In this review, we discuss the current understanding of the cells termed ‘EPCs’, examine the impact of age on EPC-mediated repair and identify therapeutic targets with potential for attenuating the age-related decline in vascular health via beneficial actions on EPCs.

  6. Progenitor cells in arteriosclerosis: good or bad guys?

    Science.gov (United States)

    Campagnolo, Paola; Wong, Mei Mei; Xu, Qingbo

    2011-08-15

    Accumulating evidence indicates that the mobilization and recruitment of circulating or tissue-resident progenitor cells that give rise to endothelial cells (ECs) and smooth muscle cells (SMCs) can participate in atherosclerosis, neointima hyperplasia after arterial injury, and transplant arteriosclerosis. It is believed that endothelial progenitor cells do exist and can repair and rejuvenate the arteries under physiologic conditions; however, they may also contribute to lesion formation by influencing plaque stability in advanced atherosclerotic plaque under specific pathologic conditions. At the same time, smooth muscle progenitors, despite their capacity to expedite lesion formation during restenosis, may serve to promote atherosclerotic plaque stabilization by producing extracellular matrix proteins. This profound evidence provides support to the hypothesis that both endothelial and smooth muscle progenitors may act as a double-edged sword in the pathogenesis of arteriosclerosis. Therefore, the understanding of the regulatory networks that control endothelial and smooth muscle progenitor differentiation is undoubtedly fundamental both for basic research and for improving current therapeutic avenues for atherosclerosis. We update the progress in progenitor cell study related to the development of arteriosclerosis, focusing specifically on the role of progenitor cells in lesion formation and discuss the controversial issues that regard the origins, frequency, and impact of the progenitors in the disease.

  7. EGFR signaling regulates the proliferation of Drosophila adult midgut progenitors

    OpenAIRE

    Jiang, Huaqi; Edgar, Bruce A.

    2009-01-01

    In holometabolous insects, the adult appendages and internal organs form anew from larval progenitor cells during metamorphosis. As described here, the adult Drosophila midgut, including intestinal stem cells (ISCs), develops from adult midgut progenitor cells (AMPs) that proliferate during larval development in two phases. Dividing AMPs first disperse, but later proliferate within distinct islands, forming large cell clusters that eventually fuse during metamorphosis ...

  8. T Lymphocyte Potential Marks the Emergence of Definitive Hematopoietic Progenitors in Human Pluripotent Stem Cell Differentiation Cultures

    Directory of Open Access Journals (Sweden)

    Marion Kennedy

    2012-12-01

    Full Text Available The efficient generation of hematopoietic stem cells from human pluripotent stem cells is dependent on the appropriate specification of the definitive hematopoietic program during differentiation. In this study, we used T lymphocyte potential to track the onset of definitive hematopoiesis from human embryonic and induced pluripotent stem cells differentiated with specific morphogens in serum- and stromal-free cultures. We show that this program develops from a progenitor population with characteristics of hemogenic endothelium, including the expression of CD34, VE-cadherin, GATA2, LMO2, and RUNX1. Along with T cells, these progenitors display the capacity to generate myeloid and erythroid cells. Manipulation of Activin/Nodal signaling during early stages of differentiation revealed that development of the definitive hematopoietic progenitor population is not dependent on this pathway, distinguishing it from primitive hematopoiesis. Collectively, these findings demonstrate that it is possible to generate T lymphoid progenitors from pluripotent stem cells and that this lineage develops from a population whose emergence marks the onset of human definitive hematopoiesis.

  9. Constraints for the Progenitor Masses of 17 Historic Core-Collapse Supernovae

    CERN Document Server

    Williams, Benjamin F; Murphy, Jeremiah; Gilbert, Karoline; Dalcanton, Julianne J; Dolphin, Andrew E; Jennings, Zachary G

    2015-01-01

    Using resolved stellar photometry measured from archival HST imaging, we generate color-magnitude diagrams of the stars within 50 pc of the locations of historic core-collapse supernovae that took place in galaxies within 8 Mpc. We fit these color-magnitude distributions with stellar evolution models to determine the best-fit age distribution of the young population. We then translate these age distributions into probability distributions for the progenitor mass of each SNe. The measurements are anchored by the main-sequence stars surrounding the event, making them less sensitive to assumptions about binarity, post-main-sequence evolution, or circumstellar dust. We demonstrate that, in cases where the literature contains masses that have been measured from direct imaging, our measurements are consistent with (but less precise than) these measurements. Using this technique, we constrain the progenitor masses of 17 historic SNe, 11 of which have no previous estimates from direct imaging. Our measurements still ...

  10. Computational Image Analysis Reveals Intrinsic Multigenerational Differences between Anterior and Posterior Cerebral Cortex Neural Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Mark R. Winter

    2015-10-01

    Full Text Available Time-lapse microscopy can capture patterns of development through multiple divisions for an entire clone of proliferating cells. Images are taken every few minutes over many days, generating data too vast to process completely by hand. Computational analysis of this data can benefit from occasional human guidance. Here we combine improved automated algorithms with minimized human validation to produce fully corrected segmentation, tracking, and lineaging results with dramatic reduction in effort. A web-based viewer provides access to data and results. The improved approach allows efficient analysis of large numbers of clones. Using this method, we studied populations of progenitor cells derived from the anterior and posterior embryonic mouse cerebral cortex, each growing in a standardized culture environment. Progenitors from the anterior cortex were smaller, less motile, and produced smaller clones compared to those from the posterior cortex, demonstrating cell-intrinsic differences that may contribute to the areal organization of the cerebral cortex.

  11. Low Density Lipoprotein Receptor Related Proteins as Regulators of Neural Stem and Progenitor Cell Function

    Directory of Open Access Journals (Sweden)

    Loic Auderset

    2016-01-01

    Full Text Available The central nervous system (CNS is a highly organised structure. Many signalling systems work in concert to ensure that neural stem cells are appropriately directed to generate progenitor cells, which in turn mature into functional cell types including projection neurons, interneurons, astrocytes, and oligodendrocytes. Herein we explore the role of the low density lipoprotein (LDL receptor family, in particular family members LRP1 and LRP2, in regulating the behaviour of neural stem and progenitor cells during development and adulthood. The ability of LRP1 and LRP2 to bind a diverse and extensive range of ligands, regulate ligand endocytosis, recruit nonreceptor tyrosine kinases for direct signal transduction and signal in conjunction with other receptors, enables them to modulate many crucial neural cell functions.

  12. FGF-dependent midline-derived progenitor cells in hypothalamic infundibular development.

    Science.gov (United States)

    Pearson, Caroline Alayne; Ohyama, Kyoji; Manning, Liz; Aghamohammadzadeh, Soheil; Sang, Helen; Placzek, Marysia

    2011-06-01

    The infundibulum links the nervous and endocrine systems, serving as a crucial integrating centre for body homeostasis. Here we describe that the chick infundibulum derives from two subsets of anterior ventral midline cells. One set remains at the ventral midline and forms the posterior-ventral infundibulum. A second set migrates laterally, forming a collar around the midline. We show that collar cells are composed of Fgf3(+) SOX3(+) proliferating progenitors, the induction of which is SHH dependent, but the maintenance of which requires FGF signalling. Collar cells proliferate late into embryogenesis, can generate neurospheres that passage extensively, and differentiate to distinct fates, including hypothalamic neuronal fates and Fgf10(+) anterior-dorsal infundibular cells. Together, our study shows that a subset of anterior floor plate-like cells gives rise to Fgf3(+) SOX3(+) progenitor cells, demonstrates a dual origin of infundibular cells and reveals a crucial role for FGF signalling in governing extended infundibular growth. PMID:21610037

  13. Environmental cues from CNS, PNS, and ENS cells regulate CNS progenitor differentiation

    DEFF Research Database (Denmark)

    Brännvall, Karin; Corell, Mikael; Forsberg-Nilsson, Karin;

    2008-01-01

    Cellular origin and environmental cues regulate stem cell fate determination. Neuroepithelial stem cells form the central nervous system (CNS), whereas neural crest stem cells generate the peripheral (PNS) and enteric nervous system (ENS). CNS neural stem/progenitor cell (NSPC) fate determination...... was investigated in combination with dissociated cultures or conditioned media from CNS, PNS, or ENS. Cells or media from ENS or PNS cultures efficiently promoted NSPC differentiation into neurons, glia, and smooth muscle cells with a similar morphology as the feeder culture. Together with CNS cells or its...... conditioned medium, NSPC differentiation was partly inhibited and cells remained immature. Here, we demonstrate that secreted factors from the environment can influence CNS progenitor cells to choose a PNS-like cell fate....

  14. Effect of human neural progenitor cells on injured spinal cord

    Institute of Scientific and Technical Information of China (English)

    XU Guang-hui; BAI Jin-zhu; CAI Qin-lin; LI Xiao-xia; LI Ling-song; SHEN Li

    2005-01-01

    Objective: To study whether human neural progenitor cells can differentiate into neural cells in vivo and improve the recovery of injured spinal cord in rats.Methods: Human neural progenitor cells were transplanted into the injured spinal cord and the functional recovery of the rats with spinal cord contusion injury was evaluated with Basso-Beattie-Bresnahan (BBB) locomotor scale and motor evoked potentials. Additionally, the differentiation of human neural progenitor cells was shown by immunocytochemistry.Results: Human neural progenitor cells developed into functional cells in the injured spinal cord and improved the recovery of injured spinal cord in both locomotor scores and electrophysiological parameters in rats.Conclusions: Human neural progenitor cells can treat injured spinal cord, which may provide a new cell source for research of clinical application.

  15. Excessive Wnt/beta-catenin signaling promotes midbrain floor plate neurogenesis, but results in vacillating dopamine progenitors.

    Science.gov (United States)

    Nouri, Navid; Patel, Meera J; Joksimovic, Milan; Poulin, Jean-Francois; Anderegg, Angela; Taketo, M Mark; Ma, Yong-Chao; Awatramani, Rajeshwar

    2015-09-01

    The floor plate (FP), a ventral midline structure of the developing neural tube, has differential neurogenic capabilities along the anterior-posterior axis. The midbrain FP, unlike the hindbrain and spinal cord floor plate, is highly neurogenic and produces midbrain dopaminergic (mDA) neurons. Canonical Wnt/beta-catenin signaling, at least in part, is thought to account for the difference in neurogenic capability. Removal of beta-catenin results in mDA progenitor specification defects as well as a profound reduction of neurogenesis. To examine the effects of excessive Wnt/beta-catenin signaling on mDA specification and neurogenesis, we have analyzed a model wherein beta-catenin is conditionally stabilized in the Shh+domain. Here, we show that the Foxa2+/Lmx1a+ domain is extended rostrally in mutant embryos, suggesting that canonical Wnt/beta-catenin signaling can drive FP expansion along the rostrocaudal axis. Although excess canonical Wnt/beta-catenin signaling generally promotes neurogenesis at midbrain levels, less tyrosine hydroxylase (Th)+, mDA neurons are generated, particularly impacting the Substantia Nigra pars compacta. This is likely because of improper progenitor specification. Excess canonical Wnt/beta-catenin signaling causes downregulation of net Lmx1b, Shh and Foxa2 levels in mDA progenitors. Moreover, these progenitors assume a mixed identity to that of Lmx1a+/Lmx1b+/Nkx6-1+/Neurog1+ progenitors. We also show by lineage tracing analysis that normally, Neurog1+ progenitors predominantly give rise to Pou4f1+ neurons, but not Th+ neurons. Accordingly, in the mutant embryos, Neurog1+ progenitors at the midline generate ectopic Pou4f1+ neurons at the expense of Th+ mDA neurons. Our study suggests that an optimal dose of Wnt/beta-catenin signaling is critical for proper establishment of the mDA progenitor character. Our findings will impact embryonic stem cell protocols that utilize Wnt pathway reagents to derive mDA neuron models and therapeutics for

  16. Progenitor model of cosmic ray knee

    Science.gov (United States)

    Bijay, Biplab; Bhadra, Arunava

    2016-01-01

    The primary energy spectrum of cosmic rays exhibits a knee at about 3 PeV where a change in the spectral index occurs. Despite many efforts, the origin of such a feature in the spectrum is not satisfactorily solved yet. Here it is proposed that the steepening of the spectrum beyond the knee may be a consequence of the mass distribution of the progenitor of the cosmic ray source. The proposed speculative model can account for all the major observed features of cosmic rays without invoking any fine tuning to match flux or spectra at any energy point. The prediction of the proposed model regarding the primary composition scenario beyond the knee is quite different from most of the prevailing models of the knee, and thereby can be discriminated from precise experimental measurement of the primary composition.

  17. PET imaging of adoptive progenitor cell therapies.

    Energy Technology Data Exchange (ETDEWEB)

    Gelovani, Juri G.

    2008-05-13

    Objectives. The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive “tracking” of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to

  18. PET imaging of adoptive progenitor cell therapies

    International Nuclear Information System (INIS)

    The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive 'tracking' of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to stem cell imaging

  19. Human umbilical cord-derived endothelial progenitor cells promote growth cytokines-mediated neorevascularization in rat myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    HU Cheng-heng; LI Zhi-ming; DU Zhi-min; ZHANG Ai-xia; YANG Da-ya; WU Gui-fu

    2009-01-01

    Background Cell-based vascular therapies of endothelial progenitor cells (EPCs) mediated neovascularization is still a novel but promising approach for the treatment of ischemic disease. The present study was designed to investigate the therapeutic potentials of human umbilical cord blood-derived EPCs (hUCB-EPCs) in rat with acute myocardial infarction.Methods Human umbilical cord blood (hUCB) mononuclear cells were isolated using density gradient centrifugation from the fresh human umbilical cord in healthy delivery woman, and cultured in M199 medium for 7 days. The EPCs were identified by double-positive staining with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine percholorate-labeled acetylated low-density lipoprotein (Dil-Ac-LDL) and fluorescein isothiocyanate-conjugated Ulex europaeus lectin (FITC-UEA-I). The rat acute myocardial infarction model was established by the ligation of the left anterior descending artery. The hUCB-EPCs were intramyocardially injected into the peri-infarct area. Four weeks later, left ventricular function was assessed by a pressure-volume catheter. The average capillary density (CAD) was evaluated by anti-VⅢ immunohistochemistry staining to reflect the development of neovascularization at the peri-infarct area. The graft cells were identified by double immunofluorescence staining with human nuclear antigen (HNA) and CD31 antibody,representing human origin of EPCs and vascular endothelium, respectively. Expressions of cytokines, proliferating cell nuclear angigen (PCNA), platelet endothelial cell adhesion molecule (PECAM) and vascular endothelial growth factor (VEGF) were detected to investigate the underlying mechanisms of cell differentiation and revascularization.Results The donor EPCs were detectable and integrated into the host myocardium as confirmed by double-positive immunofluorescence staining with HNA and CD31. And the anti-VⅢ staining demonstrated a higher degree of microvessel formation in EPCs transplanted

  20. A subset of chondrogenic cells provides early mesenchymal progenitors in growing bones.

    Science.gov (United States)

    Ono, Noriaki; Ono, Wanida; Nagasawa, Takashi; Kronenberg, Henry M

    2014-12-01

    The hallmark of endochondral bone development is the presence of cartilaginous templates, in which osteoblasts and stromal cells are generated to form mineralized matrix and support bone marrow haematopoiesis. However, the ultimate source of these mesenchymal cells and the relationship between bone progenitors in fetal life and those in later life are unknown. Fate-mapping studies revealed that cells expressing cre-recombinases driven by the collagen II (Col2) promoter/enhancer and their descendants contributed to, in addition to chondrocytes, early perichondrial precursors before Runx2 expression and, subsequently, to a majority of osteoblasts, Cxcl12 (chemokine (C-X-C motif) ligand 12)-abundant stromal cells and bone marrow stromal/mesenchymal progenitor cells in postnatal life. Lineage-tracing experiments using a tamoxifen-inducible creER system further revealed that early postnatal cells marked by Col2-creER, as well as Sox9-creER and aggrecan (Acan)-creER, progressively contributed to multiple mesenchymal lineages and continued to provide descendants for over a year. These cells are distinct from adult mesenchymal progenitors and thus provide opportunities for regulating the explosive growth that occurs uniquely in growing mammals. PMID:25419849

  1. Apoptotic neurons induce proliferative responses of progenitor cells in the postnatal neocortex.

    Science.gov (United States)

    Petrenko, Volodymyr; Mihhailova, Jevgenia; Salmon, Patrick; Kiss, Jozsef Z

    2015-11-01

    Apoptotic cell death is the leading cause of neuronal loss after neonatal brain injury. Little is known about the intrinsic capacity of the immature cerebral cortex for replacing dead cells. Here we test the hypothesis that neuronal apoptosis is able to trigger compensatory proliferation in surrounding cells. In order to establish a "pure" apoptotic cell death model and to avoid the confounding effects of broken blood-brain barrier and inflammatory reactions, we used a diphtheria toxin (DT) and diphtheria toxin receptor (DTR) system to induce ablation of layer IV neurons in the rodent somatosensory cortex during the early postnatal period. We found that DT-triggered apoptosis is a slowly progressing event lasting about for 7 days. While dying cells expressed the morphological features of apoptosis, we could not detect immunoreactivity for activated caspase-3 in these cells. Microglia activation and proliferation represented the earliest cellular responses to apoptotic cell death. In addition, we found that induced apoptosis triggered a massive proliferation of undifferentiated progenitor cell pool including Sox2 as well as NG2 cells. The default differentiation pattern of proliferating progenitors appears to be the glial phenotype; we could not find evidence for newly generated neurons in response to apoptotic neuronal death. These results suggest that mitotically active progenitor populations are intrinsically capable to contribute to the repair process of injured cortical tissue and may represent a potential target for neuronal replacement strategies.

  2. Human-derived neural progenitors functionally replace astrocytes in adult mice

    Science.gov (United States)

    Chen, Hong; Qian, Kun; Chen, Wei; Hu, Baoyang; Blackbourn, Lisle W.; Du, Zhongwei; Ma, Lixiang; Liu, Huisheng; Knobel, Karla M.; Ayala, Melvin; Zhang, Su-Chun

    2015-01-01

    Astrocytes are integral components of the homeostatic neural network as well as active participants in pathogenesis of and recovery from nearly all neurological conditions. Evolutionarily, compared with lower vertebrates and nonhuman primates, humans have an increased astrocyte-to-neuron ratio; however, a lack of effective models has hindered the study of the complex roles of human astrocytes in intact adult animals. Here, we demonstrated that after transplantation into the cervical spinal cords of adult mice with severe combined immunodeficiency (SCID), human pluripotent stem cell–derived (PSC-derived) neural progenitors migrate a long distance and differentiate to astrocytes that nearly replace their mouse counterparts over a 9-month period. The human PSC-derived astrocytes formed networks through their processes, encircled endogenous neurons, and extended end feet that wrapped around blood vessels without altering locomotion behaviors, suggesting structural, and potentially functional, integration into the adult mouse spinal cord. Furthermore, in SCID mice transplanted with neural progenitors derived from induced PSCs from patients with ALS, astrocytes were generated and distributed to a similar degree as that seen in mice transplanted with healthy progenitors; however, these mice exhibited motor deficit, highlighting functional integration of the human-derived astrocytes. Together, these results indicate that this chimeric animal model has potential for further investigating the roles of human astrocytes in disease pathogenesis and repair. PMID:25642771

  3. Otospheres derived from neonatal mouse cochleae retain the progenitor cell phenotype after ex vivo expansions.

    Science.gov (United States)

    Lou, Xiang-Xin; Nakagawa, Takayuki; Ohnishi, Hiroe; Nishimura, Koji; Ito, Juichi

    2013-02-01

    Because of their limited regenerative potential, cochlear hair cell loss is one of the major causes of permanent hearing loss in mammals. However, recent studies have shown that postnatal cochlear epithelia retain the progenitor cells that form otospheres. Otospheres are capable of self-renewing and differentiating into inner ear cell lineages, thereby suggesting a promising source for hair cell regeneration. We investigated retention of the progenitor cell phenotype in otospheres after ex vivo expansion, which is crucial for transplantation approaches. Reverse transcriptase-polymerase chain reaction and immunocytochemical analyses showed that otospheres derived from neonatal mice retained expression of stem and cochlear cell markers. After in vitro differentiation, otosphere-consisting cells differentiated into hair cell phenotypes after ex vivo expansion. However, the capacity of otospheres for self-renewal weakened with subsequent generations of ex vivo expansion. Our results indicate that ex vivo expanded-otospheres are useful experimental tools for studying hair cell regeneration in transplantation approaches and that the mechanisms for retention of the progenitor cell phenotype in otospheres should be investigated. PMID:23238450

  4. An insulin signaling feedback loop regulates pancreas progenitor cell differentiation during islet development and regeneration.

    Science.gov (United States)

    Ye, Lihua; Robertson, Morgan A; Mastracci, Teresa L; Anderson, Ryan M

    2016-01-15

    As one of the key nutrient sensors, insulin signaling plays an important role in integrating environmental energy cues with organism growth. In adult organisms, relative insufficiency of insulin signaling induces compensatory expansion of insulin-secreting pancreatic beta (β) cells. However, little is known about how insulin signaling feedback might influence neogenesis of β cells during embryonic development. Using genetic approaches and a unique cell transplantation system in developing zebrafish, we have uncovered a novel role for insulin signaling in the negative regulation of pancreatic progenitor cell differentiation. Blocking insulin signaling in the pancreatic progenitors hastened the expression of the essential β cell genes insulin and pdx1, and promoted β cell fate at the expense of alpha cell fate. In addition, loss of insulin signaling promoted β cell regeneration and destabilization of alpha cell character. These data indicate that insulin signaling constitutes a tunable mechanism for β cell compensatory plasticity during early development. Moreover, using a novel blastomere-to-larva transplantation strategy, we found that loss of insulin signaling in endoderm-committed blastomeres drove their differentiation into β cells. Furthermore, the extent of this differentiation was dependent on the function of the β cell mass in the host. Altogether, our results indicate that modulation of insulin signaling will be crucial for the development of β cell restoration therapies for diabetics; further clarification of the mechanisms of insulin signaling in β cell progenitors will reveal therapeutic targets for both in vivo and in vitro β cell generation. PMID:26658317

  5. Lgr5+ve Stem/Progenitor Cells Contribute to Nephron Formation during Kidney Development

    Directory of Open Access Journals (Sweden)

    Nick Barker

    2012-09-01

    Full Text Available Multipotent stem cells and their lineage-restricted progeny drive nephron formation within the developing kidney. Here, we document expression of the adult stem cell marker Lgr5 in the developing kidney and assess the stem/progenitor identity of Lgr5+ve cells via in vivo lineage tracing. The appearance and localization of Lgr5+ve cells coincided with that of the S-shaped body around embryonic day 14. Lgr5 expression remained restricted to cell clusters within developing nephrons in the cortex until postnatal day 7, when expression was permanently silenced. In vivo lineage tracing identified Lgr5 as a marker of a stem/progenitor population within nascent nephrons dedicated to generating the thick ascending limb of Henle’s loop and distal convoluted tubule. The Lgr5 surface marker and experimental models described here will be invaluable for deciphering the contribution of early nephron stem cells to developmental defects and for isolating human nephron progenitors as a prerequisite to evaluating their therapeutic potential.

  6. Coordination of heart and lung co-development by a multipotent cardiopulmonary progenitor.

    Science.gov (United States)

    Peng, Tien; Tian, Ying; Boogerd, Cornelis J; Lu, Min Min; Kadzik, Rachel S; Stewart, Kathleen M; Evans, Sylvia M; Morrisey, Edward E

    2013-08-29

    Co-development of the cardiovascular and pulmonary systems is a recent evolutionary adaption to terrestrial life that couples cardiac output with the gas exchange function of the lung. Here we show that the murine pulmonary vasculature develops even in the absence of lung development. We have identified a population of multipotent cardiopulmonary mesoderm progenitors (CPPs) within the posterior pole of the heart that are marked by the expression of Wnt2, Gli1 and Isl1. We show that CPPs arise from cardiac progenitors before lung development. Lineage tracing and clonal analysis demonstrates that CPPs generate the mesoderm lineages within the cardiac inflow tract and lung including cardiomyocytes, pulmonary vascular and airway smooth muscle, proximal vascular endothelium, and pericyte-like cells. CPPs are regulated by hedgehog expression from the foregut endoderm, which is required for connection of the pulmonary vasculature to the heart. Together, these studies identify a novel population of multipotent cardiopulmonary progenitors that coordinates heart and lung co-development that is required for adaptation to terrestrial existence.

  7. Substrate stiffness and matrix composition coordinately control the differentiation of liver progenitor cells.

    Science.gov (United States)

    Kourouklis, Andreas P; Kaylan, Kerim B; Underhill, Gregory H

    2016-08-01

    Recent approaches have utilized microfabricated platforms to examine combinations of microenvironmental signals that regulate stem and progenitor cell differentiation. However, the majority of these efforts have focused on the biochemical properties of extracellular matrix (ECM) or soluble factors without simultaneously exploring the biomechanical effects of cell-substrate interactions. To address this need, we combined a high-throughput approach for the analysis of combinatorial ECM cues with substrates of modular stiffness and traction force microscopy. This integrated approach enabled the characterization of cell-generated traction stress and phenotypic expression in response to ECM cues. We investigated the impact of substrate stiffness and ECM composition on the differentiation of bipotential mouse embryonic liver (BMEL) progenitor cells. We observed that hepatocyte differentiation was primarily regulated by ECM composition, and cholangiocyte differentiation was cooperatively influenced by ECM proteins and stiffness properties. In particular, stiffness-mediated cholangiocyte differentiation was observed for cells cultured on fibronectin, while collagen IV promoted differentiation independent of substrate stiffness. We demonstrated the influence of cell contractility and traction stress in early cholangiocyte specification and further uncovered the roles of ERK and ROCK in this differentiation process. Overall, these findings illustrate the involvement of biomechanical signals in liver progenitor differentiation. Further, this approach could enable investigations for a broad range of cell types and ECM proteins, providing an integrated platform for evaluating the combinatorial effects of biochemical and biophysical signals in cell differentiation.

  8. Common-Lymphoid-Progenitor-Independent Pathways of Innate and T Lymphocyte Development

    Directory of Open Access Journals (Sweden)

    Maryam Ghaedi

    2016-04-01

    Full Text Available All lymphocytes are thought to develop from common lymphoid progenitors (CLPs. However, lymphoid-primed multipotent progenitors (LMPPs are more efficient than CLPs in differentiating into T cells and group 2 innate lymphoid cells (ILC2s. Here, we have divided LMPPs into CD127− (LMPP−s and CD127+ (LMPP+s subsets and compared them with Ly6D− and Ly6D+ CLPs. Adult LMPP+s differentiated into T cells and ILCs more rapidly and efficiently than other progenitors in transplantation assays. The development of T cells and ILC2s is highly active in the neonatal period. Neonatal CLPs are rare and, unlike prominent neonatal LMPP+s, do not efficiently differentiate into T cells and ILC2s. ILC2s generated in the neonatal period are long lived and persist in adult tissues. These results suggest that some ILCs and T cells may develop from LMPP+s via CLP-independent pathways.

  9. Matter Mixing in Core-collapse Supernova Ejecta: Large Density Perturbations in the Progenitor Star?

    CERN Document Server

    Mao, J; Nagataki, S; Hashimoto, M; Ito, H; Matsumoto, J; Dainotti, M G; Lee, S -H

    2015-01-01

    Matter mixing is one important topic in the study of core-collapse supernova (CCSN) explosions. In this paper, we perform two-dimensional hydrodynamic simulations to reproduce the high velocity $^{56}$Ni clumps observed in SN 1987A. This is the first time that large density perturbation is proposed in the CCSN progenitor to generate Rayleigh-Taylor (RT) instability and make the effective matter mixing. In the case of a spherical explosion, RT instability is efficient at both C+O/He and He/H interfaces of the SN progenitor. Radial coherent structures shown in perturbation patterns are important for obtaining high velocity $^{56}$Ni clumps. We can also obtain matter mixing features and high velocity $^{56}$Ni clumps in some cases of aspherical explosion. We find that one of the most favorable models in our work has a combination of bipolar and equatorially asymmetric explosions in which at least 25\\% of density perturbation is introduced at different composition interfaces of the CCSN progenitor. These simulati...

  10. Multilineage Potential and Self-Renewal Define an Epithelial Progenitor Cell Population in the Adult Thymus

    Directory of Open Access Journals (Sweden)

    Kahlia Wong

    2014-08-01

    Full Text Available Thymic epithelial cells (TECs are critical for T cell development and self-tolerance but are gradually lost with age. The existence of thymic epithelial progenitors (TEPCs in the postnatal thymus has been inferred, but their identity has remained enigmatic. Here, we assessed the entire adult TEC compartment in order to reveal progenitor capacity is retained exclusively within a subset of immature thymic epithelium displaying several hallmark features of stem/progenitor function. These adult TEPCs generate mature cortical and medullary lineages in a stepwise fashion, including Aire+ TEC, within fetal thymus reaggregate grafts. Although relatively quiescent in vivo, adult TEPCs demonstrate significant in vitro colony formation and self-renewal. Importantly, 3D-cultured TEPCs retain their capacity to differentiate into cortical and medullary TEC lineages when returned to an in vivo thymic microenvironment. No other postnatal TEC subset exhibits this combination of properties. The characterization of adult TEPC will enable progress in understanding TEC biology in aging and regeneration.

  11. An insulin signaling feedback loop regulates pancreas progenitor cell differentiation during islet development and regeneration.

    Science.gov (United States)

    Ye, Lihua; Robertson, Morgan A; Mastracci, Teresa L; Anderson, Ryan M

    2016-01-15

    As one of the key nutrient sensors, insulin signaling plays an important role in integrating environmental energy cues with organism growth. In adult organisms, relative insufficiency of insulin signaling induces compensatory expansion of insulin-secreting pancreatic beta (β) cells. However, little is known about how insulin signaling feedback might influence neogenesis of β cells during embryonic development. Using genetic approaches and a unique cell transplantation system in developing zebrafish, we have uncovered a novel role for insulin signaling in the negative regulation of pancreatic progenitor cell differentiation. Blocking insulin signaling in the pancreatic progenitors hastened the expression of the essential β cell genes insulin and pdx1, and promoted β cell fate at the expense of alpha cell fate. In addition, loss of insulin signaling promoted β cell regeneration and destabilization of alpha cell character. These data indicate that insulin signaling constitutes a tunable mechanism for β cell compensatory plasticity during early development. Moreover, using a novel blastomere-to-larva transplantation strategy, we found that loss of insulin signaling in endoderm-committed blastomeres drove their differentiation into β cells. Furthermore, the extent of this differentiation was dependent on the function of the β cell mass in the host. Altogether, our results indicate that modulation of insulin signaling will be crucial for the development of β cell restoration therapies for diabetics; further clarification of the mechanisms of insulin signaling in β cell progenitors will reveal therapeutic targets for both in vivo and in vitro β cell generation.

  12. Blockade of prostaglandin E2 signaling through EP1 and EP3 receptors attenuates Flt3L-dependent dendritic cell development from hematopoietic progenitor cells

    Science.gov (United States)

    Singh, Pratibha; Hoggatt, Jonathan; Hu, Peirong; Speth, Jennifer M.; Fukuda, Seiji; Breyer, Richard M.

