Dynamic integration of enteric neural stem cells in ex vivo organotypic colon cultures

Abstract Enteric neural stem cells (ENSC) have been identified as a possible treatment for enteric neuropathies. After in vivo transplantation, ENSC and their derivatives have been shown to engraft within colonic tissue, migrate and populate endogenous ganglia, and functionally integrate with the en...

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Autores principales:	Georgina Navoly, Conor J. McCann
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/14dab72e09ae4bf9a2d07b45c2ac9674
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spelling	oai:doaj.org-article:14dab72e09ae4bf9a2d07b45c2ac96742021-12-02T18:49:28ZDynamic integration of enteric neural stem cells in ex vivo organotypic colon cultures10.1038/s41598-021-95434-42045-2322https://doaj.org/article/14dab72e09ae4bf9a2d07b45c2ac96742021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95434-4https://doaj.org/toc/2045-2322Abstract Enteric neural stem cells (ENSC) have been identified as a possible treatment for enteric neuropathies. After in vivo transplantation, ENSC and their derivatives have been shown to engraft within colonic tissue, migrate and populate endogenous ganglia, and functionally integrate with the enteric nervous system. However, the mechanisms underlying the integration of donor ENSC, in recipient tissues, remain unclear. Therefore, we aimed to examine ENSC integration using an adapted ex vivo organotypic culture system. Donor ENSC were obtained from Wnt1 cre/+ ;R26R YFP/YFP mice allowing specific labelling, selection and fate-mapping of cells. YFP+ neurospheres were transplanted to C57BL6/J (6–8-week-old) colonic tissue and maintained in organotypic culture for up to 21 days. We analysed and quantified donor cell integration within recipient tissues at 7, 14 and 21 days, along with assessing the structural and molecular consequences of ENSC integration. We found that organotypically cultured tissues were well preserved up to 21-days in ex vivo culture, which allowed for assessment of donor cell integration after transplantation. Donor ENSC-derived cells integrated across the colonic wall in a dynamic fashion, across a three-week period. Following transplantation, donor cells displayed two integrative patterns; longitudinal migration and medial invasion which allowed donor cells to populate colonic tissue. Moreover, significant remodelling of the intestinal ECM and musculature occurred upon transplantation, to facilitate donor cell integration within endogenous enteric ganglia. These results provide critical evidence on the timescale and mechanisms, which regulate donor ENSC integration, within recipient gut tissue, which are important considerations in the future clinical translation of stem cell therapies for enteric disease.Georgina NavolyConor J. McCannNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Georgina Navoly Conor J. McCann Dynamic integration of enteric neural stem cells in ex vivo organotypic colon cultures
description	Abstract Enteric neural stem cells (ENSC) have been identified as a possible treatment for enteric neuropathies. After in vivo transplantation, ENSC and their derivatives have been shown to engraft within colonic tissue, migrate and populate endogenous ganglia, and functionally integrate with the enteric nervous system. However, the mechanisms underlying the integration of donor ENSC, in recipient tissues, remain unclear. Therefore, we aimed to examine ENSC integration using an adapted ex vivo organotypic culture system. Donor ENSC were obtained from Wnt1 cre/+ ;R26R YFP/YFP mice allowing specific labelling, selection and fate-mapping of cells. YFP+ neurospheres were transplanted to C57BL6/J (6–8-week-old) colonic tissue and maintained in organotypic culture for up to 21 days. We analysed and quantified donor cell integration within recipient tissues at 7, 14 and 21 days, along with assessing the structural and molecular consequences of ENSC integration. We found that organotypically cultured tissues were well preserved up to 21-days in ex vivo culture, which allowed for assessment of donor cell integration after transplantation. Donor ENSC-derived cells integrated across the colonic wall in a dynamic fashion, across a three-week period. Following transplantation, donor cells displayed two integrative patterns; longitudinal migration and medial invasion which allowed donor cells to populate colonic tissue. Moreover, significant remodelling of the intestinal ECM and musculature occurred upon transplantation, to facilitate donor cell integration within endogenous enteric ganglia. These results provide critical evidence on the timescale and mechanisms, which regulate donor ENSC integration, within recipient gut tissue, which are important considerations in the future clinical translation of stem cell therapies for enteric disease.
format	article
author	Georgina Navoly Conor J. McCann
author_facet	Georgina Navoly Conor J. McCann
author_sort	Georgina Navoly
title	Dynamic integration of enteric neural stem cells in ex vivo organotypic colon cultures
title_short	Dynamic integration of enteric neural stem cells in ex vivo organotypic colon cultures
title_full	Dynamic integration of enteric neural stem cells in ex vivo organotypic colon cultures
title_fullStr	Dynamic integration of enteric neural stem cells in ex vivo organotypic colon cultures
title_full_unstemmed	Dynamic integration of enteric neural stem cells in ex vivo organotypic colon cultures
title_sort	dynamic integration of enteric neural stem cells in ex vivo organotypic colon cultures
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/14dab72e09ae4bf9a2d07b45c2ac9674
work_keys_str_mv	AT georginanavoly dynamicintegrationofentericneuralstemcellsinexvivoorganotypiccoloncultures AT conorjmccann dynamicintegrationofentericneuralstemcellsinexvivoorganotypiccoloncultures
_version_	1718377547184472064

Dynamic integration of enteric neural stem cells in ex vivo organotypic colon cultures

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