Curcumin-Preconditioned Adipose-Derived Stem Cells Improve Cardiac Function in Aged Rats via miR-3575 Modulation

Aging causes a decrease in cardiac function in living organisms. Although stem cell transplantation shows therapeutic potential for aging hearts, distinct types of evidence have indicated that preconditioning is an effective therapeutic strategy for stem cells to improve tissue regenerative function. This study investigates the therapeutic effect of mesenchymal stem cell preconditioning with curcumin and miR-3575 in the treatment of an aging heart. Cell models have confirmed that preconditioning with curcumin enables stem cells to increase cell viability and CXCR4/p-Akt signal activation. Intervention of miR-3575 mimic significantly enhances viability and CXCR4/p-Akt signal in curcumin preconditioned stem cells. The beneficial effects are suppressed in curcumin preconditioned stem cells receiving miR-3575 inhibitor. The aging animal groups were designed to test the above hypothesis including Aging (rats with 20 months), Aging + ADSC (aging rats receiving adipose-derived stem cells), Aging + Cur-ADSC (aging rats receiving curcumin preconditioned ADSC), Aging + miR mic-ADSC (aging rats receiving miR-3575 mimic preconditioned ADSC), and Aging + miR inh-ADSC (aging rats receiving miR-3575 inhibitor preconditioned ADSC). Compared to Aging, Aging + ADSC slightly improves cardiac function, structure, and pathological protein markers, whereas Aging + Cur-ADSC and Aging + miR mic-ADSC significantly improve the above pathological status. On the other hand, the improvement is suppressed in the ADSC group preconditioned with a miR-3575 inhibitor (Aging + miR inh-ADSC). These findings suggest that ADSC preconditioning with curcumin and miR-3575 shows clinical potential in the treatment of heart failure induced by aging.