Conditioned medium harvested from Hif1 alpha engineered mesenchymal stem cells ameliorates LAD-occlusion -induced injury in rat acute myocardial ischemia model

Abstract

Acute myocardial infarction (AMI) is the most common type of ischemic heart diseases with a high mortality rate. Although recent advances in medical cares and therapies have increased the patient's outcomes, but, still there is no real and effective therapeutic modality for AMI. Hence, development of novel therapeutic strategies is under focus of investigations. MSCs-based therapy has been proposed for AMI, though its efficacy is controversial yet. It is believed that MSCs exert their healing effects via secretion of growth factors/cytokines. However, these cells produce a very minute amount of the factors under normal cultivation. Here, in an attempt to improve the potential therapeutic effect of MSCs-derived conditioned medium (CM) on AMI, we transfected the cells with a recombinant plasmid encoding Hif1 alpha-3A (a mutant form of Hif1 alpha stable under normoxic condition), so Hif1 alpha expression and secretion into CM (MSCs-Hif1 alpha-CM) could be up-regulated under normoxic condition. The therapeutic potential of the MSCs-Hif1 alpha-3A-CM was investigated in a rat model of AMI and compared to the CM harvested from non-manipulated MSCs. Our results showed that the MSCs-Hif1 alpha-3A-CM mitigated MI-induced tissues injury, decreased fibrosis, reduced apoptosis, and limited infarct area size. These findings propose a potential therapeutic strategy for treatment of AMI. However, further preclinical and clinical investigations in this regard are still needed.