Effects of Mesenchymal Stromal Cells on Diabetic Cardiomyopathy

S.      Van Linthout; F.      Spillmann; H.-P.      Schultheiss; C.      Tschope

Abstract

Diabetic cardiopathy includes a specific cardiomyopathy, which occurs in the absence of coronary heart disease under diabetes mellitus. Hallmarks of diabetic cardiomyopathy are besides others, interstitial inflammation, cardiac oxidative stress, interstitial and perivascular fibrosis, cardiac apoptosis, intramyocardial microangiopathy, endothelial dysfunction, abnormal intracellular Ca2+-handling, cardiomyocyte hypertrophy, and impaired cardiac stem cells. Since mesenchymal stromal cells have been shown to have anti-diabetic as well as cardioprotective features, we summarize in this review how they can indirectly affect diabetic cardiomyopathy via their influence on the metabolic trigger hyperglycemia, and how they can directly influence the cardiac cellular consequences typical for diabetic cardiomyopathy via their immunomodulatory, anti-oxidative, anti-fibrotic, anti-apoptotic, pro-angiogenic, and endothelial-protective features, and their ability to activate cardiac progenitor cells. Furthermore, the dysfunctionality of (bone marrow-derived) mesenchymal stromal cells under diabetes mellitus and potential strategies to overcome this impairment in cell functionality are outlined.

Keywords: Diabetes mellitus, mesenchymal stromal cells, endothelial dysfunction, fibrosis, cardiomyopathy, hypertension, apoptosis, hypoxia, extracellular matrix proteins, interleukin