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Implantation of bFGF-treated islet progenitor cells ameliorates streptozotocin-induced diabetes in rats.

ABSTRACT: AIM: To examine whether implantation of islet preparation-derived proliferating islet cells (PIC) could ameliorate diabetes in rats. METHODS: PIC were expanded from rat islet preparation by supplementation of basic fibroblast growth factor (bFGF) and implanted into rats with streptozotocin (STZ)-induced diabetes through the portal vein. Body weight and blood glucose levels were measured. Serum insulin levels were measured by radioimmunoassay. The presence of insulin-positive cells was determined by hematoxylin and immunohistochemical staining. RESULTS: Cultured islet cells (CIC) were demonstrated to dedifferentiate in vitro, and the apoptosis ratios reached more than 50% by the 15th day post-isolation. PIC cells treated with bFGF (20 ng/mL) continued growing within 30 days after isolation, and no apoptotic cells were detected. Implantation of PIC into diabetic rats was capable of ameliorating diabetes, in terms of the restoration of euglycemia, weight gain, improved glucose response and elevated serum insulin levels for up to 130 days. Livers derived from PIC-implanted rats were examined for insulin expression and single insulin-positive cells. In addition, most islets of PIC-implanted STZ-induced diabetic rats were intact at 130 days post-transplantation and comparable to those of normal rats. CONCLUSION: Implantation of bFGF-treated proliferating islet cells is a promising cellular therapeutic approach for diabetes.

SUBMITTER: Li G

PROVIDER: S-EPMC4003334 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Implantation of bFGF-treated islet progenitor cells ameliorates streptozotocin-induced diabetes in rats.

Li Ge G Huang Li-song LS Jiang Ming-hong MH Wu Hui-ling HL Chen Jing J Huang Yin Y Shen Yan Y He-Xi-Ge SaiYin S Fan Wei-wei WW Lu Zhi-qiang ZQ Lu Da-ru DR

Acta pharmacologica Sinica 20101018 11

<h4>Aim</h4>To examine whether implantation of islet preparation-derived proliferating islet cells (PIC) could ameliorate diabetes in rats.<h4>Methods</h4>PIC were expanded from rat islet preparation by supplementation of basic fibroblast growth factor (bFGF) and implanted into rats with streptozotocin (STZ)-induced diabetes through the portal vein. Body weight and blood glucose levels were measured. Serum insulin levels were measured by radioimmunoassay. The presence of insulin-positive cells w ...[more]

PMID: 20953209

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Project description:Introduction: Diabetes Mellitus is a major health problem characterized by hyperglycemia and disturbances in metabolism and implicated in causing oxidative stress. Treatment includes administration of oral hypoglycaemic agents with lifestyle modifications, these offer glycemic control, however, present limitations about availability, affordability and side effects. Traditional anti-diabetic plants are becoming popular in management of diabetes mellitus. This study was carried out to determine the efficacy of Leptadenaia hastata in treatment of diabetes.Materials and methodsDiabetes mellitus was induced in using a single injection of streptozotocin (50 mg kg- 1 i.p.). The rats were divided into four groups of 5 rats each. Groups 3-6 received olive oil, 100 mg kg- 1 extract, 200 mg.kg- 1 extract and insulin (6IU kg- 1), respectively. 10 non-diabetic rats were grouped into two group receiving olive oil and 200 mg kg- 1 extract for 28 days. All groups were sacrificed by injecting with ketamine hydrochloride, blood was collected by cardiac puncture and centrifuged. The serum was analyzed for biochemical parameters. The liver was removed and homogenized with the supernatant of the resultant homogenate collected and used for analysis of oxidative stress enzymes.ResultsThe extract significantly decreased serum AST (p < 0.05), ALP (p < 0.001), ALT (p < 0.05), TG (p < 0.01), TC (p < 0.001), creatinine (p < 0.001). It had no effect on SOD and CAT levels but it significantly increased (p < 0.001) GSH levels and reduced (p < 0.05) MDA level.ConclusionsThe n-hexane extract of Leptadenia hastata significantly decreased the levels of hepatic and renal serum biomarkers proving that it was beneficial in ameliorating diabetic related complications. The extract significantly increased GSH levels and reduced MDA level.Supplementary informationThe online version contains supplementary material available at 10.1007/s40200-022-01017-z.

Project description:BackgroundDiabetic nephropathy (DN) is a severe complication of diabetes mellitus (DM). Pancreas or islet transplantation has been reported to prevent the development of DN lesions and ameliorate or reverse existing glomerular lesions in animal models. Shortage of pancreas donor is a severe problem. Islets derived from stem cells may offer a potential solution to this problem.ObjectiveTo evaluate the effect of stem cell-derived islet transplantation on DN in a rat model of streptozotocin-induced DM.MethodsPancreatic progenitor cells were isolated from aborted fetuses of 8 weeks of gestation. And islets were prepared by suspension culture after a differentiation of progenitor cells in medium containing glucagon-like peptide-1 (Glp-1) and nicotinamide. Then islets were transplanted into the liver of diabetic rats via portal vein. Blood glucose, urinary volume, 24 h urinary protein and urinary albumin were measured once biweekly for 16 weeks. Graft survival was evaluated by monitoring human C-peptide level in rat sera and by immunohistochemical staining for human mitochondrial antigen and human C-peptide in liver tissue. The effect of progenitor-derived islets on filtration membrane was examined by electron microscopy and real-time polymerase chain reaction (PCR). Immunohistochemical staining, real-time PCR and western blot were employed for detecting fibronectin, protein kinase C beta (PKCβ), protein kinase A (PKA), inducible nitric oxide synthase (iNOS) and superoxide dismutase (SOD).ResultsIslet-like clusters derived from 8th gestational-week human fetal pancreatic progenitors survived in rat liver. And elevated serum level of human C-peptide was detected. Blood glucose, 24 h urinary protein and urinary albumin were lower in progenitor cell group than those in DN or insulin treatment group. Glomerular basement membrane thickness and fibronectin accumulation decreased significantly while podocytes improved morphologically in progenitor cell group. Furthermore, receptor of advanced glycation end products and PKCβ became down-regulated whereas PKA up-regulated by progenitor cell-derived islets. And iNOS rose while SOD declined.ConclusionsDN may be reversed by transplantation of human fetal pancreatic progenitor cell-derived islets. And fetal pancreatic progenitor cells offer potential resources for cell replacement therapy.

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Implantation of bFGF-treated islet progenitor cells ameliorates streptozotocin-induced diabetes in rats.

Publications

Implantation of bFGF-treated islet progenitor cells ameliorates streptozotocin-induced diabetes in rats.

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