Transplantation of human fetal pancreatic progenitor cells ameliorates renal injury in streptozotocin-induced diabetic nephropathy View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Yongwei Jiang, Wenjian Zhang, Shiqing Xu, Hua Lin, Weiguo Sui, Honglin Liu, Liang Peng, Qing Fang, Li Chen, Jinning Lou

ABSTRACT

BACKGROUND: Diabetic 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. OBJECTIVE: To evaluate the effect of stem cell-derived islet transplantation on DN in a rat model of streptozotocin-induced DM. METHODS: Pancreatic 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). RESULTS: Islet-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. CONCLUSIONS: DN 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. More... »

PAGES

147

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12967-017-1253-1

DOI

http://dx.doi.org/10.1186/s12967-017-1253-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1086319837

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28655312


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