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The Role Of Bone Marrow-derived Stromal Cells In Hematopoietic Regulation

Posted on:2005-09-14Degree:MasterType:Thesis
Country:ChinaCandidate:X F ShiFull Text:PDF
GTID:2144360125966148Subject:Hematology
Abstract/Summary:PDF Full Text Request
HSC(Hematopoietic stem cell)is responsible for forming all of the types of blood cells in body, which was recognized as a stem cell more than 40 years ago . BMSCs were described shortly after the discovery of HSCs. BMSCs are a mixed cell population that generate bone cartilage ,fat, fibrous connective tissue and the reticular network and all these cells make up the microenvironment of hematopoisis.Whether BMSCs are best classified as stem cells of progenitor cells for these tissues is still in question .There is also a question whether BM SCs and so-called mesenchymal stem cells(MSCs) are the same population .BMSCs differ easily from HSCs, forming the nonhematopoietic adherent cell component from long-term cultures . Many a specialist takes focus on BMSCs resently just because of following items: (1) Plasticity Its ability to differentiate into cartilage can be used to reconstitute bone of the people suffering from osteogenesis imperfecta .Futhermore BMSCs, when injected in the right place , can be converted into cardiomyocytes which can replace heart cells damaged from myocardial infarction or congestive hear failure ,and literally restore cardiac function. Neural cells differentiated from BMSCs can relieve symptoms and limit further damage of brain and spinal cord .(2)Supporting hematopoiesis HSC transplantation can cure for varies of diseases ,while the small number of HSCs usually limits its application . Proliferating system using BMSCs as feeder-cells is found a valid way to expanse HSCs with decades of population doublings without losing stem cell nature.(3)Enhancinghematopoietic reconstition Animals transplanted with BMCs plus stromal cells had larger WBC and smaller incidence to bleed and infect than those with BMCs only did . How do BMSCs enhance hematopoietic reconstitution and how do they distribute in vivo? Must BMSCs home to bone marrow ?There are only several reports on this topic outboard and little articles are seen home.Cytobiological technology and animal experiment were used : (l)To investigate the general character of human stroma or mice stroma ,the ability to differentiate into other tissues and the role in supporting hematopoiesis.(2)To study the effect of cotransplantation HSCs and BMSCs on hematopoietic reconstitution .(3)To observe the distribution of BMSCs after infusion in vivo.1. General characteristic of BMSCs BMSCs from human were proliferated in vitro ..comparing to those from mice. The effects of bFGF on BMSCs were observed and phenotypes of BMSCs were examined with flow cytometry .Sudan HI staining was used to confirm whether BMSCs could transdifferentiate into lipocyte . In addition BMSCs were used as feeder-cells to support the long-term repopulating cells ( LTRC) . As a result ,we found there was much difference between human BMSCs and mice BMSCs and BMSCs could proliferate for 7 population doublings in medium with only hydrocortisone, while for 14 population doublings with bFGF without recessing .Phenotypes associated to hematopoietic cells were not expressed in BMSCs, while adhesion moleculars such as integrin family VLA- ?(very late antigen ?subunit)CD29,LFA(leukocyte function antigen ) CD 11 a, CDllb ;other molecular CD44 were strongly expressed . We found BMSCs could transdifferentiate into adipocytes and Sudan III staining was positive .Stroma-feeder cells could support LTRC and prevent them from apoptosis .2. BMSCs enhancing hematopoietic reconstitution Cultured BMSCs plus whole BMCs were injected in vein into Balb/c mice irradiated lethally ,then mortality rate and leukocytes were counted . Results expressed that more mice transplanted with BMCs plus BMSCs survived than those with BMCs only did and hematopoietic recovery with BMCs plus BMSCs was rapid . BMSCs can enhance hematopoitic reconstitution and be transplanted i.v. in security without any toxicity.3. Distribution characteristic of BMSCs in SCID mice BMSCs were expanded in the medium with bFGF in vitro, tagged with CFDA SE and injected in vein into SCI...
Keywords/Search Tags:bone marrow stromal cell, mesenchymal stem cells, hematopoietic stem cells, hematopoietic reconstitution
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