    2012-01-01

    Dendritic cell (DC) homeostasis, like all mature blood cells, is maintained via hierarchal generation from hematopoietic precursors; however, little is known about the regulatory mechanisms governing DC generation. Here, we show that prostaglandin E2 (PGE2) is required for optimal Flt3 ligand–mediated DC development and regulates expression of the Flt3 receptor on DC-committed progenitor cells. Inhibition of PGE2 biosynthesis reduces Flt3-mediated activation of STAT3 and expression of the antiapoptotic protein survivin, resulting in increased apoptosis of DC-committed progenitor cells. Reduced DC development caused by diminished PGE2 signaling is reversed by overexpression of Flt3 or survivin in DC progenitors and conversely is mimicked by STAT3 inhibition. PGE2 regulation of DC generation is specifically mediated through the EP1 and EP3 G protein PGE2 receptors. These studies define a novel DC progenitor regulatory pathway in which PGE2 signaling through EP1/EP3 receptors regulates Flt3 expression and downstream STAT3 activation and survivin expression, required for optimal DC progenitor survival and DC development in vivo. PMID:22110249

  13. A scalable system for production of functional pancreatic progenitors from human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Thomas C Schulz

    Full Text Available Development of a human embryonic stem cell (hESC-based therapy for type 1 diabetes will require the translation of proof-of-principle concepts into a scalable, controlled, and regulated cell manufacturing process. We have previously demonstrated that hESC can be directed to differentiate into pancreatic progenitors that mature into functional glucose-responsive, insulin-secreting cells in vivo. In this study we describe hESC expansion and banking methods and a suspension-based differentiation system, which together underpin an integrated scalable manufacturing process for producing pancreatic progenitors. This system has been optimized for the CyT49 cell line. Accordingly, qualified large-scale single-cell master and working cGMP cell banks of CyT49 have been generated to provide a virtually unlimited starting resource for manufacturing. Upon thaw from these banks, we expanded CyT49 for two weeks in an adherent culture format that achieves 50-100 fold expansion per week. Undifferentiated CyT49 were then aggregated into clusters in dynamic rotational suspension culture, followed by differentiation en masse for two weeks with a four-stage protocol. Numerous scaled differentiation runs generated reproducible and defined population compositions highly enriched for pancreatic cell lineages, as shown by examining mRNA expression at each stage of differentiation and flow cytometry of the final population. Islet-like tissue containing glucose-responsive, insulin-secreting cells was generated upon implantation into mice. By four- to five-months post-engraftment, mature neo-pancreatic tissue was sufficient to protect against streptozotocin (STZ-induced hyperglycemia. In summary, we have developed a tractable manufacturing process for the generation of functional pancreatic progenitors from hESC on a scale amenable to clinical entry.

  14. Severe insulin resistance alters metabolism in mesenchymal progenitor cells.

    Science.gov (United States)

    Balhara, Bharti; Burkart, Alison; Topcu, Vehap; Lee, Youn-Kyoung; Cowan, Chad; Kahn, C Ronald; Patti, Mary-Elizabeth

    2015-06-01

    Donohue syndrome (DS) is characterized by severe insulin resistance due to mutations in the insulin receptor (INSR) gene. To identify molecular defects contributing to metabolic dysregulation in DS in the undifferentiated state, we generated mesenchymal progenitor cells (MPCs) from induced pluripotent stem cells derived from a 4-week-old female with DS and a healthy newborn male (control). INSR mRNA and protein were significantly reduced in DS MPC (for β-subunit, 64% and 89% reduction, respectively, P consumption in both the basal state (87% higher, P =.09) and in response to the uncoupler carbonyl cyanide-p-triflouromethoxyphenylhydrazone (2-fold increase, P =.06). Although mitochondrial DNA or mass did not differ, oxidative phosphorylation protein complexes III and V were increased in DS (by 37% and 6%, respectively; P < .05). Extracellular acidification also tended to increase in DS (91% increase, P = .07), with parallel significant increases in lactate secretion (34% higher at 4 h, P < .05). In summary, DS MPC maintain signaling downstream of the INSR, suggesting that IGF-1R signaling may partly compensate for INSR mutations. However, alterations in receptor expression and pathway-specific defects in insulin signaling, even in undifferentiated cells, can alter cellular oxidative metabolism, potentially via transcriptional mechanisms. PMID:25811318

  15. Methods and Strategies for Lineage Tracing of Mesenchymal Progenitor Cells.

    Science.gov (United States)

    Scott, R Wilder; Underhill, T Michael

    2016-01-01

    Mesenchymal progenitors (MP) are found to varying extents in most tissues and organs. Their relationship to bone marrow-derived mesenchymal stem cells (MSCs) remains unclear, however, both populations appear to share a number of properties as defined by functional assays, clonogenic activity, and genetic and cell surface markers. MSCs were originally defined by their in vitro colony forming unit-fibroblast (CFU-F) activity and their ability to contribute to various mesenchymal lineages (i.e. cartilage, bone, and fat). MSCs also appear to exhibit some unique properties, in that expanded clones in the absence of bone-inducing factors generate bone spicules/organs in vivo. Subsequent analysis of these elements has demonstrated that the transplanted cells directly contribute to multiple mesenchymal lineages. Our ability to study MP and/or MSC behavior and lineage potential in vivo has been hampered by a lack of suitable Cre lines in which to effectively genetically mark and follow the fate and activity of these cells in development, growth, homeostasis and following injury or in disease. The emergence of several new genetic lines is enabling us to now address critical questions regarding MP/MSC location, behavior, function, and fate. The use of these lines and others in conjunction with suitable reporter lines will be described for MP/MSC cell fate analysis. PMID:27236672

  16. In Vitro Colony Assays for Characterizing Tri-potent Progenitor Cells Isolated from the Adult Murine Pancreas.

    Science.gov (United States)

    Tremblay, Jacob R; LeBon, Jeanne M; Luo, Angela; Quijano, Janine C; Wedeken, Lena; Jou, Kevin; Riggs, Arthur D; Tirrell, David A; Ku, H Teresa

    2016-01-01

    Stem and progenitor cells from the adult pancreas could be a potential source of therapeutic beta-like cells for treating patients with type 1 diabetes. However, it is still unknown whether stem and progenitor cells exist in the adult pancreas. Research strategies using cre-lox lineage-tracing in adult mice have yielded results that either support or refute the idea that beta cells can be generated from the ducts, the presumed location where adult pancreatic progenitors may reside. These in vivo cre-lox lineage-tracing methods, however, cannot answer the questions of self-renewal and multi-lineage differentiation-two criteria necessary to define a stem cell. To begin addressing this technical gap, we devised 3-dimensional colony assays for pancreatic progenitors. Soon after our initial publication, other laboratories independently developed a similar, but not identical, method called the organoid assay. Compared to the organoid assay, our method employs methylcellulose, which forms viscous solutions that allow the inclusion of extracellular matrix proteins at low concentrations. The methylcellulose-containing assays permit easier detection and analyses of progenitor cells at the single-cell level, which are critical when progenitors constitute a small sub-population, as is the case for many adult organ stem cells. Together, results from several laboratories demonstrate in vitro self-renewal and multi-lineage differentiation of pancreatic progenitor-like cells from mice. The current protocols describe two methylcellulose-based colony assays to characterize mouse pancreatic progenitors; one contains a commercial preparation of murine extracellular matrix proteins and the other an artificial extracellular matrix protein known as a laminin hydrogel. The techniques shown here are 1) dissociation of the pancreas and sorting of CD133(+)Sox9/EGFP(+) ductal cells from adult mice, 2) single cell manipulation of the sorted cells, 3) single colony analyses using microfluidic q

  17. On Measuring the Metallicity of Supernovae Type Ia Progenitors

    CERN Document Server

    Miles, Broxton J; Townsley, Dean M; Timmes, F X; Jackson, Aaron P; Calder, Alan C; Brown, Edward F

    2015-01-01

    In Type Ia Supernovae (\\sneia), the relative abundances of chemical elements are affected by the neutron excess in the composition of the progenitor white dwarf. Since these products leave signatures in the spectra near maximum light, spectral features may be used to constrain the composition of the progenitor. We calculate the nucleosynthetic yields for three \\snia simulations for a wide range of progenitor metallicities, and calculate synthetic light curves and spectra to explore correlations between progenitor metallicity and the strength of spectral features. We use two 2D simulations of the deflagration-detonation-transition scenario with different $^{56}$Ni yields and the W7 simulation to control for differences between explosion models and total yields. While the overall yields of intermediate mass elements (16 $<$ A $\\leq$ 40) differ between the three cases, trends in the yields are similar. With increasing metallicity, $^{28}$Si yields remain nearly constant, $^{40}$Ca yields decline, and Ti and $...

  18. Senegenin promotes in vitro proliferation of human neural progenitor cells

    Institute of Scientific and Technical Information of China (English)

    Fang Shi; Zhigang Liang; Zixuan Guo; Ran Li; Fen Yu; Zhanjun Zhang; Xuan Wang; Xiaomin Wang

    2011-01-01

    Senegenin, an effective component of Polygala tenuifolia root extract, promotes proliferation and differentiation of neural progenitor cells in the hippocampus.However, the effects of senegenin on mesencephalon-derived neural progenitor cells remain poorly understood.Cells from a ventral mesencephalon neural progenitor cell line (ReNcell VM) were utilized as models for pharmaceutical screening.The effects of various senegenin concentrations on cell proliferation were analyzed,demonstrating that high senegenin concentrations (5, 10, 50, and 100 pmo/L), particularly 50 pmol/L, significantly promoted proliferation of ReNcell VM cells.In the mitogen-activated protein kinase signal transduction pathway, senegenin significantly increased phosphorylation levels of extracellular signal-regulated kinases.Moreover, cell proliferation was suppressed by extracellular signal-regulated kinase inhibitors.Results suggested that senegenin contributed to in vitro proliferation of human neural progenitor cells by upregulating phosphorylation of extracellular signal-regulated kinase.

  19. Observational clues to the progenitors of Type-Ia supernovae

    CERN Document Server

    Maoz, Dan; Nelemans, Gijs

    2013-01-01

    Type-Ia supernovae (SNe Ia) are important distance indicators, element factories, cosmic-ray accelerators, kinetic-energy sources in galaxy evolution, and endpoints of stellar binary evolution. It has long been clear that a SN Ia must be the runaway thermonuclear explosion of a degenerate carbon-oxygen stellar core, most likely a white dwarf (WD). However, the specific progenitor systems of SNe Ia, and the processes that lead to their ignition, have not been identified. Two broad classes of progenitor binary systems have long been considered: single-degenerate (SD), in which a WD gains mass from a non-degenerate star; and double-degenerate (DD), involving the merger of two WDs. New theoretical work has enriched these possibilities with some interesting updates and variants. We review the significant recent observational progress in addressing the progenitor problem. We consider clues that have emerged from the observed properties of the various proposed progenitor populations, from studies of their sites, pre...

  20. Moderate traumatic brain injury promotes proliferation of quiescent neural progenitors in the adult hippocampus

    OpenAIRE

    Gao, Xiang; Enikolopov, Grigori; Chen, Jinhui

    2009-01-01

    Recent evidence shows that traumatic brain injury (TBI) regulates proliferation of neural stem/progenitor cells in the dentate gyrus (DG) of adult hippocampus. There are distinct classes of neural stem/progenitor cells in the adult DG, including quiescent neural progenitors (QNPs), which carry stem cell properties, and their progeny, amplifying neural progenitors (ANPs). The response of each class of progenitors to TBI is not clear. We here used a transgenic reporter Nestin-GFP mouse line, in...

  1. Endothelial progenitor cells with Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    KONG Xiao-dong; ZHANG Yun; LIU Li; SUN Ning; ZHANG Ming-yi; ZHANG Jian-ning

    2011-01-01

    Background Endothelial dysfunction is thought to be critical events in the pathogenesis of Alzheimer's disease (AD).Endothelial progenitor cells (EPCs) have provided insight into maintaining and repairing endothelial function. To study the relation between EPCs and AD, we explored the number of circulating EPCs in patients with AD.Methods A total of 104 patients were recruited from both the outpatients and inpatients of the geriatric neurology department at General Hospital, rianjin Medical University. Consecutive patients with newly diagnosed AD (n=30),patients with vascular dementia (VaD, n=34), and healthy elderly control subjects with normal cognition (n=40) were enrolled after matching for age, gender, body mass index, medical history, current medication and Mini Mental State Examination. Middle cerebral artery flow velocity was examined with transcranial Doppler. Endothelial function was evaluated according to the level of EPCs, and peripheral blood EPCs was counted by flow cytometry.Results There were no significant statistical differences of clinical data in AD, VaD and control groups (P >0.05). The patients with AD showed decreased CD34-positive (CD34+) or CD133-positive (CD133+) levels compared to the control subjects, but there were no significant statistical differences in patients with AD. The patients with AD had significantly lower CD34+CD133+ EPCs(CD34 and CD133 double positive endothelial progenitor cells) than the control subjects (P <0.05). In the patients with AD, a lower CD34+CD133+ EPCs count was independently associated with a lower Mini-Mental State Examination score (r=0.514, P=0.004). Patients with VaD also showed a significant decrease in CD34+CD133+ EPCs levels, but this was not evidently associated with the Mini-Mental State Examination score. The changes of middle cerebral artery flow velocity were similar between AD and VaD. Middle cerebral artery flow velocity was decreased in the AD and VaD groups and significantly lower than

  2. Endothelial progenitors in sepsis: vox clamantis in deserto?

    OpenAIRE

    Goligorsky, Michael S

    2011-01-01

    In this issue of Critical Care, Patschan and colleagues present a study of endothelial progenitor cells (EPCs) in patients with sepsis. The importance of this study is in focusing attention on several frequently ignored aspects of sepsis. Among those are the phenomenon of microvascular dysfunction, which is potentially responsible for profound metabolic perturbations at the tissue level, and the role of endothelial progenitors in repair processes. Other important aspects of the study are the ...

  3. Endometrial stem/progenitor cells: the first 10 years

    OpenAIRE

    Gargett, Caroline E; Schwab, Kjiana E.; Deane, James A

    2015-01-01

    BACKGROUND The existence of stem/progenitor cells in the endometrium was postulated many years ago, but the first functional evidence was only published in 2004. The identification of rare epithelial and stromal populations of clonogenic cells in human endometrium has opened an active area of research on endometrial stem/progenitor cells in the subsequent 10 years. METHODS The published literature was searched using the PubMed database with the search terms ‘endometrial stem cells and menstru...

  4. Human pancreatic islet progenitor cells demonstrate phenotypic plasticity in vitro

    Indian Academy of Sciences (India)

    Maithili P Dalvi; Malati R Umrani; Mugdha V Joglekar; Anandwardhan A Hardikar

    2009-10-01

    Phenotypic plasticity is a phenomenon that describes the occurrence of 2 or more distinct phenotypes under diverse conditions. This article discusses the work carried out over the past few years in understanding the potential of human pancreatic islet-derived progenitors for cell replacement therapy in diabetes. The phenotypic plasticity exhibited by pancreatic progenitors during reversible epithelial-to-mesenchymal transition (EMT) and possible role of microRNAs in regulation of this process is also presented herein.

  5. Osteocytes serve as a progenitor cell of osteosarcoma

    OpenAIRE

    Sottnik, Joseph L.; Campbell, Brittany; Mehra, Rohit; Behbahani-Nejad, Omid; Hall, Christopher L.; Keller, Evan T.

    2014-01-01

    Osteosarcoma (OSA) is the most common primary bone tumor in humans. However, the cell of origin of OSA is not clearly defined although there is evidence that osteoblasts may serve as OSA progenitors. The role of osteocytes, terminally differentiated osteoblasts, as OSA progenitors has yet to be described. Analysis of patient cDNA from publicly available microarray data revealed that patients with OSA have increased expression of dentin matrix phosphoprotein 1 (DMP1), a marker of osteocytes. A...

  6. Lung Stem and Progenitor Cells in Tissue Homeostasis and Disease

    OpenAIRE

    Leeman, Kristen T.; Fillmore, Christine M.; Kim, Carla F.

    2014-01-01

    The mammalian lung is a complex organ containing numerous putative stem/progenitor cell populations that contribute to region-specific tissue homeostasis and repair. In this review, we discuss recent advances in identifying and studying these cell populations in the context of lung homeostasis and disease. Genetically engineered mice now allow for lineage tracing of several lung stem and progenitor cell populations in vivo during different types of lung injury repair. Using specific sets of c...

  7. Trasplante de progenitores hemopoyéticos Transplant of hemopoietic progenitors

    Directory of Open Access Journals (Sweden)

    J. J. Rifón

    2006-08-01

    Full Text Available En la segunda mitad del siglo XX el trasplante de progenitores hemopoyéticos ha pasado de ser un tratamiento desesperado con una alta incidencia de complicaciones que implicaba una elevada mortalidad, a ser un tratamiento curativo para miles de pacientes con neoplasias hematológicas y otras enfermedades. Desde entonces se han ampliado los conocimientos sobre las células madre hemopoyéticas, la sangre periférica ha sustituido a la médula ósea como fuente de progenitores, la sangre de cordón se ha establecido como fuente viable de progenitores, la realización de trasplantes no emparentados es una realidad para muchos pacientes. La mejora en los regímenes de acondicionamiento y la introducción de los regímenes no mieloablativos han disminuido las recaídas. Las nuevas técnicas diagnósticas y los nuevos tratamientos antimicrobianos han disminuido las complicaciones infecciosas y su mortalidad. Se han desarrollado los conocimientos en determinación de enfermedad mínima residual y el efecto antitumoral de los linfocitos del donante lo que ha permitido ampliar las indicaciones. Además, los nuevos conocimientos en la inmunobiología del trasplante han mejorado por un lado las opciones de controlar una de las principales complicaciones como es la enfermedad injerto contra huésped, y por otro un mejor aprovechamiento del efecto inmunoterápico del trasplante.In the second half of the XX century, the transplant of hemopoietic progenitors ceased to be a desperate treatment with a high incidence of complications implying a high mortality, and became a curative treatment for thousands of patients with hematological neoplasias and other diseases. Since then understanding of the hemopoietic stem cells has increased, peripheral blood has replaced bone marrow as a source of progenitors, cord blood has been established as a viable source of progenitors and the realisation of unrelated transplants is a reality for many patients. The improvement of

  8. Postnatal Pancreas of Mice Contains Tripotent Progenitors Capable of Giving Rise to Duct, Acinar, and Endocrine Cells In Vitro.

    Science.gov (United States)

    Ghazalli, Nadiah; Mahdavi, Alborz; Feng, Tao; Jin, Liang; Kozlowski, Mark T; Hsu, Jasper; Riggs, Arthur D; Tirrell, David A; Ku, H Teresa

    2015-09-01

    Postnatal pancreas is a potential source for progenitor cells to generate endocrine β-cells for treating type 1 diabetes. However, it remains unclear whether young (1-week-old) pancreas harbors multipotent progenitors capable of differentiating into duct, acinar, and endocrine cells. Laminin is an extracellular matrix (ECM) protein important for β-cells' survival and function. We established an artificial extracellular matrix (aECM) protein that contains the functional IKVAV (Ile-Lys-Val-Ala-Val) sequence derived from laminin (designated aECM-lam). Whether IKVAV is necessary for endocrine differentiation in vitro is unknown. To answer these questions, we cultured single cells from 1-week-old pancreas in semi-solid media supplemented with aECM-lam, aECM-scr (which contains a scrambled sequence instead of IKVAV), or Matrigel. We found that colonies were generated in all materials. Individual colonies were examined by microfluidic reverse transcription-polymerase chain reaction, immunostaining, and electron microscopy analyses. The majority of the colonies expressed markers for endocrine, acinar, and ductal lineages, demonstrating tri-lineage potential of individual colony-forming progenitors. Colonies grown in aECM-lam expressed higher levels of endocrine markers Insulin1, Insulin2, and Glucagon compared with those grown in aECM-scr and Matrigel, indicating that the IKVAV sequence enhances endocrine differentiation. In contrast, Matrigel was inhibitory for endocrine gene expression. Colonies grown in aECM-lam displayed the hallmarks of functional β-cells: mature insulin granules and glucose-stimulated insulin secretion. Colony-forming progenitors were enriched in the CD133(high) fraction and among 230 micro-manipulated single CD133(high) cells, four gave rise to colonies that expressed tri-lineage markers. We conclude that young postnatal pancreas contains multipotent progenitor cells and that aECM-lam promotes differentiation of β-like cells in vitro. PMID

  9. Differential Apoptosis Radiosensitivity of Neural Progenitors in Adult Mouse Hippocampus

    Directory of Open Access Journals (Sweden)

    Yu-Qing Li

    2016-06-01

    Full Text Available Mammalian tissue-specific stem cells and progenitors demonstrate differential DNA damage response. Neural progenitors in dentate gyrus of the hippocampus are known to undergo apoptosis after irradiation. Using a mouse model of hippocampal neuronal development, we characterized the apoptosis sensitivity of the different neural progenitor subpopulations in adult mouse dentate gyrus after irradiation. Two different bromodeoxyuridine incorporation paradigms were used for cell fate mapping. We identified two apoptosis sensitive neural progenitor subpopulations after irradiation. The first represented non-proliferative and non-newborn neuroblasts and immature neurons that expressed doublecortin, calretinin or both. The second consisted of proliferative intermediate neural progenitors. The putative radial glia-like neural stem cells or type-1 cells, regardless of proliferation status, were apoptosis resistant after irradiation. There was no evidence of radiation-induced apoptosis in the absence of the Trp53 (p53 gene but absence of Cdkn1a (p21 did not alter the apoptotic response. Upregulation of nuclear p53 was observed in neuroblasts after irradiation. We conclude that adult hippocampal neural progenitors may demonstrate differential p53-dependent apoptosis sensitivity after irradiation.

  10. Possible Progenitor of Special Supernova Type Detected

    Science.gov (United States)

    2008-04-01

    caused by material being pulled off a companion star onto the white dwarf, fusion of this material on the surface of the star should heat the star and produce a strong source of X-radiation prior to the explosion. Once the supernova explosion occurs, the white dwarf is expected to be completely destroyed and then would be undetectable in X-rays. In the merger scenario, the intensity of X-ray emission prior to the explosion is expected to be much weaker. Based on the detection of a fairly strong X-ray source at approximately the position of SN 2007on 4 years before the explosion, Voss and Nelemans conclude that the data support the scenario where matter is pulled off a companion star. The small number of X-ray sources in the field implies that there is only a small chance of an unrelated source being so close by coincidence. Also, the X-ray source has similar properties to those expected for fusion on a white dwarf, unlike most X-ray sources in the sky. However, in follow-up studies, Voss, Nelemans and colleagues Gijs Roelofs (Harvard-Smithsonian Center for Astrophysics, Cambridge, Mass.) and Cees Bassa (McGill University, Canada) used higher-quality optical images to better determine the supernova's position. This work, which is not yet published, shows a small, but significant difference in the measured positions of the supernova and the X-ray source, suggesting the source may not be the progenitor. Follow-up Chandra observations hint that the X-ray object has disappeared, but further observations are needed to finally decide whether the source was the progenitor or not. The team is also applying this new method to other supernovas and has high hopes that they will eventually succeed in identifying the elusive cause of at least some of these explosions. "We're very excited about opening up a new way of studying supernovas, even though we're not sure that we've seen this particular stellar bomb before it exploded," said Gijs Roelofs. "We're very confident that we

  11. Binary progenitor models of type IIb supernovae

    CERN Document Server

    Claeys, J S W; Pols, O R; Eldridge, J J; Baes, M

    2011-01-01

    Massive stars that lose their hydrogen-rich envelope down to a few tenths of a solar mass explode as extended type IIb supernovae, an intriguing subtype that links the hydrogen-rich type II supernovae with the hydrogen-poor type Ib and Ic. The progenitors may be very massive single stars that lose their envelope due to their stellar wind, but mass stripping due to interaction with a companion star in a binary system is currently considered to be the dominant formation channel. We computed an extensive grid of binary models with the Eggleton binary evolution code. The predicted rate from our standard models, which assume conservative mass transfer, is about 6 times smaller than the current rate indicated by observations. It is larger but still comparable to the rate expected from single stars. To recover the observed rate we must generously allow for uncertainties and low accretion efficiencies in combination with limited angular momentum loss from the system. Motivated by the claims of detection and non-detec...

  12. The Evolution of Relativistic Binary Progenitor Systems

    CERN Document Server

    Francischelli, G J; Brown, G E

    2001-01-01

    Relativistic binary pulsars, such as B1534+12 and B1913+16 are characterized by having close orbits with a binary separation of ~ 3 R_\\sun. The progenitor of such a system is a neutron star, helium star binary. The helium star, with a strong stellar wind, is able to spin up its compact companion via accretion. The neutron star's magnetic field is then lowered to observed values of about 10^{10} Gauss. As the pulsar lifetime is inversely proportional to its magnetic field, the possibility of observing such a system is, thus, enhanced by this type of evolution. We will show that a nascent (Crab-like) pulsar in such a system can, through accretion-braking torques (i.e. the "propeller effect") and wind-induced spin-up rates, reach equilibrium periods that are close to observed values. Such processes occur within the relatively short helium star lifetimes. Additionally, we find that the final outcome of such evolutionary scenarios depends strongly on initial parameters, particularly the initial binary separation a...

  13. Subretinal transplantation of mouse retinal progenitor cells

    Institute of Scientific and Technical Information of China (English)

    Caihui Jiang; Maonian Zhang; Henry Klassen; Michael Young

    2011-01-01

    The development of cell replacement techniques is promising as a potential treatment for photoreceptor loss. However, the limited integration ability of donor and recipient cells presents a challenge following transplantation. In the present study, retinal progenitor cells (RPCs) were harvested from the neural retinas of enhanced green fluorescent protein mice on postnatal day 1, and expanded in a neurobasal medium supplemented with fetal bovine serum without endothelial growth factor. Using a confocal microscope, immunohistochemistry demonstrated that expanded RPCs in vitro maintain retinal stem cell properties and can be differentiated into photoreceptor cells. Three weeks after transplantation, subretinal transplanted RPCs were found to have migrated and integrated into the outer nuclear layer of recipient retinas with laser injury, some of the integrated cells had differentiated into photoreceptors, and a subpopulation of these cells expressed photoreceptor specific synaptic protein, appearing to form synaptic connections with bipolar cells. These results suggest that subretinal transplantation of RPCs may provide a feasible therapeutic strategy for the loss of retinal photoreceptor cells.

  14. Type Ia Supernovae: Colors, Rates, and Progenitors

    CERN Document Server

    Heringer, Epson; Kezwer, Jason; Graham, Melissa L; Sand, David; Bildfell, Chris

    2016-01-01

    The rate of type Ia supernovae (SNe Ia) in a galaxy depends not only on stellar mass, but also on star formation history. Here we show that two simple observational quantities ($g-r$ or $u-r$ host galaxy color, and $r$-band luminosity), coupled with an assumed delay time distribution (the rate of SNe Ia as a function of time for an instantaneous burst of star formation), are sufficient to accurately determine a galaxy's SN Ia rate, with very little sensitivity to the precise details of the star formation history. Using this result, we compare observed and predicted color distributions of SN Ia hosts for the MENeaCS cluster supernova survey, and for the SDSS Stripe 82 supernova survey. The observations are consistent with a continuous delay time distribution (DTD), without any cutoff. For old progenitor systems the power-law slope for the DTD is found to be $-1.50 ^{+0.19} _{-0.15}$. This result favours the double degenerate scenario for SN Ia, though other interpretations are possible. We find that the late-t...

  15. Hepatic progenitors for liver disease: current position

    Directory of Open Access Journals (Sweden)

    Alice Conigliaro

    2010-02-01

    Full Text Available Alice Conigliaro1, David A Brenner2, Tatiana Kisseleva21University “La Sapienza”, Dipartimento di Biotecnologie Cellulari ed Ematologia Policlinico Umberto I, V Clinica Medica, Rome, Italy; 2Department of Medicine, University of California, San Diego, La Jolla, CA, USAAbstract: Liver regeneration restores the original functionality of hepatocytes and cholangiocytes in response to injury. It is regulated on several levels, with different cellular populations contributing to this process, eg, hepatocytes, liver precursor cells, intrahepatic stem cells. In response to injury, mature hepatocytes have the capability to proliferate and give rise to new hepatocytes and cholangiocytes. Meanwhile, liver precursor cells (oval cells have become the most recognized bipotential precursor cells in the damaged liver. They rapidly proliferate, change their cellular composition, and differentiate into hepatocytes and cholangiocytes to compensate for the cellular loss and maintain liver homeostasis. There is a growing body of evidence that oval cells originate from the intrahepatic stem cell(s, which in turn give(s rise to epithelial, including oval cells, and/or other hepatic cells of nonepithelial origin. Since there is a close relationship between the liver and hematopoiesis, bone marrow derived cells can also contribute to liver regeneration by the fusion of myeloid cells with damaged hepatocytes, or differentiation of mesenchymal stem cells into hepatocyte-like cells. The current review discusses the contribution of different cells to liver regeneration and their characteristics.Keywords: hepatic progenitor, liver disease, liver precursor cells, oval cells, hepatocytes, intrahepatic stem cells, cholangiocytes

  16. FolR1: a novel cell surface marker for isolating midbrain dopamine neural progenitors and nascent dopamine neurons

    Science.gov (United States)

    Gennet, Nicole; Tamburini, Claudia; Nan, Xinsheng; Li, Meng

    2016-01-01

    Cell type-specific surface markers offer a powerful tool for purifying defined cell types for restorative therapies and drug screenings. Midbrain dopaminergic neurons (mesDA) are the nerve cells preferentially lost in the brains of Parkinson’s disease patients. Clinical trials of transplantation of fetal neural precursors suggest that cell therapy may offer a cure for this devastating neurological disease. Many lines of preclinical studies demonstrate that neural progenitors committed to dopaminergic fate survive and integrate better than postmitotic DA neurons. We show that the folate-receptor 1 (FolR1), a GPI-anchored cell surface molecule, specifically marks mesDA neural progenitors and immature mesDA neurons. FolR1 expression superimposes with Lmx1a, a bona-fide mesDA lineage marker, during the active phase of mesDA neurogenesis from E9.5 to E14.5 during mouse development, as well as in ESC-derived mesDA lineage. FolR1+ neural progenitors can be isolated by FACS or magnetic sorting (MAC) which give rise to dopamine neurons expressing TH and Pitx3, whilst FolR1 negative cells generate non-dopaminergic neurons and glia cells. This study identifies FolR1 as a new cell surface marker selectively expressed in mesDA progenitors in vivo and in vitro and that can be used to enrich in vitro differentiated TH neurons. PMID:27580818

  17. Ascl3 expression marks a progenitor population of both acinar and ductal cells in mouse salivary glands.

    Science.gov (United States)

    Bullard, Tara; Koek, Laurie; Roztocil, Elisa; Kingsley, Paul D; Mirels, Lily; Ovitt, Catherine E

    2008-08-01

    Ascl3, also know as Sgn1, is a member of the mammalian achaete scute (Mash) gene family of transcription factors, which have been implicated in cell fate specification and differentiation. In the mouse salivary gland, expression of Ascl3 is restricted to a subset of duct cells. Salivary gland function depends on the secretory acinar cells, which are responsible for saliva formation, and duct cells, which modify the saliva and conduct it to the oral cavity. The salivary gland ducts are also the putative site of progenitor cells in the adult gland. Using a Cre recombinase-mediated reporter system, we followed the fate of Ascl3-expressing cells after the introduction of an EGFP-Cre expression cassette into the Ascl3 locus by homologous recombination. Lineage tracing shows that these cells are progenitors of both acinar and ductal cell types in all three major salivary glands. In the differentiated progeny, expression of Ascl3 is down-regulated. These data directly demonstrate a progenitor-progeny relationship between duct cells and the acinar cell compartment, and identify a population of multipotent progenitor cells, marked by expression of Ascl3, which is capable of generating both gland cell types. We conclude that Ascl3-expressing cells contribute to the maintenance of the adult salivary glands.

