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Bone Marrow Source Of Flk-1 ~ + Mesenchymal Stem Cells In Immune Regulation And Related Applications

Posted on:2007-10-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q HanFull Text:PDF
GTID:1114360185468545Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Bone marrow derived mesenchymal stem cell (bMSC) is a non-hematopoietic population that resides in bone marrow compartment. Investigations on stem cell plasticity showed that MSCs are primordial cells that could differentiate into multiple cell types including stromal cells, osteoblasts, adipocytes, myocardiocytes, myocytes, neural cells, endothelial cells and so on. More striking is the immuno-modulotory function of MSCs that might contribute to developing immunotherapies for refractory diseases.In the first part, we investigated MSCs' immunomodulatory effects on normal immune system. In an in vitro co-culture system, MSCs were observed to modulate the proliferation, activation, and maturation of T and B lymphocytes. And these immunomodulatory effects were not MHC-restricted. Upon transplantation, MSCs could also modulate immune reponses of recipients in vivo.The second part primarily presented MSCs' immunomodulation on BXSB mice, which were born with immunological deficiency and developed lupus naturally. Here we first reported the immunomodulatory effects of MSCs on abnormal immune system of BXSB mice model, and provided positive results for developing effective therapy for autoimmune diseases.The third part mainly investigated possible mechanisms of inducing immuno-tolerance by MSCs. Our results showed that allogenic MSC transplantation could induce stable chimerism and stable immuno-tolerance. This opened a prospect for developing new strategies for organ transplantation, bone marrow transplantation, and treating autoimmune diseases.In the forth part, we investigated therapuetical effect of MSCs in acute injury models. MSCs were shown effective in ischemia-reperfusion renal injury model. The underlining mechanism involves alleviating inflammations.
Keywords/Search Tags:mesenchymal stem cell, immune modulation, autoimmune disease, SLE, immune tolerance, organ transplantation, ischemia-reperfusion, side population cell(SP cell), stem cell transplantation
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