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The hemogenic endothelium: a critical source for the generation of PSC-derived hematopoietic stem and progenitor cells

In vitro generation of hematopoietic cells and especially hematopoietic stem cells (HSCs) from human pluripotent stem cells (PSCs) are subject to intensive research in recent decades, as these cells hold great potential for regenerative medicine and autologous cell replacement therapies. Despite man...

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Detalles Bibliográficos
Autores principales: Lange, Lucas, Morgan, Michael, Schambach, Axel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164610/
https://www.ncbi.nlm.nih.gov/pubmed/33559689
http://dx.doi.org/10.1007/s00018-021-03777-y
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author Lange, Lucas
Morgan, Michael
Schambach, Axel
author_facet Lange, Lucas
Morgan, Michael
Schambach, Axel
author_sort Lange, Lucas
collection PubMed
description In vitro generation of hematopoietic cells and especially hematopoietic stem cells (HSCs) from human pluripotent stem cells (PSCs) are subject to intensive research in recent decades, as these cells hold great potential for regenerative medicine and autologous cell replacement therapies. Despite many attempts, in vitro, de novo generation of bona fide HSCs remains challenging, and we are still far away from their clinical use, due to insufficient functionality and quantity of the produced HSCs. The challenges of generating PSC-derived HSCs are already apparent in early stages of hemato-endothelial specification with the limitation of recapitulating complex, dynamic processes of embryonic hematopoietic ontogeny in vitro. Further, these current shortcomings imply the incompleteness of our understanding of human ontogenetic processes from embryonic mesoderm over an intermediate, specialized hemogenic endothelium (HE) to their immediate progeny, the HSCs. In this review, we examine the recent investigations of hemato-endothelial ontogeny and recently reported progress for the conversion of PSCs and other promising somatic cell types towards HSCs with the focus on the crucial and inevitable role of the HE to achieve the long-standing goal—to generate therapeutically applicable PSC-derived HSCs in vitro.
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spelling pubmed-81646102021-06-17 The hemogenic endothelium: a critical source for the generation of PSC-derived hematopoietic stem and progenitor cells Lange, Lucas Morgan, Michael Schambach, Axel Cell Mol Life Sci Review In vitro generation of hematopoietic cells and especially hematopoietic stem cells (HSCs) from human pluripotent stem cells (PSCs) are subject to intensive research in recent decades, as these cells hold great potential for regenerative medicine and autologous cell replacement therapies. Despite many attempts, in vitro, de novo generation of bona fide HSCs remains challenging, and we are still far away from their clinical use, due to insufficient functionality and quantity of the produced HSCs. The challenges of generating PSC-derived HSCs are already apparent in early stages of hemato-endothelial specification with the limitation of recapitulating complex, dynamic processes of embryonic hematopoietic ontogeny in vitro. Further, these current shortcomings imply the incompleteness of our understanding of human ontogenetic processes from embryonic mesoderm over an intermediate, specialized hemogenic endothelium (HE) to their immediate progeny, the HSCs. In this review, we examine the recent investigations of hemato-endothelial ontogeny and recently reported progress for the conversion of PSCs and other promising somatic cell types towards HSCs with the focus on the crucial and inevitable role of the HE to achieve the long-standing goal—to generate therapeutically applicable PSC-derived HSCs in vitro. Springer International Publishing 2021-02-09 2021 /pmc/articles/PMC8164610/ /pubmed/33559689 http://dx.doi.org/10.1007/s00018-021-03777-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review
Lange, Lucas
Morgan, Michael
Schambach, Axel
The hemogenic endothelium: a critical source for the generation of PSC-derived hematopoietic stem and progenitor cells
title The hemogenic endothelium: a critical source for the generation of PSC-derived hematopoietic stem and progenitor cells
title_full The hemogenic endothelium: a critical source for the generation of PSC-derived hematopoietic stem and progenitor cells
title_fullStr The hemogenic endothelium: a critical source for the generation of PSC-derived hematopoietic stem and progenitor cells
title_full_unstemmed The hemogenic endothelium: a critical source for the generation of PSC-derived hematopoietic stem and progenitor cells
title_short The hemogenic endothelium: a critical source for the generation of PSC-derived hematopoietic stem and progenitor cells
title_sort hemogenic endothelium: a critical source for the generation of psc-derived hematopoietic stem and progenitor cells
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164610/
https://www.ncbi.nlm.nih.gov/pubmed/33559689
http://dx.doi.org/10.1007/s00018-021-03777-y
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