FDNC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction

Abstract

Background: The beneficial functions of bone marrow mesenchymal stem cells (BM-MSCs) decline with decreased cells survival, limiting their therapeutic efficacy for myocardial infarction (MI). Irisin, a novel myokine which is cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), is believed involved in a cardioprotective effect but little was known on injured BM-MSCs and MI repair yet. Here, we investigated whether FNDC5 or irisin could improve the low viability of transplanted BM-MSCs and increase their therapeutic efficacy after MI. Methods: BM-MSCs, isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein positive (Fluc+– eGFP+) transgenic mice, were exposed to normoxic condition and hypoxic stress for 12 h, 24 h, and 48 h, respectively. In addition, BM-MSCs were treated with irisin (20 nmol/L) and FNDC5-OV in serum deprivation (H/SD) injury. Furthermore, BM-MSCs were engrafted into infarcted hearts with or without FNDC5-OV. Results: Hypoxic stress contributed to increased apoptosis, decreased cells viability and paracrine effects of BM-MSCs while irisin or FNDC5-OV alleviated these injuries. Longitudinal in vivo bioluminescence imaging illustrated that FNDC5-MSCs treatment improved the survival of transplanted BM-MSCs, which ameliorated the increased apoptosis and decreased angiogenesis of BM-MSCs in vivo. Furthermore, FNDC5-MSCs therapy significantly reduced fibrosis and alleviated injured heart function. Conclusions: The present study indicated that irisin or FNDC5 improved BM-MSCs engraftment and paracrine effects in infarcted hearts, which might provide a potential therapeutic target for MI.