  18. A competitive advantage by neonatally engrafted human glial progenitors yields mice whose brains are chimeric for human glia

    DEFF Research Database (Denmark)

    Windrem, Martha S; Schanz, Steven J; Morrow, Carolyn;

    2014-01-01

    Neonatally transplanted human glial progenitor cells (hGPCs) densely engraft and myelinate the hypomyelinated shiverer mouse. We found that, in hGPC-xenografted mice, the human donor cells continue to expand throughout the forebrain, systematically replacing the host murine glia. The differentiat......Neonatally transplanted human glial progenitor cells (hGPCs) densely engraft and myelinate the hypomyelinated shiverer mouse. We found that, in hGPC-xenografted mice, the human donor cells continue to expand throughout the forebrain, systematically replacing the host murine glia....... The differentiation of the donor cells is influenced by the host environment, such that more donor cells differentiated as oligodendrocytes in the hypomyelinated shiverer brain than in myelin wild-types, in which hGPCs were more likely to remain as progenitors. Yet in each recipient, both the number and relative...... and ultimately replaced the host population of mouse GPCs, ultimately generating mice with a humanized glial progenitor population. These human glial chimeric mice should permit us to define the specific contributions of glia to a broad variety of neurological disorders, using human cells in vivo....

  19. FolR1: a novel cell surface marker for isolating midbrain dopamine neural progenitors and nascent dopamine neurons.

    Science.gov (United States)

    Gennet, Nicole; Tamburini, Claudia; Nan, Xinsheng; Li, Meng

    2016-01-01

    Cell type-specific surface markers offer a powerful tool for purifying defined cell types for restorative therapies and drug screenings. Midbrain dopaminergic neurons (mesDA) are the nerve cells preferentially lost in the brains of Parkinson's disease patients. Clinical trials of transplantation of fetal neural precursors suggest that cell therapy may offer a cure for this devastating neurological disease. Many lines of preclinical studies demonstrate that neural progenitors committed to dopaminergic fate survive and integrate better than postmitotic DA neurons. We show that the folate-receptor 1 (FolR1), a GPI-anchored cell surface molecule, specifically marks mesDA neural progenitors and immature mesDA neurons. FolR1 expression superimposes with Lmx1a, a bona-fide mesDA lineage marker, during the active phase of mesDA neurogenesis from E9.5 to E14.5 during mouse development, as well as in ESC-derived mesDA lineage. FolR1(+) neural progenitors can be isolated by FACS or magnetic sorting (MAC) which give rise to dopamine neurons expressing TH and Pitx3, whilst FolR1 negative cells generate non-dopaminergic neurons and glia cells. This study identifies FolR1 as a new cell surface marker selectively expressed in mesDA progenitors in vivo and in vitro and that can be used to enrich in vitro differentiated TH neurons. PMID:27580818

  20. Period 2 regulates neural stem/progenitor cell proliferation in the adult hippocampus

    OpenAIRE

    Albrecht Urs; Maquet Pierre; Moonen Gustave; Nguyen Laurent; Vandenbosch Renaud; Beukelaers Pierre; Borgs Laurence; Belachew Shibeshih; Malgrange Brigitte

    2009-01-01

    Abstract Background Newborn granule neurons are generated from proliferating neural stem/progenitor cells and integrated into mature synaptic networks in the adult dentate gyrus of the hippocampus. Since light/dark variations of the mitotic index and DNA synthesis occur in many tissues, we wanted to unravel the role of the clock-controlled Period2 gene (mPer2) in timing cell cycle kinetics and neurogenesis in the adult DG. Results In contrast to the suprachiasmatic nucleus, we observed a non-...

  1. Construction of tissue-engineered heart valves by using decellularized scaffolds and endothelial progenitor cells

    Institute of Scientific and Technical Information of China (English)

    FANG Ning-tao; XIE Shang-zhe; WANG Song-mei; GAO Hong-yang; WU Chun-gen; PAN Luan-feng

    2007-01-01

    Background Tissue-engineered heart valves have the potential to overcome the limitations of present heart valve replacements. This study was designed to develop a tissue engineering heart valve by using human umbilical cord blood-derived endothelial progenitor cells (EPCs) and decellularized valve scaffolds.Methods Decellularized valve scaffolds were prepared from fresh porcine heart valves. EPCs were isolated from fresh human umbilical cord blood by density gradient centrifugation, cultured for 3 weeks in EGM-2-MV medium, by which time the resultant cell population became endothelial in nature, as assessed by immunofluorescent staining. EPC-derived endothelial cells were seeded onto the decellularized scaffold at 3 × 106 cells/cm2 and cultured under static conditions for 7 days. Proliferation of the seeded cells on the scaffolds was detected using the MTT assay. Tissue-engineered heart valves were analyzed by HE staining, immunofluorescent staining and scanning electron microscopy. The anti-thrombogenic function of the endothelium on the engineered heart valves was evaluated by platelet adhesion experiments and reverse transcription-polymerase chain reaction (RT-PCR) analysis for the expression of endothelial nitric oxide synthase (eNOS) and tissue-type plasminogen activator (t-PA).Results EPC-derived endothelial cells showed a histolytic cobblestone morphology, expressed specific markers of the endothelial cell lineage including von Willebrand factor (vWF) and CD31, bound a human endothelial cell-specific lectin,Ulex Europaeus agglutinin-1 (UEA-1), and took up Dil-labeled low density lipoprotein (Dil-Ac-LDL). After seeding on the decellularized scaffold, the cells showed excellent metabolic activity and proliferation. The cells formed confluent endothelial monolayers atop the decellularized matrix, as assessed by HE staining and immunostaining for vWF and CD31. Scanning electron microscopy demonstrated the occurrence of tight junctions between cells forming the

  2. PPAR-α and glucocorticoid receptor synergize to promote erythroid progenitor self-renewal.

    Science.gov (United States)

    Lee, Hsiang-Ying; Gao, Xiaofei; Barrasa, M Inmaculada; Li, Hu; Elmes, Russell R; Peters, Luanne L; Lodish, Harvey F

    2015-06-25

    Many acute and chronic anaemias, including haemolysis, sepsis and genetic bone marrow failure diseases such as Diamond-Blackfan anaemia, are not treatable with erythropoietin (Epo), because the colony-forming unit erythroid progenitors (CFU-Es) that respond to Epo are either too few in number or are not sensitive enough to Epo to maintain sufficient red blood cell production. Treatment of these anaemias requires a drug that acts at an earlier stage of red cell formation and enhances the formation of Epo-sensitive CFU-E progenitors. Recently, we showed that glucocorticoids specifically stimulate self-renewal of an early erythroid progenitor, burst-forming unit erythroid (BFU-E), and increase the production of terminally differentiated erythroid cells. Here we show that activation of the peroxisome proliferator-activated receptor α (PPAR-α) by the PPAR-α agonists GW7647 and fenofibrate synergizes with the glucocorticoid receptor (GR) to promote BFU-E self-renewal. Over time these agonists greatly increase production of mature red blood cells in cultures of both mouse fetal liver BFU-Es and mobilized human adult CD34(+) peripheral blood progenitors, with a new and effective culture system being used for the human cells that generates normal enucleated reticulocytes. Although Ppara(-/-) mice show no haematological difference from wild-type mice in both normal and phenylhydrazine (PHZ)-induced stress erythropoiesis, PPAR-α agonists facilitate recovery of wild-type but not Ppara(-/-) mice from PHZ-induced acute haemolytic anaemia. We also show that PPAR-α alleviates anaemia in a mouse model of chronic anaemia. Finally, both in control and corticosteroid-treated BFU-E cells, PPAR-α co-occupies many chromatin sites with GR; when activated by PPAR-α agonists, additional PPAR-α is recruited to GR-adjacent sites and presumably facilitates GR-dependent BFU-E self-renewal. Our discovery of the role of PPAR-α agonists in stimulating self-renewal of early erythroid

  3. PPARα and glucocorticoid receptor synergize to promote erythroid progenitor self-renewal

    Science.gov (United States)

    Lee, Hsiang-Ying; Gao, Xiaofei; Barrasa, M. Inmaculada; Li, Hu; Elmes, Russell R.; Peters, Luanne L.; Lodish, Harvey F.

    2015-01-01

    Summary Many acute and chronic anemias, including hemolysis, sepsis, and genetic bone marrow failure diseases such as Diamond-Blackfan Anemia (DBA), are not treatable with erythropoietin (Epo), because the colony-forming unit erythroid progenitors (CFU-Es) that respond to Epo are either too few in number or are not sensitive enough to Epo to maintain sufficient red blood cell production 1,2,3–5,6,7,8,9. Treatment of these anemias requires a drug that acts at an earlier stage of red cell formation and enhances the formation of Epo-sensitive CFU-E progenitors. Recently we showed that glucocorticoids specifically stimulate self-renewal of the early erythroid progenitor, the burst-forming unit erythroid (BFU-E), and increase the production of terminally differentiated erythroid cells 10,11. Here we demonstrate that activation of the peroxisome proliferator-activated receptor alpha (PPARα) by PPARα agonists, GW7647 and fenofibrate, synergizes with glucocorticoid receptor (GR) to promote BFU-E self-renewal. Over time these agonists greatly increase production of mature red blood cells in cultures both of mouse fetal liver BFU-Es and of mobilized human adult CD34+ peripheral blood progenitors, the latter employing a new and effective culture system that generates normal enucleated reticulocytes. While PPARα−/− mice show no hematological difference from wild-type mice in both normal and phenylhydrazine (PHZ)-induced stress erythropoiesis, PPARα agonists facilitate recovery of wild-type mice, but not PPARα−/− mice, from PHZ-induced acute hemolytic anemia. We also showed that PPARα alleviates anemia in a mouse model of chronic anemia. Finally, both in control and corticosteroid-treated BFU-E cells PPARα co-occupies many chromatin sites with GR; when activated by PPARα agonists, additional PPARα is recruited to GR-adjacent sites and presumably facilitates GR-dependent BFU-E self-renewal. Our discovery of the role of PPARα agonists in stimulating self

  4. Endothelial Progenitor Cells Promote Directional Three-Dimensional Endothelial Network Formation by Secreting Vascular Endothelial Growth Factor

    OpenAIRE

    Yoshinori Abe; Yoshiyuki Ozaki; Junichi Kasuya; Kimiko Yamamoto; Joji Ando; Ryo Sudo; Mariko Ikeda; Kazuo Tanishita

    2013-01-01

    Endothelial progenitor cell (EPC) transplantation induces the formation of new blood-vessel networks to supply nutrients and oxygen, and is feasible for the treatment of ischemia and cardiovascular diseases. However, the role of EPCs as a source of proangiogenic cytokines and consequent generators of an extracellular growth factor microenvironment in three-dimensional (3D) microvessel formation is not fully understood. We focused on the contribution of EPCs as a source of proangiogenic cytoki...

  5. NTPDase2 and Purinergic Signaling Control Progenitor Cell Proliferation in Neurogenic Niches of the Adult Mouse Brain

    OpenAIRE

    Gampe, Kristine; Stefani, Jennifer; Hammer, Klaus; Brendel, Peter; Pötzsch, Alexandra; Enikolopov, Grigori; Enjyoji, Keiichi; Acker-Palmer, Amparo; Robson, Simon C.; Zimmermann, Herbert

    2015-01-01

    Nerve cells are continuously generated from stem cells in the adult mammalian subventricular zone (SVZ) and hippocampal dentate gyrus. We have previously noted that stem/progenitor cells in the SVZ and the subgranular layer (SGL) of the dentate gyrus express high levels of plasma membrane-bound nucleoside triphosphate diphosphohydrolase 2 (NTPDase2), an ectoenzyme that hydrolyzes extracellular nucleoside di- and triphosphates. We inferred that deletion of NTPDase2 would increase local extrace...

  6. 经血源子宫内膜干细胞复合3D打印PLGA支架体外培养的相容性研究%Cellular Compatibility of Menstrual Blood-derived Mesenchymal Stem Cells in Three-dimensional Printing PLGA Scaffolds

    Institute of Scientific and Technical Information of China (English)

    许世兵; 单乐天; 金红婷; 王萍儿; 童培建; 肖鲁伟

    2015-01-01

    Objective] To investigate the feasibility of using three-dimensional(3D) printing PLGA loaded with menstrual blood-derived mesenchymal stem cells(MenSCs) as scaffolds for bone cartilage tissue engineering. [Methods] Three-dimensional printing PLGA was preprocessed. The five generation MenSCs were utilized. use invert microscope to observe cells biological property. According to 1.0 ×106/mL cells seeded onto PLGA scaffold composite culture, invert microscope, Mico-CT, scanning electron microscope and histopathology were observed.[Results] MSCs grew well, cells were plated to grow, fusiform or spindle row, thin cytoplasmic and nuclear circle centered, with fibroblast morphology. Cells to the fifth generation had long spindle cell monolayer and swirling arrangement. PLGA scaffolds exhibited microscopic interconnected porous structure, loose structure, large pores and mutual traffic, thinner hole wall. MenSCs on PLGA scaffold grew well, mainly in the scaffolds surface and inside growth, the scaffolds aperture had cell matrix organization connection.[Conclusion] MenSCs are ideal seeding cells for bone cartilage tissue engineering. And the PLGA scaffolds by three-dimensional printing with MenSCs may be in vitro construction as bone cartilage formation.%[目的]通过经血源子宫内膜干细胞(menstrual blood-derived mesenchymal stem cells, MenSCs)与3D打印PLGA支架材料的复合培养,探讨构建组织工程化骨软骨的可行性。[方法]预处理3D打印PLGA支架,取第5代MenSCs,倒置显微镜下观察细胞生物学特性,按1.0×106/mL的密度接种到PLGA支架材料上复合培养,通过倒置显微镜、Mico-CT、扫描电镜和组织病理学进行观察,并借此判断MenSCs与3D打印PLGA支架材料复合体外培养的融合性。[结果] MenSCs生长良好,细胞平铺生长,呈梭形或纺锤形,胞质薄,核圆居中,具有成纤维细胞形态。细胞传至第5代,为长梭形细胞单层,呈漩涡状排列

  7. The complexity of the calretinin-expressing progenitors in the human cerebral cortex

    Directory of Open Access Journals (Sweden)

    Nevena V Radonjic

    2014-08-01

    Full Text Available The complex structure and function of the cerebral cortex critically depend on the balance of excitation and inhibition provided by the pyramidal projection neurons and GABAergic interneurons, respectively. The calretinin-expressing (CalR+ cell is a subtype of GABAergic cortical interneurons that is more prevalent in humans than in rodents. In rodents, CalR+ interneurons originate in the caudal ganglionic eminence (CGE from Gsx2+ progenitors, but in humans it has been suggested that a subpopulation of CalR+ cells can also be generated in the cortical ventricular/subventricular zone (VZ/SVZ. The progenitors for cortically generated CalR+ subpopulation in primates are not yet characterized. Hence, the aim of this study was to identify patterns of expression of the transcription factors (TFs that commit cortical stem cells to the CalR fate, with a focus on Gsx2. First, we studied the expression of Gsx2 and its downstream effectors, Ascl1 and Sp8 in the cortical regions of the fetal human forebrain at midgestation. Next, we established that a subpopulation of cells expressing these TFs are proliferating in the cortical SVZ, and can be co-labeled with CalR. The presence and proliferation of Gsx2+ cells, not only in the ventral telencephalon (GE as previously reported, but also in the cerebral cortex suggests cortical origin of a subpopulation of CalR+ neurons in humans. In vitro treatment of human cortical progenitors with Sonic hedgehog (Shh, an important morphogen in the specification of interneurons, decreased levels of Ascl1 and Sp8 proteins, but did not affect Gsx2 levels. Taken together, our ex-vivo and in vitro results on human fetal brain suggest complex endogenous and exogenous regulation of TFs implied in the specification of different subtypes of CalR+ cortical interneurons.

  8. Human cord blood progenitors with high aldehyde dehydrogenase activity improve vascular density in a model of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Creer Michael H

    2010-03-01

    Full Text Available Abstract Human stem cells from adult sources have been shown to contribute to the regeneration of muscle, liver, heart, and vasculature. The mechanisms by which this is accomplished are, however, still not well understood. We tested the engraftment and regenerative potential of human umbilical cord blood-derived ALDHhiLin-, and ALDHloLin- cells following transplantation to NOD/SCID or NOD/SCID β2m null mice with experimentally induced acute myocardial infarction. We used combined nanoparticle labeling and whole organ fluorescent imaging to detect human cells in multiple organs 48 hours post transplantation. Engraftment and regenerative effects of cell treatment were assessed four weeks post transplantation. We found that ALDHhiLin- stem cells specifically located to the site of injury 48 hours post transplantation and engrafted the infarcted heart at higher frequencies than ALDHloLin- committed progenitor cells four weeks post transplantation. We found no donor derived cardiomyocytes and few endothelial cells of donor origin. Cell treatment was not associated with any detectable functional improvement at the four week endpoint. There was, however, a significant increase in vascular density in the central infarct zone of ALDHhiLin- cell-treated mice, as compared to PBS and ALDHloLin- cell-treated mice. Conclusions Our data indicate that adult human stem cells do not become a significant part of the regenerating tissue, but rapidly home to and persist only temporarily at the site of hypoxic injury to exert trophic effects on tissue repair thereby enhancing vascular recovery.

  9. Supernovae with two peaks in the optical light curve and the signature of progenitors with low-mass extended envelopes

    International Nuclear Information System (INIS)

    Early observations of supernova light curves are powerful tools for shedding light on the pre-explosion structures of their progenitors and their mass-loss histories just prior to explosion. Some core-collapse supernovae that are detected during the first days after the explosion prominently show two peaks in the optical bands, including the R and I bands, where the first peak appears to be powered by the cooling of shocked surface material and the second peak is clearly powered by radioactive decay. Such light curves have been explored in detail theoretically for SN 1993J and 2011dh, where it was found that they may be explained by progenitors with extended, low-mass envelopes. Here, we generalize these results. We first explore whether any double-peaked light curve of this type can be generated by a progenitor with a 'standard' density profile, such as a red supergiant or a Wolf-Rayet star. We show that a standard progenitor (1) cannot produce a double-peaked light curve in the R and I bands and (2) cannot exhibit a fast drop in the bolometric luminosity as is seen after the first peak. We then explore the signature of a progenitor with a compact core surrounded by extended, low-mass material. This may be a hydrostatic low-mass envelope or material ejected just prior to the explosion. We show that it naturally produces both of these features. We use this result to provide simple formulae to estimate (1) the mass of the extended material from the time of the first peak, (2) the extended material radius from the luminosity of the first peak, and (3) an upper limit on the core radius from the luminosity minimum between the two peaks.

  10. ZFP36L2 is required for self-renewal of early burst-forming unit erythroid progenitors.

    Science.gov (United States)

    Zhang, Lingbo; Prak, Lina; Rayon-Estrada, Violeta; Thiru, Prathapan; Flygare, Johan; Lim, Bing; Lodish, Harvey F

    2013-07-01

    Stem cells and progenitors in many lineages undergo self-renewing divisions, but the extracellular and intracellular proteins that regulate this process are largely unknown. Glucocorticoids stimulate red blood cell formation by promoting self-renewal of early burst-forming unit-erythroid (BFU-E) progenitors. Here we show that the RNA-binding protein ZFP36L2 is a transcriptional target of the glucocorticoid receptor (GR) in BFU-Es and is required for BFU-E self-renewal. ZFP36L2 is normally downregulated during erythroid differentiation from the BFU-E stage, but its expression is maintained by all tested GR agonists that stimulate BFU-E self-renewal, and the GR binds to several potential enhancer regions of ZFP36L2. Knockdown of ZFP36L2 in cultured BFU-E cells did not affect the rate of cell division but disrupted glucocorticoid-induced BFU-E self-renewal, and knockdown of ZFP36L2 in transplanted erythroid progenitors prevented expansion of erythroid lineage progenitors normally seen following induction of anaemia by phenylhydrazine treatment. ZFP36L2 preferentially binds to messenger RNAs that are induced or maintained at high expression levels during terminal erythroid differentiation and negatively regulates their expression levels. ZFP36L2 therefore functions as part of a molecular switch promoting BFU-E self-renewal and a subsequent increase in the total numbers of colony-forming unit-erythroid (CFU-E) progenitors and erythroid cells that are generated.

  11. Chief sources of brachiopod recovery from the end Ordovician mass extinction with special references to progenitors

    Institute of Scientific and Technical Information of China (English)

    戎嘉余; 詹仁斌

    1999-01-01

    Survivor, Lazarus and progenitor taxa are sources of biotic recovery following mass extinction. Investigations of the benthic brachiopods through the latest Ordovician mass extinction shows that progenitors developed many evolutionary novelties and successful surviving mechanisms. They are superior to survivors and Lazarus taxa in their ability to adapt to environmental changes. They are the primary source of macroevolution and the ancestors of a number of new taxa. Three kinds of progenitors are recognized based on the Ordovician-Silurian brachiopods from South China: survivor-progenitors, crisis-progenitors and Lazarus-progenitors; the last has the strongest ability to resist adverse environments, and is the most diverse and abundant.

  12. On the Progenitor of the Type IIb Supernova 2016gkg

    CERN Document Server

    Kilpatrick, Charles D; Abramson, Louis E; Pan, Yen-Chen; Lu, Cicero-Xinyu; Williams, Peter; Treu, Tommaso; Siebert, Matthew R; Fassnacht, Christopher D; Max, Claire E

    2016-01-01

    We present a detection in pre-explosion Hubble Space Telescope (HST) imaging of a point source consistent with being the progenitor star of the Type IIb supernova (SN IIb) 2016gkg. Post-explosion imaging from the Keck Adaptive Optics system was used to perform relative astrometry between the Keck and HST imaging. We identify a single point source in the HST images coincident with the SN position to 0.89-sigma. The HST photometry is consistent with the progenitor star being an A0Ia star with T=9500 K and log (L/Lsun)=5.15. We find that the SN 2016gkg progenitor star appears more consistent with binary than single-star evolutionary models. In addition, early-time light curve data from SN 2016gkg revealed a rapid rise in luminosity within ~0.4 days of non-detection limits, consistent with models of the cooling phase after shock break-out. We use these data to determine an explosion date of 20.15 September 2016 and progenitor star radius of log (R/Rsun)=2.41, which agrees with photometry from the progenitor star....

  13. Impaired DNA replication within progenitor cell pools promotes leukemogenesis.

    Directory of Open Access Journals (Sweden)

    Ganna Bilousova

    2005-12-01

    Full Text Available Impaired cell cycle progression can be paradoxically associated with increased rates of malignancies. Using retroviral transduction of bone marrow progenitors followed by transplantation into mice, we demonstrate that inhibition of hematopoietic progenitor cell proliferation impairs competition, promoting the expansion of progenitors that acquire oncogenic mutations which restore cell cycle progression. Conditions that impair DNA replication dramatically enhance the proliferative advantage provided by the expression of Bcr-Abl or mutant p53, which provide no apparent competitive advantage under conditions of healthy replication. Furthermore, for the Bcr-Abl oncogene the competitive advantage in contexts of impaired DNA replication dramatically increases leukemogenesis. Impaired replication within hematopoietic progenitor cell pools can select for oncogenic events and thereby promote leukemia, demonstrating the importance of replicative competence in the prevention of tumorigenesis. The demonstration that replication-impaired, poorly competitive progenitor cell pools can promote tumorigenesis provides a new rationale for links between tumorigenesis and common human conditions of impaired DNA replication such as dietary folate deficiency, chemotherapeutics targeting dNTP synthesis, and polymorphisms in genes important for DNA metabolism.

  14. Observational Clues to the Progenitors of Type Ia Supernovae

    Science.gov (United States)

    Maoz, Dan; Mannucci, Filippo; Nelemans, Gijs

    2014-08-01

    Type Ia supernovae (SNe Ia) are important distance indicators, element factories, cosmic-ray accelerators, kinetic-energy sources in galaxy evolution, and end points of stellar binary evolution. It has long been clear that a SN Ia must be the runaway thermonuclear explosion of a degenerate carbon-oxygen stellar core, most likely a white dwarf (WD). However, the specific progenitor systems of SNe Ia, and the processes that lead to their ignition, have not been identified. Two broad classes of progenitor binary systems have long been considered: single-degenerate (SD), in which a WD gains mass from a nondegenerate star; and double-degenerate (DD), involving the merger of two WDs. New theoretical work has enriched these possibilities with some interesting updates and variants. We review the significant recent observational progress in addressing the progenitor problem. We consider clues that have emerged from the observed properties of the various proposed progenitor populations, from studies of SN Ia sites—pre- and postexplosion—from analysis of the explosions themselves and from the measurement of event rates. The recent nearby and well-studied event, SN 2011fe, has been particularly revealing. The observational results are not yet conclusive and sometimes prone to competing theoretical interpretations. Nevertheless, it appears that DD progenitors, long considered the underdog option, could be behind some, if not all, SNe Ia. We point to some directions that may lead to future progress.

  15. Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential.

    Directory of Open Access Journals (Sweden)

    Francesca Oltolina

    Full Text Available A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM. We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol.

  16. Preclinical Evaluation of the Immunomodulatory Properties of Cardiac Adipose Tissue Progenitor Cells Using Umbilical Cord Blood Mesenchymal Stem Cells: A Direct Comparative Study

    Directory of Open Access Journals (Sweden)

    Isaac Perea-Gil

    2015-01-01

    Full Text Available Cell-based strategies to regenerate injured myocardial tissue have emerged over the past decade, but the optimum cell type is still under scrutiny. In this context, human adult epicardial fat surrounding the heart has been characterized as a reservoir of mesenchymal-like progenitor cells (cardiac ATDPCs with potential clinical benefits. However, additional data on the possibility that these cells could trigger a deleterious immune response following implantation are needed. Thus, in the presented study, we took advantage of the well-established low immunogenicity of umbilical cord blood-derived mesenchymal stem cells (UCBMSCs to comparatively assess the immunomodulatory properties of cardiac ATDPCs in an in vitro allostimulatory assay using allogeneic mature monocyte-derived dendritic cells (MDDCs. Similar to UCBMSCs, increasing amounts of seeded cardiac ATDPCs suppressed the alloproliferation of T cells in a dose-dependent manner. Secretion of proinflammatory cytokines (IL6, TNFα, and IFNγ was also specifically modulated by the different numbers of cardiac ATDPCs cocultured. In summary, we show that cardiac ATDPCs abrogate T cell alloproliferation upon stimulation with allogeneic mature MDDCs, suggesting that they could further regulate a possible harmful immune response in vivo. Additionally, UCBMSCs can be considered as valuable tools to preclinically predict the immunogenicity of prospective regenerative cells.

  17. Direct lineage reprogramming of mouse fibroblasts to functional midbrain dopaminergic neuronal progenitors

    Directory of Open Access Journals (Sweden)

    Han-Seop Kim

    2014-01-01

    Full Text Available The direct lineage reprogramming of somatic cells to other lineages by defined factors has led to innovative cell-fate-change approaches for providing patient-specific cells. Recent reports have demonstrated that four pluripotency factors (Oct4, Sox2, Klf4, and c-Myc are sufficient to directly reprogram fibroblasts to other specific cells, including induced neural stem cells (iNSCs. Here, we show that mouse fibroblasts can be directly reprogrammed into midbrain dopaminergic neuronal progenitors (DPs by temporal expression of the pluripotency factors and environment containing sonic hedgehog and fibroblast growth factor 8. Within thirteen days, self-renewing and functional induced DPs (iDPs were generated. Interestingly, the inhibition of both Jak and Gsk3β notably enhanced the iDP reprogramming efficiency. We confirmed the functionality of the iDPs by showing that the dopaminergic neurons generated from iDPs express midbrain markers, release dopamine, and show typical electrophysiological profiles. Our results demonstrate that the pluripotency factors-mediated direct reprogramming is an invaluable strategy for supplying functional and proliferating iDPs and may be useful for other neural progenitors required for disease modeling and cell therapies for neurodegenerative disorders.

  18. Integrating microRNA and mRNA expression profiles of neuronal progenitors to identify regulatory networks underlying the onset of cortical neurogenesis

    Directory of Open Access Journals (Sweden)

    Barker Jeffery L

    2009-08-01

    Full Text Available Abstract Background Cortical development is a complex process that includes sequential generation of neuronal progenitors, which proliferate and migrate to form the stratified layers of the developing cortex. To identify the individual microRNAs (miRNAs and mRNAs that may regulate the genetic network guiding the earliest phase of cortical development, the expression profiles of rat neuronal progenitors obtained at embryonic day 11 (E11, E12 and E13 were analyzed. Results Neuronal progenitors were purified from telencephalic dissociates by a positive-selection strategy featuring surface labeling with tetanus-toxin and cholera-toxin followed by fluorescence-activated cell sorting. Microarray analyses revealed the fractions of miRNAs and mRNAs that were up-regulated or down-regulated in these neuronal progenitors at the beginning of cortical development. Nearly half of the dynamically expressed miRNAs were negatively correlated with the expression of their predicted target mRNAs. Conclusion These data support a regulatory role for miRNAs during the transition from neuronal progenitors into the earliest differentiating cortical neurons. In addition, by supplying a robust data set in which miRNA and mRNA profiles originate from the same purified cell type, this empirical study may facilitate the development of new algorithms to integrate various "-omics" data sets.

  19. Impaired progenitor cell function in HIV-negative infants of HIV-positive mothers results in decreased thymic output and low CD4 counts

    DEFF Research Database (Denmark)

    Nielsen, S D; Jeppesen, D L; Kolte, L;

    2001-01-01

    Hematologic and immunologic functions were examined in 19 HIV-negative infants of HIV-positive mothers and 19 control infants of HIV-negative mothers. Control infants were selected to match for gestational age, weight, and mode of delivery. Cord blood was obtained from all infants and used for flow...... cytometric determination of lymphocyte subsets, including the naive CD4 count. Furthermore, to determine thymic output, cord blood mononuclear cells were used for determination of T-cell receptor excision circles (TRECs). Evaluation of progenitor cell function was done by means of colony-forming cell assay......). In combination with lower red blood cell counts in infants of HIV-positive mothers, this finding suggested impairment of progenitor cell function. Indeed, progenitors from infants of HIV-positive mothers had decreased cloning efficiency (15.7% +/- 2.6% vs 55.8% +/- 15.9%, P =.009) and seemed to generate fewer T...

  20. Rates and progenitors of type Ia supernovae

    Energy Technology Data Exchange (ETDEWEB)

    Wood-Vasey, William Michael [Univ. of California, Berkeley, CA (United States)

    2004-01-01

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z ~ 0.01-0.1 of rV = 4.26$+1.39 +0.10\\atop{-1.93 -0.10}$h3 x 10-4 SNe Ia/yr/Mpc3 from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae.

  1. Rates and progenitors of type Ia supernovae

    Energy Technology Data Exchange (ETDEWEB)

    Wood-Vasey, William Michael

    2004-08-16

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z {approx} 0.01-0.1 of r{sub V} = 4.26{sub -1.93 -0.10}{sup +1.39 +0.10} h{sup 3} x 10{sup -4} SNe Ia/yr/Mpc{sup 3} from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae.

