Simultaneous Delivery of Wharton's Jelly Mesenchymal Stem Cells and Insulin-Like Growth Factor-1 in Acute Myocardial Infarction.

Abstract

Wharton's jelly mesenchymal stem cells (HWJMSCs) hold promise for myocardial regeneration, but optimal treatment regimen (preferably with a growth factor) is required to maximize functional benefits. The aim of this study was to explore the cardioprotective and angiogenesis effects of HWJMSCs combined with insulin-like growth factor-1 (IGF-1) in the treatment of acute myocardial infarction. The hydrogel consisted of Polyethylene glycol (PEG) and hyaluronic acid was prepared and characterized with regards to rheology, morphology, swelling, degradation, and release behaviors. To examine in-vivo effects, the hydrogels containing HWJMSCs either alone (Cells/hydrogel group) or with IGF-1 (Cells/hydrogel/IGF-1 group) were intra-myocardially injected into a rabbit myocardial infarction model. In-vivo efficacy was evaluated histological, immunohistochemical, echocardiography, scanning electron microscopy, and SPECT analyses. Eight weeks after infusion, the Cells/hydrogel and Cells/hydrogel/IGF-1 groups exhibited significantly increased left ventricular ejection fraction by echocardiography. Percent of ejection fraction was respectively 18.5% and 40% greater than control (P < 0.01). Vascular density (CD31 positive cells) of both treatment groups were more than the control group and this superiority was more remarkable in Cells/hydrogel/IGF-1 group. Cells/hydrogel/IGF-1 group showed the least defect size in SPECT analysis. Combinatory therapy with HWJMSCs and IGF-1 may additionally improve cardiac function and promote angiogenesis.