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The Preliminary Research Of Transplanting Bone Marrow Stromal Cells Into Heart

Posted on:2004-05-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:T TangFull Text:PDF
GTID:1104360092487078Subject:Surgery
Abstract/Summary:PDF Full Text Request
Background Ventricular remodeling is a major cause of progressive heart failure and death after myocardial infarction. As adaptive reaction to myocardial ischemia and one of remodeling integral processes , body can accelerate the creation of coronary collateral circulation by proliferating capillary vessel. But in most conditions, this compensatory process is insufficient. Accelerating the formation and open of coronary collateral circulation can ameliorate relieve ischemia of myocardium and relieve ventricular remodeling. Bone marrow stromal cell is multipotential stem cell which has the potential ability to induce angionesis in ischemic tissue. So we transplanting bone marrow stromal cells into rat infarct area to observe its effect to angiogenesis and secretion of cytokines after rat myocardial infarction.Method Wistar inbred rats were used to stimulate autograft. Harvested rat bone marrow stromal cells were cultivated, proliferated and labeled in vitro. And at the same time, myocardial infarct models were set up by liguid nitrogen cryoinjuring the left ventricular free wall. 4 weeks later, 2×106bone marrow stromal cells or cold D-Hanks liquid were injected into several different points of infarct area. After one, two and four weeks, specimens from infarct area were got in order. Then cell morphology, capillary density were evaluated and cytokine VEGF, TGF- P mRNA expression levels were assayed by RT-PCR.Result 30 inbred rat myocardial infarct models were created. Bone marrow stromal cells were got by attaching separation, cultured in vitro, and amplified to 5×106 per bottle successfully. The labeling rate confirmed in vitro was 80%. Antibodies against BrdU immunohistochemistry showed that bone marrow stromalcells were alive in one, two and four weeks after transplantation and had a trend to differentiation and maturation in vivo. With antibodies against factor VI, capillary density test demonstrated that the number of capillary vessels in per infart area (0.1 mm2 ) was greater increased in experiment group ( 67.600± 7.162, 43.200 ±1.087, 32.800+2.168) than reference group (22.800±1.924, 20.800± 2.280, 18.800 ± 2.108) (P<0.01), and it had the trend to decrease in step (P<0.01). But the number of capillary vessels in reference group had no obvious change. RT-PCR test displayed that VEGF mRNA express level in one, two, and four weeks were all obviously promoted in experiment group (3.426± 0.043, 1.536±0.024, 0.729±0.010) than in reference group ( 2.689± 0.045, 1.245 ± 0.016, 0.463 ± 0.007 ) (P<0.01), and quickly decreased with time. TGF- ?mRNA express level in one, two, and four weeks were all obviously depressed in experiment group (0.445±0.014, 1.034 ± 0.015, 0.393± 0.0183 ) than in reference group (2.000±0.023, 1.502±0.035, 1.351 ±0.173) (P<0.01). Conclusion1. bone marrow stromal cell is easy to culture and proliferation.2. bone marrow stromal cells can live a relative long time and have a trend to differentiation and maturation in vivo.3. bone marrow stromal cells transplantation can accelerate angiogenesis in infarct area.4. bone marrow stromal cells transplantation can promote the creation of VEGF and restrain the creation of TGF- P , which may benefit angionesis and relieve ventricular remodeling.
Keywords/Search Tags:Marrow stromal cell, Cellular cardiomyoplasty, Transplantation, Angiogenesis, Myocardial infarction, VEGF, TGF-β
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