Therapeutic angiogenesis of three-dimensionally cultured adipose-derived stem cells in rat infarcted hearts

Title
Therapeutic angiogenesis of three-dimensionally cultured adipose-derived stem cells in rat infarcted hearts
Authors
김지현박인수박용두정영미김수현김상헌
Keywords
angiogenesis; cell adhesion substrate; differentiation; human adipose-derived stem cells; myocardial infarction; stem cell transplant; three-dimensional cell mass; vascularization
Issue Date
2013-05
Publisher
Cytotherapy
Citation
VOL 15, NO 5, 542-556
Abstract
Background aims. To successfully treat myocardial infarction (MI), blood must be resupplied to the ischemic myocardium by inducing angiogenesis. Many studies report enhanced angiogenesis using stem cells; however, the therapeutic efficacy of cell transplant remains low because transplanted cells may not survive, be retained at the site of transplant, or develop into vascular tissue. In this study, we assessed the therapeutic potential of three-dimensional cell masses (3DCM) composed of human adipose-derived stem cells (hASC) in a rat MI model. Methods. For formation of 3DCM, hASC were cultured on a substrate with immobilized fibroblast growth factor 2. The morphology and phenotypes of 3DCM were analyzed 1 day after culture. The cells (hASC and 3DCM, 5 x 105 cells) were injected into ischemic regions after ligation of the left coronary artery (n = 6 in each group). Cell retention ratio, therapeutic efficacy and vascularization were evaluated 4 weeks after transplant. Results. A spheroid-type 3DCM, which included vascular cells (CD34+/CD31+/KDR+/α-SMA+) with high production of human vascular endothelial growth factor, was obtained. Infarct size and cardiomyocyte apoptosis were reduced in the 3DCM-injected group compared with the hASC-injected group. The retention ratio of hASC was 14-fold higher in the 3DCM-injected group. Many transplanted cells differentiated into endothelial and smooth muscle cells and formed vascular networks incorporated into host vessels. Conclusions. Transplant of 3DCM may be useful for angiogenic cell therapy to treat MI.
URI
http://pubs.kist.re.kr/handle/201004/44767
ISSN
14653249
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KIST Publication > Article
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