Abstract 10586: Cardiac Adipose Tissue-Derived Stem Cells Exhibit High Differentiation Potential to Cardiovascular Lineage Cells
Background: Adipose-derived stem cells (AdSCs) have recently been shown to differentiate into cardiovascular lineage cells. However, little is known about fat tissue origin-dependent difference of AdSC functions and differentiation potential.
Methods and Results: AdSC-rich cells were isolated from subcutaneous (SC), visceral (VL), cardiac (CA), and subscapular (SS) adipose tissue in C57BL6 mice by density-gradient centrifugation method. The freshly isolated AdSCs (fAdSCs) were cultured with 10%FCS/DMEM for 7 days to obtain adherent AdSCs (aAdSCs). Cell densities of fAdSCs and aAdSCs in each fat tissue were significantly higher in CA-derived fAdSCs (CA-fAdSCs) compared with other fAdSCs (CA>SC=VL=SS). FACS analysis exhibited that the percentage of CD90+ cells in CA- (33%) and SC-fAdSCs (31%) were significantly higher than that in VL- (14%) and SS-fAdSCs (7%), while there were no significant differences for CD44 (90-100%), CD34 (30-40%), CD31 (80-90%), Sca-1 (70-90%), c-Kit (3-9%), and PDGFR-β (1-3%) expressions. Proliferation activities of CA- and SS-aAdSCs assessed by BrdU incorporation were significantly higher than those of SC- and VL-AdSCs. After the aAdSCs were cultured with specific differentiation mediums for endothelial cell (EC), smooth muscle cell (SMC), and cardiomyocyte (CM), we then evaluated the differentiation potential immunocytochemically. CA-AdSCs exhibited the highest appearance rates of Isolectin B4 (ILB4)+/CD31+ ECs and Gata4+/cardiac troponin-T(cTn-T)+ CMs among all aAdSCs. There was no significant difference in appearance rate of SM22+ SMCs. Finally, we examined the differentiation potential of fAdSCs in ischemic tissue using a mouse myocardial infarction (MI) model. DiI-labeled fAdSCs (10+5/mouse) were systemically transfused to mice with MI, and the double-fluorescent immunostaining for ILB4, SM22, and cTn-T were evaluated in the recruited DiI+ cells. The frequency of DiI-labeled fAdSCs co-stained with ILB4, SM22, or cTn-T was similar to the data in vitro, except that only CA-fAdSCs were co-stained with cTn-T in ischemic myocardium.
Conclusion: Cardiac adipose tissue could be an ideal source to isolate therapeutically effective AdSCs for cardiac regeneration in ischemic heart diseases.
- © 2011 by American Heart Association, Inc.