Abstract 014: Bone Marrow Mesenchymal Stromal Cells Rescue Cardiac Function In Streptozotocin-induced Diabetic Rats

Abstract

Cardiac complications are one of the main causes of death in diabetes. Several studies have shown the anti-diabetic effects of bone marrow mesenchymal stromal cells (MSC). In the present study, we investigated whether MSC-transplantation can revert cardiac dysfunction in streptozotocin-induced diabetic rats and the immunoregulatory effects of MSC were examined. The rats were divided in three groups: Non-diabetic, Diabetic and Diabetic-Treated that received 5x106 MSC 4 weeks after establishment of diabetes. Four weeks after MSC-therapy, systemic metabolic parameters, immunological profile and cardiac function were assessed. MSC-transplantation was able to revert the hyperglycemia and body weight loss of the animals, while decreasing to control levels sera corticosterone and the proinflammatory cytokine CINC2 without restoring insulin and leptin plasma levels and oral glucose tolerance. Also, MSC-therapy improved electrical remodeling, shortening the QT and QTc in the ECG and the action potential duration of left ventricular myocytes. No arrhythmic events were observed after MSC-transplantation. MSC-therapy rescued the cardiac beta-adrenergic sensitivity by increasing beta-1 adrenergic receptor expression. Both alpha and beta cardiac AMPK and p-AMPK returned to baseline values after MSC-therapy. However, the total ERK1 and p-ERK1/2 were not different among groups. MSC-therapy reestablished the cardiac control levels of key proinflammatory cytokines/chemokines (IL-6, IL-18, CINC2, CINC3). However MSC-therapy did not modulate toll-like receptor signaling pathways. The results indicate that MSC-therapy was able to rescue cardiac impairment induced by diabetes, normalize cardiac AMPK subunit expression and activity, decrease corticosterone and glycemia and exert local (cardiac) and systemic immunoregulation.