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 d… Show more
“…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].…”
Section: Conflict Of Interestsupporting
confidence: 81%
“…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.…”
Section: A B Csupporting
confidence: 80%
“…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.…”
Type 2 diabeTes melliTus (T2DM) accounts for more than 90% of all diabetic patients and is characterized by insulin resistance, hyperglycemia, systemic low-grade inflammation, and relative lack of insulin. Most T2DM patients experience β-cell exhaustion several years after diagnosis, and thus have to accept insulin therapy. However, insulin therapy is inconvenient for patients and does not completely prevent the development of diabetic complications. Stem cells are an attractive option to ameliorate diabetes for its abundant source and potential to acquire glucose-dependent insulin secretory function. Adult stem cells are an especially good candidate for its safety in terms of tumorigenicity and ethical concerns.Adipose-derived stem cells (ASC) have been stud- The effects and possible mechanisms of adipose-derived stem cells (ASC) infusion on type 2 diabetic rats were investigated in this study. Twenty normal male Sprague-Dawley rats were included in normal control group, and 40 male diabetic rats were randomly divided into diabetic control group and ASC group (which received ASC infusion). After therapy, levels of fasting plasma glucose (FPG), HbA1c, serum insulin and C-peptide, recovery of islet cells, inflammatory cytokines, and insulin sensitivity were analyzed. After ASC infusion, compared with diabetic control group, hyperglycemia in ASC group was ameliorated in 2 weeks and maintained for about 6 weeks, and plasma concentrations of insulin and C-peptide were significantly improved (P<0.01). Number of islet β cells and concentration of vWF in islets in ASC group increased, while activity of caspase-3 in islets was reduced. Moreover, concentrations of TNF-α, IL-6 and IL-1β in ASC group obviously decreased (P<0.05). The expression of GLUT4, INSR, and phosphorylation of insulin signaling molecules in insulin target tissues were effectively improved. ASC infusion could aid in T2DM through recovery of islet β cells and improvement of insulin sensitivity. Autologous ASC infusion might be an effective method for T2DM.
“…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].…”
Section: Conflict Of Interestsupporting
confidence: 81%
“…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.…”
Section: A B Csupporting
confidence: 80%
“…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.…”
Type 2 diabeTes melliTus (T2DM) accounts for more than 90% of all diabetic patients and is characterized by insulin resistance, hyperglycemia, systemic low-grade inflammation, and relative lack of insulin. Most T2DM patients experience β-cell exhaustion several years after diagnosis, and thus have to accept insulin therapy. However, insulin therapy is inconvenient for patients and does not completely prevent the development of diabetic complications. Stem cells are an attractive option to ameliorate diabetes for its abundant source and potential to acquire glucose-dependent insulin secretory function. Adult stem cells are an especially good candidate for its safety in terms of tumorigenicity and ethical concerns.Adipose-derived stem cells (ASC) have been stud- The effects and possible mechanisms of adipose-derived stem cells (ASC) infusion on type 2 diabetic rats were investigated in this study. Twenty normal male Sprague-Dawley rats were included in normal control group, and 40 male diabetic rats were randomly divided into diabetic control group and ASC group (which received ASC infusion). After therapy, levels of fasting plasma glucose (FPG), HbA1c, serum insulin and C-peptide, recovery of islet cells, inflammatory cytokines, and insulin sensitivity were analyzed. After ASC infusion, compared with diabetic control group, hyperglycemia in ASC group was ameliorated in 2 weeks and maintained for about 6 weeks, and plasma concentrations of insulin and C-peptide were significantly improved (P<0.01). Number of islet β cells and concentration of vWF in islets in ASC group increased, while activity of caspase-3 in islets was reduced. Moreover, concentrations of TNF-α, IL-6 and IL-1β in ASC group obviously decreased (P<0.05). The expression of GLUT4, INSR, and phosphorylation of insulin signaling molecules in insulin target tissues were effectively improved. ASC infusion could aid in T2DM through recovery of islet β cells and improvement of insulin sensitivity. Autologous ASC infusion might be an effective method for T2DM.
“…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 ] .…”
Section: Challenges and Perspectives In The Treatment Of Chronic Wounmentioning
Summary
The elderly constitute the age group most susceptible to wound healing disorders and chronic wounds, the most prevalent being venous leg ulcers, pressure ulcers, and diabetic foot ulcers. However, other age‐associated diseases should also be taken into consideration in the diagnostic workup of chronic wounds, and not be underestimated. A better understanding of the pathomechanisms involved in the wound healing process is of key importance in combatting the difficulties associated with the treatment of chronic wounds. In recent decades, considerable progress has been made in the development of pioneering therapeutic strategies for chronic wounds. In this context, the use of growth factors and cytokines, tissue engineering, and cell therapy – including stem cells – have proven very promising. Nevertheless, prior to their introduction into routine clinical practice, large controlled clinical trials are required to assess the safety of these techniques.
“… 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.…”
Section: Bm-mscs Injection and Experimental Designmentioning
Diabetes mellitus is associated with hyperglycemia, lipoprotein abnormalities and various organs dysfunctions. Stem cell therapy offers a great promise for the repair of injured tissues and organs. The aim of this study was to explore the effects of mesenchymal stem cell derived from bone marrow of albino rats on hyperglycemia, hypoinsulinemia, dyslipidemia and liver and kidney dysfunctions in STZ diabetic rats. Rat bone marrow mesenchymal stem cells (BM-MSCs) were isolated, cultured, characterized and finally injected intravenously (2 × 10 6 , via tail vein) into STZ-induced diabetic rats. The other diabetic (STZ) rats received no treatment. The diabetic (STZ) rats showed significant (P<0.05) increase in serum glucose, HbA1c, insulin resistance (IR), total cholesterol, TGs, LDL-C, VLDL-C levels and a significant decrease of serum insulin, HDL-C levels as compared to their corresponding control. Also, higher levels of liver function tests (ALT, AST & ALP) as well as kidney function tests (urea, uric acid and creatinine) were noticed in diabetic rats when compared to control group. Treatment of diabetic rats with MSCs significantly prevented these alterations. These data indicate the efficacy of MSCs transplantation in improving hyperglycemia, dyslipidemia, liver and kidney functions in diabetes mellitus. Further work is required to examine the curative effects on larger animal models and humans.
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