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ENTPD3 Marks Mature Stem Cell–Derived β-Cells Formed by Self-Aggregation In Vitro
Stem cell–derived β-like cells (sBC) carry the promise of providing an abundant source of insulin-producing cells for use in cell replacement therapy for patients with diabetes, potentially allowing widespread implementation of a practical cure. To achieve their clinical promise, sBC need to functio...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564403/ https://www.ncbi.nlm.nih.gov/pubmed/34380694 http://dx.doi.org/10.2337/db20-0873 |
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author | Docherty, Fiona M. Riemondy, Kent A. Castro-Gutierrez, Roberto Dwulet, JaeAnn M. Shilleh, Ali H. Hansen, Maria S. Williams, Shane P.M. Armitage, Lucas H. Santostefano, Katherine E. Wallet, Mark A. Mathews, Clayton E. Triolo, Taylor M. Benninger, Richard K.P. Russ, Holger A. |
author_facet | Docherty, Fiona M. Riemondy, Kent A. Castro-Gutierrez, Roberto Dwulet, JaeAnn M. Shilleh, Ali H. Hansen, Maria S. Williams, Shane P.M. Armitage, Lucas H. Santostefano, Katherine E. Wallet, Mark A. Mathews, Clayton E. Triolo, Taylor M. Benninger, Richard K.P. Russ, Holger A. |
author_sort | Docherty, Fiona M. |
collection | PubMed |
description | Stem cell–derived β-like cells (sBC) carry the promise of providing an abundant source of insulin-producing cells for use in cell replacement therapy for patients with diabetes, potentially allowing widespread implementation of a practical cure. To achieve their clinical promise, sBC need to function comparably with mature adult β-cells, but as yet they display varying degrees of maturity. Indeed, detailed knowledge of the events resulting in human β-cell maturation remains obscure. Here we show that sBC spontaneously self-enrich into discreet islet-like cap structures within in vitro cultures, independent of exogenous maturation conditions. Multiple complementary assays demonstrate that this process is accompanied by functional maturation of the self-enriched sBC (seBC); however, the seBC still contain distinct subpopulations displaying different maturation levels. Interestingly, the surface protein ENTPD3 (also known as nucleoside triphosphate diphosphohydrolase-3 [NDPTase3]) is a specific marker of the most mature seBC population and can be used for mature seBC identification and sorting. Our results illuminate critical aspects of in vitro sBC maturation and provide important insights toward developing functionally mature sBC for diabetes cell replacement therapy. |
format | Online Article Text |
id | pubmed-8564403 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-85644032021-11-15 ENTPD3 Marks Mature Stem Cell–Derived β-Cells Formed by Self-Aggregation In Vitro Docherty, Fiona M. Riemondy, Kent A. Castro-Gutierrez, Roberto Dwulet, JaeAnn M. Shilleh, Ali H. Hansen, Maria S. Williams, Shane P.M. Armitage, Lucas H. Santostefano, Katherine E. Wallet, Mark A. Mathews, Clayton E. Triolo, Taylor M. Benninger, Richard K.P. Russ, Holger A. Diabetes Islet Studies Stem cell–derived β-like cells (sBC) carry the promise of providing an abundant source of insulin-producing cells for use in cell replacement therapy for patients with diabetes, potentially allowing widespread implementation of a practical cure. To achieve their clinical promise, sBC need to function comparably with mature adult β-cells, but as yet they display varying degrees of maturity. Indeed, detailed knowledge of the events resulting in human β-cell maturation remains obscure. Here we show that sBC spontaneously self-enrich into discreet islet-like cap structures within in vitro cultures, independent of exogenous maturation conditions. Multiple complementary assays demonstrate that this process is accompanied by functional maturation of the self-enriched sBC (seBC); however, the seBC still contain distinct subpopulations displaying different maturation levels. Interestingly, the surface protein ENTPD3 (also known as nucleoside triphosphate diphosphohydrolase-3 [NDPTase3]) is a specific marker of the most mature seBC population and can be used for mature seBC identification and sorting. Our results illuminate critical aspects of in vitro sBC maturation and provide important insights toward developing functionally mature sBC for diabetes cell replacement therapy. American Diabetes Association 2021-11 2021-08-11 /pmc/articles/PMC8564403/ /pubmed/34380694 http://dx.doi.org/10.2337/db20-0873 Text en © 2021 by the American Diabetes Association https://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license. |
spellingShingle | Islet Studies Docherty, Fiona M. Riemondy, Kent A. Castro-Gutierrez, Roberto Dwulet, JaeAnn M. Shilleh, Ali H. Hansen, Maria S. Williams, Shane P.M. Armitage, Lucas H. Santostefano, Katherine E. Wallet, Mark A. Mathews, Clayton E. Triolo, Taylor M. Benninger, Richard K.P. Russ, Holger A. ENTPD3 Marks Mature Stem Cell–Derived β-Cells Formed by Self-Aggregation In Vitro |
title | ENTPD3 Marks Mature Stem Cell–Derived β-Cells Formed by Self-Aggregation In Vitro |
title_full | ENTPD3 Marks Mature Stem Cell–Derived β-Cells Formed by Self-Aggregation In Vitro |
title_fullStr | ENTPD3 Marks Mature Stem Cell–Derived β-Cells Formed by Self-Aggregation In Vitro |
title_full_unstemmed | ENTPD3 Marks Mature Stem Cell–Derived β-Cells Formed by Self-Aggregation In Vitro |
title_short | ENTPD3 Marks Mature Stem Cell–Derived β-Cells Formed by Self-Aggregation In Vitro |
title_sort | entpd3 marks mature stem cell–derived β-cells formed by self-aggregation in vitro |
topic | Islet Studies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564403/ https://www.ncbi.nlm.nih.gov/pubmed/34380694 http://dx.doi.org/10.2337/db20-0873 |
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