Sweat Gland Organoids Originating from Reprogrammed Epidermal Keratinocytes Functionally Recapitulated Damaged Skin

Abstract Restoration of sweat glands (SwGs) represents a great issue in patients with extensive skin defects. Recent methods combining organoid technology with cell fate reprogramming hold promise for developing new regenerative methods for SwG regeneration. Here, a practical strategy for engineerin...

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Main Authors: Xiaoyan Sun, Jiangbing Xiang, Runkai Chen, Zhijun Geng, Lintao Wang, Yiqiong Liu, Shuaifei Ji, Huating Chen, Yan Li, Cuiping Zhang, Peng Liu, Tao Yue, Lei Dong, Xiaobing Fu
Format: Article
Language:English
Published: Wiley 2021-11-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202103079
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author Xiaoyan Sun
Jiangbing Xiang
Runkai Chen
Zhijun Geng
Lintao Wang
Yiqiong Liu
Shuaifei Ji
Huating Chen
Yan Li
Cuiping Zhang
Peng Liu
Tao Yue
Lei Dong
Xiaobing Fu
author_facet Xiaoyan Sun
Jiangbing Xiang
Runkai Chen
Zhijun Geng
Lintao Wang
Yiqiong Liu
Shuaifei Ji
Huating Chen
Yan Li
Cuiping Zhang
Peng Liu
Tao Yue
Lei Dong
Xiaobing Fu
author_sort Xiaoyan Sun
collection DOAJ
description Abstract Restoration of sweat glands (SwGs) represents a great issue in patients with extensive skin defects. Recent methods combining organoid technology with cell fate reprogramming hold promise for developing new regenerative methods for SwG regeneration. Here, a practical strategy for engineering functional human SwGs in vitro and in vivo is provided. First, by forced expression of the ectodysplasin‐A in human epidermal keratinocytes (HEKs) combined with specific SwG culture medium, HEKs are efficiently converted into SwG cells (iSwGCs). The iSwGCs show typical morphology, gene expression pattern, and functions resembling human primary SwG cells. Second, by culturing the iSwGCs in a special 3D culturing system, SwG organoids (iSwGOs) that exhibit structural and biological features characteristic of native SwGs are obtained. Finally, these iSwGOs are successfully transplanted into a mouse skin damage model and they develop into fully functioning SwGs in vivo. Regeneration of functional SwG organoids from reprogrammed HEKs highlights the great translational potential for personalized SwG regeneration in patients with large skin defects.
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spelling doaj.art-501d69988c074e13960178787ef8a9432022-12-22T04:05:18ZengWileyAdvanced Science2198-38442021-11-01822n/an/a10.1002/advs.202103079Sweat Gland Organoids Originating from Reprogrammed Epidermal Keratinocytes Functionally Recapitulated Damaged SkinXiaoyan Sun0Jiangbing Xiang1Runkai Chen2Zhijun Geng3Lintao Wang4Yiqiong Liu5Shuaifei Ji6Huating Chen7Yan Li8Cuiping Zhang9Peng Liu10Tao Yue11Lei Dong12Xiaobing Fu13Research Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Department and 4th Medical Center PLA General Hospital and PLA Medical College PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and Regeneration Research Unit of Trauma Care Tissue Repair and Regeneration Chinese Academy of Medical Sciences 2019RU051 Beijing 100048 P. R. ChinaResearch Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Department and 4th Medical Center PLA General Hospital and PLA Medical College PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and Regeneration Research Unit of Trauma Care Tissue Repair and Regeneration Chinese Academy of Medical Sciences 2019RU051 Beijing 100048 P. R. ChinaResearch Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Department and 4th Medical Center PLA General Hospital and PLA Medical College PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and Regeneration Research Unit of Trauma Care Tissue Repair and Regeneration Chinese Academy of Medical Sciences 2019RU051 Beijing 100048 P. R. ChinaResearch Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Department and 4th Medical Center PLA General Hospital and PLA Medical College PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and Regeneration Research Unit of Trauma Care Tissue Repair and Regeneration Chinese Academy of Medical Sciences 2019RU051 Beijing 100048 P. R. ChinaState Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University Nanjing Jiangsu 210023 ChinaResearch Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Department and 4th Medical Center PLA General Hospital and PLA Medical College PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and Regeneration Research Unit of Trauma Care Tissue Repair and Regeneration Chinese Academy of Medical