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UM171 expands distinct types of myeloid and NK progenitors from human pluripotent stem cells

Scaling up blood cell production from hPSCs is critical to advancing hPSC technologies for blood transfusion, immunotherapy, and transplantation. Here we explored the potential of the HSC agonist pyrimido-indole derivative UM171, to expand hematopoietic progenitors (HPs) derived from hPSCs in chemic...

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Autores principales: Mesquitta, Walatta-Tseyon, Wandsnider, Matthew, Kang, HyunJun, Thomson, James, Moskvin, Oleg, Suknuntha, Kran, Slukvin, Igor I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488662/
https://www.ncbi.nlm.nih.gov/pubmed/31036928
http://dx.doi.org/10.1038/s41598-019-43054-4
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author Mesquitta, Walatta-Tseyon
Wandsnider, Matthew
Kang, HyunJun
Thomson, James
Moskvin, Oleg
Suknuntha, Kran
Slukvin, Igor I.
author_facet Mesquitta, Walatta-Tseyon
Wandsnider, Matthew
Kang, HyunJun
Thomson, James
Moskvin, Oleg
Suknuntha, Kran
Slukvin, Igor I.
author_sort Mesquitta, Walatta-Tseyon
collection PubMed
description Scaling up blood cell production from hPSCs is critical to advancing hPSC technologies for blood transfusion, immunotherapy, and transplantation. Here we explored the potential of the HSC agonist pyrimido-indole derivative UM171, to expand hematopoietic progenitors (HPs) derived from hPSCs in chemically defined conditions. We revealed that culture of hPSC-HPs in HSC expansion conditions (SFEM with added TPO, SCF, FLT3L, IL3 and IL6) in the presence of UM171 predominantly expanded HPs with a unique CD34(+)CD41a(lo)CD45(+) phenotype that were enriched in granulocytic progenitors (G-CFCs). In contrast, in lymphoid cultures on OP9-DLL4, in the presence of SCF, FLT3L, and IL7, UM171 selectively expanded CD34(+)CD45(+)CD7(+) lymphoid progenitors with NK cell potential, and increased NK cell output up to 10-fold. These studies should improve our understanding of the effect of UM171 on de novo generated HPs, and facilitate development of protocols for robust granulocyte and lymphoid cell production from hPSCs, for adoptive immunotherapies.
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spelling pubmed-64886622019-05-16 UM171 expands distinct types of myeloid and NK progenitors from human pluripotent stem cells Mesquitta, Walatta-Tseyon Wandsnider, Matthew Kang, HyunJun Thomson, James Moskvin, Oleg Suknuntha, Kran Slukvin, Igor I. Sci Rep Article Scaling up blood cell production from hPSCs is critical to advancing hPSC technologies for blood transfusion, immunotherapy, and transplantation. Here we explored the potential of the HSC agonist pyrimido-indole derivative UM171, to expand hematopoietic progenitors (HPs) derived from hPSCs in chemically defined conditions. We revealed that culture of hPSC-HPs in HSC expansion conditions (SFEM with added TPO, SCF, FLT3L, IL3 and IL6) in the presence of UM171 predominantly expanded HPs with a unique CD34(+)CD41a(lo)CD45(+) phenotype that were enriched in granulocytic progenitors (G-CFCs). In contrast, in lymphoid cultures on OP9-DLL4, in the presence of SCF, FLT3L, and IL7, UM171 selectively expanded CD34(+)CD45(+)CD7(+) lymphoid progenitors with NK cell potential, and increased NK cell output up to 10-fold. These studies should improve our understanding of the effect of UM171 on de novo generated HPs, and facilitate development of protocols for robust granulocyte and lymphoid cell production from hPSCs, for adoptive immunotherapies. Nature Publishing Group UK 2019-04-29 /pmc/articles/PMC6488662/ /pubmed/31036928 http://dx.doi.org/10.1038/s41598-019-43054-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Mesquitta, Walatta-Tseyon
Wandsnider, Matthew
Kang, HyunJun
Thomson, James
Moskvin, Oleg
Suknuntha, Kran
Slukvin, Igor I.
UM171 expands distinct types of myeloid and NK progenitors from human pluripotent stem cells
title UM171 expands distinct types of myeloid and NK progenitors from human pluripotent stem cells
title_full UM171 expands distinct types of myeloid and NK progenitors from human pluripotent stem cells
title_fullStr UM171 expands distinct types of myeloid and NK progenitors from human pluripotent stem cells
title_full_unstemmed UM171 expands distinct types of myeloid and NK progenitors from human pluripotent stem cells
title_short UM171 expands distinct types of myeloid and NK progenitors from human pluripotent stem cells
title_sort um171 expands distinct types of myeloid and nk progenitors from human pluripotent stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488662/
https://www.ncbi.nlm.nih.gov/pubmed/31036928
http://dx.doi.org/10.1038/s41598-019-43054-4
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