Epidermal stem cells maintain stemness via a biomimetic micro/nanofiber scaffold that promotes wound healing by activating the Notch signaling pathway

Abstract Background Epidermal stem cells (EpSCs) play a vital role in wound healing and skin renewal. Although biomaterial scaffolds have been used for transplantation of EpSCs in wound healing, the ex vivo differentiation of EpSCs limits their application. Methods To inhibit the differentiation of...

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Main Authors: Zhixiao Lin, Congying Zhao, Zhanjun Lei, Yuheng Zhang, Rong Huang, Bin Lin, Yuchen Dong, Hao Zhang, Jinqing Li, Xueyong Li
Format: Article
Language:English
Published: BMC 2021-06-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-021-02418-2
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author Zhixiao Lin
Congying Zhao
Zhanjun Lei
Yuheng Zhang
Rong Huang
Bin Lin
Yuchen Dong
Hao Zhang
Jinqing Li
Xueyong Li
author_facet Zhixiao Lin
Congying Zhao
Zhanjun Lei
Yuheng Zhang
Rong Huang
Bin Lin
Yuchen Dong
Hao Zhang
Jinqing Li
Xueyong Li
author_sort Zhixiao Lin
collection DOAJ
description Abstract Background Epidermal stem cells (EpSCs) play a vital role in wound healing and skin renewal. Although biomaterial scaffolds have been used for transplantation of EpSCs in wound healing, the ex vivo differentiation of EpSCs limits their application. Methods To inhibit the differentiation of EpSCs and maintain their stemness, we developed an electrospun polycaprolactone (PCL)+cellulose acetate (CA) micro/nanofiber for the culture and transplantation of EpSCs. The modulation effect on EpSCs of the scaffold and the underlying mechanism were explored. Liquid chromatography-tandem mass spectrometry for label-free quantitative proteomics was used to analyze proteomic changes in EpSCs cultured on scaffolds. In addition, the role of transplanted undifferentiated EpSCs in wound healing was also studied. Results In this study, we found that the PCL+CA micro/nanofiber scaffold can inhibit the differentiation of EpSCs through YAP activation-mediated inhibition of the Notch signaling pathway. Significantly differentially expressed proteomics was observed in EpSCs cultured on scaffolds and IV collagen-coated culture dishes. Importantly, differential expression levels of ribosome-related proteins and metabolic pathway-related proteins were detected. Moreover, undifferentiated EpSCs transplanted with the PCL+CA scaffold can promote wound healing through the activation of the Notch signaling pathway in rat full-thickness skin defect models. Conclusions Overall, our study demonstrated the role of the PCL+CA micro-nanofiber scaffold in maintaining the stemness of EpSCs for wound healing, which can be helpful for the development of EpSCs maintaining scaffolds and exploration of interactions between biomaterials and EpSCs.
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spelling doaj.art-338df8680ce641629c2bcff4ed0286192022-12-21T18:44:02ZengBMCStem Cell Research & Therapy1757-65122021-06-0112111210.1186/s13287-021-02418-2Epidermal stem cells maintain stemness via a biomimetic micro/nanofiber scaffold that promotes wound healing by activating the Notch signaling pathwayZhixiao Lin0Congying Zhao1Zhanjun Lei2Yuheng Zhang3Rong Huang4Bin Lin5Yuchen Dong6Hao Zhang7Jinqing Li8Xueyong Li9Department of Plastic Surgery, Tangdu Hospital, Airforce Military Medical UniversityDepartment of Plastic Surgery, Tangdu Hospital, Airforce Military Medical UniversityDepartment of Plastic Surgery, Tangdu Hospital, Airforce Military Medical UniversityDepartment of Plastic Surgery, Tangdu Hospital, Airforce Military Medical UniversityDepartment of Plastic Surgery, Tangdu Hospital, Airforce Military Medical UniversityDepartment of Plastic Surgery, Tangdu Hospital, Airforce Military Medical UniversityDepartment of Plastic Surgery, Tangdu Hospital, Airforce Military Medical UniversityDepartment of Plastic Surgery, Tangdu Hospital, Airforce Military Medical UniversityDepartment of Plastic Surgery, Tangdu Hospital, Airforce Military Medical UniversityDepartment of Plastic Surgery, Tangdu Hospital, Airforce Military Medical UniversityAbstract Background Epidermal stem cells (EpSCs) play a vital role in wound healing and skin renewal. Although biomaterial scaffolds have been used for transplantation of EpSCs in wound healing, the ex vivo differentiation of EpSCs limits their application. Methods To inhibit the differentiation of EpSCs and maintain their stemness, we developed an electrospun polycaprolactone (PCL)+cellulose acetate (CA) micro/nanofiber for the culture and transplantation of EpSCs. The modulation effect on EpSCs of the scaffold and the underlying mechanism were explored. Liquid chromatography-tandem mass spectrometry for label-free quantitative proteomics was used to analyze proteomic changes in EpSCs cultured on scaffolds. In addition, the role of transplanted undifferentiated EpSCs in wound healing was also studied. Results In this study, we found that the PCL+CA micro/nanofiber scaffold can inhibit the differentiation of EpSCs through YAP activation-mediated inhibition of the Notch signaling pathway. Significantly differentially expressed proteomics was observed in EpSCs cultured on scaffolds and IV collagen-coated culture dishes. Importantly, differential expression levels of ribosome-related proteins and metabolic pathway-related proteins were detected. Moreover, undifferentiated EpSCs transplanted with the PCL+CA scaffold can promote wound healing through the activation of the Notch signaling pathway in rat full-thickness skin defect models. Conclusions Overall, our study demonstrated the role of the PCL+CA micro-nanofiber scaffold in maintaining the stemness of EpSCs for wound healing, which can be helpful for the development of EpSCs maintaining scaffolds and exploration of interactions between biomaterials and EpSCs.https://doi.org/10.1186/s13287-021-02418-2Epidermal stem cellMicro/nanofiber scaffoldCell differentiationWound healingNotch pathway
spellingShingle Zhixiao Lin
Congying Zhao
Zhanjun Lei
Yuheng Zhang
Rong Huang
Bin Lin
Yuchen Dong
Hao Zhang
Jinqing Li
Xueyong Li
Epidermal stem cells maintain stemness via a biomimetic micro/nanofiber scaffold that promotes wound healing by activating the Notch signaling pathway
Stem Cell Research & Therapy
Epidermal stem cell
Micro/nanofiber scaffold
Cell differentiation
Wound healing
Notch pathway
title Epidermal stem cells maintain stemness via a biomimetic micro/nanofiber scaffold that promotes wound healing by activating the Notch signaling pathway
title_full Epidermal stem cells maintain stemness via a biomimetic micro/nanofiber scaffold that promotes wound healing by activating the Notch signaling pathway
title_fullStr Epidermal stem cells maintain stemness via a biomimetic micro/nanofiber scaffold that promotes wound healing by activating the Notch signaling pathway
title_full_unstemmed Epidermal stem cells maintain stemness via a biomimetic micro/nanofiber scaffold that promotes wound healing by activating the Notch signaling pathway
title_short Epidermal stem cells maintain stemness via a biomimetic micro/nanofiber scaffold that promotes wound healing by activating the Notch signaling pathway
title_sort epidermal stem cells maintain stemness via a biomimetic micro nanofiber scaffold that promotes wound healing by activating the notch signaling pathway
topic Epidermal stem cell
Micro/nanofiber scaffold
Cell differentiation
Wound healing
Notch pathway
url https://doi.org/10.1186/s13287-021-02418-2
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