Improvement of Heart Function After Transplantation of Encapsulated Stem Cells Induced with miR-1/Myocd in Myocardial Infarction Model of Rat

Abstract

Cardiovascular disease is one of the most common causes of death worldwide. Mesenchymal stem cells (MSCs) are one of the most common sources in cell-based therapies in heart regeneration. There are several methods to differentiate MSCs into cardiac-like cells, such as gene induction. Moreover, using a three-dimensional (3D) culture, such as hydrogels increases efficiency of differentiation. In the current study, mouse adipose-derived MSCs were co-transduced with lentiviruses containing microRNA-1 ( miR-1) and Myocardin ( Myocd). Then, expression of cardiac markers, such as NK2 homeobox 5( Nkx2-5), GATA binding protein 4 ( Gata4), and troponin T type 2 ( Tnnt2) was investigated, at both gene and protein levels in two-dimensional (2D) culture and chitosan/collagen hydrogel (CS/CO) as a 3D culture. Additionally, after induction of myocardial infarction (MI) in rats, a patch containing the encapsulated induced cardiomyocytes (iCM/P) was implanted to MI zone. Subsequently, 30 days after MI induction, echocardiography, immunohistochemistry staining, and histological examination were performed to evaluate cardiac function. The results of quantitative real -time polymerase chain reaction (qRT-PCR) and immunocytochemistry showed that co-induction of miR-1 and Myocd in MSCs followed by 3D culture of transduced cells increased expression of cardiac markers. Besides, results of in vivo study implicated that heart function was improved in MI model of rats in iCM/P-treated group. The results suggested that miR-1/Myocd induction combined with encapsulation of transduced cells in CS/CO hydrogel increased efficiency of MSCs differentiation into iCMs and could improve heart function in MI model of rats after implantation.

Chitosan-Based Scaffolds for the Treatment of Myocardial Infarction: A Systematic Review

“…The chitosan-derived hydrogels encapsulate the stem cells and promote their maturation into the cardiomyocytes [ 107 ]. Chitosan, protein and stem cell hydrogels have been applied intramuscularly to promote the secretion of the growth factors that improve the myocardial conditions [ 108 ], as in the case of the expression of the vascular endothelial growth factor (VEGF), which allows for the revascularization in the infarcted area [ 109 ]. In addition, the porous and fibrous chitosan scaffolds are used as support structures to promote the stem cells’ maturation into the cardiomyocytes [ 110 ].…”

“…For example, it has been shown that protein-containing hydrogels can promote cell growth and anchoring by promoting the maturation of the stem cells within the hydrogel [ 108 ]. However, the rapid biodegradability of the protein-containing hydrogels, such as gelatin hydrogels, limits the time required for progenitor cell maturation [ 108 , 131 ].…”

“…For example, it has been shown that protein-containing hydrogels can promote cell growth and anchoring by promoting the maturation of the stem cells within the hydrogel [ 108 ]. However, the rapid biodegradability of the protein-containing hydrogels, such as gelatin hydrogels, limits the time required for progenitor cell maturation [ 108 , 131 ]. Thus, incorporating chitosan with proteins such as gelatin or collagen to create hydrogels prolongs the life of the hydrogel, improving the maturation of the cardiomyocytes, mimicking the extracellular matrix of the myocardium and supporting the restoration of the cardiac function [ 132 , 133 ].…”

Research Advances of Injectable Functional Hydrogel Materials in the Treatment of Myocardial Infarction

“…This method of silencing the ACE gene could completely block the effect of ACE after myocardial infarction compared with lowering Ang II (Human angiotension Ⅱ) level with ACE inhibitor [ 190 ]. In addition, the induction of MSCs by microRNA and cardiomyocytes combined with hydrogel can improve the differentiation efficiency of MSCs into iCMs (induced cardiomyocyte-like cells) to improve the cardiac function of the MI model after transplantation [ 191 ]. In particular, miR-21-5p (microRNA-21-5p), which is highly expressed in endothelial cells, can stimulate angiogenesis by targeting anti-angiogenic genes [ 192 ].…”

Effects of Semaglutide on Cardiac Protein Expression and Cardiac Function of Obese Mice

“…Unless appropriate interventions are implemented, the prevalence and mortality from cardiovascular diseases would increase further. 1 , 2 In recent years, the occurrence of CVD has been markedly younger, and the incidence and mortality of aging cardiovascular disease have also increased significantly. 3 Therefore, controlling cardiovascular disease-related risk factors is of major clinical significance and social value for the effective prevention and treatment of CVD.…”