Stem Cell Therapy of Myocardial Infarction: A Promising Opportunity in Bioengineering

Abstract

Myocardial infarction (MI) is a life‐threatening disease resulting from the irreversible death of cardiomyocytes (CMs). Stem cell‐based therapies have been studied for MI treatment over the last two decades with promising outcomes. Here, the past work in this field is critically reviewed to elucidate the advantages and disadvantages of treating MI using pluripotent stem cells (PSCs) including both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), adult stem cells, and cardiac progenitor cells. Overall, PSCs (particularly iPSCs) have more advantages than the other cells for cardiac regeneration. However, the use of iPSCs is also facing critical challenges, which may be resolved by using biomaterials to engineer stem cells for reduced immunogenicity, improved immobilization/survival in the heart, and increased integration with the host cardiac tissue to eliminate arrhythmia. Biomaterials have also been applied in the derivation of CMs in vitro to increase the efficiency and maturation of cardiac differentiation. Collectively, a lot has been learned from the past failures of simply injecting intact stem cells or their derivatives in vivo for treating MI, and bioengineering stem cells with biomaterials may be a valuable strategy for advancing stem cell therapy towards its widespread application for MI treatment in the clinic.

Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient Engraftment

“…Instead, this scenario argues for the paracrine effects described for these cells in multiple reports (Nascimento et al, 2014 ; Yao et al, 2015 ; Cai et al, 2016 ) in which immunomodulatory properties, ECM remodeling ability and capacity to promote angiogenesis are the main mechanisms (Guo et al, 2020 ). Several bioengineering strategies are under development to improve retention, survival, and engraftment of transplanted cells in the myocardium (Jiang et al, 2020 ). Of interest, a recently developed hydrogel-based combination of UCM-MSC with endothelial cells showed that in vitro maturation prior to transplantation promotes vasculogenic potential and cell survival/retention after transplantation in mice (Torres et al, 2020 ).…”

Rock inhibitor may compromise human induced pluripotent stem cells for cardiac differentiation in 3D

“…This means the human iPSC may still possess some of the phenotypic properties of the more differentiated cells from which they are reprogrammed, leading to less potent potential of differentiation of human iPSCs than human ESCs [ 59 , 61 ]. Therefore, protocols of cardiac differentiation for human ESCs may not work well for human iPSCs and usually have an OBT ranging over ~7 days [ 31 , 62 , 63 ]. This is consistent with our observation that cardiac differentiation of the human eiPSCs and IMR90-1 iPSCs cultured in 3D with the commonly used RI concentration (10 μM) results in significantly heterogeneous cell populations and compromises the efficiency of cardiac differentiation, although the high concentration of RI has been used to culture human ESCs for cardiac differentiation (mostly under 2D) with high efficiency (the cTnT-positive cells may be up to 90 %) [ 26 , 35 , 36 ].…”

“…However, these protocols are lengthy (typically requiring at least 14 days) and generate CSs with high heterogeneity [ [28] , [29] , [30] ]. The latter is evidently reflected by the large variation of the outset beating time (OBT) of the CSs, which is typically over ~7 or more days for all contemporary 3D cardiac differentiation approaches [ 21 , 31 ]. The OBT is a direct indicator of the maturity of the PSC-derived CSs because their beating is a result of the maturation of the intra- and inter-cellular protein system that drives the motion.…”

Microencapsulation-based cell therapies

“…Zhao et al, bioengineered an injectable nanomatrix gel containing an amphiphilic peptide and a cell adhesive ligand Arg-Gly-Asp-Ser (PA-RGDS). Upon evaluation of the therapeutic potential and long-term effect of the suspension of mouse embryonic stem cells (mESCs)-derived cardiomyocytes for engraftment in an MI rat model, their results showed retention of engrafted cardiomyocytes for up to 3 months and improved function of the heart post-administration [ 68 ].…”