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Human induced pluripotent stem cells differentiate into insulin-producing cells able to engraft in vivo
- Source :
- Acta Diabetologica
- Publication Year :
- 2015
-
Abstract
- Aims: New sources of insulin-secreting cells are strongly required for the cure of diabetes. Recent successes in differentiating embryonic stem cells, in combination with the discovery that it is possible to derive human induced pluripotent stem cells (iPSCs) from somatic cells, have raised the possibility that patient-specific beta cells might be derived from patients through cell reprogramming and differentiation. In this study, we aimed to obtain insulin-producing cells from human iPSCs and test their ability to secrete insulin in vivo. Methods: Human iPSCs, derived from both fetal and adult fibroblasts, were differentiated in vitro into pancreas-committed cells and then transplanted into immunodeficient mice at two different stages of differentiation (posterior foregut and endocrine cells). Results: IPSCs were shown to differentiate in insulin-producing cells in vitro, following the stages of pancreatic organogenesis. At the end of the differentiation, the production of INSULIN mRNA was highly increased and 5 ± 2.9 % of the cell population became insulin-positive. Terminally differentiated cells also produced C-peptide in vitro in both basal and stimulated conditions. In vivo, mice transplanted with pancreatic cells secreted human C-peptide in response to glucose stimulus, but transplanted cells were observed to lose insulin secretion capacity during the time. At histological evaluation, the grafts resulted to be composed of a mixed population of cells containing mature pancreatic cells, but also pluripotent and some neuronal cells. Conclusion: These data overall suggest that human iPSCs have the potential to generate insulin-producing cells and that these differentiated cells can engraft and secrete insulin in vivo.
- Subjects :
- KOSR
Diabetes
Differentiation
Induced pluripotent stem cells
Insulin-producing cells
Endocrinology
Internal Medicine
Endocrinology, Diabetes and Metabolism
induced pluripotent stem cells
Mice, SCID
Embryoid body
Biology
Diabete
Insulin-producing cell
Mice, Inbred NOD
Insulin-Secreting Cells
Journal Article
Animals
Humans
Insulin
Fluorometry
Fetu
Induced pluripotent stem cell
Induced stem cells
C-Peptide
Animal
Research Support, Non-U.S. Gov't
Cell Differentiation
General Medicine
Fibroblasts
Embryonic stem cell
3. Good health
Cell biology
Diabetes and Metabolism
fetus
Insulin-Secreting Cell
Immunology
Fibroblast
Pancreas Transplantation
C-peptide
Stem cell
Reprogramming
Human
Adult stem cell
Subjects
Details
- ISSN :
- 09405429
- Database :
- OpenAIRE
- Journal :
- Acta Diabetologica
- Accession number :
- edsair.doi.dedup.....513924a06461c92a1981cebbe921d297
- Full Text :
- https://doi.org/10.1007/s00592-015-0726-z