  2. Obstructive sleep apnea and endothelial progenitor cells

    Directory of Open Access Journals (Sweden)

    Wang Q

    2013-10-01

    Full Text Available Qing Wang,1,* Qi Wu,2,* Jing Feng,3,4 Xin Sun5 1The Second Respiratory Department of the First People's Hospital of Kunming, Yunnan, People's Republic of China; 2Tianjin Haihe Hospital, Tianjin, People's Republic of China; 3Respiratory Department of Tianjin Medical University General Hospital, Tianjin, People's Republic of China; 4Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, NC, USA; 5Respiratory Department of Tianjin Haihe Hospital, Tianjin, People's Republic of China *These authors contributed equally to this work Background: Obstructive sleep apnea (OSA occurs in 4% of middle-aged men and 2% of middle-aged women in the general population, and the prevalence is even higher in specific patient groups. OSA is an independent risk factor for a variety of cardiovascular diseases. Endothelial injury could be the pivotal determinant in the development of cardiovascular pathology in OSA. Endothelial damage ultimately represents a dynamic balance between the magnitude of injury and the capacity for repair. Bone marrow–derived endothelial progenitor cells (EPCs within adult peripheral blood present a possible means of vascular maintenance that could home to sites of injury and restore endothelial integrity and normal function. Methods: We summarized pathogenetic mechanisms of OSA and searched for available studies on numbers and functions of EPCs in patients with OSA to explore the potential links between the numbers and functions of EPCs and OSA. In particular, we tried to elucidate the molecular mechanisms of the effects of OSA on EPCs. Conclusion: Intermittent hypoxia cycles and sleep fragmentation are major pathophysiologic characters of OSA. Intermittent hypoxia acts as a trigger of oxidative stress, systemic inflammation, and sympathetic activation. Sleep fragmentation is associated with a burst of sympathetic activation and systemic inflammation. In most studies, a reduction in circulating EPCs has

  3. Rates and progenitors of type Ia supernovae

    International Nuclear Information System (INIS)

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z ∼ 0.01-0.1 of rV = 4.26-1.93-0.10+1.39+0.10 h3 x 10-4 SNe Ia/yr/Mpc3 from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae

  4. CXCR4 expression in prostate cancer progenitor cells.

    Directory of Open Access Journals (Sweden)

    Anna Dubrovska

    Full Text Available Tumor progenitor cells represent a population of drug-resistant cells that can survive conventional chemotherapy and lead to tumor relapse. However, little is known of the role of tumor progenitors in prostate cancer metastasis. The studies reported herein show that the CXCR4/CXCL12 axis, a key regulator of tumor dissemination, plays a role in the maintenance of prostate cancer stem-like cells. The CXCL4/CXCR12 pathway is activated in the CD44(+/CD133(+ prostate progenitor population and affects differentiation potential, cell adhesion, clonal growth and tumorigenicity. Furthermore, prostate tumor xenograft studies in mice showed that a combination of the CXCR4 receptor antagonist AMD3100, which targets prostate cancer stem-like cells, and the conventional chemotherapeutic drug Taxotere, which targets the bulk tumor, is significantly more effective in eradicating tumors as compared to monotherapy.

  5. A neutron star progenitor for FRBs? Insights from polarisation measurements

    CERN Document Server

    Ravi, Vikram

    2016-01-01

    Fast Radio Bursts (FRBs) are intense, millisecond-duration broadband radio transients, the emission mechanisms of which are not understood. Masui et al. recently presented Green Bank Telescope observations of FRB 110523, which displayed temporal variation of the linear polarisation position angle (PA). This effect is commonly seen in radio pulsars and is attributed to a changing projected magnetic field orientation in the emission region as the star rotates. If a neutron star is the progenitor of this FRB, and the emission mechanism is pulsar-like, we show that the progenitor is either rapidly rotating, or the emission originates from a region of complex magnetic field geometry. The observed PA variation could also be caused by propagation effects within a neutron-star magnetosphere, or by spatially varying magnetic fields if the progenitor lies in a dense, highly magnetised environment. Although we urge caution in generalising results from FRB 110523 to the broader FRB population, our analysis serves as a gu...

  6. Osteocytes serve as a progenitor cell of osteosarcoma.

    Science.gov (United States)

    Sottnik, Joseph L; Campbell, Brittany; Mehra, Rohit; Behbahani-Nejad, Omid; Hall, Christopher L; Keller, Evan T

    2014-08-01

    Osteosarcoma (OSA) is the most common primary bone tumor in humans. However, the cell of origin of OSA is not clearly defined although there is evidence that osteoblasts may serve as OSA progenitors. The role of osteocytes, terminally differentiated osteoblasts, as OSA progenitors has yet to be described. Analysis of patient cDNA from publicly available microarray data revealed that patients with OSA have increased expression of dentin matrix phosphoprotein 1 (DMP1), a marker of osteocytes. Analysis of multiple murine, human, and canine OSA cell lines revealed DMP1 expression. To test the tumorigenic potential of osteocytes, MLO-Y4, a SV-40 immortalized murine osteocyte cell line, was injected into subcutaneous and orthotopic (intratibial) sites of mice. Tumor growth occurred in both locations. Orthotopic MLO-Y4 tumors produced mixed osteoblastic/osteolytic radiographic lesions; a hallmark of OSA. Together, these data demonstrate for the first time that osteocytes can serve as OSA progenitors. PMID:24700678

  7. Gravitational Wave Constraints on the Progenitors of Fast Radio Bursts

    CERN Document Server

    Callister, Thomas; Weinstein, Alan

    2016-01-01

    The nature of fast radio bursts (FRBs) remains enigmatic. Highly energetic radio pulses of millisecond duration, fast radio bursts are observed with dispersion measures consistent with an extragalactic source. A variety of models have been proposed to explain their origin. One popular class of theorized FRB progenitor is the coalescence of compact binaries composed of neutron stars and/or black holes. We demonstrate that measurements made by the LIGO and Virgo gravitational wave observatories can be leveraged to severely constrain the validity of FRB binary coalescence models. Existing measurements rule out binary black holes as FRB progenitors, and results from Advanced LIGO's O1 and O2 observing runs will either confirm or strongly rule out binary neutron star and neutron star-black hole progenitors.

  8. Immortalized neural progenitor cells for CNS gene transfer and repair.

    Science.gov (United States)

    Martínez-Serrano, A; Björklund, A

    1997-11-01

    Immortalized multipotent neural stem and progenitor cells have emerged as a highly convenient source of tissue for genetic manipulation and ex vivo gene transfer to the CNS. Recent studies show that these cells, which can be maintained and genetically transduced as cell lines in culture, can survive, integrate and differentiate into both neurons and glia after transplantation to the intact or damaged brain. Progenitors engineered to secrete trophic factors, or to produce neurotransmitter-related or metabolic enzymes can be made to repopulate diseased or injured brain areas, thus providing a new potential therapeutic tool for the blockade of neurodegenerative processes and reversal of behavioural deficits in animal models of neurodegenerative diseases. With further technical improvements, the use of immortalized neural progenitors may bring us closer to the challenging goal of targeted and effective CNS repair.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Endothelial progenitors in sepsis: vox clamantis in deserto?

    Science.gov (United States)

    Goligorsky, Michael S

    2011-01-01

    In this issue of Critical Care, Patschan and colleagues present a study of endothelial progenitor cells (EPCs) in patients with sepsis. The importance of this study is in focusing attention on several frequently ignored aspects of sepsis. Among those are the phenomenon of microvascular dysfunction, which is potentially responsible for profound metabolic perturbations at the tissue level, and the role of endothelial progenitors in repair processes. Other important aspects of the study are the regenerative capacity of mobilized EPCs and the dissociation between the numerical value and clonogenic competence. Attempting to restore the competence to EPCs should be a priority in the future. PMID:21489327

  11. Evolutionary Models for Type Ib/c Supernova Progenitors

    OpenAIRE

    Yoon, Sung-Chul

    2015-01-01

    Type Ib/c supernovae (SNe Ib/c) mark the deaths of hydrogen-deficient massive stars. The evolutionary scenarios for SNe Ib/c progenitors involve many important physical processes including mass loss by winds and its metallicity dependence, stellar rotation, and binary interactions. This makes SNe Ib/c an excellent test bed for stellar evolution theory. We review the main results of evolutionary models for SN Ib/c progenitors available in the literature and their confrontation with recent obse...

  12. Cellular plasticity : the good, the bad, and the ugly? Microenvironmental influences on progenitor cell therapy

    NARCIS (Netherlands)

    Moonen, Jan-Renier A. J.; Harmsen, Martin C.; Krenning, Guido

    2012-01-01

    Progenitor cell based therapies have emerged for the treatment of ischemic cardiovascular diseases where there is insufficient endogenous repair. However, clinical success has been limited, which challenges the original premise that transplanted progenitor cells would orchestrate repair. In this rev

  13. Human induced pluripotent stem cells differentiation into oligodendrocyte progenitors and transplantation in a rat model of optic chiasm demyelination.

    Directory of Open Access Journals (Sweden)

    Alireza Pouya

    Full Text Available BACKGROUND: This study aims to differentiate human induced pluripotent stem cells (hiPSCs into oligodendrocyte precursors and assess their recovery potential in a demyelinated optic chiasm model in rats. METHODOLOGY/PRINCIPAL FINDINGS: We generated a cell population of oligodendrocyte progenitors from hiPSCs by using embryoid body formation in a defined medium supplemented with a combination of factors, positive selection and mechanical enrichment. Real-time polymerase chain reaction and immunofluorescence analyses showed that stage-specific markers, Olig2, Sox10, NG2, PDGFRα, O4, A2B5, GalC, and MBP were expressed following the differentiation procedure, and enrichment of the oligodendrocyte lineage. These results are comparable with the expression of stage-specific markers in human embryonic stem cell-derived oligodendrocyte lineage cells. Transplantation of hiPSC-derived oligodendrocyte progenitors into the lysolecithin-induced demyelinated optic chiasm of the rat model resulted in recovery from symptoms, and integration and differentiation into oligodendrocytes were detected by immunohistofluorescence staining against PLP and MBP, and measurements of the visual evoked potentials. CONCLUSIONS/SIGNIFICANCE: These results showed that oligodendrocyte progenitors generated efficiently from hiPSCs can be used in future biomedical studies once safety issues have been overcome.

  14. Roles of CDX2 and EOMES in human induced trophoblast progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ying, E-mail: ying.chen@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503 (United States); Wang, Kai [Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503 (United States); Gong, Yun Guo; Khoo, Sok Kean [Genomic Microarray Core Facility, Van Andel Research Institute, Grand Rapids, MI 49503 (United States); Leach, Richard, E-mail: Richard.Leach@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503 (United States); Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group, Grand Rapids, MI 49503 (United States)

    2013-02-08

    Highlights: ► CDX2 and EOMES play critical roles in human induced trophoblast progenitors (iTP). ► iTP cells directly transformed from fibroblasts. ► Differentiation of iTP cells into extravillous trophoblasts and syncytiotrophoblasts. -- Abstract: Abnormal trophoblast lineage proliferation and differentiation in early pregnancy have been associated with the pathogenesis of placenta diseases of pregnancy. However, there is still a gap in understanding the molecular mechanisms of early placental development due to the limited primary trophoblast cultures and fidelity of immortalized trophoblast lines. Trophoblasts stem (TS) cells, an in vitro model of trophectoderm that can differentiate into syncytiotrophoblasts and extravillous trophoblasts, can be an attractive tool for early pregnancy research. TS cells are well established in mouse but not in humans due to insufficient knowledge of which trophoblast lineage-specific transcription factors are involved in human trophectoderm (TE) proliferation and differentiation. Here, we applied induced pluripotent stem cell technique to investigate the human trophoblast lineage-specific transcription factors. We established human induced trophoblast progenitor (iTP) cells by direct reprogramming the fibroblasts with a pool of mouse trophoblast lineage-specific transcription factors consisting of CDX2, EOMES, and ELF5. The human iTP cells exhibit epithelial morphology and can be maintained in vitro for more than 2 months. Gene expression profile of these cells was tightly clustered with human trophectoderm but not with human neuron progenitor cells, mesenchymal stem cells, or endoderm cells. These cells are capable of differentiating into cells with an invasive capacity, suggesting extravillous trophoblasts. They also form multi-nucleated cells which secrete human chorionic gonadotropin and estradiol, consistent with a syncytiotrophoblast phenotype. Our results provide the evidence that transcription factors CDX2 and

  15. AKT signaling mediates IGF-I survival actions on otic neural progenitors.

    Directory of Open Access Journals (Sweden)

    Maria R Aburto

    Full Text Available BACKGROUND: Otic neurons and sensory cells derive from common progenitors whose transition into mature cells requires the coordination of cell survival, proliferation and differentiation programmes. Neurotrophic support and survival of post-mitotic otic neurons have been intensively studied, but the bases underlying the regulation of programmed cell death in immature proliferative otic neuroblasts remains poorly understood. The protein kinase AKT acts as a node, playing a critical role in controlling cell survival and cell cycle progression. AKT is activated by trophic factors, including insulin-like growth factor I (IGF-I, through the generation of the lipidic second messenger phosphatidylinositol 3-phosphate by phosphatidylinositol 3-kinase (PI3K. Here we have investigated the role of IGF-dependent activation of the PI3K-AKT pathway in maintenance of otic neuroblasts. METHODOLOGY/PRINCIPAL FINDINGS: By using a combination of organotypic cultures of chicken (Gallus gallus otic vesicles and acoustic-vestibular ganglia, Western blotting, immunohistochemistry and in situ hybridization, we show that IGF-I-activation of AKT protects neural progenitors from programmed cell death. IGF-I maintains otic neuroblasts in an undifferentiated and proliferative state, which is characterised by the upregulation of the forkhead box M1 (FoxM1 transcription factor. By contrast, our results indicate that post-mitotic p27(Kip-positive neurons become IGF-I independent as they extend their neuronal processes. Neurons gradually reduce their expression of the Igf1r, while they increase that of the neurotrophin receptor, TrkC. CONCLUSIONS/SIGNIFICANCE: Proliferative otic neuroblasts are dependent on the activation of the PI3K-AKT pathway by IGF-I for survival during the otic neuronal progenitor phase of early inner ear development.

  16. Airway Progenitor Clone Formation Is Enhanced by Y-27632-Dependent Changes in the Transcriptome.

    Science.gov (United States)

    Reynolds, Susan D; Rios, Cydney; Wesolowska-Andersen, Agata; Zhuang, Yongbin; Pinter, Mary; Happoldt, Carrie; Hill, Cynthia L; Lallier, Scott W; Cosgrove, Gregory P; Solomon, George M; Nichols, David P; Seibold, Max A

    2016-09-01

    The application of conditional reprogramming culture (CRC) methods to nasal airway epithelial cells would allow more wide-spread incorporation of primary airway epithelial culture models into complex lung disease research. In this study, we adapted the CRC method to nasal airway epithelial cells, investigated the growth advantages afforded by this technique over standard culture methods, and determined the cellular and molecular basis of CRC cell culture effects. We found that the CRC method allowed the production of 7.1 × 10(10) cells after 4 passages, approximately 379 times more cells than were generated by the standard bronchial epithelial growth media (BEGM) method. These nasal airway epithelial cells expressed normal basal cell markers and could be induced to form a mucociliary epithelium. Progenitor cell frequency was significantly higher using the CRC method in comparison to the standard culture method, and progenitor cell maintenance was dependent on addition of the Rho-kinase inhibitor Y-27632. Whole-transcriptome sequencing analysis demonstrated widespread gene expression changes in Y-27632-treated basal cells. We found that Y-27632 treatment altered expression of genes fundamental to the formation of the basal cell cytoskeleton, cell-cell junctions, and cell-extracellular matrix (ECM) interactions. Importantly, we found that Y-27632 treatment up-regulated expression of unique basal cell intermediate filament and desmosomal genes. Conversely, Y-27632 down-regulated multiple families of protease/antiprotease genes involved in ECM remodeling. We conclude that Y-27632 fundamentally alters cell-cell and cell-ECM interactions, which preserves basal progenitor cells and allows greater cell amplification.

  17. Regenerative potential of human schneiderian membrane: progenitor cells and epithelial-mesenchymal transition.

    Science.gov (United States)

    Derjac-Aramă, A I; Sarafoleanu, C; Manea, C M; Nicolescu, M I; Vrapciu, A D; Rusu, M C

    2015-12-01

    An innate osteogenic potential of the Schneiderian membrane (SM) is progressively assessed in studies ranging from non-human species to human subjects. It has relevance for endosteal placement and osseointegration. Nestin-expressing osteogenic progenitor cells are allegedly involved in bone formation and remodelling. Nestin phenotype was not assessed previously in human SM. We therefore aimed to fill that particular gap in the literature. Bioptic samples of human adult SM were obtained during surgery from eight adult patients, operated for non-malignant pathologies. Immunohistochemistry on paraffin-embedded tissue samples used primary antibodies against nestin, CD45, CD146, cytokeratin 7 (CK7), and alpha-smooth muscle actin (α-SMA). Nestin expression was consistently found in endothelial cells, and was scarcely encountered in pericytes, putative stromal stem/progenitor cells, as well as in glandular epithelial cells. Moreover, woven bone formation in the periosteal layer of the SM can also be regarded as evidence of the osteogenic potential of this membrane. Nestin and CD45 expression in cells of the primary bone supports the osteogenic potential of SM nestin-expressing cells and a possible involvement of hematopoietic stem cells in maxillary sinus floor remodeling. CD146, a known inducer of epithelial-mesenchymal transition (EMT), was expressed in epithelia, as was CK7. Isolated stromal cells were found expressing CD146, CK7 and α-SMA, suggesting that regenerative processes happening in the SM may also involve processes of EMT which generate stem/progenitor cells. This study provides additional evidence for the regenerative potential of the Schneiderian membrane and identifies potential roles for cells of its stem niche in osteogenesis. PMID:26414809

  18. Development of Cortical GABAergic Neurons: Interplay of progenitor diversity and environmental factors on fate specification

    Directory of Open Access Journals (Sweden)

    Juliana Alves Brandão

    2015-04-01

    Full Text Available Cortical GABAergic interneurons constitute an extremely diverse population of cells organized in a well-defined topology of precisely interconnected cells. They play a crucial role regulating inhibitory-excitatory balance in brain circuits, gating sensory perception and regulating spike timing to brain oscillations during distinct behaviors. Dysfunctions in the establishment of proper inhibitory circuits have been associated to several brain disorders such as autism, epilepsy and schizophrenia. In the rodent adult cortex, inhibitory neurons are generated during the second gestational week from distinct progenitor lineages located in restricted domains of the ventral telencephalon. However, only recently, studies have revealed some of the mechanisms generating the heterogeneity of neuronal subtypes and their modes of integration in brain networks. Here we will discuss some the events involved in the production of cortical GABAergic neuron diversity with focus on the interaction between intrinsically driven genetic programs and environmental signals during development.

  19. BTG1 is required to maintain the pool of stem and progenitor cells of dentate gyrus and subventricular zone

    Directory of Open Access Journals (Sweden)

    Stefano eFarioli-Vecchioli

    2012-08-01

    Full Text Available Btg1 belongs to a family of cell cycle inhibitory genes. We observed that Btg1 is highly expressed in adult neurogenic niches, i.e., the dentate gyrus and subventricular zone (SVZ. Thus, we generated Btg1 knockout mice to analyze the role of Btg1 in the process of generation of adult new neurons.Ablation of Btg1 causes a transient increase of the proliferating dentate gyrus stem and progenitor cells at post-natal day 7; however, at two months of age the number of these proliferating cells, as well as of mature neurons, greatly decreases compared to wild-type controls. Remarkably, adult dentate gyrus stem and progenitor cells of Btg1-null mice exit cell cycle after completing the S phase, highly express p53 and p21, and within 5 days undergo apoptosis. In SVZ we observed an equivalent decrease, associated to apoptosis, of Btg1-null stem cells, neuroblasts and neurons; furthermore, neurospheres derived from SVZ stem cells showed an age-dependent decrease of the self-renewal and expansion capacity.We conclude that the ablation of Btg1 reduces the pool of dividing adult stem and progenitor cells in dentate gyrus and SVZ by decreasing their proliferative capacity and inducing apoptosis, likely reflecting the impairment of the control of the cell cycle transition from G1 to S phase. As a result, the ability of Btg1-null mice to discriminate among overlapping contextual memories was affected. Thus, Btg1 appears to be required for maintaining adult stem and progenitor cells quiescence and self-renewal.

  20. Type Ia supernovae: explosions and progenitors

    Science.gov (United States)

    Kerzendorf, Wolfgang Eitel

    2011-08-01

    that they somehow need to acquire mass if they are to explode as SN Ia. Currently there are two major scenarios for this mass acquisition. In the favoured single degenerate scenario the white dwarf accretes matter from a companion star which is much younger in its evolutionary state. The less favoured double degenerate scenario sees the merger of two white dwarfs (with a total combined mass of more than 1.38 Msun). This thesis has tried to answer the question about the mass acquisition in two ways. First the single degenerate scenario predicts a surviving companion post-explosion. We undertook an observational campaign to find this companion in two ancient supernovae (SN 1572 and SN 1006). Secondly, we have extended an existing code to extract the elemental and energy yields of SNe Ia spectra by automating spectra fitting to specific SNe Ia. This type of analysis, in turn, help diagnose to which of the two major progenitor scenarios is right.

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    Full Text Available His.Oth.10.AllAg.Multipotent_otic_progenitor mm9 Histone Others Multipotent otic pr...ogenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.10.AllAg.Multipotent_otic_progenitor.bed ...

  20. File list: His.Oth.05.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.05.AllAg.Multipotent_otic_progenitor mm9 Histone Others Multipotent otic pr...ogenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.05.AllAg.Multipotent_otic_progenitor.bed ...

  1. File list: Pol.Neu.50.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.50.AllAg.Neural_progenitor_cells mm9 RNA polymerase Neural Neural progenito...r cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.50.AllAg.Neural_progenitor_cells.bed ...

  2. File list: Oth.Neu.10.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.10.AllAg.Neural_progenitor_cells mm9 TFs and others Neural Neural progenito...r cells SRX109472,SRX315274,SRX802060,SRX109471 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.10.AllAg.Neural_progenitor_cells.bed ...

  3. File list: ALL.Neu.50.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.50.AllAg.Neural_progenitor_cells mm9 All antigens Neural Neural progenitor ...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.50.AllAg.Neural_progenitor_cells.bed ...

  4. File list: His.Neu.50.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.50.AllAg.Neural_progenitor_cells mm9 Histone Neural Neural progenitor cells... SRX315278,SRX667383,SRX668241,SRX315276,SRX315277 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.50.AllAg.Neural_progenitor_cells.bed ...

  5. File list: Unc.Neu.10.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.10.AllAg.Induced_neural_progenitors mm9 Unclassified Neural Induced neural ...progenitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.10.AllAg.Induced_neural_progenitors.bed ...

  6. File list: DNS.Neu.05.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Neu.05.AllAg.Induced_neural_progenitors mm9 DNase-seq Neural Induced neural pro...genitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Neu.05.AllAg.Induced_neural_progenitors.bed ...

  7. File list: Unc.Neu.05.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.05.AllAg.Induced_neural_progenitors mm9 Unclassified Neural Induced neural ...progenitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.05.AllAg.Induced_neural_progenitors.bed ...

  8. File list: Pol.Neu.05.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.05.AllAg.Induced_neural_progenitors mm9 RNA polymerase Neural Induced neura...l progenitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.05.AllAg.Induced_neural_progenitors.bed ...

  9. File list: Oth.Neu.50.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.50.AllAg.Induced_neural_progenitors mm9 TFs and others Neural Induced neura...l progenitors SRX323564,SRX323573 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.50.AllAg.Induced_neural_progenitors.bed ...

  10. File list: Oth.Adp.10.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Adp.10.AllAg.Adipose_progenitor_cells mm9 TFs and others Adipocyte Adipose prog...enitor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Adp.10.AllAg.Adipose_progenitor_cells.bed ...

  11. File list: Unc.Adp.20.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Adp.20.AllAg.Adipose_progenitor_cells mm9 Unclassified Adipocyte Adipose progen...itor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Adp.20.AllAg.Adipose_progenitor_cells.bed ...

  12. File list: DNS.Adp.50.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Adp.50.AllAg.Adipose_progenitor_cells mm9 DNase-seq Adipocyte Adipose progenito...r cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Adp.50.AllAg.Adipose_progenitor_cells.bed ...

  13. File list: DNS.Adp.20.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Adp.20.AllAg.Adipose_progenitor_cells mm9 DNase-seq Adipocyte Adipose progenito...r cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Adp.20.AllAg.Adipose_progenitor_cells.bed ...

  14. File list: Unc.Adp.10.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Adp.10.AllAg.Adipose_progenitor_cells mm9 Unclassified Adipocyte Adipose progen...itor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Adp.10.AllAg.Adipose_progenitor_cells.bed ...

  15. File list: Unc.Adp.05.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Adp.05.AllAg.Adipose_progenitor_cells mm9 Unclassified Adipocyte Adipose progen...itor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Adp.05.AllAg.Adipose_progenitor_cells.bed ...

  16. File list: Unc.Adp.50.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Adp.50.AllAg.Adipose_progenitor_cells mm9 Unclassified Adipocyte Adipose progen...itor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Adp.50.AllAg.Adipose_progenitor_cells.bed ...

  17. File list: Oth.Adp.05.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Adp.05.AllAg.Adipose_progenitor_cells mm9 TFs and others Adipocyte Adipose prog...enitor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Adp.05.AllAg.Adipose_progenitor_cells.bed ...

  18. File list: His.Adp.10.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Adp.10.AllAg.Adipose_progenitor_cells mm9 Histone Adipocyte Adipose progenitor ...cells SRX127409,SRX127394,SRX127396,SRX127407,SRX127383,SRX127381 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Adp.10.AllAg.Adipose_progenitor_cells.bed ...

  19. File list: His.Adp.20.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Adp.20.AllAg.Adipose_progenitor_cells mm9 Histone Adipocyte Adipose progenitor ...cells SRX127394,SRX127409,SRX127396,SRX127407,SRX127381,SRX127383 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Adp.20.AllAg.Adipose_progenitor_cells.bed ...

  20. File list: Pol.Adp.20.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adp.20.AllAg.Adipose_progenitor_cells mm9 RNA polymerase Adipocyte Adipose prog...enitor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Adp.20.AllAg.Adipose_progenitor_cells.bed ...

  1. File list: DNS.Adp.05.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Adp.05.AllAg.Adipose_progenitor_cells mm9 DNase-seq Adipocyte Adipose progenito...r cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Adp.05.AllAg.Adipose_progenitor_cells.bed ...

  2. File list: Oth.Adp.20.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Adp.20.AllAg.Adipose_progenitor_cells mm9 TFs and others Adipocyte Adipose prog...enitor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Adp.20.AllAg.Adipose_progenitor_cells.bed ...

  3. File list: Pol.Adp.50.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adp.50.AllAg.Adipose_progenitor_cells mm9 RNA polymerase Adipocyte Adipose prog...enitor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Adp.50.AllAg.Adipose_progenitor_cells.bed ...

  4. File list: His.Adp.05.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Adp.05.AllAg.Adipose_progenitor_cells mm9 Histone Adipocyte Adipose progenitor ...cells SRX127409,SRX127407,SRX127394,SRX127396,SRX127383,SRX127381 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Adp.05.AllAg.Adipose_progenitor_cells.bed ...

  5. File list: Pol.Adp.05.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adp.05.AllAg.Adipose_progenitor_cells mm9 RNA polymerase Adipocyte Adipose prog...enitor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Adp.05.AllAg.Adipose_progenitor_cells.bed ...

  6. File list: DNS.Adp.10.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Adp.10.AllAg.Adipose_progenitor_cells mm9 DNase-seq Adipocyte Adipose progenito...r cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Adp.10.AllAg.Adipose_progenitor_cells.bed ...

  7. File list: Unc.Neu.50.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.50.AllAg.Neural_progenitor_cells mm9 Unclassified Neural Neural progenitor ...cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.50.AllAg.Neural_progenitor_cells.bed ...

  8. File list: His.Neu.20.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.20.AllAg.Neural_progenitor_cells mm9 Histone Neural Neural progenitor cells... SRX315278,SRX667383,SRX668241,SRX315277,SRX315276 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.20.AllAg.Neural_progenitor_cells.bed ...

  9. File list: Pol.Neu.20.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.20.AllAg.Neural_progenitor_cells mm9 RNA polymerase Neural Neural progenito...r cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.20.AllAg.Neural_progenitor_cells.bed ...

  10. File list: His.Neu.10.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.10.AllAg.Neural_progenitor_cells mm9 Histone Neural Neural progenitor cells... SRX315278,SRX315277,SRX667383,SRX668241,SRX315276 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.10.AllAg.Neural_progenitor_cells.bed ...

  11. File list: ALL.Neu.05.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.05.AllAg.Neural_progenitor_cells mm9 All antigens Neural Neural progenitor ...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.05.AllAg.Neural_progenitor_cells.bed ...

  12. File list: Pol.Neu.10.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.10.AllAg.Neural_progenitor_cells mm9 RNA polymerase Neural Neural progenito...r cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.10.AllAg.Neural_progenitor_cells.bed ...

  13. File list: Pol.Neu.05.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.05.AllAg.Neural_progenitor_cells mm9 RNA polymerase Neural Neural progenito...r cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.05.AllAg.Neural_progenitor_cells.bed ...

  14. File list: DNS.Neu.50.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Neu.50.AllAg.Neural_progenitor_cells mm9 DNase-seq Neural Neural progenitor cel...ls SRX238870,SRX238868 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Neu.50.AllAg.Neural_progenitor_cells.bed ...

  15. File list: Oth.Neu.20.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.20.AllAg.Neural_progenitor_cells mm9 TFs and others Neural Neural progenito...r cells SRX109472,SRX315274,SRX802060,SRX109471 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.20.AllAg.Neural_progenitor_cells.bed ...

  16. File list: His.Neu.05.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.05.AllAg.Neural_progenitor_cells mm9 Histone Neural Neural progenitor cells... SRX315277,SRX667383,SRX668241,SRX315278,SRX315276 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.05.AllAg.Neural_progenitor_cells.bed ...

  17. File list: Oth.Neu.50.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.50.AllAg.Neural_progenitor_cells mm9 TFs and others Neural Neural progenito...r cells SRX109472,SRX315274,SRX109471,SRX802060 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.50.AllAg.Neural_progenitor_cells.bed ...

  18. File list: DNS.Neu.20.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Neu.20.AllAg.Neural_progenitor_cells mm9 DNase-seq Neural Neural progenitor cel...ls SRX238870,SRX238868 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Neu.20.AllAg.Neural_progenitor_cells.bed ...

  19. File list: DNS.Neu.10.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Neu.10.AllAg.Neural_progenitor_cells mm9 DNase-seq Neural Neural progenitor cel...ls SRX238868,SRX238870 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Neu.10.AllAg.Neural_progenitor_cells.bed ...

  20. File list: Oth.Neu.05.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.05.AllAg.Neural_progenitor_cells mm9 TFs and others Neural Neural progenito...r cells SRX109472,SRX315274,SRX109471,SRX802060 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.05.AllAg.Neural_progenitor_cells.bed ...

  1. File list: ALL.Neu.20.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.20.AllAg.Neural_progenitor_cells mm9 All antigens Neural Neural progenitor ...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.20.AllAg.Neural_progenitor_cells.bed ...

  2. File list: DNS.Neu.05.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Neu.05.AllAg.Neural_progenitor_cells mm9 DNase-seq Neural Neural progenitor cel...ls SRX238870,SRX238868 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Neu.05.AllAg.Neural_progenitor_cells.bed ...

  3. File list: Unc.Neu.05.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.05.AllAg.Neural_progenitor_cells mm9 Unclassified Neural Neural progenitor ...cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.05.AllAg.Neural_progenitor_cells.bed ...

  4. File list: Pol.Neu.20.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.20.AllAg.Induced_neural_progenitors mm9 RNA polymerase Neural Induced neural... progenitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.20.AllAg.Induced_neural_progenitors.bed ...

  5. File list: DNS.Neu.50.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Neu.50.AllAg.Induced_neural_progenitors mm9 DNase-seq Neural Induced neural pro...genitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Neu.50.AllAg.Induced_neural_progenitors.bed ...

  6. File list: His.Neu.05.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.05.AllAg.Induced_neural_progenitors mm9 Histone Neural Induced neural proge...nitors SRX667381,SRX668240 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.05.AllAg.Induced_neural_progenitors.bed ...

  7. File list: His.Neu.20.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.20.AllAg.Induced_neural_progenitors mm9 Histone Neural Induced neural proge...nitors SRX667381,SRX668240 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.20.AllAg.Induced_neural_progenitors.bed ...

  8. File list: Unc.Neu.50.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.50.AllAg.Induced_neural_progenitors mm9 Unclassified Neural Induced neural ...progenitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.50.AllAg.Induced_neural_progenitors.bed ...

  9. File list: Oth.Neu.05.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.05.AllAg.Induced_neural_progenitors mm9 TFs and others Neural Induced neural... progenitors SRX323573,SRX323564 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.05.AllAg.Induced_neural_progenitors.bed ...

  10. File list: His.Neu.10.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.10.AllAg.Induced_neural_progenitors mm9 Histone Neural Induced neural proge...nitors SRX667381,SRX668240 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.10.AllAg.Induced_neural_progenitors.bed ...

