Finasteride as a potential tool to improve Mesenchymal stem cell transplantation for myocardial infarction

Abstract

Mesenchymal stem cells (MSCs) therapy has emerged as a potent therapeutic strategy to improve myocardial infarction. However MSCs therapy encounters a few obstacles regarding the poor viability of the transplanted cells. Therefore, it is important to explore a strategy to enhance post-transplanted MSC viability. To overcome this problem, several protocols were suggested mainly by activating PI3K/Akt pathway. The PI3K/Akt cascade regulates several cellular processes such as proliferation and apoptosis. Finasteride is a specific inhibitor of type II 5α-reductase; the enzyme converts testosterone (T) to the more potent androgen receptor agonist dihydrotestosterone (DHT). Testosterone is found to stimulate rapid phosphorylation of Akt, and thereby activate the PI3K/Akt pathway. This pathway could lead to decreased apoptosis of the MSCs via increasing the expression of Bcl-2 and reducing Bax expression. It has been also reported that DHT would confine the differentiation capacity of MSCs so that a reduction in DHT levels caused by Finasteride would be accompanied by increased facilitation in differentiation of MSCs to cardiomyocyte by means of the signals originating from the injured cardiac tissue. These mechanisms could propose the potential role for Finasteride to improve the MSCs therapy for myocardial infarction.