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.
Highlights
left ventricle (LV) samples were fixed in 10% neutral buffered formalin, embedded with paraffin, and sectioned
Chemical and physical factors provided by the SMHs promote cell growth, proliferation and differentiation
Delivery of MSCs by SMHs improved the microenvironment of transplanted stem cells
Summary
LV samples were fixed in 10% neutral buffered formalin, embedded with paraffin, and sectioned. Myocyte cross-sectional area was used to evaluate the proportion of MI in the LV. Sections were deparaffinized with xylene and stained with H&E. Sections were stained with a Masson trichrome kit (Baso, BA4079) according to the manufacturer’s instructions. The stained sections were examined under a light microscope (Nikon ECLIPSE Ti-U). The area of the MI, cross sectional area of the LV chamber, and the thickness of the wall were measured by Image Pro Plus 6.0
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