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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...

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Detalles Bibliográficos
Autores principales: Rostovskaya, Maria, Bredenkamp, Nicholas, Smith, Austin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2015
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.
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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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