Cardiomyocyte differentiation of perinatally-derived mesenchymal stem cells

Abstract

Coronary heart disease is major cause of mortality worldwide and several risk factors have been shown to play a role in its pathogenesis, including smoking, obesity, hypertension and hypercholesterolemia. A number of therapeutic methods have been developed to improve the quality of patients' lives, including stem cell therapy using mesenchymal stem cells (MSCs). Perinatal sources, including the placenta (PL) and umbilical cord (UC), are rich sources of MSCs and have been identified as a potential source of cells for therapeutic use. Their role in cardiogenic differentiation is also of contemporary medical interest. The present study demonstrated the induced differentiation of MSCs obtained from the UC, PL and Wharton's jelly (WJ) into cardiomyocytes, using 10 µM 5‑azacytidine. The characteristics of the MSCs from each source were studied and their morphology was compared. An immunofluorescence analysis for the cardiac‑specific markers, GATA4 and Troponin T (TnT), was performed and tested positive in all sources. The expression of the cardiac‑specific genes, Nkx2.5, α‑cardiac actin and TnT, was analyzed by real‑time RT‑PCR and presented as fold change increases. The expression of each of the markers was observed to be higher in the 5‑azacytidine‑treated MSCs. The differences in expression among the sources of treated MSCs was as follows: TnT had the highest level of expression in the bone marrow (BM) MSCs; α‑cardiac actin had the highest level of expression in the PLMSCs; and all the genes were expressed at significantly high levels in the WJMSCs compared with the control group. The present study showed the ability of alternative perinatally‑derived MSCs to differentiate into cardiomyocyte‑like cells and how this affects the therapeutic use of these cells.

Liraglutide alleviates diabetic cardiomyopathy by blocking CHOP-triggered apoptosis via the inhibition of the IRE-α pathway

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“…Furthermore, the mechanism underlying the pathogenesis of DCM remains elusive and treatment with specific drugs requires urgent investigation. Numerous factors may be involved in the pathogenesis of DCM, including cellular metabolism, defective calcium homeostasis, oxidative stress and others (5,6).…”

Intracoronary infusion of Wharton’s jelly-derived mesenchymal stem cells in acute myocardial infarction: double-blind, randomized controlled trial

“…Using Affymetrix GeneChip microarray and functional network analyses, we found for the first time that WJMSCs, except for their expression of stemness molecular markers in common with human ESCs (hESCs), exhibited a high expression of early cardiac transcription factor genes and could be induced to differentiate into cells expressing cardiac a-actin, troponin T and connexin-43 in vitro [ 18 ]. Moreover, growing evidence has shown that WJMSCs can be induced to differentiate into cardiomyocytes and endothelial cells and to integrate into the vasculature and ischemic cardiac tissue, as well as to improve heart function significantly [ 19 – 22 ].…”

TGF‑β1 combined with Sal‑B promotes cardiomyocyte differentiation of rat mesenchymal stem cells

“…It has been demonstrated that MSCs are able to differentiate into CMs in vivo and in vitro (17,18). 5-azacytidine is a classic inducer for MSCs to differentiate toward CMs; however, it did not induce differentiation of BMSCs in the expected cardiomyogenic manner (19).…”