Adipose-derived stem cells and their conditioned medium significantly reduced myocardial infarct size (32.2% and 35.7% vs 41.9%) and improved cardiac function compared to control medium in mice.
Does ADSC or ADSC-CM transplantation improve cardiac function and reduce infarct size in a mouse model of myocardial infarction?
ADSC conditioned medium is sufficient to improve cardiac function post-MI, demonstrating that the therapeutic benefit of ADSC transplantation is primarily mediated by paracrine effects rather than direct differentiation.
Absolute Event Rate: 32.2% vs 41.9%
p-value: p=<0.05
BACKGROUND: Recent studies have demonstrated that transplantation of adipose-derived stem cell (ADSC) can improve cardiac function in animal models of myocardial infarction (MI). However, the mechanisms underlying the beneficial effect are not fully understood. In this study, we characterized the paracrine effect of transplanted ADSC and investigated its relative importance versus direct differentiation in ADSC transplantation mediated cardiac repair. METHODOLOGY/PRINCIPAL FINDINGS: MI was experimentally induced in mice by ligation of the left anterior descending coronary artery. Either human ADSC, conditioned medium (CM) collected from the same amount of ADSC or control medium was injected into the peri-infarct region immediately after MI. Compared with the control group, both ADSC and ADSC-CM significantly reduced myocardial infarct size and improved cardiac function. The therapeutic efficacy of ADSC was moderately superior to ADSC-CM. ADSC-CM significantly reduced cardiomyocyte apoptosis in the infarct border zone, to a similar degree with ADSC treatment. ADSC enhanced angiogenesis in the infarct border zone, but to a stronger degree than that seen in the ADSC-CM treatment. ADSC was able to differentiate to endothelial cell and smooth muscle cell in post-MI heart; these ADSC-derived vascular cells amount to about 9% of the enhanced angiogenesis. No cardiomyocyte differentiated from ADSC was found. CONCLUSIONS: ADSC-CM is sufficient to improve cardiac function of infarcted hearts. The therapeutic function of ADSC transplantation is mainly induced by paracrine-mediated cardioprotection and angiogenesis, while ADSC differentiation contributes a minor benefit by being involved in angiogenesis. Highlights 1 ADSC-CM is sufficient to exert a therapeutic potential. 2. ADSC was able to differentiate to vascular cells but not cardiomyocyte. 3. ADSC derived vascular cells amount to about 9% of the enhanced angiogenesis. 4. Paracrine effect is the major mechanism of ADSC therapeutic function for MI.
Yang et al. (Tue,) conducted a other in Myocardial infarction. Adipose-derived stem cell (ADSC) or ADSC-conditioned medium (ADSC-CM) vs. Control medium (DMEM) was evaluated on Infarct size at 4 weeks (p=<0.05). Adipose-derived stem cells and their conditioned medium significantly reduced myocardial infarct size (32.2% and 35.7% vs 41.9%) and improved cardiac function compared to control medium in mice.
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