  11. File list: Unc.Neu.20.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.20.AllAg.Induced_neural_progenitors mm9 Unclassified Neural Induced neural ...progenitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.20.AllAg.Induced_neural_progenitors.bed ...

  12. File list: His.Neu.50.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.50.AllAg.Induced_neural_progenitors mm9 Histone Neural Induced neural proge...nitors SRX667381,SRX668240 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.50.AllAg.Induced_neural_progenitors.bed ...

  13. File list: Pol.Neu.10.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.10.AllAg.Induced_neural_progenitors mm9 RNA polymerase Neural Induced neural... progenitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.10.AllAg.Induced_neural_progenitors.bed ...

  14. File list: DNS.Neu.10.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Neu.10.AllAg.Induced_neural_progenitors mm9 DNase-seq Neural Induced neural pro...genitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Neu.10.AllAg.Induced_neural_progenitors.bed ...

  15. File list: Oth.Neu.20.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.20.AllAg.Induced_neural_progenitors mm9 TFs and others Neural Induced neural... progenitors SRX323564,SRX323573 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.20.AllAg.Induced_neural_progenitors.bed ...

  16. File list: DNS.Neu.20.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Neu.20.AllAg.Induced_neural_progenitors mm9 DNase-seq Neural Induced neural pro...genitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Neu.20.AllAg.Induced_neural_progenitors.bed ...

  17. File list: Pol.Neu.50.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.50.AllAg.Induced_neural_progenitors mm9 RNA polymerase Neural Induced neural... progenitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.50.AllAg.Induced_neural_progenitors.bed ...

  18. 不同培养基培养人脐血间充质干细胞的差异★%Differences of human umbilical cord blood-derived mesenchymal stem cells cultured in different media

    Institute of Scientific and Technical Information of China (English)

    赵霞; 路希敬; 刘国强; 徐敏; 邢健; 王椋; 丁慧芳

    2013-01-01

    BACKGROUND:The umbilical cord blood-derived mesenchymal stem cel s are the hot spot in the field of stem cel s, and there is no simple, effective culture method for the passage and amplification of umbilical cord blood-derived mesenchymal stem cel s. OBJECTIVE:To explore a better culture method of human umbilical cord blood-derived mesenchymal stem cel s in vitro with different media in the separation of mesenchymal stem cel s at a confluent status. METHODS:Human umbilical cord blood was sterilely col ected from ful-term deliveries scheduled for cesarean section. They were assigned randomly into five groups:low-glucose culture medium group, high-glucose culture medium group,α-culture medium group, low-glucose culture medium+stem cel factor group, low-glucose culture medium+human marrow mesenchymal stem cel s supernatant group. Al culture medium used was Dulbecco’s modIfied Eagle’s medium. The cord blood mononuclear cel s were isolated by lymphocyte separation medium. The monocytes of cord blood were inoculated into the culture medium containing 10%fetal bovine serum at 37 ℃ incubator with 0.05 volume fraction of CO2. Quantity and formation of cel s were observed with invert microscope, and surface antigenic features were analyzed with flow cytometry. RESULTS AND CONCLUSION:(1) Comparison on number of adherent cel s and survival rate of mesenchymal stem cel s cultured for 48 hours:Number of adherent cel s in the low-glucose culture medium+human marrow mesenchymal stem cel s supernatant group, and low-glucose culture medium+stem cel factor group were significantly increased (P<0.05), while the survival rate of cel s was also increased compared with low-glucose culture medium group, high-glucose culture medium group andα-culture medium group (P<0.05). (2) Comparison on growth status of mesenchymal stem cel s at different culture time points:Cel proliferation in the low-glucose culture medium+human marrow mesenchymal stem cel s supernatant group, and low

  19. Ginsenoside Rg1 protects human umbilical cord blood-derived stromal cells against tert-Butyl hydroperoxide-induced apoptosis through Akt-FoxO3a-Bim signaling pathway.

    Science.gov (United States)

    Liu, Ying; Yi, Long; Wang, Lu; Chen, Linbo; Chen, Xiongbin; Wang, Yaping

    2016-10-01

    Human umbilical cord blood-derived stromal cells (hUCBDSCs) possess strong capability of supporting hematopoiesis and immune regulation, whereas some stress conditions cause reactive oxygen species (ROS) accumulation and then lead to oxidative injury and cell apoptosis. Ginsenoside Rg1 (G-Rg1) has been demonstrated to exert antioxidative and prosurvival effects in many cell types. In this study, the tert-Butyl hydroperoxide (t-BHP), an analog of hydroperoxide, was utilized to mimic the oxidative damage to hUCBDSCs. We aimed to investigate the effects of Ginsenoside Rg1 on protecting hUCBDSCs from t-BHP-induced oxidative injury and apoptosis, as well as the possible signaling pathway involved. It was shown that the treatment of hUCBDSCs with G-Rg1 markedly restored the t-BHP-induced cell viability loss, promoted the CFU-F formation, and inhibited cell apoptosis. G-Rg1 also caused a reduced production of LDH and MDA while significantly enhancing the activity of SOD. Mechanistically, G-Rg1 promoted the phosphorylation of Akt and FoxO3a and led to the cytoplasmic translocation of FoxO3a, which in turn suppressed FoxO3a-modulated expression of proapoptotic Bim and elevated the ratio of Bcl-2 to Bax. All these results suggest that G-Rg1 enhances the survival of t-BHP-induced hUCBDSCs and protects them against apoptosis at least partially through Akt-FoxO3a-Bim signaling pathway. PMID:27522666

  20. Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors

    DEFF Research Database (Denmark)

    Paul, Franziska; Arkin, Ya'ara; Giladi, Amir;

    2015-01-01

    Within the bone marrow, stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with in vivo differentiation potential or gene regulatory m...

  1. Cosmic Supernova Rate History and Type Ia Supernova Progenitors

    OpenAIRE

    Kobayashi, Chiaki; Nomoto, Ken'ichi; Tsujimoto, Takuji

    2001-01-01

    Adopting a single degenerate scenario for Type Ia supernova progenitors with the metallicity effect, we make a prediction of the cosmic supernova rate history as a composite of the supernova rates in spiral and elliptical galaxies, and compare with the recent observational data up to z ~ 0.55.

  2. Stem cells and progenitor cells in renal disease.

    Science.gov (United States)

    Haller, Hermann; de Groot, Kirsten; Bahlmann, Ferdinand; Elger, Marlies; Fliser, Danilo

    2005-11-01

    Stem cells and progenitor cells are necessary for repair and regeneration of injured renal tissue. Infiltrating or resident stem cells can contribute to the replacement of lost or damaged tissue. However, the regulation of circulating progenitor cells is not well understood. We have analyzed the effects of erythropoietin on circulating progenitor cells and found that low levels of erythropoietin induce mobilization and differentiation of endothelial progenitor cells. In an animal model of 5/6 nephrectomy we could demonstrate that erythropoietin ameliorates tissue injury. Full regeneration of renal tissue demands the existence of stem cells and an adequate local "milieu," a so-called stem cell niche. We have previously described a stem cell niche in the kidneys of the dogfish, Squalus acanthus. Further analysis revealed that in the regenerating zone of the shark kidney, stem cells exist that can be induced by loss of renal tissue to form new glomeruli. Such animal models improve our understanding of stem cell behavior in the kidney and may eventually contribute to novel therapies. PMID:16221168

  3. Progenitor cells in the kidney: biology and therapeutic perspectives

    NARCIS (Netherlands)

    Rookmaaker, M.B.; Verhaar, M.C.; Zonneveld, A.J. van; Rabelink, T.J.

    2004-01-01

    Progenitor cells in the kidney: Biology and therapeutic perspectives. The stem cell may be viewed as an engineer who can read the blue print and become the building. The role of this fascinating cell in physiology and pathophysiology has recently attracted a great deal of interest. The archetype of

  4. Progenitor models of Wolf-Rayet+O binary systems

    NARCIS (Netherlands)

    Petrovic, J.; Langer, N.

    2007-01-01

    Since close WR+O binaries are the result of a strong interaction of both stars in massive close binary systems, they can be used to constrain the highly uncertain mass and angular momentum budget during the major mass- transfer phase. We explore the progenitor evolution of the three best suited WR+O

  5. Retinal progenitor cell xenografts to the pig retina

    DEFF Research Database (Denmark)

    Warfvinge, Karin; Kiilgaard, Jens Folke; Klassen, Henry;

    2006-01-01

    We evaluated the host response to murine retinal progenitor cells (RPCs) following transplantation to the subretinal space (SRS) of the pig. RPCs from GFP mice were transplanted subretinally in 18 nonimmunosuppressed normal or laser-treated pigs. Evaluation of the SRS was performed on hematoxylin-eosin...

  6. Transcriptome analysis reveals transmembrane targets on transplantable midbrain dopamine progenitors.

    Science.gov (United States)

    Bye, Chris R; Jönsson, Marie E; Björklund, Anders; Parish, Clare L; Thompson, Lachlan H

    2015-04-14

    An important challenge for the continued development of cell therapy for Parkinson's disease (PD) is the establishment of procedures that better standardize cell preparations for use in transplantation. Although cell sorting has been an anticipated strategy, its application has been limited by lack of knowledge regarding transmembrane proteins that can be used to target and isolate progenitors for midbrain dopamine (mDA) neurons. We used a "FACS-array" approach to identify 18 genes for transmembrane proteins with high expression in mDA progenitors and describe the utility of four of these targets (Alcam, Chl1, Gfra1, and Igsf8) for isolating mDA progenitors from rat primary ventral mesencephalon through flow cytometry. Alcam and Chl1 facilitated a significant enrichment of mDA neurons following transplantation, while targeting of Gfra1 allowed for robust separation of dopamine and serotonin neurons. Importantly, we also show that mDA progenitors isolated on the basis of transmembrane proteins are capable of extensive, functional innervation of the host striatum and correction of motor impairment in a unilateral model of PD. These results are highly relevant for current efforts to establish safe and effective stem cell-based procedures for PD, where clinical translation will almost certainly require safety and standardization measures in order to deliver well-characterized cell preparations.

  7. The progenitor of Nova Cygni 2006 (=V2362 Cyg)

    NARCIS (Netherlands)

    Steeghs, D.; Greimel, R.; Drew, J.; Irwin, M.; Gaensicke, B.; Groot, P.J.; Knigge, C.

    2006-01-01

    We report on the detection of the likely progenitor to Nova Cygni 2006 = V2362 Cyg (IAUC #8697, #8698, ATel #792) using images from the INT Photometric H-Alpha Survey (IPHAS; http://www.iphas.org). The field containing the classical nova was observed as part of our galactic plane survey on Aug. 3rd

  8. Functional cardiomyocytes derived from Isl1 cardiac progenitors via Bmp4 stimulation.

    Directory of Open Access Journals (Sweden)

    Esra Cagavi

    Full Text Available As heart failure due to myocardial infarction remains a leading cause of morbidity worldwide, cell-based cardiac regenerative therapy using cardiac progenitor cells (CPCs could provide a potential treatment for the repair of injured myocardium. As adult CPCs may have limitations regarding tissue accessibility and proliferative ability, CPCs derived from embryonic stem cells (ESCs could serve as an unlimited source of cells with high proliferative ability. As one of the CPCs that can be derived from embryonic stem cells, Isl1 expressing cardiac progenitor cells (Isl1-CPCs may serve as a valuable source of cells for cardiac repair due to their high cardiac differentiation potential and authentic cardiac origin. In order to generate an unlimited number of Isl1-CPCs, we used a previously established an ESC line that allows for isolation of Isl1-CPCs by green fluorescent protein (GFP expression that is directed by the mef2c gene, specifically expressed in the Isl1 domain of the anterior heart field. To improve the efficiency of cardiac differentiation of Isl1-CPCs, we studied the role of Bmp4 in cardiogenesis of Isl1-CPCs. We show an inductive role of Bmp directly on cardiac progenitors and its enhancement on early cardiac differentiation of CPCs. Upon induction of Bmp4 to Isl1-CPCs during differentiation, the cTnT+ cardiomyocyte population was enhanced 2.8±0.4 fold for Bmp4 treated CPC cultures compared to that detected for vehicle treated cultures. Both Bmp4 treated and untreated cardiomyocytes exhibit proper electrophysiological and calcium signaling properties. In addition, we observed a significant increase in Tbx5 and Tbx20 expression in differentiation cultures treated with Bmp4 compared to the untreated control, suggesting a link between Bmp4 and Tbx genes which may contribute to the enhanced cardiac differentiation in Bmp4 treated cultures. Collectively these findings suggest a cardiomyogenic role for Bmp4 directly on a pure population of

  9. Giant Panda (Ailuropoda melanoleuca Buccal Mucosa Tissue as a Source of Multipotent Progenitor Cells.

    Directory of Open Access Journals (Sweden)

    Hilary M A Prescott

    Full Text Available Since the first mammal was cloned, the idea of using this technique to help endangered species has aroused considerable interest. However, several issues limit this possibility, including the relatively low success rate at every stage of the cloning process, and the dearth of usable tissues from these rare animals. iPS cells have been produced from cells from a number of rare mammalian species and this is the method of choice for strategies to improve cloning efficiency and create new gametes by directed differentiation. Nevertheless information about other stem cell/progenitor capabilities of cells from endangered species could prove important for future conservation approaches and adds to the knowledge base about cellular material that can be extremely limited. Multipotent progenitor cells, termed skin-derived precursor (SKP cells, can be isolated directly from mammalian skin dermis, and human cheek tissue has also been shown to be a good source of SKP-like cells. Recently we showed that structures identical to SKPs termed m-SKPs could be obtained from monolayer/ two dimensional (2D skin fibroblast cultures. Here we aimed to isolate m-SKPs from cultured cells of three endangered species; giant panda (Ailuropoda melanoleuca; red panda (Ailurus fulgens; and Asiatic lion (Panthera leo persica. m-SKP-like spheres were formed from the giant panda buccal mucosa fibroblasts; whereas dermal fibroblast (DF cells cultured from abdominal skin of the other two species were unable to generate spheres. Under specific differentiation culture conditions giant panda spheres expressed neural, Schwann, adipogenic and osteogenic cell markers. Furthermore, these buccal mucosa derived spheres were shown to maintain expression of SKP markers: nestin, versican, fibronectin, and P75 and switch on expression of the stem cell marker ABCG2. These results demonstrate that giant panda cheek skin can be a useful source of m-SKP multipotent progenitors. At present lack of

  10. Giant Panda (Ailuropoda melanoleuca) Buccal Mucosa Tissue as a Source of Multipotent Progenitor Cells.

    Science.gov (United States)

    Prescott, Hilary M A; Manning, Craig; Gardner, Aaron; Ritchie, William A; Pizzi, Romain; Girling, Simon; Valentine, Iain; Wang, Chengdong; Jahoda, Colin A B

    2015-01-01

    Since the first mammal was cloned, the idea of using this technique to help endangered species has aroused considerable interest. However, several issues limit this possibility, including the relatively low success rate at every stage of the cloning process, and the dearth of usable tissues from these rare animals. iPS cells have been produced from cells from a number of rare mammalian species and this is the method of choice for strategies to improve cloning efficiency and create new gametes by directed differentiation. Nevertheless information about other stem cell/progenitor capabilities of cells from endangered species could prove important for future conservation approaches and adds to the knowledge base about cellular material that can be extremely limited. Multipotent progenitor cells, termed skin-derived precursor (SKP) cells, can be isolated directly from mammalian skin dermis, and human cheek tissue has also been shown to be a good source of SKP-like cells. Recently we showed that structures identical to SKPs termed m-SKPs could be obtained from monolayer/ two dimensional (2D) skin fibroblast cultures. Here we aimed to isolate m-SKPs from cultured cells of three endangered species; giant panda (Ailuropoda melanoleuca); red panda (Ailurus fulgens); and Asiatic lion (Panthera leo persica). m-SKP-like spheres were formed from the giant panda buccal mucosa fibroblasts; whereas dermal fibroblast (DF) cells cultured from abdominal skin of the other two species were unable to generate spheres. Under specific differentiation culture conditions giant panda spheres expressed neural, Schwann, adipogenic and osteogenic cell markers. Furthermore, these buccal mucosa derived spheres were shown to maintain expression of SKP markers: nestin, versican, fibronectin, and P75 and switch on expression of the stem cell marker ABCG2. These results demonstrate that giant panda cheek skin can be a useful source of m-SKP multipotent progenitors. At present lack of sample numbers

  11. Reactive microglia and macrophage facilitate the formation of Müller glia-derived retinal progenitors.

    Science.gov (United States)

    Fischer, Andy J; Zelinka, Christopher; Gallina, Donika; Scott, Melissa A; Todd, Levi

    2014-10-01

    In retinas where Müller glia have been stimulated to become progenitor cells, reactive microglia are always present. Thus, we investigated how the activation or ablation of microglia/macrophage influences the formation of Müller glia-derived progenitor cells (MGPCs) in the retina in vivo. Intraocular injections of the Interleukin-6 (IL6) stimulated the reactivity of microglia/macrophage, whereas other types of retinal glia appear largely unaffected. In acutely damaged retinas where all of the retinal microglia/macrophage were ablated, the formation of proliferating MGPCs was greatly diminished. With the microglia ablated in damaged retinas, levels of Notch and related genes were unchanged or increased, whereas levels of ascl1a, TNFα, IL1β, complement component 3 (C3) and C3a receptor were significantly reduced. In the absence of retinal damage, the combination of insulin and Fibroblast growth factor 2 (FGF2) failed to stimulate the formation of MGPCs when the microglia/macrophage were ablated. In addition, intraocular injections of IL6 and FGF2 stimulated the formation of MGPCs in the absence of retinal damage, and this generation of MGPCs was blocked when the microglia/macrophage were absent. We conclude that the activation of microglia and/or infiltrating macrophage contributes to the formation of proliferating MGPCs, and these effects may be mediated by components of the complement system and inflammatory cytokines.

  12. Renewal of the Holocrine Meibomian Glands by Label-Retaining, Unipotent Epithelial Progenitors

    Directory of Open Access Journals (Sweden)

    Geraint J. Parfitt

    2016-09-01

    Full Text Available The meibomian and sebaceous glands secrete lipids to prevent desiccation of the ocular surface and skin, respectively. Precisely how these holocrine tissues regenerate is not well understood. To address this, we characterized keratin 5+ (K5 label-retaining cells (LRCs and the lineage tracing of keratin 14 (K14 progenitors in mouse meibomian glands. Using the tet-off H2B-GFP/K5tTA mouse, H2B-GFP fluorescence dilutes 2-fold with every division in K5+ cell nuclei after doxycycline administration. In 3D reconstructions generated over a >28-day doxycycline chase, we observed LRCs at the acinus entrance where K6+ ductal epithelium terminates. For lineage tracing, K14CreERT2-Confetti mice were injected intraperitoneally with tamoxifen and euthanized at 23 and 59 weeks later. Meibomian gland acini in these mice were either monochromatic or dual-colored, whereas the duct exhibited multiple colors. In conclusion, LRCs are likely to direct meibomian gland turnover and may exist as two distinct unipotent progenitors that renew ductal and acinar tissue separately.

  13. Differential Reponses of Hematopoietic Stem and Progenitor Cells to mTOR Inhibition

    Directory of Open Access Journals (Sweden)

    Aimin Yang

    2015-01-01

    Full Text Available Abnormal activation of the mammalian target of rapamycin (mTOR signaling pathway has been observed in a variety of human cancers. Therefore, targeting of the mTOR pathway is an attractive strategy for cancer treatment and several mTOR inhibitors, including AZD8055 (AZD, a novel dual mTORC1/2 inhibitor, are currently in clinical trials. Although bone marrow (BM suppression is one of the primary side effects of anticancer drugs, it is not known if pharmacological inhibition of dual mTORC1/2 affects BM hematopoietic stem and progenitor cells (HSPCs function and plasticity. Here we report that dual inhibition of mTORC1/2 by AZD or its analogue (KU-63794 depletes mouse BM Lin−Sca-1+c-Kit+ cells in cultures via the induction of apoptotic cell death. Subsequent colony-forming unit (CFU assays revealed that inhibition of mTORC1/2 suppresses the clonogenic function of hematopoietic progenitor cells (HPCs in a dose-dependent manner. Surprisingly, we found that dual inhibition of mTORC1/2 markedly inhibits the growth of day-14 cobblestone area-forming cells (CAFCs but enhances the generation of day-35 CAFCs. Given the fact that day-14 and day-35 CAFCs are functional surrogates of HPCs and hematopoietic stem cells (HSCs, respectively, these results suggest that dual inhibition of mTORC1/2 may have distinct effects on HPCs versus HSCs.

  14. Human Bone Marrow Mesenchymal Progenitors: Perspectives on an Optimized In Vitro Manipulation

    Directory of Open Access Journals (Sweden)

    Eric eCordeiro-Spinetti

    2014-03-01

    Full Text Available When it comes to regenerative medicine, mesenchymal stem cells (MSCs are considered one of the most promising cell types for use in many cell therapies and bioengineering protocols. The International Society of Cellular Therapy recommended minimal criteria for defining multipotential MSC is based on adhesion and multipotency in vitro, and the presence or absence of select surface markers. Though these criteria help minimize discrepancies and allow some comparisons of data generated in different laboratories, the conditions in which cells are isolated and expanded are often not considered. Herein, we propose and recommend a few procedures to be followed to facilitate the establishment of quality control standards when working with mesenchymal progenitors isolation and expansion. Following these procedures, the classic Colony-Forming Unit-Fibroblast (CFU-f assay is revisited and three major topics are considered to define conditions and to assist on protocol optimization and data interpretation. We envision that the creation of a guideline will help in the identification and isolation of long-term stem cells and short-term progenitors to better explore their regenerative potential for multiple therapeutic purposes.

  15. Gingival Mesenchymal Stem/Progenitor Cells: A Unique Tissue Engineering Gem

    Science.gov (United States)

    Fawzy El-Sayed, Karim M.; Dörfer, Christof E.

    2016-01-01

    The human gingiva, characterized by its outstanding scarless wound healing properties, is a unique tissue and a pivotal component of the periodontal apparatus, investing and surrounding the teeth in their sockets in the alveolar bone. In the last years gingival mesenchymal stem/progenitor cells (G-MSCs), with promising regenerative and immunomodulatory properties, have been isolated and characterized from the gingival lamina propria. These cells, in contrast to other mesenchymal stem/progenitor cell sources, are abundant, readily accessible, and easily obtainable via minimally invasive cell isolation techniques. The present review summarizes the current scientific evidence on G-MSCs' isolation, their characterization, the investigated subpopulations, the generated induced pluripotent stem cells- (iPSC-) like G-MSCs, their regenerative properties, and current approaches for G-MSCs' delivery. The review further demonstrates their immunomodulatory properties, the transplantation preconditioning attempts via multiple biomolecules to enhance their attributes, and the experimental therapeutic applications conducted to treat multiple diseases in experimental animal models in vivo. G-MSCs show remarkable tissue reparative/regenerative potential, noteworthy immunomodulatory properties, and primary experimental therapeutic applications of G-MSCs are very promising, pointing at future biologically based therapeutic techniques, being potentially superior to conventional clinical treatment modalities. PMID:27313628

  16. Stem and progenitor cells in biostructure of blood vessel walls

    Directory of Open Access Journals (Sweden)

    Krzysztof Korta

    2013-09-01

    Full Text Available Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, “anchored” in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC. Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as “subendothelial or vasculogenic zones”. Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

  17. Alteration of cardiac progenitor cell potency in GRMD dogs.

    Science.gov (United States)

    Cassano, M; Berardi, E; Crippa, S; Toelen, J; Barthelemy, I; Micheletti, R; Chuah, M; Vandendriessche, T; Debyser, Z; Blot, S; Sampaolesi, M

    2012-01-01

    Among the animal models of Duchenne muscular dystrophy (DMD), the Golden Retriever muscular dystrophy (GRMD) dog is considered the best model in terms of size and pathological onset of the disease. As in human patients presenting with DMD or Becker muscular dystrophies (BMD), the GRMD is related to a spontaneous X-linked mutation of dystrophin and is characterized by myocardial lesions. In this respect, GRMD is a useful model to explore cardiac pathogenesis and for the development of therapeutic protocols. To investigate whether cardiac progenitor cells (CPCs) isolated from healthy and GRMD dogs may differentiate into myocardial cell types and to test the feasibility of cell therapy for cardiomyopathies in a preclinical model of DMD, CPCs were isolated from cardiac biopsies of healthy and GRMD dogs. Gene profile analysis revealed an active cardiac transcription network in both healthy and GRMD CPCs. However, GRMD CPCs showed impaired self-renewal and cardiac differentiation. Population doubling and telomerase analyses highlighted earlier senescence and proliferation impairment in progenitors isolated from GRMD cardiac biopsies. Immunofluorescence analysis revealed that only wt CPCs showed efficient although not terminal cardiac differentiation, consistent with the upregulation of cardiac-specific proteins and microRNAs. Thus, the pathological condition adversely influences the cardiomyogenic differentiation potential of cardiac progenitors. Using PiggyBac transposon technology we marked CPCs for nuclear dsRed expression, providing a stable nonviral gene marking method for in vivo tracing of CPCs. Xenotransplantation experiments in neonatal immunodeficient mice revealed a valuable contribution of CPCs to cardiomyogenesis with homing differences between wt and dystrophic progenitors. These results suggest that cardiac degeneration in dystrophinopathies may account for the progressive exhaustion of local cardiac progenitors and shed light on cardiac stemness in

  18. MiR-128-2 inhibits common lymphoid progenitors from developing into progenitor B cells

    Science.gov (United States)

    Chen, Huo; Fei, Xia; Tang, YuXu; Yan, Yunqiu; Zhang, Huimin; Zhang, Jinping

    2016-01-01

    A considerable number of studies revealed that B cell development is finely regulated by transcription factors (TFs). Recent studies suggested that TFs are coordinated with microRNAs to control the development of B cells in numerous checkpoints. In the present study, we first found that miR-128-2 was differentially expressed in various immune organs and immunocytes. B cell development was inhibited in miR-128-2-overexpressed chimera and transgenic (TG) mice in bone marrow with decreased preproB, preB, proB, immature B, and recirculating B cells, as well as increased common lymphoid progenitors (CLPs). Further experiments showed that the apoptosis of CLP decreased, but proliferation was not altered in miR-128-2-overexpressed mice. Extensive studies suggested that the inhibition of apoptosis of CLP may be caused by miR-128-2 targeting A2B and MALT1, thereby increasing the phosphorylation of ERK and P38 MAPK. Such findings have prompted future investigations on the function of miR-128-2 in lymph genesis. PMID:27008703

  19. Cross-talk between the epidermal growth factor-like repeats/fibronectin 6-8 repeats domains of Tenascin-R and microglia modulates neural stem/progenitor cell proliferation and differentiation.

    Science.gov (United States)

    Liao, Hong; Huang, Wenhui; Niu, Rui; Sun, Lixin; Zhang, Luyong

    2008-01-01

    Mounting evidence has demonstrated that the microenvironment of stem/progenitor cells plays an important role in their proliferation and commitment to their fate. However, it remains unclear how all elements, such as astrocytes, microglia, extracellular matrix molecules, soluble factors, and their cross-talk interactions in the microenvironments, affect neural stem/progenitor cell fate. This work explored the influences of cross-talk between Tenascin-R (TN-R) and microglia on neural stem/progenitor cell proliferation and differentiation. Our results show that microglia triggered by TN-R distinct domains EGF-like repeats (EGFL) and fibronectin 6-8 repeats (FN6-8) significantly enhanced the proliferation of neural stem/progenitor cells and also obviously induced the differentiation into neurons but not oligodendrocytes. Neurite processes of neurons generated from neural progenitor cells were promoted by both EGFL and FN6-8 domains-activated microglia. Microglia triggered by EGFL and FN6-8 secreted brain-derived neurotrophic factor (BDNF) and transforming growth factor-beta (TGF-beta); interestingly, FN6-8 could activate microglia to secrete nerve growth factor in addition to BDNF and TGF-beta, but EGFL domain could not. All these data implied that the cross-talk between TN-R distinct domains EGFL/FN6-8 and microglia promoted neural stem/progenitor cell proliferation and induced their differentiation into neurons.

  20. Uncovering the Number and Clonal Dynamics of Mesp1 Progenitors during Heart Morphogenesis

    Directory of Open Access Journals (Sweden)

    Samira Chabab

    2016-01-01

    Full Text Available The heart arises from distinct sources of cardiac progenitors that independently express Mesp1 during gastrulation. The precise number of Mesp1 progenitors that are specified during the early stage of gastrulation, and their clonal behavior during heart morphogenesis, is currently unknown. Here, we used clonal and mosaic tracing of Mesp1-expressing cells combined with quantitative biophysical analysis of the clonal data to define the number of cardiac progenitors and their mode of growth during heart development. Our data indicate that the myocardial layer of the heart derive from ∼250 Mesp1-expressing cardiac progenitors born during gastrulation. Despite arising at different time points and contributing to different heart regions, the temporally distinct cardiac progenitors present very similar clonal dynamics. These results provide insights into the number of cardiac progenitors and their mode of growth and open up avenues to decipher the clonal dynamics of progenitors in other organs and tissues.

  1. Treating diet-induced diabetes and obesity with human embryonic stem cell-derived pancreatic progenitor cells and antidiabetic drugs.

    Science.gov (United States)

    Bruin, Jennifer E; Saber, Nelly; Braun, Natalie; Fox, Jessica K; Mojibian, Majid; Asadi, Ali; Drohan, Campbell; O'Dwyer, Shannon; Rosman-Balzer, Diana S; Swiss, Victoria A; Rezania, Alireza; Kieffer, Timothy J

    2015-04-14

    Human embryonic stem cell (hESC)-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported. An immunodeficient model of type 2 diabetes was generated by high-fat diet (HFD) feeding in SCID-beige mice. Exposure to HFDs did not impact the maturation of macroencapsulated pancreatic progenitor cells into glucose-responsive insulin-secreting cells following transplantation, and the cell therapy improved glucose tolerance in HFD-fed transplant recipients after 24 weeks. However, since diet-induced hyperglycemia and obesity were not fully ameliorated by transplantation alone, a second cohort of HFD-fed mice was treated with pancreatic progenitor cells combined with one of three antidiabetic drugs. All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks. Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs.

  2. A Gene Regulatory Network Cooperatively Controlled by Pdx1 and Sox9 Governs Lineage Allocation of Foregut Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Hung Ping Shih

    2015-10-01

    Full Text Available The generation of pancreas, liver, and intestine from a common pool of progenitors in the foregut endoderm requires the establishment of organ boundaries. How dorsal foregut progenitors activate pancreatic genes and evade the intestinal lineage choice remains unclear. Here, we identify Pdx1 and Sox9 as cooperative inducers of a gene regulatory network that distinguishes the pancreatic from the intestinal lineage. Genetic studies demonstrate dual and cooperative functions for Pdx1 and Sox9 in pancreatic lineage induction and repression of the intestinal lineage choice. Pdx1 and Sox9 bind to regulatory sequences near pancreatic and intestinal differentiation genes and jointly regulate their expression, revealing direct cooperative roles for Pdx1 and Sox9 in gene activation and repression. Our study identifies Pdx1 and Sox9 as important regulators of a transcription factor network that initiates pancreatic fate and sheds light on the gene regulatory circuitry that governs the development of distinct organs from multi-lineage-competent foregut progenitors.

  3. Treating Diet-Induced Diabetes and Obesity with Human Embryonic Stem Cell-Derived Pancreatic Progenitor Cells and Antidiabetic Drugs

    Directory of Open Access Journals (Sweden)

    Jennifer E. Bruin

    2015-04-01

    Full Text Available Human embryonic stem cell (hESC-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported. An immunodeficient model of type 2 diabetes was generated by high-fat diet (HFD feeding in SCID-beige mice. Exposure to HFDs did not impact the maturation of macroencapsulated pancreatic progenitor cells into glucose-responsive insulin-secreting cells following transplantation, and the cell therapy improved glucose tolerance in HFD-fed transplant recipients after 24 weeks. However, since diet-induced hyperglycemia and obesity were not fully ameliorated by transplantation alone, a second cohort of HFD-fed mice was treated with pancreatic progenitor cells combined with one of three antidiabetic drugs. All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks. Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs.

