FNDC5/irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction.

Stem Cell Research & Therapy
Jingyu DengZheng Zhang

Abstract

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. 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. 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 result...Continue Reading

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Citations

Oct 8, 2020·International Journal of Molecular Sciences·Kamila RaziyevaArman Saparov
Jan 26, 2021·Endocrine Reviews·Steffen MaakHarold P Erickson
Aug 6, 2021·Stem Cell Research & Therapy·Yuling Huang, Lina Yang
Oct 9, 2021·Journal of the American Heart Association·Jinjuan FuJian Yang

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Methods Mentioned

BETA
PCR
flow cytometry
bioluminescence imaging
Enzyme-linked immunosorbent assay
transmission electron microscopy
electrophoresis
ELISA
transfection
Confocal microscopy
genetic modification

Software Mentioned

VisionWorks LS
Nanoparticle Tracking Analysis ( NTA )
GraphPad Prism
Imaging Pro Plus
Living Image®
NanoSight

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis