Abstract 16935: Transferring Ischemia-Resistant Phenotype From Stem Cells into Mouse Hearts by microRNA
INTRODUCTION: It was observed that adipose stem cells (ASC) are more resistant to ischemic injury than adult cardiomyocytes. We hypothesized that introducing microRNA (miRNA) pool extracted from ASC (miRNA-ASC) into mouse hearts transfer ASC's ischemia-resistant phenotype and reduce myocardial infarct size following ischemia/reperfusion injury.
METHODS: CD-1 mice were treated with either miRNA-ASC (2 µg per heart) or volume-matched PBS (30 µl) through direct, multi-site cardiac injection. Twenty-four hours later, both groups were subjected to 30 min of ischemia by coronary artery occlusion and 24 hrs of reperfusion (I/R). Infarct size was measured by tetrazolium staining at the end of I/R. miRNA profiling was performed using microarray technique and verified by q-PCR. Potential targets of miRNA-ASC were studied by q-PCR and Western blot.
RESULTS: miRNA-ASC reproduced stem cells’ ischemia-resistant phenotype in the recipient mouse hearts, showing a much smaller infarct size (24.2±1.6%; 44% reduction) versus the PBS group (43.5±2.1%; n=6, p<0.05). The miRNA profile of ASC showed that miRNA-21, a predominant and cardioprotective miRNA, was 3.7-folds more (microarray, n=3, p<0.01) or 7.8-folds more (RT-PCR, n=3, p<0.001) than in wild type mouse hearts. More importantly, mRNA of the pro-apoptotic PDCD-4 (programmed cell death 4), a target of miRNA-21, was suppressed by 39.3% (n=3, p<0.01) in the miRNA-ASC treated group, as compared to the PBS group. Interestingly, mRNA of PDCD-4 was not detected in the stem cells. Immunohistochemistry data further confirmed that PDCD-4 positive cells were 77.1% less in the miRNA-ASC treated group versus the PBS group (n=3, p<0.001). The suppression of both mRNA and protein of PDCD-4 in the miRNA-ASC group may contribute to the observed ischemia-resistant phenotype transferred into the hearts.
CONCLUSION: miRNA-ASC is capable of carrying the stem cells’ ischemia-resistant attribute into the recipient hearts and reduces infarct size following ischemia/reperfusion. This property of miRNA-ASC may be explored and used as a molecular tool against I/R injury, a new approach to traditional cellular therapy of stem cells.
- © 2011 by American Heart Association, Inc.