Infusion of Mesenchymal Stem Cells Ameliorates Hyperglycemia in Type 2 Diabetic Rats

Abstract

Infusion of mesenchymal stem cells (MSCs) has been shown to effectively lower blood glucose in diabetic individuals, but the mechanism involved could not be adequately explained by their potential role in promoting islet regeneration. We therefore hypothesized that infused MSCs might also contribute to amelioration of the insulin resistance of peripheral insulin target tissues. To test the hypothesis, we induced a diabetic rat model by high-fat diet/streptozotocin (STZ) administration, performed MSC infusion during the early phase (7 days) or late phase (21 days) after STZ injection, and then evaluated the therapeutic effects of MSC infusion and explored the possible mechanisms involved. MSC infusion ameliorated hyperglycemia in rats with type 2 diabetes (T2D). Infusion of MSCs during the early phase not only promoted β-cell function but also ameliorated insulin resistance, whereas infusion in the late phase merely ameliorated insulin resistance. Infusion of MSCs resulted in an increase of GLUT4 expression and an elevation of phosphorylated insulin receptor substrate 1 (IRS-1) and Akt (protein kinase B) in insulin target tissues. This is the first report of MSC treatment improving insulin sensitivity in T2D. These data indicate that multiple roles and mechanisms are involved in the efficacy of MSCs in ameliorating hyperglycemia in T2D.

Effects of autologous adipose-derived stem cell infusion on type 2 diabetic rats

“…IRS-1, PDK1, and PKCζ are also important for conferring insulin signaling transduction and glucose uptake besides protein kinase Akt [40]. This result was consistent with Si' study, which found MSC infusion could restore the concentration of total GLUT4 and promote GLUT4 translocation to the cell memberane [23].…”

“…In the present study, we induced T2DM in a rat model by a high-fat diet combined with STZ administration and performed ASC infusion at the 28 th day after STZ injection. We found that ASC infusion could effectively ameliorate hyperglycemia in T2DM rats, which was consistent with other reports [1,2,23]. Furthermore, our results of hyperinsulinemic-euglycemic clamp studies demon-INSR in skeletal muscle and adipose and liver tissues after therapy to investigate the possible mechanisms involved in the effect of ASC infusion on insulin sensitivity.…”

“…We considered 28 days after STZ injection as the late phase of diabetes according to a previous study [23]. A single infusion of ASC ameliorated the hyperglycemia of diabetic rats and maintained that level for about six weeks, while the concentrations of serum insulin and C-peptide in ASC group increased compared to diabetic control group and maintained that level until the end of the study.…”

Pathogenesis of wound healing disorders in the elderly

“…In human diabetic foot ulcers, implantation of autologous BM-MSCs signifi cantly improves clinical parameters such as ulcer size and pain-free walking distance [ 97 ] . Apart from accelerating wound healing, infusion of MSCs has been shown to reverse diabetic symptoms in type 2 diabetic rodents [ 98 ] . In other studies, combination protocols of antioxidant agents, such as epigallocatechin-3-gallate (EGCG), along with MSCs promote wound healing by modulating chronic infl ammation [ 99 ] .…”

Bone Marrow-Derived Mesenchymal Stem cells Infusion Ameliorates Hyperglycemia, Dyslipidemia, Liver and Kidney Functions in Diabetic Rats

“… Diabetic + Stem cell (STZ+ MSCs) group: 10 diabetic rats received i.v. injection (through tail vein) of 2 × 10 6 MSCs suspended into 0.2 mL physiological saline for each rat [20], for one time [21] . Similarly, for the control group and diabetic group, 0.2 mL of physiological saline was injected instead of MSCs.…”