Sciences 2019RU051 Beijing 100048 P. R. ChinaResearch Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Department and 4th Medical Center PLA General Hospital and PLA Medical College PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and Regeneration Research Unit of Trauma Care Tissue Repair and Regeneration Chinese Academy of Medical Sciences 2019RU051 Beijing 100048 P. R. ChinaResearch Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Department and 4th Medical Center PLA General Hospital and PLA Medical College PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and Regeneration Research Unit of Trauma Care Tissue Repair and Regeneration Chinese Academy of Medical Sciences 2019RU051 Beijing 100048 P. R. ChinaResearch Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Department and 4th Medical Center PLA General Hospital and PLA Medical College PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and Regeneration Research Unit of Trauma Care Tissue Repair and Regeneration Chinese Academy of Medical Sciences 2019RU051 Beijing 100048 P. R. ChinaResearch Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Department and 4th Medical Center PLA General Hospital and PLA Medical College PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and Regeneration Research Unit of Trauma Care Tissue Repair and Regeneration Chinese Academy of Medical Sciences 2019RU051 Beijing 100048 P. R. ChinaDepartment of Biomedical Engineering School of Medicine Tsinghua University Haidian District Beijing 100084 ChinaSchool of Mechatronic Engineering and Automation Shanghai University Shanghai 200444 ChinaState Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University Nanjing Jiangsu 210023 ChinaResearch Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Department and 4th Medical Center PLA General Hospital and PLA Medical College PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and Regeneration Research Unit of Trauma Care Tissue Repair and Regeneration Chinese Academy of Medical Sciences 2019RU051 Beijing 100048 P. R. ChinaAbstract Restoration of sweat glands (SwGs) represents a great issue in patients with extensive skin defects. Recent methods combining organoid technology with cell fate reprogramming hold promise for developing new regenerative methods for SwG regeneration. Here, a practical strategy for engineering functional human SwGs in vitro and in vivo is provided. First, by forced expression of the ectodysplasin‐A in human epidermal keratinocytes (HEKs) combined with specific SwG culture medium, HEKs are efficiently converted into SwG cells (iSwGCs). The iSwGCs show typical morphology, gene expression pattern, and functions resembling human primary SwG cells. Second, by culturing the iSwGCs in a special 3D culturing system, SwG organoids (iSwGOs) that exhibit structural and biological features characteristic of native SwGs are obtained. Finally, these iSwGOs are successfully transplanted into a mouse skin damage model and they develop into fully functioning SwGs in vivo. Regeneration of functional SwG organoids from reprogrammed HEKs highlights the great translational potential for personalized SwG regeneration in patients with large skin defects.https://doi.org/10.1002/advs.202103079organoidsregenerationreprogrammingskinstem cellssweat glands
spellingShingle Xiaoyan Sun
Jiangbing Xiang
Runkai Chen
Zhijun Geng
Lintao Wang
Yiqiong Liu
Shuaifei Ji
Huating Chen
Yan Li
Cuiping Zhang
Peng Liu
Tao Yue
Lei Dong
Xiaobing Fu
Sweat Gland Organoids Originating from Reprogrammed Epidermal Keratinocytes Functionally Recapitulated Damaged Skin
Advanced Science
organoids
regeneration
reprogramming
skin
stem cells
sweat glands
title Sweat Gland Organoids Originating from Reprogrammed Epidermal Keratinocytes Functionally Recapitulated Damaged Skin
title_full Sweat Gland Organoids Originating from Reprogrammed Epidermal Keratinocytes Functionally Recapitulated Damaged Skin
title_fullStr Sweat Gland Organoids Originating from Reprogrammed Epidermal Keratinocytes Functionally Recapitulated Damaged Skin
title_full_unstemmed Sweat Gland Organoids Originating from Reprogrammed Epidermal Keratinocytes Functionally Recapitulated Damaged Skin
title_short Sweat Gland Organoids Originating from Reprogrammed Epidermal Keratinocytes Functionally Recapitulated Damaged Skin
title_sort sweat gland organoids originating from reprogrammed epidermal keratinocytes functionally recapitulated damaged skin
topic organoids
regeneration
reprogramming
skin
stem cells
sweat glands
url https://doi.org/10.1002/advs.202103079
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