Abstract 11453: Cardiac Adipose-derived Stem Cells Exhibit High Therapeutic Effect on Cardiac Functional Recovery Following Myocardial Infraction
Background: Adipose-derived stem cells (AdSCs) have recently been shown to differentiate into cardiovascular lineage cells. However, little is known about the tissue origin-dependent difference of AdSC functions and their therapeutic potentials for myocardial infarction (MI).
Methods and Results: AdSCs were isolated from subcutaneous (SC), visceral (VL), cardiac (CA), and subscapular (SS) adipose tissue in mice. AdSC density in each fat tissue was significantly higher in CA-derived AdSCs (CA-AdSCs) compared with others (CA>SC=VL=SS). When AdSCs were cultured with special differentiation medium for endothelial cell (EC), smooth muscle cell (SMC), or cardiomyocyte (CM), CA-AdSCs exhibited the highest appearance rate of ECs or CMs among all types of AdSC by immunocytostaining, while no significant difference of SMC appearance was observed. We then examined whether CA-AdSCs had a therapeutic efficacy in a mouse MI model comparing with SC-AdSCs and PBS control. The freshly isolated AdSCs (5x104) or PBS was systemically administered 24 hours after MI induction and cardiac function was sequentially evaluated by echocardiography on day 1 and at week 2, 4, and 6 after surgery. Cardiac functional recovery assessed by parameters of EF (CA: 58.6±3.6, SC: 47.3±3.7, and control: 34.5±5.0%, P<0.001, CA/SC vs. control; P<0.05, CA vs. SC; n=8) and LVDd (CA: 4.3±0.4, SC: 4.7±0.3, and control: 5.3±0.6mm, P<0.001, CA/SC vs. control; P<0.05, CA vs. SC; n=8) significantly improved at 6 weeks after surgery in the CA-AdSC treated group compared with the SC-AdSC treated group and control group. Finally, the hearts were harvested for histological analysis, and Masson’s trichrome-stained sections revealed that the % of LV fibrosis length in the CA-AdSC group but not SC-AdSC group was significantly smaller than that in control group (CA: 20.4±3.8, SC: 29.4±6.5, and control: 36.0±9.9%; P<0.001, CA and SC vs. control; P<0.05, CA vs. SC; NS, SC vs. control; n=8), while no significant difference of capillary density was observed between the two groups.
Conclusion: Cardiac adipose tissue could be an ideal source for obtaining highly therapeutic AdSCs. Thus autologous CA-AdSC transplantation may be an effective cardiac regeneration therapy in severe ischemic heart diseases.
- © 2012 by American Heart Association, Inc.