Abstract
IntroductionWith 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.MethodsHuman 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.ResultsHuman 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.ConclusionsHuman fetal pancreatic progenitor cells have good capacity for generating insulin producing cells and provide a promising potential source for diabetes treatment.
Highlights
With the shortage of donor organs for islet transplantation, insulin-producing cells have been generated from different types of stem cell
We demonstrate that pancreatic stem cells isolated from human fetal pancreas have the capacity to expand and differentiate extensively into islet endocrine cell in vitro and to correct high blood glucose efficiently in diabetic animals
The results showed that stem cell markers Oct4, carbonic anhydrase II (CAII) and Pancreatic duodenal homeobox-1 (PDX-1) did not fluctuate during expansion
Summary
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. The functions of pancreatic islets derived from human fetal pancreatic progenitor cells were evaluated in vitro and in vivo. The possibility of generating insulin-producing cells routinely from both human embryo stem cells (ESC) and human induced pluripotent stem (iPS) cells is quite encouraging, significant challenges still remain [4]. Applying ESC-derived cells in treatment presents more challenges including the risk of cancer formation, functional deficiency of such cells and controversial ethical issues. Several small molecules were able to efficiently induce iPS cells into insulin-producing cells, only about 10% of the cells became productive [7]
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