Dermal Pericytes Exhibit Declined Ability to Promote Human Skin Regeneration with Ageing in 3D Organotypic Culture Models

The well documented decline in the regenerative ability of ageing human skin has been attributed to many factors including genomic instability, telomere shortening, poor nutrient sensing, cellular senescence, and stem cell exhaustion. However, a role for the dermal cellular and molecular microenviro...

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Autores principales:	Lizhe Zhuang, Rahul M. Visalakshan, Pritinder Kaur
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	skin dermis pericyte microenvironment human ageing Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/edc6b0d549db49b594f1315cdfb6f584
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spelling	oai:doaj.org-article:edc6b0d549db49b594f1315cdfb6f5842021-11-25T17:10:51ZDermal Pericytes Exhibit Declined Ability to Promote Human Skin Regeneration with Ageing in 3D Organotypic Culture Models10.3390/cells101130512073-4409https://doaj.org/article/edc6b0d549db49b594f1315cdfb6f5842021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3051https://doaj.org/toc/2073-4409The well documented decline in the regenerative ability of ageing human skin has been attributed to many factors including genomic instability, telomere shortening, poor nutrient sensing, cellular senescence, and stem cell exhaustion. However, a role for the dermal cellular and molecular microenvironment in skin ageing is just emerging. We previously showed that dermal pericytes co-operate with fibroblasts to improve human skin regeneration in an organotypic skin culture model, and even do so in the absence of fibroblasts. Here, we report that the number of dermal cells, particularly pericytes, declines significantly in human skin of donors aged > 50 years. Notably, aged pericytes promoted epidermal regeneration of neonatal keratinocytes in organotypic cultures and the resulting epithelium exhibited a Ki67<sup>+</sup>/ΔNp63<sup>+</sup> basal layer and terminal differentiation. However, the epithelium lacked several features of homeostasis displaying lower levels of ΔNp63 expression, decreased LAMA5 deposition at the dermo-epidermal junction, and the absence of basement membrane and hemi-desmosome assembly. We conclude that a decline in pericyte incidence and function contribute to an impaired epidermal microenvironment and poor skin regeneration with ageing in the human skin.Lizhe ZhuangRahul M. VisalakshanPritinder KaurMDPI AGarticleskindermispericytemicroenvironmenthumanageingBiology (General)QH301-705.5ENCells, Vol 10, Iss 3051, p 3051 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	skin dermis pericyte microenvironment human ageing Biology (General) QH301-705.5
spellingShingle	skin dermis pericyte microenvironment human ageing Biology (General) QH301-705.5 Lizhe Zhuang Rahul M. Visalakshan Pritinder Kaur Dermal Pericytes Exhibit Declined Ability to Promote Human Skin Regeneration with Ageing in 3D Organotypic Culture Models
description	The well documented decline in the regenerative ability of ageing human skin has been attributed to many factors including genomic instability, telomere shortening, poor nutrient sensing, cellular senescence, and stem cell exhaustion. However, a role for the dermal cellular and molecular microenvironment in skin ageing is just emerging. We previously showed that dermal pericytes co-operate with fibroblasts to improve human skin regeneration in an organotypic skin culture model, and even do so in the absence of fibroblasts. Here, we report that the number of dermal cells, particularly pericytes, declines significantly in human skin of donors aged > 50 years. Notably, aged pericytes promoted epidermal regeneration of neonatal keratinocytes in organotypic cultures and the resulting epithelium exhibited a Ki67<sup>+</sup>/ΔNp63<sup>+</sup> basal layer and terminal differentiation. However, the epithelium lacked several features of homeostasis displaying lower levels of ΔNp63 expression, decreased LAMA5 deposition at the dermo-epidermal junction, and the absence of basement membrane and hemi-desmosome assembly. We conclude that a decline in pericyte incidence and function contribute to an impaired epidermal microenvironment and poor skin regeneration with ageing in the human skin.
format	article
author	Lizhe Zhuang Rahul M. Visalakshan Pritinder Kaur
author_facet	Lizhe Zhuang Rahul M. Visalakshan Pritinder Kaur
author_sort	Lizhe Zhuang
title	Dermal Pericytes Exhibit Declined Ability to Promote Human Skin Regeneration with Ageing in 3D Organotypic Culture Models
title_short	Dermal Pericytes Exhibit Declined Ability to Promote Human Skin Regeneration with Ageing in 3D Organotypic Culture Models
title_full	Dermal Pericytes Exhibit Declined Ability to Promote Human Skin Regeneration with Ageing in 3D Organotypic Culture Models
title_fullStr	Dermal Pericytes Exhibit Declined Ability to Promote Human Skin Regeneration with Ageing in 3D Organotypic Culture Models
title_full_unstemmed	Dermal Pericytes Exhibit Declined Ability to Promote Human Skin Regeneration with Ageing in 3D Organotypic Culture Models
title_sort	dermal pericytes exhibit declined ability to promote human skin regeneration with ageing in 3d organotypic culture models
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/edc6b0d549db49b594f1315cdfb6f584
work_keys_str_mv	AT lizhezhuang dermalpericytesexhibitdeclinedabilitytopromotehumanskinregenerationwithageingin3dorganotypicculturemodels AT rahulmvisalakshan dermalpericytesexhibitdeclinedabilitytopromotehumanskinregenerationwithageingin3dorganotypicculturemodels AT pritinderkaur dermalpericytesexhibitdeclinedabilitytopromotehumanskinregenerationwithageingin3dorganotypicculturemodels
_version_	1718412686394392576

Dermal Pericytes Exhibit Declined Ability to Promote Human Skin Regeneration with Ageing in 3D Organotypic Culture Models

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