Adipose Mesenchymal Stem Cells Promote Wound Healing by Modulating Expression of SERPINE1 in Dermal Fibroblasts and Keratinocytes

Sep 30, 2026

Uploaded by Rowan

Adipose-derived mesenchymal stem cells (ADSCs) are investigated for their impact on skin wound repair and for the molecular mechanisms driving fibroblast and keratinocyte responses. Using an in vivo murine wound model and in vitro Transwell coculture, the study evaluates proliferation and migration of human dermal fibroblasts and HaCaT cells alongside transcriptome sequencing. Functional manipulation of SERPINE1 determines causality, and enrichment analyses link SERPINE1 to PI3K-Akt and MAPK signaling pathways.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages32

Reading Time1 h 21 min

AccessFree to download

Introduction

Wound healing overview and challenges

Roles of fibroblasts and keratinocytes

ADSCs in skin repair and current knowledge gaps

SERPIN/protease axis and SERPINE1 rationale

Methods

In vivo murine model and in vitro Transwell coculture

Transcriptome sequencing and target validation

Results

ADSC extraction, expansion, and identification

Effects of ADSCs on healing and cell behavior

SERPINE1 regulation and functional knockdown/overexpression

Pathway enrichment and signaling associations

Conclusion

Wiley Stem Cells International Volume 2026, Article ID 5541440, 32 pages [https://doi.org/10.1155/sci/5541440](https://doi.org/10.1155/sci/5541440) Research Article Adipose Mesenchymal Stem Cells Promote Wound Healing by Modulating Expression of SERPINE1 in Dermal Fibroblasts and Keratinocytes YeHua Liang , 1 Qinqian Sun ,2 Jiaqi Sun ,3 Mingyuan Xu , 1 Jinghong Xu , 1 and Yijia Yu 1 1Department of Plastic Surgery, The First Afﬁliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China 2Zhejiang University School of Medicine, Hangzhou, Zhejiang, China 3Department of Plastic Surgery, The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China Correspondence should be addressed to Jinghong Xu; [1304017@zju.edu.cn and Yijia Yu](1304017@zju.edu.cn and Yijia Yu); [poka@zju.edu.cn](poka@zju.edu.cn) Received 14 August 2024; Revised 27 October 2025; Accepted 12 November 2025 Academic Editor: Simona Ceccarelli Copyright © 2026 YeHua Liang et al. Stem Cells International published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Background: Adipose-derived mesenchymal stem cells (ADSCs) have great potential in the realm of tissue repair and regenerative medicine. However, the exact effects ofADSCs on the healing of skin wounds and the underlying mechanisms remain unexplored. Here, we investigated the effects of ADSCs on ﬁbroblasts and keratinocytes and their related molecular mechanisms in wound healing. Methods: We used a murine model in vivo and a Transwell coculture system in vitro. The proliferation and migration abilities of human dermal ﬁbroblasts (HDFs) and human immortalized keratinocytes (HaCaT) were analyzed after coculture with ADSCs, and the target molecules were investigated by transcriptome sequencing. We further investigated phenotypic changes by knocking down and overexpressing the target molecule and analyzed the potential mechanisms. Results: We successfully extracted, expanded, and identiﬁed ADSCs. ADSCs not only accelerated wound healing in mice but also improved healing quality. Coculture with ADSCs augmented the proliferation and migration capacities of main skin cells in vitro. RNA sequencing analysis revealed that the level of serpin family E member 1 (SERPINE1) in both HDF and HaCaT was signiﬁcantly regulated by ADSCs. Knockdown of SERPINE1 restrained the proliferation and migration phenotypes of HDF and HaCaT, while overexpression of SERPINE1 did exactly the opposite. Pathway enrichment analysis revealed that SERPINE1 was mainly related to PI3K-Akt and MAPK signaling pathways. Conclusion: The in vivo model and in vitro cell test demonstrate that ADSC effectively promotes cutaneous wound healing by augmenting the proliferation and migration of ﬁbroblasts and keratinocytes through upregulating SERPINE1, which provides novel insights into the biological roles of SERPINE1 in wound healing and suggests ADSC has a promising future in skin injury therapy. Keywords: adipose-derived stem cell; ﬁbroblasts; keratinocytes; SERPINE1; wound healing 1. Introduction Wound healing is a fundamental and complex process of skin barrier function restoration that consists of a highly sequential, coordinated, and temporally overlapping series of events: hemostasis, inﬂammation, proliferation, andremodeling [1] . Disruptions of these physiologic processes can lead to the formation of complex wounds. Chronic wounds (CWs) pose a growing health and economic burden to society. In developed countries, the annual management of CWs allocates 6% of total healthcare expenditures. Statistical reports from NIH demonstrated an annual cost of $20 billion for CWs management [2] . Despite the considerable progress involved in wound healing, the speciﬁc mechanism 2 Stem C

FAQs

What is the central question of this study?

How ADSCs affect skin wound healing and what molecular mechanism regulates the behavior of dermal fibroblasts and keratinocytes.

How were the effects of ADSCs tested?

A murine in vivo wound model and an in vitro Transwell coculture system were used to assess proliferation and migration, with transcriptome sequencing and target perturbation experiments.

What role does SERPINE1 play in the reported mechanism?

ADSCs significantly regulate SERPINE1 expression in fibroblasts and keratinocytes; SERPINE1 knockdown suppresses proliferation/migration while SERPINE1 overexpression produces the opposite effect.

Sep 30, 2026

Uploaded by Rowan