Novel MicroRNA Prosurvival Cocktail for Improving Engraftment and Function of Cardiac Progenitor Cell Transplantation

• DOI: 10.1161/circulationaha.111.017954
• Publication Date: 2011-09-12T22:01:50Z
• Authors: Shijun Hu; Mei Huang; Patricia K. Nguyen; Yongquan Gong; Zongjin Li; Fangjun Jia; Feng Lan; Junwei Liu; Divya Nag; Robert C. Robbins; Joseph C. Wu
• Keywords: Bioluminescence imaging; Cell therapy; Stem Cell Therapy

Background— Although stem cell therapy has provided a promising treatment for myocardial infarction, the low survival of transplanted cells in infarcted myocardium is possibly primary reason failure long-term improvement. Therefore, development novel prosurvival strategies to boost will be significant benefit this field. Methods and Results— Cardiac progenitor (CPCs) were isolated from transgenic mice, which constitutively express firefly luciferase green fluorescent protein. The CPCs transduced with individual lentivirus carrying precursor miR-21, miR-24, miR-221, cocktail these 3 microRNA precursors, or protein as control. After challenge serum free medium, treated showed significantly higher viability compared untreated CPCs. intramuscular intramyocardial injections, vivo bioluminescence imaging that cocktail-treated survived longer after transplantation. left anterior descending artery ligation, therapeutic efficacy terms functional recovery. Histological analysis confirmed increased wall thickness CPC engraftment cocktail. Finally, we used bioinformatics experimental validation assays show Bim, critical apoptotic activator, an important target gene cocktail, collectively can bind 3′UTR region Bim suppress its expression. Conclusions— We have demonstrated (miR-21, miR-221) improve cardiac ischemic heart disease.