  4. Characterization of neural stem/progenitor cells expressing VEGF and its receptors in the subventricular zone of newborn piglet brain.

    Science.gov (United States)

    Ara, Jahan; Fekete, Saskia; Zhu, Anli; Frank, Melissa

    2010-09-01

    Neural stem/progenitor cell (NSP) biology and neurogenesis in adult central nervous system (CNS) are important both towards potential future therapeutic applications for CNS repair, and for the fundamental function of the CNS. In the present study, we report the characterization of NSP population from subventricular zone (SVZ) of neonatal piglet brain using in vivo and in vitro systems. We show that the nestin and vimentin-positive neural progenitor cells are present in the SVZ of the lateral ventricles of neonatal piglet brain. In vitro, piglet NSPs proliferated as neurospheres, expressed the typical protein of neural progenitors, nestin and a range of well-established neurodevelopmental markers. Upon dissociation and subculture, piglet NSPs differentiated into neurons and glial cells. Clonal analysis demonstrates that piglet NSPs are multipotent and retain the capacity to generate both glia and neurons. These cells expressed VEGF, VEGFR1, VEGFR2 and Neuropilin-1 and -2 mRNAs. Real time PCR revealed that SVZ NSPs from newborn piglet expressed total VEGF and all VEGF splice variants. These findings show that piglet NSPs may be helpful to more effectively design growth factor based strategies to enhance endogenous precursor cells for cell transplantation studies potentially leading to the application of this strategy in the nervous system disease and injury.

  5. OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Xiaoli Chen

    2015-09-01

    Full Text Available Generating engraftable hematopoietic stem cells (HSCs from pluripotent stem cells (PSCs is an ideal approach for obtaining induced HSCs for cell therapy. However, the path from PSCs to robustly induced HSCs (iHSCs in vitro remains elusive. We hypothesize that the modification of hematopoietic niche cells by transcription factors facilitates the derivation of induced HSCs from PSCs. The Lhx2 transcription factor is expressed in fetal liver stromal cells but not in fetal blood cells. Knocking out Lhx2 leads to a fetal hematopoietic defect in a cell non-autonomous role. In this study, we demonstrate that the ectopic expression of Lhx2 in OP9 cells (OP9-Lhx2 accelerates the hematopoietic differentiation of PSCs. OP9-Lhx2 significantly increased the yields of hematopoietic progenitor cells via co-culture with PSCs in vitro. Interestingly, the co-injection of OP9-Lhx2 and PSCs into immune deficient mice also increased the proportion of hematopoietic progenitors via the formation of teratomas. The transplantation of phenotypic HSCs from OP9-Lhx2 teratomas but not from the OP9 control supported a transient repopulating capability. The upregulation of Apln gene by Lhx2 is correlated to the hematopoietic commitment property of OP9-Lhx2. Furthermore, the enforced expression of Apln in OP9 cells significantly increased the hematopoietic differentiation of PSCs. These results indicate that OP9-Lhx2 is a good cell line for regeneration of hematopoietic progenitors both in vitro and in vivo.

  6. A novel lymphoid progenitor cell population (LSK(low)) is restricted by p18(INK4c).

    Science.gov (United States)

    Dong, Fang; Hao, Sha; Ma, Shihui; Cheng, Hui; Wang, Yajie; Zhou, Wen; Yuan, Weiping; Ema, Hideo; Cheng, Tao

    2016-09-01

    The cyclin-dependent kinase inhibitor CDKN2C (p18(INK4c)) restrains self-renewal in hematopoietic stem cells (HSCs) and participates in the development and maturation of lymphoid cells. Deficiency in p18 predisposes mice and humans to hematopoietic lymphoid malignancies such as T-cell leukemia and multiple myeloma. However, the mechanism by which p18 regulates differentiation from HSCs to lymphoid cells is poorly understood. In this study, we found that a progenitor population characterized by its expression of surface markers, Lin(-) Sca-1(+) c-Kit(low) (LSK(low)), was markedly expanded in the bone marrow of p18 knock-out (p18(-/-)) mice. This novel population possessed lymphoid differentiation potential, but not myeloid differentiation potential, both in vitro and in vivo. Whereas LSK(low) cells and common lymphoid progenitors (CLPs) overlapped functionally in generating lymphoid cells, they were distinct cell populations, because they had different gene expression profiles. Unlike CLPs, LSK(low) cells did not express the interleukin-7 receptor. LSK(low) cells were derived from HSCs and were independent of the p18-deleted microenvironment. This cell population may represent a previously unappreciated transitional stage from HSCs to lymphoid progenitors that is strictly restricted by p18 under physiological conditions. Likewise, LSK(low) might serve as a new cellular target of lymphoid malignances in the absence of p18.

  7. La violencia de hijos adolescentes contra sus progenitores La violencia de hijos adolescentes contra sus progenitores

    Directory of Open Access Journals (Sweden)

    Concepción Aroca Montolío

    2013-10-01

    Full Text Available According to Prosecutor’s Office of the Minor, the accusation interposed by mothers and/or fathers victims by theirs children, along 2007 were 2603, in 2008 amounted 4.211, in 2009 there were 5.209 and in 2010 there were 8.000 accusations. Suede this worrying increase, the principal aim of our article is to check the scientific international and national documentation, from 1957 until the year 2010 that analyses the phenomenon of the adolescent violence against parents, to achieve an approximation to its keys that there allows us the comprehension and analysis of this serious familiar problem. For it we will analyse: (a the importance of this crime by means of criminological mediators: prevalence and incidence; (b the age and sex variables’ aggressors to be able to establish a basic profile about theirs and, (c the violence types that the teenagers wield to damage, prejudice and suffering against their progenitors, with the aim to obtain what they want. The information obtained in this research review and qualitative analysis, change in base to the methodology used and the type of sample under study to obtain conclusions. Even though, we wantto do research into needs to investigate this type of familiar violence, and from there, to do researches with rigorous scientific methodologies, unifying criteria and variables to be investigating, to be able to anticipate in this increasing problem that the parents have. Según la Fiscalía del Menor en el año 2007, las denuncias interpuestas por madres y/o padres, víctimas de malos tratos por sus hijos e hijas menores de edad, fueron 2.683. En 2008 ascendieron a 4.211, en 2009 se presentaron 5.209 y en el año 2010 se registraron 8.000 denuncias. Ante éste preocupante incremento, el objetivo principal de nuestro artículo es revisar la documentación científica que analiza la violencia filio-parental,  desde 1957 hasta el año 2011, para lograr una aproximación a sus claves que nos permita la

  8. GDE2 regulates subtype-specific motor neuron generation through inhibition of Notch signaling.

    Science.gov (United States)

    Sabharwal, Priyanka; Lee, Changhee; Park, Sungjin; Rao, Meenakshi; Sockanathan, Shanthini

    2011-09-22

    The specification of spinal interneuron and motor neuron identities initiates within progenitor cells, while motor neuron subtype diversification is regulated by hierarchical transcriptional programs implemented postmitotically. Here we find that mice lacking GDE2, a six-transmembrane protein that triggers motor neuron generation, exhibit selective losses of distinct motor neuron subtypes, specifically in defined subsets of limb-innervating motor pools that correlate with the loss of force-generating alpha motor neurons. Mechanistically, GDE2 is expressed by postmitotic motor neurons but utilizes extracellular glycerophosphodiester phosphodiesterase activity to induce motor neuron generation by inhibiting Notch signaling in neighboring motor neuron progenitors. Thus, neuronal GDE2 controls motor neuron subtype diversity through a non-cell-autonomous feedback mechanism that directly regulates progenitor cell differentiation, implying that subtype specification initiates within motor neuron progenitor populations prior to their differentiation into postmitotic motor neurons.

  9. Properties of Adult Lung Stem and Progenitor Cells.

    Science.gov (United States)

    Bertoncello, Ivan

    2016-12-01

    The last decade has seen significant progress in understanding the organisation of regenerative cells in the adult lung. Cell-lineage tracing and in vitro clonogenic assays have enabled the identification and characterisation of endogenous lung epithelial stem and progenitor cells. Selective lung injury models, and genetically engineered mice have revealed highly conserved gene networks, factors, signalling pathways, and cellular interactions important in maintaining lung homeostasis and regulating lung regeneration and repair following injury. This review describes the current models of lung epithelial stem and progenitor cell organisation in adult mice, and the impediments encountered in translational studies aiming to identify and characterise their human homologs. J. Cell. Physiol. 231: 2582-2589, 2016. © 2016 Wiley Periodicals, Inc. PMID:27062064

  10. Glial progenitor cell-based treatment of the childhood leukodystrophies

    DEFF Research Database (Denmark)

    Osorio, M Joana; Goldman, Steven A

    2016-01-01

    stem cell-derived human neural or glial progenitor cells may comprise a promising strategy for both structural remyelination and metabolic rescue. A broad variety of pediatric white matter disorders, including the primary hypomyelinating disorders, the lysosomal storage disorders, and the broader group...... genetic editing of pluripotent stem cells. Yet these challenges notwithstanding, the promise of glial progenitor cell-based treatment of the childhood myelin disorders offers hope to the many victims of this otherwise largely untreatable class of disease....... and astrocytes are the major affected cell populations, and are either structurally impaired or metabolically compromised through cell-intrinsic pathology, or are the victims of mis-accumulated toxic byproducts of metabolic derangement. In either case, glial cell replacement using implanted tissue or pluripotent...

  11. Massive Binaries, Wolf-Rayet Stars and Supernova Progenitors

    Directory of Open Access Journals (Sweden)

    J.J. Eldridge

    2007-01-01

    Full Text Available La estrellas binarias son importantes para entender la evoluci on estelar. Presentamos un resumen de c omo las predicciones de las tasas relativas de supernova var an entre estrellas aisladas y binarias. Tambi en mostramos c omo el espacio de par ametros de tipos diferentes de supernovas di eren entre estrellas aisladas y binarias. Entonces, consideramos una pregunta importante sobre c omo saber las propiedades del progenitor de supernova a trav es de las im agenes previas a la explosi on y a trav es del trabajo reciente de producir colores sint eticos de nuestros modelos estelares para hacer una comparaci on directa con cualquier detecci on o l mite obtenido de las im agenes pre-explosi on de los progenitores de supernova

  12. Epigenetic Reprogramming of Muscle Progenitors: Inspiration for Clinical Therapies

    Directory of Open Access Journals (Sweden)

    Silvia Consalvi

    2016-01-01

    Full Text Available In the context of regenerative medicine, based on the potential of stem cells to restore diseased tissues, epigenetics is becoming a pivotal area of interest. Therapeutic interventions that promote tissue and organ regeneration have as primary objective the selective control of gene expression in adult stem cells. This requires a deep understanding of the epigenetic mechanisms controlling transcriptional programs in tissue progenitors. This review attempts to elucidate the principle epigenetic regulations responsible of stem cells differentiation. In particular we focus on the current understanding of the epigenetic networks that regulate differentiation of muscle progenitors by the concerted action of chromatin-modifying enzymes and noncoding RNAs. The novel exciting role of exosome-bound microRNA in mediating epigenetic information transfer is also discussed. Finally we show an overview of the epigenetic strategies and therapies that aim to potentiate muscle regeneration and counteract the progression of Duchenne Muscular Dystrophy (DMD.

  13. Is black-hole ringdown a memory of its progenitor?

    Science.gov (United States)

    Kamaretsos, Ioannis; Hannam, Mark; Sathyaprakash, B S

    2012-10-01

    We perform an extensive numerical study of coalescing black-hole binaries to understand the gravitational-wave spectrum of quasinormal modes excited in the merged black hole. Remarkably, we find that the masses and spins of the progenitor are clearly encoded in the mode spectrum of the ringdown signal. Some of the mode amplitudes carry the signature of the binary's mass ratio, while others depend critically on the spins. Simulations of precessing binaries suggest that our results carry over to generic systems. Using Bayesian inference, we demonstrate that it is possible to accurately measure the mass ratio and a proper combination of spins even when the binary is itself invisible to a detector. Using a mapping of the binary masses and spins to the final black-hole spin allows us to further extract the spin components of the progenitor. Our results could have tremendous implications for gravitational astronomy by facilitating novel tests of general relativity using merging black holes.

  14. Repair of calvarial defects with human umbilical cord blood derived mesenchymal stem cells and demineralized bone matrix in athymic rats%人脐血间充质干细胞修复颅骨缺损的实验研究

    Institute of Scientific and Technical Information of China (English)

    刘广鹏; 李宇琳; 孙剑; 崔磊; 张文杰; 曹谊林

    2010-01-01

    Objective To investigate the feasibility of using human umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) and demineralized bone matrix (DBM) scaffolds to repair critical-sized calvarial defects in athymic rats. Methods Human UCB-MSCs were isolated, expanded and osteogenically induced in vitro. Osteogenic differentiation of UCB-MSCs was evaluated by Alizarin Red staining and measurement of calcium content respectively, and then the cells were seeded onto DBM scaffolds. Bilateral full-thickness defects (5 mm in diameter) of parietal bone were created in an athymic rat model. The defects were either repaired with UCB-MSC/DBM constructs (experimental group) or with DBM scaffolds alone (control group). Animals were harvested at 6 and 12 weeks post-implantation respectively, and defect repair was evaluated with gross observation, micro-CT measurement and histological analysis. Results Micro-CT showed that new bone was formed in the experimental group at 6 weeks post-implantation, while no sign of new bone formation was observed in the control group. At 12 weeks post-transplantation, scaffolds had been degraded almost completely in both sides. It was shown that an average of (78.19±6.45)% of each defect volume had been repaired in experimental side; while in the control side, only limited bone formed at the periphery of the defect. Histological examination revealed that the defect was repaired by trabecular bone tissue in experimental side at 12 weeks, while only fibrous connection was observed in the control group. Conclusions Tissue-engineered bone composed of osteogenically-induced human UCB-MSCs on DBM scaffolds could successfully repair the critical-sized calvarial defects in athymic rat models.%目的 应用人脐血间充质干细胞(umbilical cord blood derived mesenchymal stem cells,UCB-MSCs)复合脱钙骨材料构建组织工程化骨,修复裸大鼠颅骨标准缺损.方法 体外扩增培养、成骨诱导人UCB-MSCs,采用Alizarin Red染色

  15. Stem and Progenitor Cell-Derived Astroglia Therapies for Neurological Diseases.

    Science.gov (United States)

    Chen, Chen; Chan, Albert; Wen, Han; Chung, Seung-Hyuk; Deng, Wenbin; Jiang, Peng

    2015-11-01

    Astroglia are a major cellular constituent of the central nervous system (CNS) and play crucial roles in brain development, function, and integrity. Increasing evidence demonstrates that astroglia dysfunction occurs in a variety of neurological disorders ranging from CNS injuries to genetic diseases and chronic degenerative conditions. These new insights herald the concept that transplantation of astroglia could be of therapeutic value in treating the injured or diseased CNS. Recent technological advances in the generation of human astroglia from stem and progenitor cells have been prominent. We propose that a better understanding of the suitability of astroglial cells in transplantation as well as of their therapeutic effects in animal models may lead to the establishment of astroglia-based therapies to treat neurological diseases. PMID:26443123

  16. Measuring the Angular Momentum Distribution in Core-Collapse Supernova Progenitors with Gravitational Waves

    CERN Document Server

    Abdikamalov, Ernazar; DeMaio, Alexandra M; Ott, Christian D

    2013-01-01

    The late collapse, core bounce, and the early postbounce phase of rotating core collapse leads to a characteristic gravitational wave (GW) signal. The precise shape of the signal is governed by the interplay of gravity, rotation, nuclear equation of state (EOS), and electron capture during collapse. We explore the dependence of the signal on total angular momentum and its distribution in the progenitor core by means of a large set of axisymmetric general-relativistic core collapse simulations in which we vary the initial angular momentum distribution in the core. Our simulations include a microphysical finite-temperature EOS, an approximate electron capture treatment during collapse, and a neutrino leakage scheme for the postbounce evolution. We find that the precise distribution of angular momentum is relevant only for very rapidly rotating cores with T/|W|>~8% at bounce. We construct a numerical template bank from our baseline set of simulations, and carry out additional simulations to generate trial wavefo...

  17. Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development ☆

    OpenAIRE

    M.T. Abd El Aziz; Abd El Nabi, E.A.; Abd El Hamid, M.; D. Sabry; Atta, H.M.; L.A. Rahed; A. Shamaa; Mahfouz, S.; Taha, F.M.; S. Elrefaay; Gharib, D.M.; Elsetohy, Khaled A

    2013-01-01

    We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs), examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-...

  18. Neural progenitor cells regulate microglia functions and activity.

    Science.gov (United States)

    Mosher, Kira I; Andres, Robert H; Fukuhara, Takeshi; Bieri, Gregor; Hasegawa-Moriyama, Maiko; He, Yingbo; Guzman, Raphael; Wyss-Coray, Tony

    2012-11-01

    We found mouse neural progenitor cells (NPCs) to have a secretory protein profile distinct from other brain cells and to modulate microglial activation, proliferation and phagocytosis. NPC-derived vascular endothelial growth factor was necessary and sufficient to exert at least some of these effects in mice. Thus, neural precursor cells may not only be shaped by microglia, but also regulate microglia functions and activity.

  19. Therapeutic Roles of Tendon Stem/Progenitor Cells in Tendinopathy

    OpenAIRE

    Xin Zhang; Yu-cheng Lin; Yun-feng Rui; Hong-liang Xu; Hui Chen; Chen Wang,; Gao-jun Teng

    2016-01-01

    Tendinopathy is a tendon disorder characterized by activity-related pain, local edema, focal tenderness to palpation, and decreased strength in the affected area. Tendinopathy is prevalent in both athletes and the general population, highlighting the need to elucidate the pathogenesis of this disorder. Current treatments of tendinopathy are both conservative and symptomatic. The discovery of tendon stem/progenitor cells (TSPCs) and erroneous differentiation of TSPCs have provided new insights...

  20. Adiponectin promotes endothelial progenitor cell number and function

    OpenAIRE

    Shibata, Rei; Skurk, Carsten; Ouchi, Noriyuki; Galasso, Gennaro; Kondo, Kazuhisa; Ohashi, Taiki; Shimano, Masayuki; Kihara, Shinji; Murohara, Toyoaki; Walsh, Kenneth

    2008-01-01

    Obesity-linked diseases are associated with suppressed endothelial progenitor cell (EPC) function. Adiponectin is an adipose-derived protein that is downregulated in obese and diabetic subjects. Here, we investigated the effects of adiponectin on EPCs. EPC levels did not increase in adiponectin deficient (APN-KO) in response to hindlimb ischemia. Adenovirus-mediated delivery of adiponectin increased EPC levels in both WT and APN-KO mice. Incubation of human peripheral blood mononuclear cells ...

  1. Natural Helper cells derive from lymphoid progenitors1

    OpenAIRE

    Yang, Qi; Saenz, Steven A.; Zlotoff, Daniel A.; Artis, David; Bhandoola, Avinash

    2011-01-01

    Natural Helper (NH) cells are recently discovered innate immune cells that confer protective type 2 immunity during helminth infection and mediate influenza induced airway hypersensitivity. Little is known about the ontogeny of NH cells. We now report NH cells derive from bone marrow lymphoid progenitors. Using RAG-1Cre/ROSA26YFP mice, we show that the majority of NH cells are marked with a history of RAG-1 expression, implying lymphoid developmental origin. The development of NH cells depend...

  2. Viral disruption of olfactory progenitors is exacerbated in allergic mice

    OpenAIRE

    Ueha, R.; Mukherjee, S.; Ueha, S.; de Almeida Nagata, D.E.; Sakamoto, T.; K. Kondo; Yamasoba, T.; Lukacs, N W; Kunkel, S. L.

    2014-01-01

    Upper airway viral infection in patients with airway allergy often exacerbates olfactory dysfunction, but the mechanism for this exacerbation remains unclear. Here, we examined the effects of respiratory syncytial virus (RSV) infection, in the presence or absence of airway allergy, on olfactory receptor neurons (ORNs) and their progenitors in mice. Immunohistological analyses revealed that cockroach allergen (CRA)-induced airway allergy alone did not affect the number of OMP+ mature ORNs and ...

  3. Mobilization of stem and progenitor cells in cardiovascular diseases

    OpenAIRE

    Wojakowski, W; Landmesser, U.; Bachowski, R; Jadczyk, T; M. Tendera

    2012-01-01

    Circulating bone marrow (BM)-derived stem and progenitor cells (SPCs) participate in turnover of vascular endothelium and myocardial repair after acute coronary syndromes. Acute myocardial infarction (MI) produces a generalized inflammatory reaction, including mobilization of SPCs, increased local production of chemoattractants in the ischemic myocardium, as well as neural and humoral signals activating the SPC egress from the BM. Several types of circulating BM cells were identified in the p...

  4. The progenitor of SN 2011ja: Clues from circumstellar interaction

    OpenAIRE

    Chakraborti, Sayan; Ray, Alak; Smith, Randall; Ryder, Stuart; Yadav, Naveen; Sutaria, Firoza; Dwarkadas, Vikram V; Chandra, Poonam; Pooley, David; Roy, Rupak

    2013-01-01

    Massive stars, possibly red supergiants, which retain extended hydrogen envelopes until core collapse, produce Type II Plateau (IIP) supernovae. The ejecta from these explosions shock the circumstellar matter originating from the mass loss of the progenitor during the final phases of its life. This interaction accelerates particles to relativistic energies which then lose energy via synchrotron radiation in the shock-amplified magnetic fields and inverse Compton scattering against optical pho...

  5. Cryopreserved Ex Vivo-Expanded Allogeneic Myeloid Progenitor Cell Product Protects Neutropenic Mice From a Lethal Fungal Infection.

    Science.gov (United States)

    Domen, Jos; Christensen, Julie L; Gille, Daphne; Smith-Berdan, Stephanie; Fong, Timothy; Brown, Janice M Y; Sedello, Anna K

    2016-01-01

    Severe neutropenia induced by chemotherapy or conditioning for hematopoietic cell transplantation often results in morbidity and mortality due to infection by opportunistic pathogens. A system has been developed to generate ex vivo-expanded mouse myeloid progenitor cells (mMPCs) that produce functional neutrophils in vivo upon transplantation in a pathogen challenge model. It has previously been demonstrated that transplantation of large numbers of freshly isolated myeloid progenitors from a single donor provides survival benefit in radiation-induced neutropenic mice. In the present work, an ex vivo-expanded and cryopreserved mMPC product generated from an allogeneic donor pool retains protective activity in vivo in a lethal fungal infection model. Infusion of the allogeneic pooled mMPC product is effective in preventing death from invasive Aspergillus fumigatus in neutropenic animals, and protection is dose dependent. Cell progeny from the mMPC product is detected in the bone marrow, spleen, blood, and liver by flow cytometry 1 week postinfusion but is no longer evident in most animals 4 weeks posttransplant. In this model, the ex vivo-generated pooled allogeneic mMPC product (i) expands and differentiates in vivo; (ii) is functional and prevents death from invasive fungal infection; and (iii) does not permanently engraft or cause allosensitization. These data suggest that an analogous ex vivo-expanded human myeloid progenitor cell product may be an effective off-the-shelf bridging therapy for the infectious complications that develop during hematopoietic recovery following hematopoietic cell transplantation or intensive chemotherapy. PMID:25812169

  6. Differential Stem and Progenitor Cell Trafficking by Prostaglandin E2

    Science.gov (United States)

    Hoggatt, Jonathan; Mohammad, Khalid S.; Singh, Pratibha; Hoggatt, Amber F.; Chitteti, Brahmananda Reddy; Speth, Jennifer M.; Hu, Peirong; Poteat, Bradley A.; Stilger, Kayla N.; Ferraro, Francesca; Silberstein, Lev; Wong, Frankie K.; Farag, Sherif S.; Czader, Magdalena; Milne, Ginger L.; Breyer, Richard M.; Serezani, Carlos H.; Scadden, David T.; Guise, Theresa; Srour, Edward F.; Pelus, Louis M.

    2013-01-01

    SUMMARY To maintain lifelong production of blood cells, hematopoietic stem cells (HSC) are tightly regulated by inherent programs and extrinsic regulatory signals received from their microenvironmental niche. Long-term repopulating HSC (LT-HSC) reside in several, perhaps overlapping, niches that produce regulatory molecules/signals necessary for homeostasis and increased output following stress/injury 1–5. Despite significant advances in specific cellular or molecular mechanisms governing HSC/niche interactions, little is understood about regulatory function within the intact mammalian hematopoietic niche. Recently, we and others described a positive regulatory role for Prostaglandin E2 (PGE2) on HSC function ex vivo 6,7. While exploring the role of endogenous PGE2 we unexpectedly observed hematopoietic egress after nonsteroidal anti-inflammatory drug (NSAID) treatment. Surprisingly, this was independent of the SDF-1/CXCR4 axis. Stem and progenitor cells were found to have differing mechanisms of egress, with HSC transit to the periphery dependent on niche attenuation and reduction in the retentive molecule osteopontin (OPN). Hematopoietic grafts mobilized with NSAIDs had superior repopulating ability and long-term engraftment. Treatment of non-human primates and healthy human volunteers confirmed NSAID-mediated egress in higher species. PGE2 receptor knockout mice demonstrated that progenitor expansion and stem/progenitor egress resulted from reduced EP4 receptor signaling. These results not only uncover unique regulatory roles for EP4 signaling in HSC retention in the niche but also define a rapidly translatable strategy to therapeutically enhance transplantation. PMID:23485965

  7. Decoding the stellar fossils of the dusty Milky Way progenitors

    CERN Document Server

    de Bennassuti, Matteo; Valiante, Rosa; Salvadori, Stefania

    2014-01-01

    We investigate the metallicity distribution function (MDF) in the Galactic halo and the relative fraction of Carbon-normal and Carbon-rich stars. To this aim, we use an improved version of the semi-analytical code GAlaxy MErger Tree and Evolution (GAMETE), that reconstructs the hierarchical merger tree of the MW, following the star formation history and the metal and dust evolution in individual progenitors. The predicted scaling relations between the dust, metal and gas masses for MW progenitors show a good agreement with observational data of local galaxies and of Gamma Ray Burst (GRB) host galaxies at 0.1 140 M_{sun}, into the Pair-Instability SN progenitor mass range. The relative contribution of C-normal and C-enhanced stars to the MDF and its dependence on [Fe/H] points to a scenario where the Pop III/II transition is driven by dust-cooling and the first low-mass stars form when the dust-to-gas ratio in their parent clouds exceeds a critical value of D_crit = 4.4 x 10^{-9}.

  8. Identification of human erythroid lineage-committed progenitors.

    Science.gov (United States)

    Mori, Yasuo; Akashi, Koichi; Weissman, Irving L

    2016-05-01

    Elucidating the developmental pathway leading to erythrocytes and being able to isolate their progenitors is crucial to understanding and treating disorders of red cell imbalance such as anemia, myelodysplastic syndrome, and polycythemia vera. Endoglin (CD105) is a key marker for purifying mouse erythroid lineage-committed progenitors (EPs) from bone marrow. Herein, we show that human EPs can also be isolated from adult bone marrow. We identified three subfractions that possessed different expression patterns of CD105 and CD71 within the previously defined human megakaryocyte/erythrocyte progenitor (hMEP; Lineage-CD34(+)CD38(+)IL-3Rα(-)CD45RA(-)) population. Both CD71(-)CD105(-) and CD71(+)CD105(-) MEPs, at least in vitro, retained bipotency for the megakaryocyte (MegK) and erythrocyte (E) lineages, although the latter sub-population had a differentiation potential skewed toward the E-lineage. Notably, the differentiation output of the CD71(+)CD105(+) subset of cells within the MEP population was completely restricted to the E-lineage with the loss of MegK potential; thus, we termed CD71(+)CD105(-) MEPs and CD71(+)CD105(+) cells as E-biased MEPs (E-MEPs) and EPs, respectively. These previously unclassified populations may facilitate understanding of the molecular mechanisms governing human erythroid development and serve as potential therapeutic targets in disorders of the erythroid lineage. PMID:27263782

  9. Morphological and functional aspects of progenitors perturbed in cortical malformations

    Directory of Open Access Journals (Sweden)

    Sara eBizzotto

    2015-02-01

    Full Text Available In this review, we discuss molecular and cellular mechanisms important for the function of neuronal progenitors during development, revealed by their perturbation in different cortical malformations. We focus on a class of neuronal progenitors, radial glial cells (RGCs, which are renowned for their unique morphological and behavioural characteristics, constituting a key element during the development of the mammalian cerebral cortex. We describe how the particular morphology of these cells is related to their roles in the orchestration of cortical development and their influence on other progenitor types and post-mitotic neurons. Important for disease mechanisms, we overview what is currently known about RGC cellular components, cytoskeletal mechanisms, signalling pathways and cell cycle characteristics, focusing on how defects lead to abnormal development and cortical malformation phenotypes. The multiple recent entry points from human genetics and animal models are contributing to our understanding of this important cell type. Combining data from phenotypes in the mouse reveals molecules which potentially act in common pathways. Going beyond this, we discuss future directions that may provide new data in this expanding area.

  10. Endothelial Progenitor Cells for Diagnosis and Prognosis in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Caterina Oriana Aragona

    2016-01-01

    Full Text Available Objective. To identify, evaluate, and synthesize evidence on the predictive power of circulating endothelial progenitor cells (EPCs in cardiovascular disease, through a systematic review of quantitative studies. Data Sources. MEDLINE was searched using keywords related to “endothelial progenitor cells” and “endothelium” and, for the different categories, respectively, “smoking”; “blood pressure”; “diabetes mellitus” or “insulin resistance”; “dyslipidemia”; “aging” or “elderly”; “angina pectoris” or “myocardial infarction”; “stroke” or “cerebrovascular disease”; “homocysteine”; “C-reactive protein”; “vitamin D”. Study Selection. Database hits were evaluated against explicit inclusion criteria. From 927 database hits, 43 quantitative studies were included. Data Syntheses. EPC count has been suggested for cardiovascular risk estimation in the clinical practice, since it is currently accepted that EPCs can work as proangiogenic support cells, maintaining their importance as regenerative/reparative potential, and also as prognostic markers. Conclusions. EPCs showed an important role in identifying cardiovascular risk conditions, and to suggest their evaluation as predictor of outcomes appears to be reasonable in different defined clinical settings. Due to their capability of proliferation, circulation, and the development of functional progeny, great interest has been directed to therapeutic use of progenitor cells in atherosclerotic diseases. This trial is registered with registration number: Prospero CRD42015023717.

  11. Stem and progenitor cells: advancing bone tissue engineering.

    Science.gov (United States)

    Tevlin, R; Walmsley, G G; Marecic, O; Hu, Michael S; Wan, D C; Longaker, M T

    2016-04-01

    Unlike many other postnatal tissues, bone can regenerate and repair itself; nevertheless, this capacity can be overcome. Traditionally, surgical reconstructive strategies have implemented autologous, allogeneic, and prosthetic materials. Autologous bone--the best option--is limited in supply and also mandates an additional surgical procedure. In regenerative tissue engineering, there are myriad issues to consider in the creation of a functional, implantable replacement tissue. Importantly, there must exist an easily accessible, abundant cell source with the capacity to express the phenotype of the desired tissue, and a biocompatible scaffold to deliver the cells to the damaged region. A literature review was performed using PubMed; peer-reviewed publications were screened for relevance in order to identify key advances in stem and progenitor cell contribution to the field of bone tissue engineering. In this review, we briefly introduce various adult stem cells implemented in bone tissue engineering such as mesenchymal stem cells (including bone marrow- and adipose-derived stem cells), endothelial progenitor cells, and induced pluripotent stem cells. We then discuss numerous advances associated with their application and subsequently focus on technological advances in the field, before addressing key regenerative strategies currently used in clinical practice. Stem and progenitor cell implementation in bone tissue engineering strategies have the ability to make a major impact on regenerative medicine and reduce patient morbidity. As the field of regenerative medicine endeavors to harness the body's own cells for treatment, scientific innovation has led to great advances in stem cell-based therapies in the past decade.

