Metabolic and pancreatic effects of bone marrow mesenchymal stem cells transplantation in mice fed high-fat diet.
The purpose of this study was to investigate the effects of multiple infusions of allogeneic MSCs on glucose homeostasis and morphometry of pancreatic islets in high- fat diet (HFD) fed mice. Swiss mice were fed standard diet (C group) or HFD (HFD group). After 8 weeks, animals of HFD group received sterile phosphate-buffered saline infusions (HFD-PBS) or four infusions of MSCs one week apart (HFD-MSCs). Fasting glycemia (FG) was determined weekly and glucose (GTT) and insulin (ITT) tolerance tests were performed 4, 8, 12, and 16 weeks after the infusions of MSCs. The MSCs transplanted mice were classified as responder (FG < 180 mg/dL, 72.2% of transplanted mice) or non-responder (FG > 180mg/dL, 28.8%) Seven weeks after MSCs infusions, FG decreased in HFD-MSCs responder mice compared with the HFD-PBS group. Sixteen weeks post MSCs infusions, GTT and ITT areas under the curve (AUC) decreased in HFD-MSCs responder mice compared to HFD-PBS group. Serum insulin concentration was higher in HFD-PBS group than in control animals and was not different compared with the other groups. The relative volume of α-cells was significantly smaller in HFD-PBS group than in C group and significantly higher in HFD-MSCs-NR than in HFD-PBS and HFD-MSCs-R groups. Cell apoptosis in the islets was higher in HFD-PBS group than in C group, and lower in HFD-MSCs responder mice than in HFD-PBS group and non-responder animals. The results demonstrate the ability of multiple infusions of MSCs to promote prolonged decrease in hyperglycemia and apoptosis in pancreatic islets and increase in insulin sensitivity in HFD fed mice.
Department of Physiological Science, Center of Biological Sciences and Health, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
Patricia de Godoy
Pde G
Bueno
Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, São Paulo, Brazil.
Juliana Navarro Ueda
JN
Yochite
Department of Physiological Science, Center of Biological Sciences and Health, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
Graziela Fernanda
GF
Derigge-Pisani
Department of Clinical, Toxicological and Bromatological Analyses, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirao Preto, São Paulo, Brazil.
Kelen Cristina Ribeiro
KC
Malmegrim de Farias
Department of Medicine, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
Lucimar Retto da Silva
LR
de Avó
Department of Physiological Science, Center of Biological Sciences and Health, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
Júlio César
JC
Voltarelli
Department of Medicine, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
Ângela Merice de Oliveira
ÂM
Leal
D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000009:adverse effects*; D005215:Fasting; D050416:Glucagon-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D014183:Transplantation, Heterologous
D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin