Mammals fail to regenerate organs when wound contraction drives scar formation

Abstract To understand why mammals generally do not regenerate injured organs, we considered the exceptional case of spontaneous skin regeneration in the early lamb fetus. Whereas during the early fetal stage skin wounds heal by regeneration, in the late fetal stage, and after birth, skin wounds clo...

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Autores principales:	Ioannis V. Yannas, Dimitrios S. Tzeranis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/ad16cca10bae407b9336d1a3c9500474
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spelling	oai:doaj.org-article:ad16cca10bae407b9336d1a3c95004742021-12-02T16:26:41ZMammals fail to regenerate organs when wound contraction drives scar formation10.1038/s41536-021-00149-92057-3995https://doaj.org/article/ad16cca10bae407b9336d1a3c95004742021-07-01T00:00:00Zhttps://doi.org/10.1038/s41536-021-00149-9https://doaj.org/toc/2057-3995Abstract To understand why mammals generally do not regenerate injured organs, we considered the exceptional case of spontaneous skin regeneration in the early lamb fetus. Whereas during the early fetal stage skin wounds heal by regeneration, in the late fetal stage, and after birth, skin wounds close instead by scar formation. We review independent evidence that this switch in wound healing response coincides with the onset of wound contraction, which is also enabled during late fetal gestation. The crucial role of wound contraction in determining the wound healing outcome in adults has been demonstrated in three mammalian models of severe injury (excised guinea pig skin, transected rat sciatic nerve, excised rabbit conjunctival stroma) where grafting the injury with DRT, a contraction-blocking scaffold of highly-specific structure, altered significantly the wound healing outcome. While spontaneous healing resulted in scar formation in these animal models, DRT grafting significantly reduced the extent of wound contraction, prevented scar synthesis, and resulted in partial regeneration. These findings, as well as independent data from species that heal spontaneously via regeneration, point to a striking hypothesis: The process of regeneration lies dormant in mammals until appropriately activated by injury. In spontaneous wound healing of the late fetus and in adult mammals, wound contraction impedes such endogenous regeneration mechanisms. However, engineered treatments, such as DRT, that block wound contraction can cancel its effects and favor wound healing by regeneration instead of scar formation.Ioannis V. YannasDimitrios S. TzeranisNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-6 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Ioannis V. Yannas Dimitrios S. Tzeranis Mammals fail to regenerate organs when wound contraction drives scar formation
description	Abstract To understand why mammals generally do not regenerate injured organs, we considered the exceptional case of spontaneous skin regeneration in the early lamb fetus. Whereas during the early fetal stage skin wounds heal by regeneration, in the late fetal stage, and after birth, skin wounds close instead by scar formation. We review independent evidence that this switch in wound healing response coincides with the onset of wound contraction, which is also enabled during late fetal gestation. The crucial role of wound contraction in determining the wound healing outcome in adults has been demonstrated in three mammalian models of severe injury (excised guinea pig skin, transected rat sciatic nerve, excised rabbit conjunctival stroma) where grafting the injury with DRT, a contraction-blocking scaffold of highly-specific structure, altered significantly the wound healing outcome. While spontaneous healing resulted in scar formation in these animal models, DRT grafting significantly reduced the extent of wound contraction, prevented scar synthesis, and resulted in partial regeneration. These findings, as well as independent data from species that heal spontaneously via regeneration, point to a striking hypothesis: The process of regeneration lies dormant in mammals until appropriately activated by injury. In spontaneous wound healing of the late fetus and in adult mammals, wound contraction impedes such endogenous regeneration mechanisms. However, engineered treatments, such as DRT, that block wound contraction can cancel its effects and favor wound healing by regeneration instead of scar formation.
format	article
author	Ioannis V. Yannas Dimitrios S. Tzeranis
author_facet	Ioannis V. Yannas Dimitrios S. Tzeranis
author_sort	Ioannis V. Yannas
title	Mammals fail to regenerate organs when wound contraction drives scar formation
title_short	Mammals fail to regenerate organs when wound contraction drives scar formation
title_full	Mammals fail to regenerate organs when wound contraction drives scar formation
title_fullStr	Mammals fail to regenerate organs when wound contraction drives scar formation
title_full_unstemmed	Mammals fail to regenerate organs when wound contraction drives scar formation
title_sort	mammals fail to regenerate organs when wound contraction drives scar formation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ad16cca10bae407b9336d1a3c9500474
work_keys_str_mv	AT ioannisvyannas mammalsfailtoregenerateorganswhenwoundcontractiondrivesscarformation AT dimitriosstzeranis mammalsfailtoregenerateorganswhenwoundcontractiondrivesscarformation
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Mammals fail to regenerate organs when wound contraction drives scar formation

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