Can the outcomes of mesenchymal stem cell‐based therapy for myocardial infarction be improved? Providing weapons and armour to cells

Abstract

Use of mesenchymal stem cell (MSC) transplantation after myocardial infarction (MI) has been found to have infarct-limiting effects in numerous experimental and clinical studies. However, recent meta-analyses of randomized clinical trials on MSC-based MI therapy have highlighted the need for improving its efficacy. There are two principal approaches for increasing therapeutic effect of MSCs: (i) preventing massive MSC death in ischaemic tissue and (ii) increasing production of cardioreparative growth factors and cytokines with transplanted MSCs. In this review, we aim to integrate our current understanding of genetic approaches that are used for modification of MSCs to enable their improved survival, engraftment, integration, proliferation and differentiation in the ischaemic heart. Genetic modification of MSCs resulting in increased secretion of paracrine factors has also been discussed. In addition, data on MSC preconditioning with physical, chemical and pharmacological factors prior to transplantation are summarized. MSC seeding on three-dimensional polymeric scaffolds facilitates formation of both intercellular connections and contacts between cells and the extracellular matrix, thereby enhancing cell viability and function. Use of genetic and non-genetic approaches to modify MSC function holds great promise for regenerative therapy of myocardial ischaemic injury.

IGF‐1 promotes angiogenesis in endothelial cells/adipose‐derived stem cells co‐culture system with activation of PI3K/Akt signal pathway

“…Cell-based vessel regeneration therapies are applied to ischaemic disorders, such as myocardial infarction and PVD. 8,9,24 The combined F I G U R E 5 Protein expressions of VEGF-A, MMP-2, MMP-9 and p-Akt in ASCs were up-regulated by IGF-1 and crosstalk. Western blot showed that protein levels of VEGF-A, α-SMA, MMP-2 and MMP-9 in ASCs exposed to IGF-1 and crosstalk were enhanced.…”

Concise Review: Rational Use of Mesenchymal Stem Cells in the Treatment of Ischemic Heart Disease

“…Many preclinical studies have shown benefit of cell modification to enhance their survival, proliferative capacity, and secretion of paracrine factors. These include genetic manipulation, in vitro preconditioning (with hypoxia or with pharmaceutical agents, for example), or pretreatment with growth factors or other cytokines . Gene delivery of Akt or haem‐oxygenase 1 ( HO‐1 ) in MSCs prior to transplantation have shown benefit in cell survival, with resulting improvement in rat myocardial function postdelivery.…”

Hydrogel from Acellular Porcine Adipose Tissue Accelerates Wound Healing by Inducing Intradermal Adipocyte Regeneration

“…All of these factors attribute to necrosis and apoptosis of transplanted cells. Recent studies focused on improving the effectiveness of cell therapy, with two main approaches to overcoming these problems: preventing massive cell death and increasing the secretion of wound healing-promoting growth factors and cytokines (Karpov et al, 2017).…”