| Mesenchymal stem cells (MSCs) can be isolated from various adult tissues of human by their ability of adhering plastic culture plate wall. MSCs can proliferate extensively in vitro, and differentiate not only to bone, cartilage, and other mesenchymal tissues but also to multiple other cells of the 3 germ layers including neural cells under appropriate conditions. MSCs have been used in various disease including acute myocardial infarction, auto immunologic disease, nervous system disorder. Flkl+CD34-CD31- MSCs from human bone marrow can differentiate into endothelial and hematopoietic cells, suggesting their characteristics as hemangioblasts. Therefore, this kind of cells can be used as good source in cardiovascular disease.Transmyocardial revascularization (TMR) is a promising therapy for the patients with end-stage coronary artery disease who are not eligible for surgical intervention and other conventional treatments. Our previous study has showed that wide-aperture transmyocardial drilling with bFGF/heparin stent in it could stimulate formation of vascular net around the channel and avoid thermal injury to normal myocardium.In this study, after obtaining and identifying MSCs of mini-swine, we combined the previous methods in pig acute myocardial infracted (AMI) therapy to test the action of MSCs and search for an effective method for ischemic heart disease. Meanwhile, we also hope to find more effective method of MSCs transplantation.Part one was designed to test the biological characteristic and potential of mini-swine bone marrow derived mesenchymal stem cells (BMSCs) differentiating into cardiovascular tissue. Methods:BMSCs were induced to differentiate into endothelial cells by VEGF. Immunofluorescence was performed to evaluate differentiation in vitro. Results:BMSCs induced by VEGF expressed CD31 in vitro. Conclusions:These BMSCs are ideal seed cells in cardiovascular disease through differentiate into endothelial cell.Part two was designed to manufacture the medicine stent consistent with systolic function of myocardium with PCL/PLGA and detecte them in vitro. The stent with good blood compatibility could resist systolic pressure of myocardium, and could meet the requirement of drug release.Part three was designed to test the mechanisms and availability of BMSCs injection into myocardium combined with TMDR and bFGF/heparin stent in AMI. Method:On the basis of AMI model produced by coronary occlusion, the animals were grouped:Control group(T), TMDR with stent group(TS), TMDR with cell transplantation group(TC), and combined group(TSC). Two transmycoardial channels were created through the left ventricle infarct areas and stent was implanted into each channel. Labeled BMSCs were then transplanted by intramyocardial injection.6 weeks after AMI, single photon emission computed tomography was used to evaluate the myocardial perfusion. Left ventricular function was assessed by echocardiography. Vascular density was measured, and immunofluorescence was performed to evaluate BMSCs engrafment and differentiation. Conclusions:6 weeks after operation, TC group, TS group and TSC group significantly improved vascular density and myocardial perfusion than control group (P<0.001). Left ventricular function showed the same result. What's more, the above data of TSC group showed significantly improved compared with TC and TS group(P<0.05). Grafted cells expressed vWF antigen and distributed generally around infarcted region even in the center of infarcted region. Therefore, combined therapy was more benefit not only to heart function and myocardial perfusion but also to cellular survival and differentiation.
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