Running the full human developmental clock in interspecies chimeras using alternative human stem cells with expanded embryonic potential

Abstract Human pluripotent stem cells (hPSCs) can generate specialized cell lineages that have great potential for regenerative therapies and disease modeling. However, the developmental stage of the lineages generated from conventional hPSC cultures in vitro are embryonic in phenotype, and may not...

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Autores principales:	Justin Thomas, Ludovic Zimmerlin, Jeffrey S. Huo, Michael Considine, Leslie Cope, Elias T. Zambidis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/2d63db817ceb45c390898d2afa8999ce
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spelling	oai:doaj.org-article:2d63db817ceb45c390898d2afa8999ce2021-12-02T15:45:19ZRunning the full human developmental clock in interspecies chimeras using alternative human stem cells with expanded embryonic potential10.1038/s41536-021-00135-12057-3995https://doaj.org/article/2d63db817ceb45c390898d2afa8999ce2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41536-021-00135-1https://doaj.org/toc/2057-3995Abstract Human pluripotent stem cells (hPSCs) can generate specialized cell lineages that have great potential for regenerative therapies and disease modeling. However, the developmental stage of the lineages generated from conventional hPSC cultures in vitro are embryonic in phenotype, and may not possess the cellular maturity necessary for corrective regenerative function in vivo in adult recipients. Here, we present the scientific evidence for how adult human tissues could generate human–animal interspecific chimeras to solve this problem. First, we review the phenotypes of the embryonic lineages differentiated from conventional hPSC in vitro and through organoid technologies and compare their functional relevance to the tissues generated during normal human in utero fetal and adult development. We hypothesize that the developmental incongruence of embryo-stage hPSC-differentiated cells transplanted into a recipient adult host niche is an important mechanism ultimately limiting their utility in cell therapies and adult disease modeling. We propose that this developmental obstacle can be overcome with optimized interspecies chimeras that permit the generation of adult-staged, patient-specific whole organs within animal hosts with human-compatible gestational time-frames. We suggest that achieving this goal may ultimately have to await the derivation of alternative, primitive totipotent-like stem cells with improved embryonic chimera capacities. We review the scientific challenges of deriving alternative human stem cell states with expanded embryonic potential, outline a path forward for conducting this emerging research with appropriate ethical and regulatory oversight, and defend the case of why current federal funding restrictions on this important category of biomedical research should be liberalized.Justin ThomasLudovic ZimmerlinJeffrey S. HuoMichael ConsidineLeslie CopeElias T. ZambidisNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Justin Thomas Ludovic Zimmerlin Jeffrey S. Huo Michael Considine Leslie Cope Elias T. Zambidis Running the full human developmental clock in interspecies chimeras using alternative human stem cells with expanded embryonic potential
description	Abstract Human pluripotent stem cells (hPSCs) can generate specialized cell lineages that have great potential for regenerative therapies and disease modeling. However, the developmental stage of the lineages generated from conventional hPSC cultures in vitro are embryonic in phenotype, and may not possess the cellular maturity necessary for corrective regenerative function in vivo in adult recipients. Here, we present the scientific evidence for how adult human tissues could generate human–animal interspecific chimeras to solve this problem. First, we review the phenotypes of the embryonic lineages differentiated from conventional hPSC in vitro and through organoid technologies and compare their functional relevance to the tissues generated during normal human in utero fetal and adult development. We hypothesize that the developmental incongruence of embryo-stage hPSC-differentiated cells transplanted into a recipient adult host niche is an important mechanism ultimately limiting their utility in cell therapies and adult disease modeling. We propose that this developmental obstacle can be overcome with optimized interspecies chimeras that permit the generation of adult-staged, patient-specific whole organs within animal hosts with human-compatible gestational time-frames. We suggest that achieving this goal may ultimately have to await the derivation of alternative, primitive totipotent-like stem cells with improved embryonic chimera capacities. We review the scientific challenges of deriving alternative human stem cell states with expanded embryonic potential, outline a path forward for conducting this emerging research with appropriate ethical and regulatory oversight, and defend the case of why current federal funding restrictions on this important category of biomedical research should be liberalized.
format	article
author	Justin Thomas Ludovic Zimmerlin Jeffrey S. Huo Michael Considine Leslie Cope Elias T. Zambidis
author_facet	Justin Thomas Ludovic Zimmerlin Jeffrey S. Huo Michael Considine Leslie Cope Elias T. Zambidis
author_sort	Justin Thomas
title	Running the full human developmental clock in interspecies chimeras using alternative human stem cells with expanded embryonic potential
title_short	Running the full human developmental clock in interspecies chimeras using alternative human stem cells with expanded embryonic potential
title_full	Running the full human developmental clock in interspecies chimeras using alternative human stem cells with expanded embryonic potential
title_fullStr	Running the full human developmental clock in interspecies chimeras using alternative human stem cells with expanded embryonic potential
title_full_unstemmed	Running the full human developmental clock in interspecies chimeras using alternative human stem cells with expanded embryonic potential
title_sort	running the full human developmental clock in interspecies chimeras using alternative human stem cells with expanded embryonic potential
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2d63db817ceb45c390898d2afa8999ce
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Running the full human developmental clock in interspecies chimeras using alternative human stem cells with expanded embryonic potential

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