Intra-myocardial injection of both growth factors and heart derived Sca-1+/CD31- cells attenuates post-MI LV remodeling more than does cell transplantation Alone: Neither intervention enhances functionally significant cardiomyocyte regeneration

Xiaohong Wang, Qinglu Li, Qingsong Hu, Piradeep Suntharalingam, Arthur H From, Jianyi Zhang

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17 Scopus citations

Abstract

Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are two potent cell survival and regenerative factors in response to myocardial injury (MI). We hypothesized that simultaneous delivery of IGF+HGF combined with Sca-1+/CD31- cells would improve the outcome of transplantation therapy in response to the altered hostile microenvironment post MI. One million adenovirus nuclear LacZ-labeled Sca-1+/CD31 - cells were injected into the peri-infarction area after left anterior descending coronary artery (LAD) ligation in mice. Recombinant mouse IGF-1+HGF was added to the cell suspension prior to the injection. The left ventricular (LV) function was assessed by echocardiography 4 weeks after the transplantation. The cell engraftment, differentiation and cardiomyocyte regeneration were evaluated by histological analysis. Sca-1+/ CD31- cells formed viable grafts and improved LV ejection fraction (EF) (Control, 54.5+/-2.4; MI, 17.6+/- 3.1; Cell, 28.2+/-4.2, n = 9, P<0.01). IGF+HGF significantly enhanced the benefits of cell transplantation as evidenced by increased EF (38.8+/-2.2; n = 9, P<0.01) and attenuated adverse structural remodeling. Furthermore, IGF+HGF supplementation increased the cell engraftment rate, promoted the transplanted cell survival, enhanced angiogenesis, and minimally stimulated endogenous cardiomyocyte regeneration in vivo. The in vitro experiments showed that IGF+HGF treatment stimulated Sca-1+/CD31- cell proliferation and inhibited serum free medium induced apoptosis. Supperarray profiling of Sca-1+/CD31 - cells revealed that Sca-1+/CD31- cells highly expressed various trophic factor mRNAs and IGF+ HGF treatment altered the mRNAs expression patterns of these cells. These data indicate that IGF-1+HGF could serve as an adjuvant to cell transplantation for myocardial repair by stimulating donor cell and endogenous cardiac stem cell survival, regeneration and promoting angiogenesis.

Original languageEnglish (US)
Article numbere95247
JournalPloS one
Volume9
Issue number6
DOIs
StatePublished - Jun 11 2014

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