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Mesenchymal stem cells and their exosomes: a novel approach to skin regeneration via signaling pathways activation

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Abstract

Accelerating wound healing is a crucial objective in surgical and regenerative medicine. The wound healing process involves three key stages: inflammation, cell proliferation, and tissue repair. Mesenchymal stem cells (MSCs) have demonstrated significant therapeutic potential in promoting tissue regeneration, particularly by enhancing epidermal cell migration and proliferation. However, the precise molecular mechanisms underlying MSC-mediated wound healing remain unclear. This review highlights the pivotal role of MSCs and their exosomes in wound repair, with a specific focus on critical signaling pathways, including PI3K/Akt, WNT/β-catenin, Notch, and MAPK. These pathways regulate essential cellular processes such as proliferation, differentiation, and angiogenesis. Moreover, in vitro and in vivo studies reveal that MSCs accelerate wound closure, enhance collagen deposition, and modulate immune responses, contributing to improved tissue regeneration. Understanding these mechanisms provides valuable insights into MSC-based therapeutic strategies for enhancing wound healing.

Graphical abstract

Effects of mesenchymal stem cell and its derived-exosome treatment on skin regeneration and tissue repair via activation of different signaling pathways

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Data availability

No datasets were generated or analysed during the current study.

Abbreviations

MSC:

Mesenchymal stem cell

Exo:

Exosome

EC:

Endothelial cell

PI3K:

Phosphatidylinositol 3-kinase

HypADSCs-exo:

Hypoxic adipose stem cells exosomes

p-AKT:

Phosphorylated AKT

p-eNOS:

Phosphorylated eNOS

HG:

High glucose

NO:

Nitric oxide

RM:

Rapamycin

SMV:

Simvastatin

RI:

Ribonuclease inhibitor

siRNA:

Small Interfering RNA

GSK-3β:

Glycogen synthase kinase 3β

H/R:

Hypoxia/Reoxygenation

PIP2:

Phosphatidylinositol P2

A375:

Malignant melanoma cell line

ECM:

Extracellular matrix

EPSC:

Epidermal stem cell

HNSCC:

Head and neck squamous cell carcinoma

MK2:

P38MAPK/MAPKAP Kinase 2

PCNA:

Proliferating cell nuclear antigen

FDMSC:

Fetal dermal mesenchymal stem cells

ADF:

Adult dermal fibroblast

DAPT:

Dual antiplatelet treatment

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Acknowledgements

None declared. The authors declare that they have not use AI-generated work in this manuscript.

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Author notes

  1. Maryam Kananivand and Fatemeh Nouri are co-first authors.

Authors and Affiliations

  1. Medical Department, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Maryam Kananivand

  2. Department of Biology, School of Basic Sciences, Science and Research Branch, Islamic Azad University (SRBIAU), Tehran, Iran

    Fatemeh Nouri

  3. Department of Tissue Engineering and Applied Cell Sciences, School of Medicine, Qom University of Medical Sciences, Qom, Iran

    Mohammad Hasan Yousefi

  4. Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran

    Mohammad Hasan Yousefi & Hamed Afkhami

  5. Student Research Committee, USERN Office, Lorestan University of Medical Sciences, Khorramabad, Iran

    Ali Pajouhi

  6. Department of Sciences, Faculty of Biological Sciences, Tabriz University of Sciences, Tabriz, Iran

    Hakimeah Ghorbani

  7. Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran

    Hamed Afkhami

  8. Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran

    Hamed Afkhami

  9. Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran

    Zahra Sadat Razavi

  10. Student Research Committee, Qom University of Medical Sciences, Qom, Iran

    Mohammad Hasan Yousefi & Hamed Afkhami

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Contributions

MK-FN: wrote the manuscript, MH.Y-AP-HG: edited manuscript and designed graphical abstract of manuscript, H.A-ZS.R: design and Supervision. All authors read and approved the final manuscript.

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Correspondence to Hamed Afkhami or Zahra Sadat Razavi.

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Kananivand, M., Nouri, F., Yousefi, M.H. et al. Mesenchymal stem cells and their exosomes: a novel approach to skin regeneration via signaling pathways activation. J Mol Histol 56, 132 (2025). https://doi.org/10.1007/s10735-025-10394-7

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