Human pluripotent stem cell differentiation to functional pancreatic cells for diabetes therapies: Innovations, challenges and future directions

Abstract Recent advances in the expansion and directed pancreatogenic differentiation of human pluripotent stem cells (hPSCs) have intensified efforts to generate functional pancreatic islet cells, especially insulin-secreting β-cells, for cell therapies against diabetes. However, the consistent gen...

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Main Authors: Elena F. Jacobson, Emmanuel S. Tzanakakis
Format: Article
Language:English
Published: BMC 2017-07-01
Series:Journal of Biological Engineering
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13036-017-0066-3
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author Elena F. Jacobson
Emmanuel S. Tzanakakis
author_facet Elena F. Jacobson
Emmanuel S. Tzanakakis
author_sort Elena F. Jacobson
collection DOAJ
description Abstract Recent advances in the expansion and directed pancreatogenic differentiation of human pluripotent stem cells (hPSCs) have intensified efforts to generate functional pancreatic islet cells, especially insulin-secreting β-cells, for cell therapies against diabetes. However, the consistent generation of glucose-responsive insulin-releasing cells remains challenging. In this article, we first present basic concepts of pancreatic organogenesis, which frequently serves as a basis for engineering differentiation regimens. Next, past and current efforts are critically discussed for the conversion of hPSCs along pancreatic cell lineages, including endocrine β-cells and α-cells, as well as exocrine cells with emphasis placed on the later stages of commitment. Finally, major challenges and future directions are examined, such as the identification of factors for in vivo maturation, large-scale culture and post processing systems, cell loss during differentiation, culture economics, efficiency, and efficacy and exosomes and miRNAs in pancreatic differentiation.
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spelling doaj.art-7f1277c7c3114cdfaaef289ecd89b6fe2022-12-21T19:10:42ZengBMCJournal of Biological Engineering1754-16112017-07-0111111310.1186/s13036-017-0066-3Human pluripotent stem cell differentiation to functional pancreatic cells for diabetes therapies: Innovations, challenges and future directionsElena F. Jacobson0Emmanuel S. Tzanakakis1Department of Chemical and Biological Engineering, Tufts UniversityDepartment of Chemical and Biological Engineering, Tufts UniversityAbstract Recent advances in the expansion and directed pancreatogenic differentiation of human pluripotent stem cells (hPSCs) have intensified efforts to generate functional pancreatic islet cells, especially insulin-secreting β-cells, for cell therapies against diabetes. However, the consistent generation of glucose-responsive insulin-releasing cells remains challenging. In this article, we first present basic concepts of pancreatic organogenesis, which frequently serves as a basis for engineering differentiation regimens. Next, past and current efforts are critically discussed for the conversion of hPSCs along pancreatic cell lineages, including endocrine β-cells and α-cells, as well as exocrine cells with emphasis placed on the later stages of commitment. Finally, major challenges and future directions are examined, such as the identification of factors for in vivo maturation, large-scale culture and post processing systems, cell loss during differentiation, culture economics, efficiency, and efficacy and exosomes and miRNAs in pancreatic differentiation.http://link.springer.com/article/10.1186/s13036-017-0066-3Pluripotent stem cellsEmbryonic stem cellsInduced pluripotent stem cellsPancreatic differentiationEndocrine cellsExocrine cells
spellingShingle Elena F. Jacobson
Emmanuel S. Tzanakakis
Human pluripotent stem cell differentiation to functional pancreatic cells for diabetes therapies: Innovations, challenges and future directions
Journal of Biological Engineering
Pluripotent stem cells
Embryonic stem cells
Induced pluripotent stem cells
Pancreatic differentiation
Endocrine cells
Exocrine cells
title Human pluripotent stem cell differentiation to functional pancreatic cells for diabetes therapies: Innovations, challenges and future directions
title_full Human pluripotent stem cell differentiation to functional pancreatic cells for diabetes therapies: Innovations, challenges and future directions
title_fullStr Human pluripotent stem cell differentiation to functional pancreatic cells for diabetes therapies: Innovations, challenges and future directions
title_full_unstemmed Human pluripotent stem cell differentiation to functional pancreatic cells for diabetes therapies: Innovations, challenges and future directions
title_short Human pluripotent stem cell differentiation to functional pancreatic cells for diabetes therapies: Innovations, challenges and future directions
title_sort human pluripotent stem cell differentiation to functional pancreatic cells for diabetes therapies innovations challenges and future directions
topic Pluripotent stem cells
Embryonic stem cells
Induced pluripotent stem cells
Pancreatic differentiation
Endocrine cells
Exocrine cells
url http://link.springer.com/article/10.1186/s13036-017-0066-3
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AT emmanuelstzanakakis humanpluripotentstemcelldifferentiationtofunctionalpancreaticcellsfordiabetestherapiesinnovationschallengesandfuturedirections