Treatment of Myocardial Infarction with Gene-modified Mesenchymal Stem Cells in a Small Molecular Hydrogel

Abstract

The effect of transplanted rat mesenchymal stem cells (MSCs) can be reduced by extracellular microenvironment in myocardial infarction (MI). We tested a novel small-molecular hydrogel (SMH) on whether it could provide a scaffold for hepatocyte growth factor (HGF)-modified MSCs and alleviate ventricular remodeling while preserving cardiac function after MI. Overexpression of HGF in MSCs increased Bcl-2 and reduced Bax and caspase-3 levels in response to hypoxia in vitro. Immunocytochemistry demonstrated that cardiac troponin (cTnT), desmin and connexin 43 expression were significantly enhanced in the 5-azacytidine (5-aza) with SMH group compared with the 5-aza only group in vitro and in vivo. Bioluminescent imaging indicated that retention and survival of transplanted cells was highest when MSCs transfected with adenovirus (ad-HGF) were injected with SMH. Heart function and structure improvement were confirmed by echocardiography and histology in the Ad-HGF-SMHs-MSCs group compared to other groups. Our study showed that: HGF alleviated cell apoptosis and promoted MSC growth. SMHs improved stem cell adhesion, survival and myocardial cell differentiation after MSC transplantation. SMHs combined with modified MSCs significantly decreased the scar area and improved cardiac function.

Injectable Hydrogels for Cardiac Tissue Engineering

“…Hydrogels injected directly into damaged cardiac tissue can serve as a potential delivery vehicle for cells, growth factors, and therapeutic peptides or drugs, etc . Hydrogels may also be used to support various gene delivery systems, including viral and non‐viral methods, enabling controlled delivery to the desired site and efficient localized therapy . Such deliverables could be specifically sequestered to the target tissue, reducing nonspecific spreading to other nearby tissues.…”

Bone marrow mesenchymal stem cells enhance autophagy and help protect cells under hypoxic and retinal detachment conditions

“…The anti‐apoptotic effect of BMSCs was also demonstrated in several tissues; in ischaemic myocardial cells, damaged liver cells and neural cells, BMSCs helped to reduce apoptosis and promote matrix remodelling, and the mechanisms underlying this result were thought to be cytokines produced by the paracrine effect of the BMSCs . Differentiation was also found to be another important aspect, as the transplanted BMSCs expressed several functional cell markers; however, the functions of the differentiated cells remain controversial . Recently, studies have shown that BMSCs can regulate autophagy …”

“…however, the functions of the differentiated cells remain controversial. [35][36][37] Recently, studies have shown that BMSCs can regulate autophagy. 15,16 Autophagy, one of the important mechanisms underlying survival and cellular homoeostasis maintenance, functions by decomposing cellular composition under stresses, such as starvation and hypoxia.…”

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

“…Zhao and colleagues induced overexpression of HGF in MSCs following administration into a mouse model of MI [489]. In addition to increased survival of modified MSCs probably induced by increased B cell lymphoma (Bcl)-2 and reduced Bax and caspase-3 levels [490], the authors detected an enhancement of angiogenesis, LVEF and proliferation capacity of resident cardiomyocytes upon SC treatment [489]. Moreover, overexpression of anti-apoptotic factors like Bcl-xL and Bcl-2 was found to positively influence the viability and therapeutic efficiency of applied SCs [491,492].…”