- 作者：Gustavo Monnerat-Cahli ; Mayra Trentin-Sonoda ; B谩rbara 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 ; Jos茅 H.M. Nascimento ; Antonio C. Campos de Carvalho ; Emiliano Medei
- 关键词：Mesenchymal stromal cells ; Diabetes ; Cardiac electrophysiology ; Immunoregulation ; AMPK
- 刊名：International Journal of Cardiology
- 出版年：1 February, 2014
- 年：2014
- 卷：171
- 期：2
- 页码：199-208
- 全文大小：1160 K
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 脳 106 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-纬 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.