title: Bone marrow mesenchymal stromal cells rescue cardiac function in streptozotocin-induced diabetic rats.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Monnerat-Cahli
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo Andre, Brasil.
authors.forename: Mayra
authors.initials: M
authors.lastname: Trentin-Sonoda
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Guerra
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Manso
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Andrea C F
authors.initials: AC
authors.lastname: Ferreira
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Diorney L S G
authors.initials: DL
authors.lastname: Silva
authors.affiliation: Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brasil.
authors.forename: Danielle C
authors.initials: DC
authors.lastname: Coutinho
authors.affiliation: Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brasil.
authors.forename: Marcela S
authors.initials: MS
authors.lastname: Carneiro-Ramos
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Deivid C
authors.initials: DC
authors.lastname: Rodrigues
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Mauricio C
authors.initials: MC
authors.lastname: Cabral-da-Silva
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Regina C S
authors.initials: RC
authors.lastname: Goldenberg
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: José H M
authors.initials: JH
authors.lastname: Nascimento
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil; Instituto Nacional de Cardiologia, Rio de Janeiro, Brasil.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Campos de Carvalho
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. Electronic address: emedei70@biof.ufrj.br.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Medei
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D048909:Diabetes Complications / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000276:immunology; D006329:Heart Conduction System / Q000502:physiology; D006331:Heart Diseases / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D006943:Hyperglycemia / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D003345:Corticosterone
keywords: AMPK; Cardiac electrophysiology; Diabetes; Immunoregulation; Mesenchymal stromal cells