Impact of Diabetes Mellitus on the Potential of Autologous Stem Cells and Stem Cell-Derived Microvesicles to Repair the Ischemic Heart.

Ischemic heart disease remains the leading cause of morbidity and mortality worldwide. Despite the advances in medical management and catheter-based therapy, mortality remains high, as does the risk of developing heart failure. Regenerative therapies have been widely used as an alternative option to repair the damaged heart mainly because of their paracrine-related beneficial effects. Although cell-based therapy has been demonstrated as feasible and safe, randomized controlled trials and meta-analyses show little consistent benefit from treatments with adult-derived stem cells. Mounting evidence from our group and others supports that cardiovascular risk factors and comorbidities impair stem cell potential thus hampering their autologous use. This review aims to better understand the influence of diabetes on stem cell potential. For this purpose, we will first discuss the most recent advances in the mechanistic understanding of the effects of diabetes on stem cell phenotype, function, and molecular fingerprint to further elaborate on diabetes-induced alterations in stem cell extracellular vesicle profile. Although we acknowledge that multiple sources of stem or progenitor cells are used for regenerative purposes, we will focus on bone marrow hematopoietic stem/progenitor cells, mesenchymal stem cells residing in the bone marrow, and adipose tissue and briefly discuss endothelial colony-forming cells.