Bone marrow mesenchymal stem cells for post‐myocardial infarction cardiac repair: microRNAs as novel regulators

Abstract

Transplantation of bone marrow-derived mesenchymal stem cells (MSCs) is safe and may improve cardiac function and structural remodelling in patients following myocardial infarction (MI). Cardiovascular cell differentiation and paracrine effects to promote endogenous cardiac regeneration, neovascularization, anti-inflammation, anti-apoptosis, anti-remodelling and cardiac contractility, may contribute to MSC-based cardiac repair following MI. However, current evidence indicates that the efficacy of MSC transplantation was unsatisfactory, due to the poor viability and massive death of the engrafted MSCs in the infarcted myocardium. MicroRNAs are short endogenous, conserved, non-coding RNAs and important regulators involved in numerous facets of cardiac pathophysiologic processes. There is an obvious involvement of microRNAs in almost every facet of putative repair mechanisms of MSC-based therapy in MI, such as stem cell differentiation, neovascularization, apoptosis, cardiac remodelling, cardiac contractility and arrhythmias, and others. It is proposed that therapeutic modulation of individual cardiovascular microRNA of MSCs, either mimicking or antagonizing microRNA actions, will hopefully enhance MSC therapeutic efficacy. In addition, MSCs may be manipulated to enhance functional microRNA expression or to inhibit aberrant microRNA levels in a paracrine manner. We hypothesize that microRNAs may be used as novel regulators in MSC-based therapy in MI and MSC transplantation by microRNA regulation may represent promising therapeutic strategy for MI patients in the future.

Effect and mechanism of different ways of transplanting bone marrow mesenchymal stem cells in cardiopulmonary resuscitation in rats

“…BMSCs can differentiate into neural cells both in vivo and ex vivo (Shi and Yang, 2012). In recent years, BMSC transplantation showed important progress in the treatment of stroke (Wei et al, 2012;He et al, 2013), myocardial infarction, and nervous system recovery after cardiopulmonary resuscitation (Wen et al, 2012;Williams et al, 2013). Therefore, BMSC transplantation has become a new technique for treating diseases of the nervous system.…”

Myocardial Regeneration for Humans ― Modifying Biology and Manipulating Evolution ―

“…Beneficial growth factors in the protection of cardiomyocytes and reduction of fibrosis in the infarct region include VEGF, TGF-β, SFRP-1, -2 and -4, Smad-5, endothelin, and epiregulin. 60, 61 Additional mobilization factors such as HGF, LIF, SDF-1, SCF and VE-cadherin, 62 as well as miRNAs such as miR-15, miR-17, miR-20a, miR-103, mrR-133a, miR-199a, miR-210, miR-210 and miR-451, improve myocardial structure and function after ischemia or infarction. 63-66 All the aforementioned approaches provide limited protective effects for the damaged myocardium, but efficient regeneration/replacement of cardiomyocytes still remains an unattainable goal.…”

miRNA Expression in Mesenchymal Stem Cells

“…Interestingly, the potential of MSCs and other stem cells to engraft and differentiate into endothelial cells (EC) or vascular smooth muscle cells (VSMC) has also been associated with modulation by miRNAs [33,38,39]. miR-1, miR-126, miR-210, miR-145, and miR-143 have been demonstrated to be involved in the differentiation of different stem cells to EC and VSMC [33,40].…”

“…Different miRNAs have been involved in the ability of MSCs or other stem cells to differentiate into cardiomyocytes [33]. MSCs transfected with miR-133a, which targets EGFR, expressed cardiac-specific markers [34].…”

“…If the miRNA/mRNA interaction is precise, the mRNA is immediately degraded by Ago2, one of the Argonaute family proteins. Otherwise, in the case of no exact interaction, the mRNA is translationally repressed [ [33].…”