  12. CB1 Cannabinoid Receptor-Dependent Activation of mTORC1/Pax6 Signaling Drives Tbr2 Expression and Basal Progenitor Expansion in the Developing Mouse Cortex.

    Science.gov (United States)

    Díaz-Alonso, Javier; Aguado, Tania; de Salas-Quiroga, Adán; Ortega, Zaira; Guzmán, Manuel; Galve-Roperh, Ismael

    2015-09-01

    The CB1 cannabinoid receptor regulates cortical progenitor proliferation during embryonic development, but the molecular mechanism of this action remains unknown. Here, we report that CB1-deficient mouse embryos show premature cell cycle exit, decreased Pax6- and Tbr2-positive cell number, and reduced mammalian target of rapamycin complex 1 (mTORC1) activation in the ventricular and subventricular cortical zones. Pharmacological stimulation of the CB1 receptor in cortical slices and progenitor cell cultures activated the mTORC1 pathway and increased the number of Pax6- and Tbr2-expressing cells. Likewise, acute CB1 knockdown in utero reduced mTORC1 activation and cannabinoid-induced Tbr2-positive cell generation. Luciferase reporter and chromatin immunoprecipitation assays revealed that the CB1 receptor drives Tbr2 expression downstream of Pax6 induction in an mTORC1-dependent manner. Altogether, our results demonstrate that the CB1 receptor tunes dorsal telencephalic progenitor proliferation by sustaining the transcriptional activity of the Pax6-Tbr2 axis via the mTORC1 pathway, and suggest that alterations of CB1 receptor signaling, by producing the missexpression of progenitor identity determinants may contribute to neurodevelopmental alterations.

  13. Progenitor-Explosion Connection and Remnant Birth Masses for Neutrino-Driven Supernovae of Iron-Core Progenitors

    CERN Document Server

    Ugliano, Marcella; Marek, Andreas; Arcones, Almudena

    2012-01-01

    We perform hydrodynamic supernova simulations in spherical symmetry for over 100 single stars of solar metallicity to explore the progenitor-explosion and progenitor-remnant connections established by the neutrino-driven mechanism. We use an approximative treatment of neutrino transport and replace the high-density interior of the neutron star (NS) by an inner boundary condition based on an analytic proto-NS core-cooling model, whose free parameters are chosen such that explosion energy, nickel production, and energy release by the compact remnant of progenitors around 20 solar masses are compatible with Supernova 1987A. Thus we are able to simulate the accretion phase, initiation of the explosion, subsequent neutrino-driven wind phase for 15-20 s, and the further evolution of the blast wave for hours to days until fallback is completed. Our results challenge long-standing paradigms. We find that remnant mass, launch time, and properties of the explosion depend strongly on the stellar structure and exhibit la...

  14. Differential biodistribution of intravenously administered endothelial progenitor and cytotoxic T-cells in rat bearing orthotopic human glioma

    International Nuclear Information System (INIS)

    A major challenge in the development of cell based therapies for glioma is to deliver optimal number of cells (therapeutic dose) to the tumor. Imaging tools such as magnetic resonance imaging (MRI), optical imaging, positron emission tomography (PET) and single-photon emission computed tomography (SPECT) has been used in cell tracking and/or biodistribution studies. In this study, we evaluate the dynamic biodistribution of systemic injected labeled cells [human cord blood derived endothelial progenitor cells (EPCs) and cytotoxic T-cells (CTLs)] in rat glioma model with in vivo SPECT imaging. Human cord blood EPCs, T-cells and CD14+ cells (monocytes/dendritic cells) were isolated using the MidiMACS system. CD14+ cells were converted to dendritic cells (DC) and also primed with U251 tumor cell line lysate. T-cells were co-cultured with irradiated primed DCs at 10:1 ratio to make CTLs. Both EPCs and CTLs were labeled with In-111-oxine at 37°C in serum free DMEM media. Glioma bearing animals were randomly assigned into three groups. In-111 labeled cells or In-111 oxine alone were injected through tail vein and SPECT imaging was performed on day 0, 1, and 3. In-111 oxine activity in various organs and tumor area was determined. Histochemical analysis was performed to further confirm the migration and homing of injected cells at the tumor site. EPCs and CTLs showed an In-111 labeling efficiency of 87.06 ± 7.75% and 70.8 ± 12.9% respectively. Initially cell migration was observed in lung following inravenous administration of In-111 labeled cells and decreased on day 1 and 3, which indicate re-distribution of labeled cells from lung to other organs. Relatively higher In-111 oxine activity was observed in tumor areas at 24 hours in animals received In-111 labeled cells (EPCs or CTLs). Histiological analysis revealed iron positive cells in and around the tumor area in animals that received labeled cells (CTLs and EPCs). We observed differential biodistribution of In-111

  15. 沙棘叶提取物抗登革病毒的实验研究%Effect of Hippophae rhamnoides Leaf Extract Against Dengue Virus Infection in Human Blood-derived Macrophages

    Institute of Scientific and Technical Information of China (English)

    花圣卓; 李铂岩

    2012-01-01

    Dengue virus occurs as four distinct serotypes,called Dengue 1,2,3,and 4.Symptomaticdengue virus infection ranges from a self limited febrile illness,dengue fever(DF),to a more severedisease,dengue hemorrhagic fever/dengue shock syndrome(DHF/DSS).The anti-Dengue treatmentis severely hampered as no specific therapeutic agents are available.Even present treatmentstrategies for Dengue are more supportive than curative.In the present study anti-dengue activity of Hippoplzae rhamnoides{Seabuckthorn,SBT)leaf extract 4vas evaluated in Dengue virus type-2 infected blood-derived human macrophages as macrophages are the primary target of Denguevirus infection.Infected cells were treated with SBT leaf extract and compared with commerciallyavailable anti-viral drug,Ribavirin.The extract was able to maintain the cell viability of Dengue-infected cells at par with Ribavirin along with the decrease and increase in TNF-[alpha]and IFN-[gamma]respectively.Anti-dengue activity of SBT extract was further determined by the traditionalplaque assay.These observations suggest that the SBT leaf extract has a significant anti-dengueactivity and has the potential for the treatment of Dengue.%登革病毒依抗原性不同,可分为1、2、3、4四个血清型。它除了能导致一定范围内发热的典型登革热外,还能引致更严重的登革出血热和登革休克综合症。由于没有具体有效的治疗药物,目前尚无好的治疗登革热的方法,治疗方案多是支持性的。本实验评估了在2型登革病毒感染的人血源性巨噬细胞中沙棘叶提取物的抗登革病毒活性,选择巨噬细胞的原因是因为巨噬细胞是登革病毒感染的首要目标。受感染的细胞用沙棘叶提取物治疗并与市售的抗病毒药物利巴韦林作比较,研究发现沙棘叶提取物维持登革病毒感染细胞活力的能力几乎等同于利巴韦林。传统的空斑试验进一步确定了沙棘叶提取物的抗登革病毒活性。

  16. Intrinsic Age-Dependent Changes and Cell-Cell Contacts Regulate Nephron Progenitor Lifespan.

    Science.gov (United States)

    Chen, Shuang; Brunskill, Eric W; Potter, S Steven; Dexheimer, Phillip J; Salomonis, Nathan; Aronow, Bruce J; Hong, Christian I; Zhang, Tongli; Kopan, Raphael

    2015-10-12

    During fetal development, nephrons of the metanephric kidney form from a mesenchymal progenitor population that differentiates en masse before or shortly after birth. We explored intrinsic and extrinsic mechanisms controlling progenitor lifespan in a transplantation assay that allowed us to compare engraftment of old and young progenitors into the same young niche. The progenitors displayed an age-dependent decrease in proliferation and concomitant increase in niche exit rates. Single-cell transcriptome profiling revealed progressive age-dependent changes, with heterogeneity increasing in older populations. Age-dependent elevation in mTor and reduction in Fgf20 could contribute to increased exit rates. Importantly, 30% of old progenitors remained in the niche for up to 1 week post engraftment, a net gain of 50% to their lifespan, but only if surrounded by young neighbors. We provide evidence in support of a model in which intrinsic age-dependent changes affect inter-progenitor interactions that drive cessation of nephrogenesis. PMID:26460946

  17. Prolonged Mitosis of Neural Progenitors Alters Cell Fate in the Developing Brain.

    Science.gov (United States)

    Pilaz, Louis-Jan; McMahon, John J; Miller, Emily E; Lennox, Ashley L; Suzuki, Aussie; Salmon, Edward; Silver, Debra L

    2016-01-01

    Embryonic neocortical development depends on balanced production of progenitors and neurons. Genetic mutations disrupting progenitor mitosis frequently impair neurogenesis; however, the link between altered mitosis and cell fate remains poorly understood. Here we demonstrate that prolonged mitosis of radial glial progenitors directly alters neuronal fate specification and progeny viability. Live imaging of progenitors from a neurogenesis mutant, Magoh(+/-), reveals that mitotic delay significantly correlates with preferential production of neurons instead of progenitors, as well as apoptotic progeny. Independently, two pharmacological approaches reveal a causal relationship between mitotic delay and progeny fate. As mitotic duration increases, progenitors produce substantially more apoptotic progeny or neurons. We show that apoptosis, but not differentiation, is p53 dependent, demonstrating that these are distinct outcomes of mitotic delay. Together our findings reveal that prolonged mitosis is sufficient to alter fates of radial glia progeny and define a new paradigm to understand how mitosis perturbations underlie brain size disorders such as microcephaly.

  18. Fetal hepatic progenitors support long-term expansion of hematopoietic stem cells.

    Science.gov (United States)

    Chou, Song; Flygare, Johan; Lodish, Harvey F

    2013-05-01

    We have developed a coculture system that establishes DLK(+) fetal hepatic progenitors as the authentic supportive cells for expansion of hematopoietic stem (HSCs) and progenitor cells. In 1-week cultures supplemented with serum and supportive cytokines, both cocultured DLK(+) fetal hepatic progenitors and their conditioned medium supported rapid expansion of hematopoietic progenitors and a small increase in HSC numbers. In 2- and 3-week cultures DLK(+) cells, but not their conditioned medium, continuously and significantly (>20-fold) expanded both hematopoietic stem and progenitor cells. Physical contact between HSCs and DLK(+) cells was crucial to maintaining this long-term expansion. Similar HSC expansion (approximately sevenfold) was achieved in cocultures using a serum-free, low cytokine- containing medium. In contrast, DLK(-) cells are incapable of expanding hematopoietic cells, demonstrating that hepatic progenitors are the principle supportive cells for HSC expansion in the fetal liver.

  19. Surface modification of a polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) nanocomposite polymer as a stent coating for enhanced capture of endothelial progenitor cells.

    OpenAIRE

    Tan, Aaron; Farhatnia, Yasmin; Goh, Debbie; Natasha, G; de Mel, Achala; Lim, Jing; Teoh, Swee-Hin; Malkovskiy, Andrey V; Chawla, Reema; Rajadas, Jayakumar; Cousins, Brian G; Michael R Hamblin; Alavijeh, Mohammad S; Seifalian, Alexander M

    2013-01-01

    An unmet need exists for the development of next-generation multifunctional nanocomposite materials for biomedical applications, particularly in the field of cardiovascular regenerative biology. Herein, we describe the preparation and characterization of a novel polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) nanocomposite polymer with covalently attached anti-CD34 antibodies to enhance capture of circulating endothelial progenitor cells (EPC). This material may ...

  20. Hand2 Function in Second Heart Field Progenitors is Essential for Cardiogenesis

    OpenAIRE

    Tsuchihashi, Takatoshi; Maeda, Jun; Shin, Chong; Ivey, Kathryn N.; Black, Brian; Olson, Eric N.; Yamagishi, Hiroyuki; Srivastava, Deepak

    2010-01-01

    Cardiogenesis involves the contributions of multiple progenitor pools, including mesoderm-derived cardiac progenitors known as the first and second heart fields. Disruption of genetic pathways regulating individual subsets of cardiac progenitors likely underlies many forms of human cardiac malformations. Hand2 is a member of the basic helix loop helix (bHLH) family of transcription factors and is expressed in numerous cell lineages that contribute to the developing heart. However, the early e...

  1. Redox and Metabolic Regulation of Stem/Progenitor Cells and Their Niche

    OpenAIRE

    Ushio-Fukai, Masuko; Rehman, Jalees

    2014-01-01

    Stem cells are defined as cells that have the capacity to self-renew and exhibit multipotency or pluripotency, whereas progenitor cells are committed to selected lineages but retain their self-renewal capacity. The stem or progenitor cell niche refers to the microenvironment of the regenerative cells in the bone marrow (BM) or other tissues such as the heart. It can regulate self-renewal, differentiation, migration, and proliferation of regenerative stem/progenitor cells. The precise regulato...

  2. Finding Supernova Ia Progenitors with the Chandra X-ray Observatory

    OpenAIRE

    Nielsen, M. T. B.; Nelemans, G.A.; Voss, R.

    2010-01-01

    We examine pre-supernova Chandra images to find X-ray luminosities of type Ia supernova progenitors. At present, we have one possible direct detection and upper limits for the X-ray luminosities of a number of other supernova progenitors. The method has also yielded a possible detection of a X-ray binary Wolf-Rayet system as the progenitor of a type Ib supernova.

  3. Low- and high-LET radiation drives clonal expansion of lung progenitor cells in vivo

    OpenAIRE

    Farin, Alicia M.; Manzo, Nicholas D.; Kirsch, David G.; Stripp, Barry R.

    2015-01-01

    Abundant populations of epithelial progenitor cells maintain the epithelium along the proximal-to-distal axis of the airway. Exposure of lung tissue to ionizing radiation leads to tissue remodeling and potential cancer initiation or progression. However, little is known about the effects of ionizing radiation on airway epithelial progenitor cells. We hypothesized that ionizing radiation exposure will alter the behavior of airway epithelial progenitor cells in a radiation dose- and quality-dep...

  4. Biological behaviour and role of endothelial progenitor cells in vascular diseases

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qiu-hua; SHE Ming-peng

    2007-01-01

    Obiective To review the biological behaviour of endothelial progenitor cells and their role in vascular diseases.Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1985 to March 2007.The search term was "endothelial progenitor cells".Study selection Articles about the biological behaviour of endothelial progenitor cells and their roles in the pathogenesis of vascular diseases such as atherogenesis were used.Results Progenitor cells in bone marrow,peripheral blood and adventitia can differentiate into mature endothelial cells (ECs).The progenitor cells,which express certain surface markers including AC133,CD34 and KDR,enable restoration of the microcirculation and ECs when injury or ischaemia occurs.Endothelial progenitor cells used in experimental models and clinical trials for ischaemic syndromes could restore endothelial integrity and inhibit neointima development.Moreover,their number and functional properties are influenced by certain cytokines and atherosclerotic risk factors.Impairment of the progenitor cells might limit the regenerative capacity,even lead to the development of atherosclerosis or other vascular diseases.Conclusions Endothelial progenitor cells have a particular role in prevention and treatment of certain cardiovascular diseases.However,many challenges remain in understanding differentiation of endothelial progenitor cells,their mobilization and revascularization.

  5. Mammalian neurogenesis requires Treacle-Plk1 for precise control of spindle orientation, mitotic progression, and maintenance of neural progenitor cells.

    Directory of Open Access Journals (Sweden)

    Daisuke Sakai

    Full Text Available The cerebral cortex is a specialized region of the brain that processes cognitive, motor, somatosensory, auditory, and visual functions. Its characteristic architecture and size is dependent upon the number of neurons generated during embryogenesis and has been postulated to be governed by symmetric versus asymmetric cell divisions, which mediate the balance between progenitor cell maintenance and neuron differentiation, respectively. The mechanistic importance of spindle orientation remains controversial, hence there is considerable interest in understanding how neural progenitor cell mitosis is controlled during neurogenesis. We discovered that Treacle, which is encoded by the Tcof1 gene, is a novel centrosome- and kinetochore-associated protein that is critical for spindle fidelity and mitotic progression. Tcof1/Treacle loss-of-function disrupts spindle orientation and cell cycle progression, which perturbs the maintenance, proliferation, and localization of neural progenitors during cortical neurogenesis. Consistent with this, Tcof1(+/- mice exhibit reduced brain size as a consequence of defects in neural progenitor maintenance. We determined that Treacle elicits its effect via a direct interaction with Polo-like kinase1 (Plk1, and furthermore we discovered novel in vivo roles for Plk1 in governing mitotic progression and spindle orientation in the developing mammalian cortex. Increased asymmetric cell division, however, did not promote increased neuronal differentiation. Collectively our research has therefore identified Treacle and Plk1 as novel in vivo regulators of spindle fidelity, mitotic progression, and proliferation in the maintenance and localization of neural progenitor cells. Together, Treacle and Plk1 are critically required for proper cortical neurogenesis, which has important implications in the regulation of mammalian brain size and the pathogenesis of congenital neurodevelopmental disorders such as microcephaly.

  6. Progenitors of supernova Ibc: a single Wolf-Rayet star as the possible progenitor of the SN Ib iPTF13bvn

    Science.gov (United States)

    Groh, Jose H.; Georgy, Cyril; Ekström, Sylvia

    2013-10-01

    Core-collapse supernova (SN) explosions mark the end of the tumultuous life of massive stars. Determining the nature of their progenitors is a crucial step towards understanding the properties of SNe. Until recently, no progenitor has been directly detected for SN of type Ibc, which are believed to come from massive stars that lose their hydrogen envelope through stellar winds and from binary systems where the companion has stripped the H envelope from the primary. Here we analyze recently reported observations of iPTF13bvn, which could possibly be the first detection of a SN Ib progenitor based on pre-explosion images. Very interestingly, the recently published Geneva models of single stars can reproduce the observed photometry of the progenitor candidate and its mass-loss rate, confirming a recently proposed scenario. We find that a single WR star with initial mass in the range 31-35 M⊙ fits the observed photometry of the progenitor of iPTF13bvn. The progenitor likely has a luminosity of log (L⋆/L⊙) ~ 5.55, surface temperature ~45 000 K, and mass of ~10.9 M⊙ at the time of explosion. Our non-rotating 32 M⊙ model overestimates the derived radius of the progenitor, although this could likely be reconciled with a fine-tuned model of a more massive (between 40 and 50 M⊙), hotter, and luminous progenitor. Our models indicate a very uncertain ejecta mass of ~8 M⊙, which is higher than the average of the SN Ib ejecta mass that is derived from the lightcurve (2-4 M⊙). This possibly high ejecta mass could produce detectable effects in the iPTF13bvn lightcurve and spectrum. If the candidate is indeed confirmed to be the progenitor, our results suggest that stars with relatively high initial masses (> 30 M⊙) can produce visible SN explosions at their deaths and do not collapse directly to a black hole.

  7. High-level expression of the ER-MP58 antigen on mouse bone marrow hematopoietic progenitor cells marks commitment to the myeloid lineage.

    Science.gov (United States)

    de Bruijn, M F; Ploemacher, R E; Mayen, A E; Voerman, J S; Slieker, W A; van Ewijk, W; Leenen, P J

    1996-12-01

    Studies on the early events in the differentiation of the nonspecific immune system require the identification and isolation of myeloid-committed progenitor cells. Using the monoclonal antibodies (mAb) ER-MP12 and ER-MP20, generated against immortalized macrophage precursors, we have shown previously that the earliest macrophage colony-stimulating factor (M-CSF)-responsive cells in the bone marrow have the ER-MP12hi 20- phenotype. In addition, we found that the ER-MP12hi 20- subset (comprising about 2 % of total nucleated marrow) contains progenitor cells of all hematopoietic lineages. Aiming at the identification and purification of the myeloid progenitor cells within the ER-MP12hi 20-subset, we used ER-MP58, a marker expressed at high level by all M-CSF-responsive bone marrow progenitors. With this marker the ER-MP12hi 20- cell population could be divided into three subfractions: one with absent or low level ER-MP58 expression, one with intermediate, and one with high ER-MP58 expression. These subfractions were isolated by fluorescence-activated cell sorting and tested in vitro and in vivo for their differentiation capacities. In addition, the expression of ER-MP58 on stem cell subsets was examined in the cobblestone area-forming cell (CAFC) assay. Our data indicate that in the ER-MP12hi 20- subpopulation myeloid-committed progenitors are characterized by high-level expression of the ER-MP58 antigen, whereas cells with other or broader differentiation capacities have an ER-MP58 negative/low or intermediate phenotype. These myeloid-committed progenitors have no significant repopulating ability in vivo, in contrast to the ER-MP58 intermediate cells. Primitive CAFC-28/35, corresponding to cells providing long-term hematopoietic engraftment in vivo, also did not express the ER-MP58 Ag at a high level. Thus, cells committed to the myeloid lineage can be separated from progenitor cells with other differentiation capacities by means of multiparameter cell sorting using

  8. Transplantation of enteric neural stem/progenitor cells into the irradiated young mouse hippocampus.

    Science.gov (United States)

    Osman, Ahmed M; Zhou, Kai; Zhu, Changlian; Blomgren, Klas

    2014-01-01

    Radiotherapy is an effective treatment for brain tumors but often results in cognitive deficits in survivors. Transplantation of embryonic or brain-derived neural stem/progenitor cells (BNSPCs) ameliorated cognitive impairment after irradiation (IR) in animal models. However, such an approach in patients requires a clinically relevant source of cells. We show for the first time the utilization of enteric neural stem/progenitor cells (ENSPCs) from the postnatal intestinal wall as a source of autologous cells for brain repair after injury caused by IR. Cells were isolated from the intestinal wall and propagated in vitro for 1 week. Differentiation assays showed that ENSPCs are multipotent and generated neurons, astrocytes, and myofibroblasts. To investigate whether ENSPCs can be used in vivo, postnatal day 9 mice were subjected to a single moderate irradiation dose (6 or 8 Gy). Twelve days later, mice received an intrahippocampal injection of syngeneic ENSPCs. Four weeks after transplantation, 0.5% and 1% of grafted ENSPCs were detected in the dentate gyrus of sham and irradiated animals, respectively, and only 0.1% was detected after 16 weeks. Grafted ENSPCs remained undifferentiated but failed to restore IR-induced loss of BNSPCs and the subsequent impaired growth of the dentate gyrus. We observed microglia activation, astrogliosis, and loss of granule neurons associated with grafted ENSPC clusters. Transplantation of ENSPCs did not ameliorate IR-induced impaired learning and memory. In summary, while autologous ENSPC grafting to the brain worked technically, even in the absence of immunosuppression, the protocols need to be modified to improve survival and integration.

  9. Overexpression of LOXIN Protects Endothelial Progenitor Cells From Apoptosis Induced by Oxidized Low Density Lipoprotein.

    Science.gov (United States)

    Veas, Carlos; Jara, Casandra; Willis, Naomi D; Pérez-Contreras, Karen; Gutierrez, Nicolas; Toledo, Jorge; Fernandez, Paulina; Radojkovic, Claudia; Zuñiga, Felipe A; Escudero, Carlos; Aguayo, Claudio

    2016-04-01

    Human endothelial progenitor cells (hEPC) are adult stem cells located in the bone marrow and peripheral blood. Studies have indicated that hEPC play an important role in the recovery and repair of injured endothelium, however, their quantity and functional capacity is reduced in several diseases including hypercholesterolemia. Recently, it has been demonstrated that hEPC express lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and its activation by oxidized low-density lipoprotein (ox-LDL) induces cellular dysfunction and apoptosis. This study aimed to investigate whether overexpression of LOXIN, a truncated isoform of LOX-1 that acts as a dominant negative, plays a protective role against ox-LDL-induced apoptosis in hEPC. Human endothelial progenitor cells exposed to ox-LDL showed a significant increase in LOX-1 expression, and apoptosis began at ox-LDL concentrations above 50 μg/mL. All hEPC apoptosed at 200 μg/mL ox-LDL. High LOXIN expression was generated using adenoviral systems in hEPC and SiHa cells transduced with 100 colony-forming units per cell. Transduced LOXIN localized to the plasma membrane and blocked ox-LDL uptake mediated by LOX-1. Overexpression of LOXIN protected hEPC from ox-LDL-induced apoptosis, and therefore maybe a novel way of improving hEPC function and quantity. These results suggest that adenoviral vectors of LOXIN may provide a possible treatment for diseases related to ox-LDL and vascular endothelium dysfunction, including atherosclerosis.

  10. Human astrocytes derived from glial restricted progenitors support regeneration of the injured spinal cord.

    Science.gov (United States)

    Haas, Christopher; Fischer, Itzhak

    2013-06-15

    Cellular transplantation using neural stem cells and progenitors is a promising therapeutic strategy that has the potential to replace lost cells, modulate the injury environment, and create a permissive environment for the regeneration of injured host axons. Our research has focused on the use of human glial restricted progenitors (hGRP) and derived astrocytes. In the current study, we examined the morphological and phenotypic properties of hGRP prepared from the fetal central nervous system by clinically-approved protocols, compared with astrocytes derived from hGRP prepared by treatment with ciliary neurotrophic factor or bone morphogenetic protein 4. These differentiation protocols generated astrocytes that showed morphological differences and could be classified along an immature to mature spectrum, respectively. Despite these differences, the cells retained morphological and phenotypic plasticity upon a challenge with an alternate differentiation protocol. Importantly, when hGRP and derived astrocytes were transplanted acutely into a cervical dorsal column lesion, they survived and promoted regeneration of long ascending host sensory axons into the graft/lesion site, with no differences among the groups. Further, hGRP taken directly from frozen stocks behaved similarly and also supported regeneration of host axons into the lesion. Our results underscore the dynamic and permissive properties of human fetal astrocytes to promote axonal regeneration. They also suggest that a time-consuming process of pre-differentiation may not be necessary for therapeutic efficacy, and that the banking of large quantities of readily available hGRP can be an appropriate source of permissive cells for transplantation.

  11. Id1 restrains p21 expression to control endothelial progenitor cell formation.

    Directory of Open Access Journals (Sweden)

    Alessia Ciarrocchi

    Full Text Available Loss of Id1 in the bone marrow (BM severely impairs tumor angiogenesis resulting in significant inhibition of tumor growth. This phenotype has been associated with the absence of circulating endothelial progenitor cells (EPCs in the peripheral blood of Id1 mutant mice. However, the manner in which Id1 loss in the BM controls EPC generation or mobilization is largely unknown. Using genetically modified mouse models we demonstrate here that the generation of EPCs in the BM depends on the ability of Id1 to restrain the expression of its target gene p21. Through a series of cellular and functional studies we show that the increased myeloid commitment of BM stem cells and the absence of EPCs in Id1 knockout mice are associated with elevated p21 expression. Genetic ablation of p21 rescues the EPC population in the Id1 null animals, re-establishing functional BM-derived angiogenesis and restoring normal tumor growth. These results demonstrate that the restraint of p21 expression by Id1 is one key element of its activity in facilitating the generation of EPCs in the BM and highlight the critical role these cells play in tumor angiogenesis.

  12. Type Ia supernovae: Progenitors and evolution with redshift

    Science.gov (United States)

    Nomoto, Ken'ichi; Umeda, Hideyuki; Kobayashi, Chiaki; Hachisu, Izumi; Kato, Mariko; Tsujimoto, Takuji

    2000-06-01

    Relatively uniform light curves and spectral evolution of Type Ia supernovae(SNe Ia) have led to the use of SNe Ia as a ``standard candle'' to determine cosmological parameters. Whether a statistically significant value of the cosmological constant can be obtained depends on whether the peak luminosities of SNe Ia are sufficiently free from the effects of cosmic and galactic evolutions. Here we first review the single degenerate scenario for the Chandrasekhar mass white dwarf (WD) models of SNe Ia. We identify the progenitor's evolution and population with two channels: (1) the WD+RG (red-giant) and (2) the WD+MS (near main-sequence He-rich star) channels. In these channels, the strong wind from accreting WDs plays a key role, which yields important age and metallicity effects on the evolution. We then address the questions whether the nature of SNe Ia depends systematically on environmental properties such as metallicity and age of the progenitor system and whether significant evolutionary effects exist. We suggest that the variation of the carbon mass fraction X(C) in the C+O WD (or the variation of the initial WD mass) causes the diversity of the brightness of SNe Ia. This model can explain the observed dependences of SNe Ia brightness on the galaxy types and the distance from the galactic center. Finally, applying the metallicity effect on the evolution of SN Ia progenitors, we make a prediction of the cosmic supernova rate history as a composite of the supernova rates in different types of galaxies. .

  13. Endothelial progenitor cells: what use for the cardiologist?

    Directory of Open Access Journals (Sweden)

    Siddique Aurangzeb

    2010-02-01

    Full Text Available Abstract Endothelial Progenitor Cells (EPC were first described in 1997 and have since been the subject of numerous investigative studies exploring the potential of these cells in the process of cardiovascular damage and repair. Whilst their exact definition and mechanism of action remains unclear, they are directly influenced by different cardiovascular risk factors and have a definite role to play in defining cardiovascular risk. Furthermore, EPCs may have important therapeutic implications and further understanding of their pathophysiology has enabled us to explore new possibilities in the management of cardiovascular disease. This review article aims to provide an overview of the vast literature on EPCs in relation to clinical cardiology.

  14. Endoderm Generates Endothelial Cells during Liver Development

    Directory of Open Access Journals (Sweden)

    Orit Goldman

    2014-10-01

    Full Text Available Organogenesis requires expansion of the embryonic vascular plexus that migrates into developing organs through a process called angiogenesis. Mesodermal progenitors are thought to derive endothelial cells (ECs that contribute to both embryonic vasculogenesis and the subsequent organ angiogenesis. Here, we demonstrate that during development of the liver, which is an endoderm derivative, a subset of ECs is generated from FOXA2+ endoderm-derived fetal hepatoblast progenitor cells expressing KDR (VEGFR2/FLK-1. Using human and mouse embryonic stem cell models, we demonstrate that KDR+FOXA2+ endoderm cells developing in hepatic differentiation cultures generate functional ECs. This introduces the concept that ECs originate not exclusively from mesoderm but also from endoderm, supported in Foxa2 lineage-tracing mouse embryos by the identification of FOXA2+ cell-derived CD31+ ECs that integrate the vascular network of developing fetal livers.

  15. Dynamical Evolution of the Earth-Moon Progenitors - Whence Theia?

    CERN Document Server

    Quarles, Billy

    2014-01-01

    We present integrations of a model Solar System with five terrestrial planets (beginning ~30-50 Myr after the formation of primitive Solar System bodies) in order to determine the preferred regions of parameter space leading to a giant impact that resulted in the formation of the Moon. Our results indicate which choices of semimajor axes and eccentricities for Theia (the proto-Moon) at this epoch can produce a late Giant Impact, assuming that Mercury, Venus, and Mars are near the current orbits. We find that the likely semimajor axis of Theia, at the epoch when our simulations begin, depends on the assumed mass ratio of Earth-Moon progenitors (8/1, 4/1, or 1/1). The low eccentricities of the terrestrial planets are most commonly produced when the progenitors have similar semimajor axes at the epoch when our integrations commence. Additionally, we show that mean motion resonances among the terrestrial planets and perturbations from the giant planets can affect the dynamical evolution of the system leading to a...

  16. THE PROGENITOR OF SN 2011ja: CLUES FROM CIRCUMSTELLAR INTERACTION

    International Nuclear Information System (INIS)

    Massive stars, possibly red supergiants, which retain extended hydrogen envelopes until core collapse, produce Type II plateau (IIP) supernovae. The ejecta from these explosions shocks the circumstellar matter originating from the mass loss of the progenitor during the final phases of its life. This interaction accelerates particles to relativistic energies which then lose energy via synchrotron radiation in the shock-amplified magnetic fields and inverse Compton scattering against optical photons from the supernova. These processes produce different signatures in the radio and X-ray parts of the electromagnetic spectrum. Observed together, they allow us to break the degeneracy between shock acceleration and magnetic field amplification. In this work, we use X-rays observations from the Chandra and radio observations from the Australia Telescope Compact Array to study the relative importance of processes which accelerate particles and those which amplify magnetic fields in producing the non-thermal radiation from SN 2011ja. We use radio observations to constrain the explosion date. Multiple Chandra observations allow us to probe the history of variable mass loss from the progenitor. The ejecta expands into a low-density bubble followed by interaction with a higher density wind from a red supergiant consistent with MZAMS ∼> 12 M☉. Our results suggest that a fraction of Type IIP supernovae may interact with circumstellar media set up by non-steady winds

  17. A diversity of progenitors and histories for isolated spiral galaxies

    CERN Document Server

    Martig, Marie; Croton, Darren J; Dekel, Avishai; Teyssier, Romain

    2012-01-01

    We analyze a suite of 33 cosmological simulations following the evolution of Milky Way-mass galaxies in low-density environments. Our sample at z = 0 comprises galaxies with a broad range of Hubble types, from nearly bulgeless disks to bulge-dominated galaxies. The bulges are typically pseudo-bulges, with a Sersic index lower than 2, and 70% of the galaxies have bars. Despite the fact that a large fraction of the bulge is typically in place by z = 1, we find no significant correlation between the morphology at z = 1 and at z = 0. The progenitors of disk galaxies span a whole range of morphologies at z = 1, including smooth disks, unstable disks, interacting galaxies and bulge-dominated systems. By z = 0.5, the progenitor morphology is correlated with the z = 0 morphology, with spiral arms and bars largely in place at z = 0.5. From this sample we analyze the formation histories of galaxies with a bulge-to-total ratio below 0.3 (typically Sb and later types). They do form in our simulations, but with a lower ab...

  18. Mesp1 Marked Cardiac Progenitor Cells Repair Infarcted Mouse Hearts

    Science.gov (United States)

    Liu, Yu; Chen, Li; Diaz, Andrea Diaz; Benham, Ashley; Xu, Xueping; Wijaya, Cori S.; Fa’ak, Faisal; Luo, Weijia; Soibam, Benjamin; Azares, Alon; Yu, Wei; Lyu, Qiongying; Stewart, M. David; Gunaratne, Preethi; Cooney, Austin; McConnell, Bradley K.; Schwartz, Robert J.

    2016-01-01

    Mesp1 directs multipotential cardiovascular cell fates, even though it’s transiently induced prior to the appearance of the cardiac progenitor program. Tracing Mesp1-expressing cells and their progeny allows isolation and characterization of the earliest cardiovascular progenitor cells. Studying the biology of Mesp1-CPCs in cell culture and ischemic disease models is an important initial step toward using them for heart disease treatment. Because of Mesp1’s transitory nature, Mesp1-CPC lineages were traced by following EYFP expression in murine Mesp1Cre/+; Rosa26EYFP/+ ES cells. We captured EYFP+ cells that strongly expressed cardiac mesoderm markers and cardiac transcription factors, but not pluripotent or nascent mesoderm markers. BMP2/4 treatment led to the expansion of EYFP+ cells, while Wnt3a and Activin were marginally effective. BMP2/4 exposure readily led EYFP+ cells to endothelial and smooth muscle cells, but inhibition of the canonical Wnt signaling was required to enter the cardiomyocyte fate. Injected mouse pre-contractile Mesp1-EYFP+ CPCs improved the survivability of injured mice and restored the functional performance of infarcted hearts for at least 3 months. Mesp1-EYFP+ cells are bona fide CPCs and they integrated well in infarcted hearts and emerged de novo into terminally differentiated cardiac myocytes, smooth muscle and vascular endothelial cells. PMID:27538477

  19. Resident cardiac progenitor cells: at the heart of regeneration.

    Science.gov (United States)

    Bollini, Sveva; Smart, Nicola; Riley, Paul R

    2011-02-01

    Stem cell therapy has recently emerged as an innovative strategy over conventional cardiovascular treatments to restore cardiac function in patients affected by ischemic heart disease. Various stem cell populations have been tested and their potential for cardiac repair has been analyzed. Embryonic stem cells retain the greatest differentiation potential, but concerns persist with regard to their immunogenic and teratogenic effects. Although adult somatic stem cells are not tumourigenic and easier to use in an autologous setting, they exist in small numbers and possess reduced differentiation potential. Traditionally the heart was considered to be a post-mitotic organ; however, this dogma has recently been challenged with the identification of a reservoir of resident stem cells, defined as cardiac progenitor cells (CPCs). These endogenous progenitors may represent the best candidates for cardiovascular cell therapy, as they are tissue-specific, often pre-committed to a cardiac fate, and display a greater propensity to differentiate towards cardiovascular lineages. This review will focus on current research into the biology of CPCs and their regenerative potential. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".

  20. Finding Supernova Ia Progenitors with the Chandra X-ray Observatory

    DEFF Research Database (Denmark)

    Nielsen, Mikkel T. B.; Nelemans, Gijs; Voss, Rasmus

    2011-01-01

    We examine pre-supernova Chandra images to find X-ray luminosities of type Ia supernova progenitors. At present, we have one possible direct detection and upper limits for the X-ray luminosities of a number of other supernova progenitors. The method has also yielded a possible detection of a X...

  1. Effects of hematopoietic growth factors on purified bone marrow progenitor cells

    NARCIS (Netherlands)

    F.J. Bot (Freek)

    1992-01-01

    textabstractWe have used highly enriched hematopoietic progenitor cells and in-vitro culture to examine the following questions: 1. The effects of recombinant lL-3 and GM-CSF on proliferation and differentiation of enriched hematopoietic progenitor cells have not been clearly defined: - how do IL~3

  2. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models.

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-01-01

    Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression.

  3. Isolation and characterization of progenitor cells in uninjured, adult rat lacrimal gland

    DEFF Research Database (Denmark)

    Shatos, Marie A; Haugaard-Kedstrom, Linda; Hodges, Robin R;

    2012-01-01

    PURPOSE: The purpose of this study was to investigate the presence of progenitor cells in the uninjured, adult rat lacrimal gland (LG). METHODS: The presence of progenitor cells was examined in LG sections from male rats using antibodies against selected stem cell markers and α-smooth muscle actin...

  4. On Measuring the Metallicity of a Type Ia Supernova’s Progenitor

    Science.gov (United States)

    Miles, Broxton J.; van Rossum, Daniel R.; Townsley, Dean M.; Timmes, F. X.; Jackson, Aaron P.; Calder, Alan C.; Brown, Edward F.

    2016-06-01

    In Type Ia Supernovae (SNe Ia) the relative abundances of chemical elements are affected by the neutron excess in the composition of the progenitor white dwarf. Since these products leave signatures in the spectra near maximum light, spectral features may be used to constrain the composition of the progenitor. We calculate the nucleosynthetic yields for three SN Ia simulations, assuming single degenerate, Chandrasekhar-mass progenitors, for a wide range of progenitor metallicities, and calculate synthetic light curves and spectra to explore correlations between progenitor metallicity and the strength of spectral features. We use two two-dimensional simulations of the deflagration-detonation-transition scenario with different 56Ni yields and the W7 simulation to control for differences between explosion models and total yields. While the overall yields of intermediate-mass elements (16 days post-explosion that appear to deepen with progenitor metallicity: a Ti feature around 4200 Å and an Fe feature around 5200 Å. In all three simulations, their pseudo equivalent widths show a systematic trend with progenitor metallicity. This suggests that these two features may allow for differentiation among progenitor metallicities of observed SNe Ia and potentially help to reduce the intrinsic Hubble scatter.

  5. The Disappearance of the Red Supergiant Progenitor of Supernova 2008bk

    OpenAIRE

    Mattila, Seppo; Smartt, Stephen; Maund, Justyn; Benetti, Stefano; Ergon, Mattias

    2010-01-01

    Massive stars end their lives in spectacular supernova explosions. Identifying the progenitor star is a test of stellar evolution and explosion models. Here we show that the progenitor star of the supernova SN 2008bk has now disappeared, which provides conclusive evidence that this was the death of a red supergiant star.

  6. Development and application of human adult stem or progenitor cell organoids

    NARCIS (Netherlands)

    Rookmaaker, Maarten B; Schutgens, Frans; Verhaar, Marianne C; Clevers, Hans

    2015-01-01

    Adult stem or progenitor cell organoids are 3D adult-organ-derived epithelial structures that contain self-renewing and organ-specific stem or progenitor cells as well as differentiated cells. This organoid culture system was first established in murine intestine and subsequently developed for sever

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  11. Oxidative stress due to radiation in CD34+ hematopoietic progenitor cells. Protection by IGF-1

    International Nuclear Information System (INIS)

    Radiation exerts direct as well as indirect effects on DNA through the generation of reactive oxygen species (ROS). Irradiated hematopoietic progenitor cells (HPCs) experience DNA strand breaks, favoring genetic instability, due to ROS generation. Our aim was to study the effect of a range of radiation doses in HPCs and the possible protective mechanisms activated by insulin-like growth factor-1 (IGF-1). ROS generation was evaluated, in the presence or absence of IGF-1 in liquid cultures of human HPCs-CD34+ irradiated with 1-, 2- and 5-Gy X-rays, using a flow cytometry assay. Manganese superoxide dismutase (MnSOD) expression was studied by western blot analysis and visualized by an immunofluorescence assay. Apoptosis was estimated using the following assays: Annexin-V assay, DNA degradation assay, BCL-2/BAX mRNA and protein levels and caspase-9 protein immunofluorescence visualization. Viability and clonogenic potential were studied in irradiated HPCs. The generation of superoxide anion radicals at an early and a late time point was increased, while the hydrogen peroxide generation at a late time point was stable. IGF-1 presence further enhanced the radiation-induced increase of MnSOD at 24 h post irradiation. IGF-1 inhibited the mitochondria-mediated pathway of apoptosis by regulating the m-RNA and protein expression of BAX, BCL-2 and the BCL-2/BAX ratio and by decreasing caspase-9 protein expression. IGF-1 presence in culture media of irradiated cells restored the clonogenic capacity and the viability of HPCs as well. In conclusion, IGF-1 protects HPCs-CD34+ from radiation effects, by eliminating the oxidative microenvironment through the enhancement of MnSOD activation and by regulating the mitochondria-mediated pathway of apoptosis. (author)

  12. The Role of Neonatal Carnitine Palmitoyl Transferase Deficiency Type II on Proliferation of Neuronal Progenitor Cells and Layering of the Cerebral Cortex in the Developing Brain

    Directory of Open Access Journals (Sweden)

    Heepeel Chang

    2007-06-01

    Full Text Available Neonatal Carnitine Palmitoyl Transferase Deficiency Type II, characterized by the absence of CPT II enzyme, is one of the lethal disorders of mitochondrial fatty acid oxidation. CPT II regulates the conversion of long chain fatty acids, so that its product, acyl-CoA esters, can enter the Krebs cycle and generate energy. Neonatal mutations of CPT II lead to severe disruption of the metabolism of long-chain fatty acids and result in dysmorphic features, cystic renal dysplasia, and neuronal migration defects. Examination of the brain from an approximately 15-week gestation human fetus with CPT II deficiency revealed premature formation of cerebral cortical gyri and sulci and significantly lower levels of neuronal cell proliferation in the ventricular and subventricular zones as compared to the reference cases. We used immunohistochemical markers to further characterize the effect of CPT II deficiency on progenitor cell proliferation and layering of neurons. These studies demonstrated a premature generation of layer 5 cortical neurons. In addition, both the total number and percentage of progenitor cells proliferating in the ventricular zone were markedly reduced in the CPT II case in comparison to a reference case. Our results indicate that CPT II deficiency alters the normal program of cellular proliferation and differentiation in the cortex, with early differentiation of progenitor cells associated with premature cortical maturation.

  13. Analysis of neural progenitors from embryogenesis to juvenile adult in Xenopus laevis reveals biphasic neurogenesis and continuous lengthening of the cell cycle

    Directory of Open Access Journals (Sweden)

    Raphaël Thuret

    2015-12-01

    Full Text Available Xenopus laevis is a prominent model system for studying neural development, but our understanding of the long-term temporal dynamics of neurogenesis remains incomplete. Here, we present the first continuous description of neurogenesis in X. laevis, covering the entire period of development from the specification of neural ectoderm during gastrulation to juvenile frog. We have used molecular markers to identify progenitors and neurons, short-term bromodeoxyuridine (BrdU incorporation to map the generation of newborn neurons and dual pulse S-phase labelling to characterise changes in their cell cycle length. Our study revealed the persistence of Sox3-positive progenitor cells from the earliest stages of neural development through to the juvenile adult. Two periods of intense neuronal generation were observed, confirming the existence of primary and secondary waves of neurogenesis, punctuated by a period of quiescence before metamorphosis and culminating in another period of quiescence in the young adult. Analysis of multiple parameters indicates that neural progenitors alternate between global phases of differentiation and amplification and that, regardless of their behaviour, their cell cycle lengthens monotonically during development, at least at the population level.

  14. Vascular Endothelial Growth Factor (VEGF) Bioavailability Regulates Angiogenesis and Intestinal Stem and Progenitor Cell Proliferation during Postnatal Small Intestinal Development

    Science.gov (United States)

    Holoyda, Kathleen A.; Hou, Xiaogang; Fowler, Kathryn L.; Grikscheit, Tracy C.

    2016-01-01

    Background Vascular endothelial growth factor (VEGF) is a highly conserved, master regulatory molecule required for endothelial cell proliferation, organization, migration and branching morphogenesis. Podocoryne carnea and drosophila, which lack endothelial cells and a vascular system, express VEGF homologs, indicating potential roles beyond angiogenesis and vasculogenesis. The role of VEGF in the development and homeostasis of the postnatal small intestine is unknown. We hypothesized regulating VEGF bioavailability in the postnatal small intestine would exhibit effects beyond the vasculature and influence epithelial cell stem/progenitor populations. Methods VEGF mutant mice were created that overexpressed VEGF in the brush border of epithelium via the villin promotor following doxycycline treatment. To decrease VEGF bioavailability, sFlt-1 mutant mice were generated that overexpressed the soluble VEGF receptor sFlt-1 upon doxycycline administration in the intestinal epithelium. Mice were analyzed after 21 days of doxycycline administration. Results Increased VEGF expression was confirmed by RT-qPCR and ELISA in the intestine of the VEGF mutants compared to littermates. The VEGF mutant duodenum demonstrated increased angiogenesis and vascular leak as compared to littermate controls. The VEGF mutant duodenum revealed taller villi and increased Ki-67-positive cells in the transit-amplifying zone with reduced Lgr5 expression. The duodenum of sFlt-1 mutants revealed shorter villi and longer crypts with reduced proliferation in the transit-amplifying zone, reduced expression of Dll1, Bmp4 and VE-cadherin, and increased expression of Sox9 and EphB2. Conclusions Manipulating VEGF bioavailability leads to profound effects on not only the intestinal vasculature, but epithelial stem and progenitor cells in the intestinal crypt. Elucidation of the crosstalk between VEGF signaling in the vasculature, mesenchyme and epithelial stem/progenitor cell populations may direct future

  15. Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation.

    Science.gov (United States)

    Ono, Wanida; Sakagami, Naoko; Nishimori, Shigeki; Ono, Noriaki; Kronenberg, Henry M

    2016-01-01

    Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (PTHrP) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I/C (Nfic). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP-PPR system during root morphogenesis and tooth eruption. PMID:27068606

  16. Exploring the activated adipogenic niche: interactions of macrophages and adipocyte progenitors.

    Science.gov (United States)

    Lee, Yun-Hee; Thacker, Robert I; Hall, Brian Eric; Kong, Raymond; Granneman, James G

    2014-01-01

    Adult adipose tissue contains a large supply of progenitors that can renew fat cells for homeostatic tissue maintenance and adaptive growth or regeneration in response to external challenges. However, the in vivo mechanisms that control adipocyte progenitor behavior are poorly characterized. We recently demonstrated that recruitment of adipocyte progenitors by macrophages is a central feature of adipose tissue remodeling under various adipogenic conditions. Catabolic remodeling of white adipose tissue by β3-adrenergic receptor stimulation requires anti-inflammatory M2-polarized macrophages to clear dying adipocytes and to recruit new brown adipocytes from progenitors. In this Extra Views article, we discuss in greater detail the cellular elements of adipogenic niches and report a strategy to isolate and characterize the subpopulations of macrophages and adipocyte progenitors that actively participate in adrenergic tissue remodeling. Further characterization of these subpopulations may facilitate identification of new cellular targets to improve metabolic and immune function of adipose tissue.

  17. Growth factor-and cytokine-stimulated endothelial progenitor cells in post-ischemic cerebral neovascularization

    Institute of Scientific and Technical Information of China (English)

    Philip V.Peplow

    2014-01-01

    Endothelial progenitor cells are resident in the bone marrow blood sinusoids and circulate in the peripheral circulation. They mobilize from the bone marrow after vascular injury and home to the site of injury where they differentiate into endothelial cells. Activation and mobilization of endothelial progenitor cells from the bone marrow is induced via the production and release of endothelial progenitor cell-activating factors and includes speciifc growth factors and cytokines in response to peripheral tissue hypoxia such as after acute ischemic stroke or trauma. Endotheli-al progenitor cells migrate and home to speciifc sites following ischemic stroke via growth factor/cytokine gradients. Some growth factors are less stable under acidic conditions of tissue isch-emia, and synthetic analogues that are stable at low pH may provide a more effective therapeutic approach for inducing endothelial progenitor cell mobilization and promoting cerebral neovas-cularization following ischemic stroke.

  18. TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors.

    Science.gov (United States)

    Cebola, Inês; Rodríguez-Seguí, Santiago A; Cho, Candy H-H; Bessa, José; Rovira, Meritxell; Luengo, Mario; Chhatriwala, Mariya; Berry, Andrew; Ponsa-Cobas, Joan; Maestro, Miguel Angel; Jennings, Rachel E; Pasquali, Lorenzo; Morán, Ignasi; Castro, Natalia; Hanley, Neil A; Gomez-Skarmeta, Jose Luis; Vallier, Ludovic; Ferrer, Jorge

    2015-05-01

    The genomic regulatory programmes that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic-stem-cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signalling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signalling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role for TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas. PMID:25915126

  19. Neonatal Heart-Enriched miR-708 Promotes Differentiation of Cardiac Progenitor Cells in Rats

    Directory of Open Access Journals (Sweden)

    Shengqiong Deng

    2016-06-01

    Full Text Available Cardiovascular disease is becoming the leading cause of death throughout the world. However, adult hearts have limited potential for regeneration after pathological injury, partly due to the quiescent status of stem/progenitor cells. Reactivation of cardiac stem/progenitor cells to create more myocyte progeny is one of the key steps in the regeneration of a damaged heart. In this study, miR-708 was identified to be enriched in the neonatal cardiomyocytes of rats, but this has not yet been proven in adult humans. A lower level of miR-708 in c-kit(+ stem/progenitor cells was detected compared to non-progenitors. Overexpression of miR-708 induced cardiomyocyte differentiation of cardiac stem/progenitor cells. This finding strengthened the potential of applying miRNAs in the regeneration of injured hearts, and this indicates that miR-708 could be a novel candidate for treatment of heart diseases.

  20. Progenitors of supernova Ibc: a single Wolf-Rayet star as the possible progenitor of the SN Ib iPTF13bvn

    CERN Document Server

    Groh, Jose H; Ekstrom, Sylvia

    2013-01-01

    Core-collapse supernova (SN) explosions mark the end of the tumultuous life of massive stars. Determining the nature of their progenitors is a crucial step towards understanding the properties of SNe. Until recently, no progenitor has been directly detected for SN of type Ibc, which are believed to come from massive stars that lose their Hydrogen envelope through stellar winds and from binary systems where the companion has stripped the H envelope from the primary. Here we analyze recently-reported observations of iPTF13bvn, which could possibly be the first detection of a SN Ib progenitor based on pre-explosion images. Very interestingly, the recently published Geneva models of single stars can reproduce the observed photometry of the progenitor candidate and its mass-loss rate, confirming the scenario from Cao et al 2013. We find that a single WR star with initial mass in the range 31-35 Msun fits the observed photometry of the progenitor of iPTF13bvn. The progenitor likely has a luminosity of log (L/Lsun)~...

  1. Nephron Progenitor But Not Stromal Progenitor Cells Give Rise to Wilms Tumors in Mouse Models with β-Catenin Activation or Wt1 Ablation and Igf2 Upregulation

    Directory of Open Access Journals (Sweden)

    Le Huang

    2016-02-01

    Full Text Available Wilms tumor, a common childhood tumor of the kidney, is thought to arise from undifferentiated renal mesenchyme. Variable tumor histology and the identification of tumor subsets displaying different gene expression profiles suggest that tumors may arise at different stages of mesenchyme differentiation and that this ontogenic variability impacts tumor pathology, biology, and clinical outcome. To test the tumorigenic potential of different cell types in the developing kidney, we used kidney progenitor-specific Cre recombinase alleles to introduce Wt1 and Ctnnb1 mutations, two alterations observed in Wilms tumor, into embryonic mouse kidney, with and without biallelic Igf2 expression, another alteration that is observed in a majority of tumors. Use of a Cre allele that targets nephron progenitors to introduce a Ctnnb1 mutation that stabilizes β-catenin resulted in the development of tumors with a predominant epithelial histology and a gene expression profile in which genes characteristic of early renal mesenchyme were not expressed. Nephron progenitors with Wt1 ablation and Igf2 biallelic expression were also tumorigenic but displayed a more triphasic histology and expressed early metanephric mesenchyme genes. In contrast, the targeting of these genetic alterations to stromal progenitors did not result in tumors. These data demonstrate that committed nephron progenitors can give rise to Wilms tumors and that committed stromal progenitors are less tumorigenic, suggesting that human Wilms tumors that display a predominantly stromal histology arise from mesenchyme before commitment to a stromal lineage.

  2. Injury-induced neurogenesis: consideration of resident microglia as supportive of neural progenitor cells.

    Science.gov (United States)

    McPherson, Christopher A; Kraft, Andrew D; Harry, G Jean

    2011-02-01

    The induction of neurogenesis in the adult subgranular zone (SGZ) by injury is often accompanied by changes in the extracellular environment that can have significant impacts on neural progenitor cells (NPCs). We examined the induction of neurogenesis in the SGZ at 72 h following an injection of the hippocampal toxicant, trimethyltin (TMT; 2 mg/kg, ip) inducing apoptosis in dentate granule neurons. BrdU+ incorporation during the active period of neuronal death indicated NPC proliferation and migration of newly generated cells into the granule cell layer (GCL). BrdU+ cells were transiently in contact with process bearing microglia within the inner SGZ layer. Contact with GFAP+ astrocyte processes occurred once cells were within the GCL. A small percentage of the BrdU+ cells within the SGZ region showed immunoreactivity for tumor necrosis factor (TNF) p75 receptor (TNFp75R). In mice deficient for TNFp75R, TMT injection produced an equivalent level of dentate granule cell death however; BrdU+ cells were localized at the SGZ as compared to the presence of cells within the GCL in the WT mice dosed with TMT. These data suggest that cells generated by NPCs in the SGZ induced with a focal lesion to the dentate granule neurons of adolescent mice maintain the capacity to utilize the neuroinflammation and microglia responses within their environment for migration into the GCL.

  3. Oct4-induced oligodendrocyte progenitor cells enhance functional recovery in spinal cord injury model.

    Science.gov (United States)

    Kim, Jeong Beom; Lee, Hyunah; Araúzo-Bravo, Marcos J; Hwang, Kyujin; Nam, Donggyu; Park, Myung Rae; Zaehres, Holm; Park, Kook In; Lee, Seok-Jin

    2015-12-01

    The generation of patient-specific oligodendrocyte progenitor cells (OPCs) holds great potential as an expandable cell source for cell replacement therapy as well as drug screening in spinal cord injury or demyelinating diseases. Here, we demonstrate that induced OPCs (iOPCs) can be directly derived from adult mouse fibroblasts by Oct4-mediated direct reprogramming, using anchorage-independent growth to ensure high purity. Homogeneous iOPCs exhibit typical small-bipolar morphology, maintain their self-renewal capacity and OPC marker expression for more than 31 passages, share high similarity in the global gene expression profile to wild-type OPCs, and give rise to mature oligodendrocytes and astrocytes in vitro and in vivo. Notably, transplanted iOPCs contribute to functional recovery in a spinal cord injury (SCI) model without tumor formation. This study provides a simple strategy to generate functional self-renewing iOPCs and yields insights for the in-depth study of demyelination and regenerative medicine. PMID:26497893

  4. Characterization and molecular profiling of PSEN1 familial Alzheimer's disease iPSC-derived neural progenitors.

    Directory of Open Access Journals (Sweden)

    Andrew A Sproul

    Full Text Available Presenilin 1 (PSEN1 encodes the catalytic subunit of γ-secretase, and PSEN1 mutations are the most common cause of early onset familial Alzheimer's disease (FAD. In order to elucidate pathways downstream of PSEN1, we characterized neural progenitor cells (NPCs derived from FAD mutant PSEN1 subjects. Thus, we generated induced pluripotent stem cells (iPSCs from affected and unaffected individuals from two families carrying PSEN1 mutations. PSEN1 mutant fibroblasts, and NPCs produced greater ratios of Aβ42 to Aβ40 relative to their control counterparts, with the elevated ratio even more apparent in PSEN1 NPCs than in fibroblasts. Molecular profiling identified 14 genes differentially-regulated in PSEN1 NPCs relative to control NPCs. Five of these targets showed differential expression in late onset AD/Intermediate AD pathology brains. Therefore, in our PSEN1 iPSC model, we have reconstituted an essential feature in the molecular pathogenesis of FAD, increased generation of Aβ42/40, and have characterized novel expression changes.

  5. Effect of endothelial progenitor cells in neovascularization and their application in tumor therapy

    Institute of Scientific and Technical Information of China (English)

    DONG Fang; HA Xiao-qin

    2010-01-01

    Objective To review the effect of endothelial progenitor cells in neovascularization as well as their application to the therapy of tumors.Data sources The data used in this review were mainly from PubMed for relevant English language articles published from 1997 to 2009. The search term was "endothelial progenitor cells".Study selection Articles regarding the role of endothelial progenitor cells in neovascularization and their application to the therapy of tumors were selected.Results Endothelial progenitor cells isolated from bone marrow, umbilical cord blood and peripheral blood can proliferate, mobilize and differentiate into mature endothelial cells. Experiments suggest endothelial progenitor cells take part in forming the tumor vascular through a variety of mechanisms related to vascular endothelial growth factor, matrix metalloproteinases, chemokine stromal cell-derived factor 1 and its receptor C-X-C receptor-4, erythropoietin, Notchsignal pathway and so on. Evidence demonstrates that the number and function change of endothelial progenitor cells in peripheral blood can be used as a biomarker of the response of cancer patients to anti-tumor therapy and predict the prognosis and recurrence. In addition, irradiation temporarily increased endothelial cells number and decreased the endothelial progenitor cell counts in animal models. Meanwhile, in preclinical experiments, therapeutic gene-modified endothelial progenitor cells have been approved to attenuate tumor growth and offer a novel strategy for cell therapy and gene therapy of cancer.Conclusions Endothelial progenitor cells play a particular role in neovascularization and have attractively potential prognostic and therapeutic applications to malignant tumors. However, a series of problems, such as the definitive biomarkers of endothelial progenitor cells, their interrelationship with radiotherapy and their application in cell therapy and gene therapy of tumors, need further investigation.

  6. Low- and high-LET radiation drives clonal expansion of lung progenitor cells in vivo.

    Science.gov (United States)

    Farin, Alicia M; Manzo, Nicholas D; Kirsch, David G; Stripp, Barry R

    2015-01-01

    Abundant populations of epithelial progenitor cells maintain the epithelium along the proximal-to-distal axis of the airway. Exposure of lung tissue to ionizing radiation leads to tissue remodeling and potential cancer initiation or progression. However, little is known about the effects of ionizing radiation on airway epithelial progenitor cells. We hypothesized that ionizing radiation exposure will alter the behavior of airway epithelial progenitor cells in a radiation dose- and quality-dependent manner. To address this hypothesis, we cultured primary airway epithelial cells isolated from mice exposed to various doses of 320 kVp X ray or 600 MeV/nucleon (56)Fe ions in a 3D epithelial-fibroblast co-culture system. Colony-forming efficiency of the airway epithelial progenitor cells was assessed at culture day 14. In vivo clonogenic and proliferative potentials of airway epithelial progenitor cells were measured after exposure to ionizing radiation by lineage tracing and IdU incorporation. Exposure to both X rays and (56)Fe resulted in a dose-dependent decrease in the ability of epithelial progenitors to form colonies in vitro. In vivo evidence for increased clonogenic expansion of epithelial progenitors was observed after exposure to both X rays and (56)Fe. Interestingly, we found no significant increase in the epithelial proliferative index, indicating that ionizing radiation does not promote increased turnover of the airway epithelium. Therefore, we propose a model in which radiation induces a dose-dependent decrease in the pool of available progenitor cells, leaving fewer progenitors able to maintain the airway long-term. This work provides novel insights into the effects of ionizing radiation exposure on airway epithelial progenitor cell behavior. PMID:25564721

  7. Erythropoietin Receptor Positive Circulating Progenitor Cells and Endothelial Progenitor Cells in Patients with Different Stages of Diabetic Retinopathy

    Institute of Scientific and Technical Information of China (English)

    Liu-mei Hu; Guo-xu Xu; Guo-tong XU; Wei-ye Li; Xia Lei; Bo Ma; Yu Zhang; Yan Yan; Ya-lan Wu; Ge-zhi Xu; Wen Ye; Ling Wang

    2011-01-01

    Objective To investigate the possible involvement of erythropoietin (EPO)/erythropoietin receptor(EPOR) system in neovascularization and vascular regeneration in diabetic retinopathy (DR).Methods EPOR positive circulating progenitor cells (CPCs: CD34+) and endothelial progenitor cells (EPCs: CD34+KDR+) were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients without diabetes (n=7), non-prolif-erative DR (NPDR, n=7), proliferative DR (PDR, n=8), and PDR complicated with diabetic nephropathy (PDR-DN, n=7). Results The numbers of EPOR+ CPCs and EPOR+ EPCs were reduced remarkably in NPDR compared with the control group (both P<0.01), whereas rebounded in PDR and PDR-DN groups in varying degrees. Similar changes were observed in respect of the proportion of EPOR+ CPCs in CPCs (NPDR vs.control, P< 0.01) and that of EPOR+ EPCs in EPCs (NPDR vs. control, P< 0.05). Conclusion Exogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the im-paired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR+ EPCs associated with ischemia.

  8. Cryopreserved hepatic progenitor cells derived from human embryonic stem cells can arrest progression of liver fibrosis in rats.

    Science.gov (United States)

    Mandal, Arundhati; Raju, Sheena; Viswanathan, Chandra

    2016-10-01

    Hepatocytes generated from human embryonic stem cells (hESCs) are considered to be an excellent candidate for restoring the liver function deficiencies. We have earlier standardized a three-step differentiation protocol to generate functional hepatocyte-like cells (HLCs) from hESCs, which expressed the major hepatic markers. We have also found that the HLCs remain stable and functional even after extended period of in vitro culture and cryopreservation. In the present study, we have aimed to investigate the therapeutic potential of cryopreserved-thawed hESC-derived hepatic progenitor cells following transplantation in carbon tetrachloride-induced fibrotic rat livers. Significant therapeutic effects, including improved hepatic histology and normal serum biochemistry of hepatic enzymes along with increased survival rate, were observed in the cell transplanted rats. This result is an encouraging indication to develop methods for clinical application of hESC-derived hepatic lineage cells.

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