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The Biologic Characteristics of Human Placenta-derived Mesenchymal Stem Cells and It’s Negative Co-stimulation for T Cell in Vitro

Author: GuYanZuo
Tutor: ZhangXueGuang;XueQun
School: Suzhou University
Course: Immunology
Keywords: Negative costimulatory molecules Placental source of mesenchymal stem cells Bone marrow-derived mesenchymal stem cells PD-L1 Immunomodulatory
CLC: R392
Type: Master's thesis
Year: 2009
Downloads: 89
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Abstract


Mesenchymal stem cells (mesenchymal stem cell, MSCs) are pluripotent stem cells with self-renewal and differentiation potential, it can differentiate into many types of tissue cells in a specific inducing conditions, can be derived from the development of mesoderm the formation of a variety of tissues such as bone, cartilage, fat, myocardial Initially MSCs derived from bone marrow, human bone marrow-derived mesenchymal stem cells (bone marrow mesenchymal stem cells, BMSCs) in bone marrow content is extremely low, typically only 0.01% -0.001% of the amount of bone marrow cells, and drawn more difficult in recent years has successfully separated from the placenta, umbilical cord blood, dense bone, fat, muscle, and other tissues, placenta formerly discarded as \This article aims to be obtained from the mature placenta placental source of mesenchymal stem cells (placenta derived mesenchymal stem cells, PMSCs) study compared PMSCs and BMSCs immunobiological characteristics. In recent years, research has shown that, MSCs addition to support hematopoiesis, promote hematopoietic reconstitution in vivo, and also has low immunogenicity and immunomodulatory effects suppress allogeneic immune rejection in allogeneic stem cell transplantation can reduce the host versus graft reaction (HVGR ) and graft-versus-host reaction (GVHD) prolong graft survival time and improve the success rate of transplantation, is an ideal tissue engineering seed cells specific immunomodulatory mechanism has not been fully elucidated. Studies have shown that people PMSCs T-cell activation and inhibit the proliferation. The existing experiments showed that PMSCs not the expression of HLA-DR, PMSCs have low immunogenicity, while less for the placental source MSCs immunomodulatory effects reported. This experiment, isolated from human placenta acquisition of MSCs and BMSCs further comparison of their biological characteristics and in vitro T cell cycle and activation, cytokine secretion observed high expression of negative costimulatory molecule PD-L1 PMSCs other aspects of the regulatory role for clinical applications and basic research provides the theoretical basis of the experiment. Separation of the first part of human placental source and human bone marrow source charge quality stem cells of the in vitro separation and biological characteristics comparison purposes: compare human placental source derived mesenchymal stem cells (HPMSCs) and human bone marrow source between mesenchymal stem cells (HBMSCs) the in vitro methods and biological characteristics of the two types of cells. Methods: enzyme digestion were isolated from human placental tissue, bone marrow mononuclear cells separated by density gradient centrifugation, were isolated and subcultured adherent cell morphology was observed by inverted phase contrast microscope, using flow cytometry cell surface marker expression to do a comparative analysis. Cell differentiation experiments and the effect of inducing agent, the identification of stem cells and co-cultured with PHA-stimulated T cells and PMSCs or BMSCs to observe the interaction of T cells with both. Results: (1) two sources of mesenchymal stem cells are adherent growth, showed a fibroblast-like morphology, expression of CD29, CD44, CD73, CD90, CD105, CD106, CD166, but not the expression of CD34, CD45, HLA-DR molecules; (2) two sources of mesenchymal stem cells can in vitro to differentiate into adipocytes, osteoblasts direction induced differentiation (3); these two sources of mesenchymal stem cells in vitro T cell activation, proliferation significantly inhibited. Conclusion: people PMSCs BMSCs in vitro biological characteristics similar phenotype and differentiation potential of its negative immunomodulatory effects, is an ideal tissue engineering seed cells. PD-L1, the second part of the negative costimulatory molecules in human placental source of MSCs express its negative immunomodulatory effects purpose: to explore the human placental mesenchymal stem cells (PMSCs) on the negative costimulatory molecule PD-L1 expression T cells in vitro negative synergy. Methods: amplification the PMSCs and HBMSCs three generations after in vitro, using flow cytometry and immunofluorescence method to analyze the costimulatory molecule expression on the two types of cells, ~ 3H-TdR incorporation assay PMSCs PHA stimulated T cell proliferation, and PD-L1 monoclonal antibody blocking the PMSCs inhibition of T cell proliferation; flow cytometry analysis of the impact of PMSCs on the the PHA role of T cell cycle and early activation molecule CD69 expression, ELISA assay cytokine levels change and the role of blocking PD-L1. Results: (1) PMSCs and HBMSCs, not positive expression of CD80, CD83, CD86, costimulatory molecules, while the the PMSCs high expression of PD-L1, HBMSCs low expression levels of PD-L1. (2) PMSCs inhibit T cell proliferation in vitro, and PHA stimulation of T cells remain in the G0/G1 phase of the cell cycle, reduced activation of early T-cell surface molecule CD69 expression, as well as regulation of IL-2, IFN-γ, The secretion of IL-10. Thereby indicating PMSCs mediated negative immunoregulatory action part by high expression of PD-L1 molecules, PD-L1 PMSCs expression of major negative immunoregulatory molecules. Conclusion: people PMSCs in vitro T cell activation and proliferation, the expression of PD-L1 molecules mediated immunomodulatory effects.

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