Bone marrow stem cells implantation with alpha-cyclodextrin/MPEG-PCL-MPEG hydrogel improves cardiac function after...

Cellular transplantation represents a promising therapy for myocardial infarction (MI). However, it is limited by low transplanted cell retention and survival within the ischemic tissue. This study was designed to investigate whether injectable alpha-cyclodextrin/poly(ethylene glycol)-b-polycaprolactone-(dodecanedioic acid)-polycaprolactone-poly(ethylene glycol) (MPEG-PCL-MPEG) hydrogel could improve cell transplant retention and survival, reduce infarct expansion and inhibit left ventricle (LV) remodeling. Bone marrow-derived stem cells (BMSCs) were encapsulated in alpha-cyclodextrin/MPEG-PCL-MPEG hydrogel and maintained their morphologies during the cell culturing. MTT assays were used for in vitro cell viability studies of the hydrogel and were shown to be non-cytotoxic. Seven days after MI, 100 microl of alpha-cyclodextrin solution containing 2 x 10(7) BMSCs and 100mul of MPEG-PCL-MPEG solution were injected into the infarcted myocardium simultaneously and the solutions solidified immediately. Injection of culture medium or cell alone served as controls. Four weeks after treatment, histological analysis indicated that the hydrogel was absorbed, and the injection of BMSCs with hydrogel had increased cell retention and vessel density around the infarct, and subsequently prevented scar expansion compared with BMSCs injection alone. Echocardiography studies showed that injection of BMSCs with hydrogel increased the LV ejection function and attenuated left ventricular dilatation. This study indicated that the injection of BMSCs with alpha-cyclodextrin/MPEG-PCL-MPEG hydrogel was an effective strategy which could enhance the effect of cellular transplantation therapy for myocardial infarction.