Abstract
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.
Highlights
Type 2 Diabetes Mellitus (T2D), the most common form of diabetes is caused basically by two pathogenic mechanisms-insulin resistance and secretory dysfunction/decrease of pancreatic β-cells and currently there are experimental, clinical and epidemiological evidences of the involvement of immune and inflammatory mediators in these two mechanisms [1]
The purpose of this study was to investigate the effects of multiple infusions of allogeneic Bone marrow (BM) mesenchymal stem cells (MSCs) on glucose homeostasis and morphometry of pancreatic islets in high- fat diet (HFD)-induced hyperglycemia in Swiss mice
The results show that multiple infusions of allogeneic BM-MSCs are able to promote prolonged decrease in glucose intolerance and apoptosis in pancreatic islets and increase in insulin sensitivity in hyperglycemic HFD fed mice
Summary
Type 2 Diabetes Mellitus (T2D), the most common form of diabetes (approximately 90% of cases) is caused basically by two pathogenic mechanisms-insulin resistance and secretory dysfunction/decrease of pancreatic β-cells and currently there are experimental, clinical and epidemiological evidences of the involvement of immune and inflammatory mediators in these two mechanisms [1]. The progression of obesity to insulin resistance and to T2D involves the adaptive expansion of β-cells and increase of insulin secretion, and if this compensation is inadequate, glucose intolerance and T2D develop, with subsequent decline of pancreatic β-cell mass [2,3]. Treatment of T2D can only ameliorate hyperglycemia or temporarily improve the response to insulin in target tissues. Adherence to therapy is usually low and most patients maintain hyperglycemia, which is the major factor responsible for the onset of the chronic and severe complications of diabetes [4]. The interest in regenerative therapeutics for T2D was initially motivated by the importance of preserving β-cell mass and function
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