Bone marrow mesenchymal stromal cells rescue cardiac function in streptozotocin-induced diabetic rats.

Abstract

OBJECTIVES:

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.

BACKGROUND:

Cardiac complications are one of the main causes of death in diabetes. Several studies have shown anti-diabetic effects of bone marrow mesenchymal stromal cells (MSC).

METHODS/RESULTS:

The rats were divided in three groups: Non-diabetic, Diabetic and Diabetic-Treated with 5 × 10(6) 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. In addition, after MSC-transplantation a decrease in corticosterone and IFN-γ sera levels without restoration of insulin and leptin plasma levels was observed. Also, MSC-therapy improved electrical remodeling, shortening QT and QTc in the ECG and 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, total ERK1 and p-ERK1/2 were not different among groups.

CONCLUSION:

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 systemic immunoregulation.

• Authors: Gustavo Monnerat-Cahli, Mayra Trentin-Sonoda, Bárbara Guerra, Gabriel Manso, Andrea C F Ferreira, Diorney L S G Silva, Danielle C Coutinho, Marcela S Carneiro-Ramos, Deivid C Rodrigues, Mauricio C Cabral-da-Silva, Regina C S Goldenberg, José H M Nascimento, Antonio C Campos de Carvalho, Emiliano Medei
• Journal: International journal of cardiology (Int J Cardiol) Vol. 171 Issue 2 Pg. 199-208 (Feb 01 2014) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 24374203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Biomarkers
• Blood Glucose
• Corticosterone

Topics

• Animals
• Biomarkers (blood)
• Blood Glucose (metabolism)
• Corticosterone (blood)
• Diabetes Complications (etiology, immunology, therapy)
• Diabetes Mellitus, Experimental (complications, immunology)
• Heart Conduction System (physiology)
• Heart Diseases (etiology, immunology, therapy)
• Hyperglycemia (etiology, immunology, therapy)
• Male
• Mesenchymal Stem Cell Transplantation (methods)
• Mesenchymal Stem Cells
• Rats
• Rats, Wistar
• Signal Transduction (physiology)
• Ventricular Remodeling (physiology)