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Purified Human Bone Marrow Multipotent Mesenchymal Stem Cells Regenerate Infarcted Myocardium in Experimental Rats

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Abstract:

Recent findings suggest the feasibility of cardiac repair by transplantation of bone marrow mesenchymal stem cell (MSCs). However, it remains controversial regarding which cell type is the best source for transplanting into the ischemic heart because of lack of well-defined cell markers. In this study, we investigated the in vitro and in vivo effects of the novel multipotent marrow mesenchymal stem cells (MMSCs) from human bone marrow. Pluripotent markers (Oct4, Bmi1, and Abcg2) and vascular endothelial growth factor (VEGF) were detected by RT-PCR and immunofluorescence in MMSCs. Myocardial differentiation was induced in the expanded MMSC cultures by treatment with 5-azacyline. Expressions of VEGF in the animals transplanted with MMSCs were markedly increased in comparison with the animals injected with fibroblasts or saline at both mRNA and protein levels. VEGF expression was observed in both transplanted MMSCs and recipient cardiomyocytes by immunofluorescence. Confocal immunofluorescence microscopy revealed the specific markers for cardiomyocytes and endothelial cells in transplanted MMSCs 14 days after transplantation. Vessel count was increased and left ventricular function improved post-MMSC transplantation. These results indicate that transplantation of purified MMSCs from human bone marrow upregulated VEGF expression, enhanced angiogenesis, and improved the functional recovery following myocardial infarction in rats.

Keywords: Angiogenesis; Differentiation; Mesenchymal stem cell; Myocardial infarction; Transplantation

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/000000005783982558

Affiliations: 1: Stem Cell Research Center, Peking University, 38 Xue Yuan Road, Hai Dian District, Beijing, 100083 China, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Ling Road, Shanghai, 20032 China, ┬žDepartment of Cardiology, Third Hospital of Peking University, 49 North Garden Road, Hai Dian District, Beijing, 10083 China 2: Stem Cell Research Center, Peking University, 38 Xue Yuan Road, Hai Dian District, Beijing, 100083 China, ‡Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, 38 Xue Yuan Road, Hai Dian District, Beijing, 10083 China 3: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Ling Road, Shanghai, 20032 China 4: Stem Cell Research Center, Peking University, 38 Xue Yuan Road, Hai Dian District, Beijing, 100083 China 5: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, 38 Xue Yuan Road, Hai Dian District, Beijing, 10083 China 6: Department of Cardiology, Third Hospital of Peking University, 49 North Garden Road, Hai Dian District, Beijing, 10083 China 7: Stem Cell Research Center, Peking University, 38 Xue Yuan Road, Hai Dian District, Beijing, 100083 China, Department of Cardiology, Third Hospital of Peking University, 49 North Garden Road, Hai Dian District, Beijing, 10083 China 8: Stem Cell Research Center, Peking University, 38 Xue Yuan Road, Hai Dian District, Beijing, 100083 China, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, 38 Xue Yuan Road, Hai Dian District, Beijing, 10083 China

Publication date: October 1, 2005

More about this publication?
  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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