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Empirical Study of the Role of Ex Vivo Preconditioning Mesenchymal Stem Cells before Transplantation on Myocardial Infarction

Author: CaiZuo
Tutor: HuiJie
School: Suzhou University
Course: Department of Cardiology
Keywords: Myocardial infarction Bone marrow mesenchymal stem cells Stromal cell-derived factor-1
CLC: R542.22
Type: Master's thesis
Year: 2010
Downloads: 37
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Abstract


Objective: To study the stromal cell derived factor -1 (SDF-1) series of bone marrow mesenchymal stem cells (MSCs) after pretreatment effect change; and pretreated MSCs transplantation into a rat model of myocardial infarction, the cells were observed normalized nest, proliferation, and cell apoptosis of myocardial ischemia generate new blood capillaries ventricular remodeling and cardiac function, and further explore the the MSCs role in the mechanism of ischemic heart disease. Methods: part of stem cells: SD rats tibia and femur isolated from bone marrow, differences in whole bone marrow adherent law culture of MSCs and surface marker identification; 5 - bromo-deoxyuridine (Brd U) labeled MSCs cells produced cells climb sheet, detecting the mark rate to ensure that the tag can meet the need of transplantation tracer and observation; MSCs, respectively in the absence (control group) or containing (SDF-1 pretreated group) of SDF-1 serum-free medium and incubated for 60 minutes, was detected in the supernatant of vascular endothelial growth factor (VEGF) content, and the change of the expression of the CXCR-4 receptor in the cell surface after treatment. Animal experiments: rat myocardial infarction model 48, were randomly divided into three groups: blank group (A), SDF-1 pretreatment group (C); stem cells in the control group (B), respectively after myocardial infarction days after intravenous injection of saline (A group), the untreated MSCs (B group) or of SDF-1 pretreatment of MSCs (Group C); cardiomyocyte apoptosis detection infarct border zone 24 hours after the transplant; detected after a week Brd U-positive cells in the infarct border zone homing Proliferation; surrounded detect cardiac function, calculate the infarct size, and perfused through the vascular fluorescence imaging to detect the infarct border zone neovascularization density. Results: The differences in whole bone marrow adherence method can get stable separatist rat MSCs, as identified by the phenotype CD29 ~ CD90 ~ CD34 ~ - cells; 10umol / L Brd U mark MSCs24 hours, labeling rate gt; 98% to meet the transplant the tracer needs; SDF-1 pretreatment MSCs significantly increased its ability to release VEGF (68.92 ± 5.03 pg / ml vs 38.79 ± 3.16 pg / ml, P lt; 0.05), and make the CXCR-4 receptor within a proactive role, performance decreased expression (P lt; 0.05) for the outside of the membrane. Ligating the left anterior descending artery method can be successfully established rat model of myocardial infarction; histological examination of MSCs observed after heart transplantation specimens available: tissue sections of infarct border zone group C compared with group B, HE staining muscle fibers arranged in a more orderly, nuclear morphology. uniform and relatively abundant small blood vessels like structure, the number of apoptotic cells in infarct border zone significantly decreased by (25.75 ± 4.43 vs 39.70 ± 4.10, P lt; 0.05), Brd U-positive cell number significantly increased (44.78 ± 6.21 vs 31.14 ± 6.48, P lt; 0.05); around echocardiogram of MSCs transplantation group C than in group B left ventricular ejection fraction (LVEF%) was significantly improved (55.83 ± 5.45 vs 42.14 ± 6.17, P lt; 0.005), LVDs to expand the trend of significantly reduced (4.92 ± 0.16 vs 5.75 ± 0.39, P lt; 0.005) than in group B; C group left ventricular fibrosis significantly reduced the area of ??the scar tissue is reduced (23.71 ± 2.49 vs 32.83 ± 1.58, P lt; 0.005 ); in the ischemic surrounding area, C group perfused vessel density was significantly higher than that in group B (31.16 ± 4.08 vs 19.91 ± 3.87, P lt; 0.05). Conclusion: (1) SDF-1 pretreatment MSCs can significantly increase its ability to release of VEGF, proactive role and to the occurrence of the CXCR-4 receptor, and enhance the homing ability to promote cell paracrine. ② SDF-1 pretreatment MSCs transplantation can reduce the rat infarct border zone myocardial apoptosis, increased perfusion of the ischemic area, thereby inhibiting ventricular remodeling and improve cardiac function.

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CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Heart disease > Myocardial diseases > Myocardial infarction
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