Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2021
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
_version_ 1784593611772395520
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
work_keys_str_mv AT dochertyfionam entpd3marksmaturestemcellderivedbcellsformedbyselfaggregationinvitro
AT riemondykenta entpd3marksmaturestemcellderivedbcellsformedbyselfaggregationinvitro
AT castrogutierrezroberto entpd3marksmaturestemcellderivedbcellsformedbyselfaggregationinvitro
AT dwuletjaeannm entpd3marksmaturestemcellderivedbcellsformedbyselfaggregationinvitro
AT shillehalih entpd3marksmaturestemcellderivedbcellsformedbyselfaggregationinvitro
AT hansenmarias entpd3marksmaturestemcellderivedbcellsformedbyselfaggregationinvitro
AT williamsshanepm entpd3marksmaturestemcellderivedbcellsformedbyselfaggregationinvitro
AT armitagelucash entpd3marksmaturestemcellderivedbcellsformedbyselfaggregationinvitro
AT santostefanokatherinee entpd3marksmaturestemcellderivedbcellsformedbyselfaggregationinvitro
AT walletmarka entpd3marksmaturestemcellderivedbcellsformedbyselfaggregationinvitro
AT mathewsclaytone entpd3marksmaturestemcellderivedbcellsformedbyselfaggregationinvitro
AT triolotaylorm entpd3marksmaturestemcellderivedbcellsformedbyselfaggregationinvitro
AT benningerrichardkp entpd3marksmaturestemcellderivedbcellsformedbyselfaggregationinvitro
AT russholgera entpd3marksmaturestemcellderivedbcellsformedbyselfaggregationinvitro