Amelioration of diabetic retinopathy by engrafted human adipose-derived mesenchymal stem cells in streptozotocin diabetic rats

Yang, Zhikun; Li, Kanghua; Xiao, Yan; Fang, Dong; Chun-hua, Zhao

doi:10.1007/s00417-010-1384-z

Cited by 79 publications

(70 citation statements)

References 25 publications

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“…Although most cells remained in spleen and thymus, a relatively high percentage of ASC were found in injured region. Moreover, Yang et al had found that engrafted ASC homed to retina and differentiated into photoreceptorlike cells and astrocyte-like cells induced by diabetic retinopathy, and ameliorated the integrity of the bloodretinal barrier [31]. Based on the above findings, we considered that ASC could home to the damaged islets to play their roles.…”

Section: Discussionmentioning

confidence: 80%

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

Chen

et al. 2015

Endocr J

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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.

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Section: Discussionmentioning

confidence: 80%

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

Chen

et al. 2015

Endocr J

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“…When (17) reported that co-transplantation of adipose tissuederived insulin-secreting MSCs and hematopoietic stem cells is beneficial in reducing exogenous insulin requirement in patients with insulin-dependent diabetes mellitus. It has also been demonstrated that transplantation of ADMSCs attenuates diabetic bladder dysfunction and diabetic retinopathy in a diabetic rat model (18,19). Based on these previous findings, we therefore raised the hypothesis that cytotherapy using autologous ADMSC transplantation is beneficial in alleviating diabetic nephropathy.…”

Section: Introductionmentioning

confidence: 81%

Autologous transplantation of adipose-derived mesenchymal stem cells ameliorates streptozotocin-induced diabetic nephropathy in rats by inhibiting oxidative stress, pro-inflammatory cytokines and the p38 MAPK signaling pathway

et al. 2012

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Abstract. Diabetic nephropathy is the leading cause of endstage renal disease. The aim of this study was to investigate the renoprotective effects of autologous transplantation of adiposederived mesenchymal stem cells (ADMSCs) and to delineate its underlying mechanisms of action in diabetic nephropathy. Diabetes was induced in adult male Sprague-Dawley rats by streptozotocin (STZ) injection. ADMSCs were administered intravenously 4 weeks after STZ injection and metabolic indices and renal structure were assessed (12 weeks). Markers of diabetes including blood glucose, cholesterol, triglycerides, urea nitrogen and creatinine were measured. Renal pathology, levels of oxidative stress and the expression of pro-inflammatory cytokines and the MAPK signaling pathway members were also determined. Autologous transplantation of ADMSCs significantly attenuated common metabolic disorder symptoms associated with diabetes. Furthermore, ADMSC administration minimized pathological alterations, reduced oxidative damage and suppressed the expression of pro-inflammatory cytokines in the renal tissues of diabetic rats. ADMSC transplantation also decreased the expression of p-p38, p-ERK and p-JNK, which are all important molecules of the MAPK signaling pathway. In conclusion, we provide experimental evidence demonstrating that autologous transplantation of ADMSCs can be used therapeutically to improve metabolic disorder and relieve renal damage induced by diabetes, and that the key mechanisms underlying the positive therapeutic impact of ADMSC treatment in kidneys could be due to the suppression of inflammatory response and oxidative stress. IntroductionDiabetic nephropathy is a major microvascular complication in patients with diabetes and remains the leading cause of chronic kidney disease, accounting for approximately a half of all end-stage renal disease worldwide (1,2). The key pathologic features of diabetic nephropathy include microalbuminurea, mesangial cell (MC) hypertrophy, thickened glomerular and tubular basement membrane, tubulointerstitial fibrosis, and low grade of renal inflammation. It is now well recognized that the pathogenesis of diabetic nephropathy is multifactorial. Over the last decade, diverse pathological mechanisms have been proposed to be involved in the onset and development of diabetic nephropathy, such as genetic and hemodynamic factors, oxidative stress and cytokine signaling (3,4). Nowadays, therapies for diabetic nephropathy have been limited to drugs that improve blood pressure or control blood glucose levels. However, these therapies are not very effective in blocking renal damage and co-treatment with renoprotective drugs often leads to toxicity and reduction in efficacy (5,6). There is thus an imperative need to develop effective therapeutic strategies to preserve normal renal function or to halt the progression of diabetic nephropathy.Mesenchymal stem cells (MSCs) are multipotential nonhematopoietic progenitor cells that can differentiate into a variety of cell types, including osteoblasts, ch...

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“…Another study has shown that intravenous injection of human adipose-derived MSCs into rats having established DR has led to improved blood retinal barrier integrity [102]; some donor cells differentiated into photoreceptor or astrocyte-like cells inside the retina of these rats [102]. A single intravitreal injection of placental-derived MSCs into diabetic rats has also resulted in a significant decrease in retinal cell apoptosis, such effect being related to increased intravitreal concentration of several neuroprotective growth factors [103].…”

Section: Msc-related Therapy For Diabetic Retinopathymentioning

confidence: 99%

Mesenchymal Stem Cell Therapy in Type 1 Diabetes Mellitus and Its Main Complications: From Experimental Findings to Clinical Practice

Ezquer

Arango-Rodríguez²,

Giraud-Billoud³

et al. 2014

J Stem Cell Res Ther

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Amelioration of diabetic retinopathy by engrafted human adipose-derived mesenchymal stem cells in streptozotocin diabetic rats

Cited by 79 publications

References 25 publications

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

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

Autologous transplantation of adipose-derived mesenchymal stem cells ameliorates streptozotocin-induced diabetic nephropathy in rats by inhibiting oxidative stress, pro-inflammatory cytokines and the p38 MAPK signaling pathway

Mesenchymal Stem Cell Therapy in Type 1 Diabetes Mellitus and Its Main Complications: From Experimental Findings to Clinical Practice

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