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Towards consistent generation of pancreatic lineage progenitors from human pluripotent stem cells
Human pluripotent stem cells can in principle be used as a source of any differentiated cell type for disease modelling, drug screening, toxicology testing or cell replacement therapy. Type I diabetes is considered a major target for stem cell applications due to the shortage of primary human beta c...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4633994/ https://www.ncbi.nlm.nih.gov/pubmed/26416676 http://dx.doi.org/10.1098/rstb.2014.0365 |
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author | Rostovskaya, Maria Bredenkamp, Nicholas Smith, Austin |
author_facet | Rostovskaya, Maria Bredenkamp, Nicholas Smith, Austin |
author_sort | Rostovskaya, Maria |
collection | PubMed |
description | Human pluripotent stem cells can in principle be used as a source of any differentiated cell type for disease modelling, drug screening, toxicology testing or cell replacement therapy. Type I diabetes is considered a major target for stem cell applications due to the shortage of primary human beta cells. Several protocols have been reported for generating pancreatic progenitors by in vitro differentiation of human pluripotent stem cells. Here we first assessed one of these protocols on a panel of pluripotent stem cell lines for capacity to engender glucose sensitive insulin-producing cells after engraftment in immunocompromised mice. We observed variable outcomes with only one cell line showing a low level of glucose response. We, therefore, undertook a systematic comparison of different methods for inducing definitive endoderm and subsequently pancreatic differentiation. Of several protocols tested, we identified a combined approach that robustly generated pancreatic progenitors in vitro from both embryo-derived and induced pluripotent stem cells. These findings suggest that, although there are intrinsic differences in lineage specification propensity between pluripotent stem cell lines, optimal differentiation procedures may consistently direct a substantial fraction of cells into pancreatic specification. |
format | Online Article Text |
id | pubmed-4633994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-46339942015-11-05 Towards consistent generation of pancreatic lineage progenitors from human pluripotent stem cells Rostovskaya, Maria Bredenkamp, Nicholas Smith, Austin Philos Trans R Soc Lond B Biol Sci Articles Human pluripotent stem cells can in principle be used as a source of any differentiated cell type for disease modelling, drug screening, toxicology testing or cell replacement therapy. Type I diabetes is considered a major target for stem cell applications due to the shortage of primary human beta cells. Several protocols have been reported for generating pancreatic progenitors by in vitro differentiation of human pluripotent stem cells. Here we first assessed one of these protocols on a panel of pluripotent stem cell lines for capacity to engender glucose sensitive insulin-producing cells after engraftment in immunocompromised mice. We observed variable outcomes with only one cell line showing a low level of glucose response. We, therefore, undertook a systematic comparison of different methods for inducing definitive endoderm and subsequently pancreatic differentiation. Of several protocols tested, we identified a combined approach that robustly generated pancreatic progenitors in vitro from both embryo-derived and induced pluripotent stem cells. These findings suggest that, although there are intrinsic differences in lineage specification propensity between pluripotent stem cell lines, optimal differentiation procedures may consistently direct a substantial fraction of cells into pancreatic specification. The Royal Society 2015-10-19 /pmc/articles/PMC4633994/ /pubmed/26416676 http://dx.doi.org/10.1098/rstb.2014.0365 Text en © 2015 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. |
spellingShingle | Articles Rostovskaya, Maria Bredenkamp, Nicholas Smith, Austin Towards consistent generation of pancreatic lineage progenitors from human pluripotent stem cells |
title | Towards consistent generation of pancreatic lineage progenitors from human pluripotent stem cells |
title_full | Towards consistent generation of pancreatic lineage progenitors from human pluripotent stem cells |
title_fullStr | Towards consistent generation of pancreatic lineage progenitors from human pluripotent stem cells |
title_full_unstemmed | Towards consistent generation of pancreatic lineage progenitors from human pluripotent stem cells |
title_short | Towards consistent generation of pancreatic lineage progenitors from human pluripotent stem cells |
title_sort | towards consistent generation of pancreatic lineage progenitors from human pluripotent stem cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4633994/ https://www.ncbi.nlm.nih.gov/pubmed/26416676 http://dx.doi.org/10.1098/rstb.2014.0365 |
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