FNDC5/irisin Improves the Therapeutic Efficacy of Bone Marrow-derived Mesenchymal Stem Cells for Myocardial Infarction

Overview

Journal Stem Cell Res Ther

Publisher Biomed Central

Date 2020 Jun 12

PMID 32522253

Citations 25

Authors

Jingyu Deng

Ning Zhang

Yong Wang

Chao Yang

Yabin Wang

Chao Xin

Jinming Zhao

Zhitao Jin

Feng Cao

Zheng Zhang

Affiliations

Soon will be listed here.

Abstract

Background: The beneficial functions of bone marrow mesenchymal stem cells (BM-MSCs) decline with decreased cell 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 to be 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 overexpression of FNDC5 (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 cell viability, and paracrine effects of BM-MSCs while irisin or FNDC5-OV alleviated these injuries. Longitudinal in vivo bioluminescence imaging and immunofluorescence results illustrated that BM-MSCs with overexpression of FNDC5 treatment (FNDC5-MSCs) improved the survival of transplanted BM-MSCs, which ameliorated the increased apoptosis and decreased angiogenesis of BM-MSCs in vivo. Interestingly, FNDC5-OV elevated the secretion of exosomes in BM-MSCs. Furthermore, FNDC5-MSC therapy significantly reduced fibrosis and alleviated injured heart function.

Conclusions: The present study indicated that irisin or FNDC5 improved BM-MSC engraftment and paracrine effects in infarcted hearts, which might provide a potential therapeutic target for MI.

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