Enhanced Therapeutic and Immunomodulatory Effect of Stem Cell Spheroid with Transition Metal-Based Nanoparticles in Rat Myocardial Infarction Model

Myocardial infarction (MI) which accompanies decrease in myocardium function and destruction of millions of cardiomyocytes is a leading cause of mortality worldwide. In this study, we demonstrated advanced stem cell therapy to treat cardiovascular disease with enhanced therapeutic efficacy of stem cell spheroids by upregulating angiogenesis-related paracrine factors secretion and inducing immunomodulatory ability with transition metal based nanoparticles (TMNs). Stem cell spheroids treated with TMNs (spheroids-TMNs) had widen hypoxia inducible factor (HIF) expression area in core with mild reactive oxygen species (ROS) generation. According to increased HIF expression of spheroids-TMNs, the secretion of angiogenesis-related paracrine factors was enhanced compared to untreated spheroids. Immunomodulatory effect of spheroids-TMNs was verified with Raw cell; suppression of pro-inflammatory responses and promotion of anti-inflammatory responses. Enhanced therapeutic effect and immunomodulatory effect of spheroids-TMNs were verified in vivo rat MI model. An advanced stem cell therapy we provided can be a promising therapeutic strategy for cardiovascular disease treatment.