title: Evaluation of islets derived from human fetal pancreatic progenitor cells in diabetes treatment.
abstract: BACKGROUND
  With the shortage of donor organs for islet transplantation, insulin-producing cells have been generated from different types of stem cell. Human fetal pancreatic stem cells have a better self-renewal capacity than adult stem cells and can readily differentiate into pancreatic endocrine cells, making them a potential source for islets in diabetes treatment. In the present study, the functions of pancreatic islets derived from human fetal pancreatic progenitor cells were evaluated in vitro and in vivo.
  
  
  METHODS
  Human pancreatic progenitor cells isolated from the fetal pancreas were expanded and differentiated into islet endocrine cells in culture. Markers for endocrine and exocrine functions as well as those for alpha and beta cells were analyzed by immunofluorescent staining and enzyme-linked immunosorbent assay (ELISA). To evaluate the functions of these islets in vivo, the islet-like structures were transplanted into renal capsules of diabetic nude mice. Immunohistochemical staining for human C-peptide and human mitochondrion antigen was applied to confirm the human origin and the survival of grafted islets.
  
  
  RESULTS
  Human fetal pancreatic progenitor cells were able to expand in medium containing basic fibroblast growth factor (bFGF) and leukemia inhibitor factor (LIF), and to differentiate into pancreatic endocrine cells with high efficiency upon the actions of glucagon-like peptide-1 and activin-A. The differentiated cells expressed insulin, glucagon, glucose transporter-1 (GLUT1), GLUT2 and voltage-dependent calcium channel (VDCC), and were able to aggregate into islet-like structures containing alpha and beta cells upon suspension. These structures expressed and released a higher level of insulin than adhesion cultured cells, and helped to maintain normoglycemia in diabetic nude mice after transplantation.
  
  
  CONCLUSIONS
  Human fetal pancreatic progenitor cells have good capacity for generating insulin producing cells and provide a promising potential source for diabetes treatment.
authors.forename: Wen-Jian
authors.initials: WJ
authors.lastname: Zhang
authors.forename: Shi-Qing
authors.initials: SQ
authors.lastname: Xu
authors.forename: Han-Qing
authors.initials: HQ
authors.lastname: Cai
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Men
authors.forename: Zai
authors.initials: Z
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Lin
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Yong-Wei
authors.initials: YW
authors.lastname: Jiang
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Liu
authors.forename: Cheng-Hui
authors.initials: CH
authors.lastname: Li
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Sui
authors.forename: Hong-Kui
authors.initials: HK
authors.lastname: Deng
authors.forename: Jin-Ning
authors.initials: JN
authors.lastname: Lou
mesh_terms: D028341:Activins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000601:surgery*; D005333:Fetus / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010179:Pancreas / Q000166:cytology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
chemical_list: D007328:Insulin; D053605:Leukemia Inhibitory Factor; C422405:activin A; D016222:Fibroblast Growth Factor 2; D028341:Activins; D052216:Glucagon-Like Peptide 1