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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.

Sec. Stem Cell Research

This article is part of the Research TopicMesenchymal Stem Cells in Organ Regeneration: From Laboratory to Clinical ApplicationView all articles

Extracellular Vesicles Modulate Skin Aging Biomarkers in 3D Reconstructed Full-Thickness Skin Model

Provisionally accepted
YAO  TENGYAO TENG1Elias  BOU SAMRAElias BOU SAMRA2Sarah  GIRARDEAU-HUBERTSarah GIRARDEAU-HUBERT2Richard  BETTSRichard BETTS3Franck  JUCHAUXFranck JUCHAUX4Xavier  MARATXavier MARAT2Benedicte  FALLOUBenedicte FALLOU5Lingyan  ZHONGLingyan ZHONG1Rodrigo  De VecchiRodrigo De Vecchi2Nan  HUANGNan HUANG6Qian  ZHENGQian ZHENG7Yu  GAOYu GAO1Daniel  ROYDaniel ROY7Ping  WANGPing WANG1*
  • 1Advanced Research, L'Oréal Research & Innovation, SHANGHAI, China
  • 2Advanced Research, L'Oréal Research & Innovation, Aulnay-sous-Bois, France
  • 3Advanced Research, L'Oréal Research & Innovation, Singapore, Singapore
  • 4L'Oreal Recherche Avancee, Aulnay-sous-Bois, France
  • 5EPISKIN, L'Oréal Research & Innovation, Lyon, France
  • 6Advanced Research, L'Oréal Research & Innovation, Shanghai, China
  • 7Advanced Research, L'Oréal Research & Innovation, Clark, United States

The final, formatted version of the article will be published soon.

Extracellular vesicles (EVs) are lipid-enveloped nanovesicles rich in microRNAs, proteins and lipids, serve as potent mediators of intercellular communication. While EVs have demonstrated pro-regenerative potential in 2D and preclinical models, their im-pact on skin regeneration and aging processes in 3D reconstructed skin models has remained less explored. In this study, EVs from adipose-derived stem cells (ADSCs) and umbilical cord-derived mesenchymal stem cells (UC-MSCs) were evaluated using both 2D primary skin cells and 3D full-thickness reconstructed skin models. EVs stimulated fibroblast and keratinocyte proliferation, increased epidermal thickness, and enhanced the presence of collagen IV in the dermal-epidermal junction (DEJ) and fibrillin 1 in the extracellular matrix (ECM). Bulk transcriptomic analysis of the 3D reconstructed skin revealed gene expression profiles impacted by the addition of EVs. Additionally, miRNA-seq and proteomics of EV contents revealed miRNAs and proteins that may be drivers of the biological activities observed in 3D models, suggesting EVs activate processes associated with skin regeneration. This holistic approach demonstrated that EVs previously linked to pro-regenerative behaviors also modulate biomarkers associated with cutaneous aging in full-thickness 3D reconstructed models. This work not only provides mechanics insights but also paves the way for the development of next-generation regenerative skincare active ingredients.

Keywords: Extracellular vesicle (EV), Mesenchymal Stem Cell (MSC), omics, Reconstructed skin model, Skin Regeneration

Received: 10 Jan 2026; Accepted: 02 Feb 2026.

Copyright: © 2026 TENG, BOU SAMRA, GIRARDEAU-HUBERT, BETTS, JUCHAUX, MARAT, FALLOU, ZHONG, De Vecchi, HUANG, ZHENG, GAO, ROY and WANG. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Ping WANG

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