Therapeutic Potential of Stem Cell-Derived Exosomes in Skin Wound Healing
Abstract
1. Introduction
2. Molecular Mechanisms of Skin Wound Healing Process
2.1. Hemostasis
2.2. Inflammatory Phase
2.3. Proliferative Phase
2.4. Remodeling Phase
3. Exosomes
4. Stem Cell-Derived Exosome for Skin Wound Treatment
4.1. Mesenchymal Stem Cell-Derived Exosome
4.2. Adipose-Derived Stem Cell-Derived Exosome
4.3. Induced Pluripotent Stem Cell-Derived Exosome
4.4. Other Type of Stem Cell-Derived Exosome
5. Challenges and Future Perspectives
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
SC-Exos | Stem cell-derived exosomes |
NPWT | Negative pressure wound therapy |
MSCs | Mesenchymal stem cells |
ECM | Extracellular matrix |
PGDF | Platelet-derived growth factor |
TGF-β | Transforming growth factor-β |
VEGF | Vascular endothelial growth factor |
FGF-2 | Fibroblast growth factor 2 |
ADSCs | Adipose-derived stem cells |
MMPs | Matrix metalloproteinases |
TIMPs | Tissue inhibitors |
MVBs | Multivesicular bodies |
ILVs | Intraluminal vesicles |
iPSCs | Pluripotent stem cells |
BMMSCs | Bone marrow-derived mesenchymal stem cells |
JMMSCs | Human jawbone marrow-derived mesenchymal stem cells |
HUVECs | Human umbilical vein endothelial cells |
iPSC-Exos | iPSC-derived exosomes |
HucMSCs | Human umbilical cord MSCs |
lncRNA | Long non-coding RNA |
HF-MSC-Exos | Hair follicle mesenchymal stem cells |
EV | Extracellular vesicles |
TFF | Tangential flow filtration |
GMP | Good Manufacturing Practice |
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Stem Cell Source | Study Types | Key Mechanisms | Therapeutic Outcome | Reference |
---|---|---|---|---|
MSC -derived exosomes | In vitro and in vivo | - Induces M2 macrophage polarization (↑ Arg-1, CD206) - Impaired exosome secretion leads to reduced M2 polarization and delayed wound healing | - Promoted wound regeneration in skin wound models - Increased M2 markers and accelerated wound healing | [53] |
- Inhibits M1 polarization and promotes M2 polarization of macrophages - Enhances IL-10, Arg-1 secretion; reduces IL-1β, TNF-α expression - Activates the PTEN/AKT signaling pathway | - Improved M2 polarization and wound healing in vivo - Promoted angiogenesis and collagen synthesis in skin wounds | [54] | ||
- Promotes fibroblast proliferation and migration - Enhances tube formation by endothelial cells - Increases STAT3 gene expression | - Improved cellular functions related to proliferation, migration, and angiogenesis in normal and diabetic fibroblasts | [51] | ||
Clinical trial | - Immunomodulatory effects of MSC-exosomes utilized for chronic inflammation-related condition | - Among 11 patients with complex perianal fistula: → Four showed complete healing → Six had complete cessation of discharge → One had no improvement | [59] | |
ADSC -derived exosomes | In vitro and in vivo | - Exosomes internalized by fibroblasts - Promotes fibroblast proliferation, migration, and collagen synthesis | - Accelerated wound healing in a mouse model - Enhanced collagen deposition - IV delivery is more effective than local injection | [23] |
- Reduces ROS production in HUVECs - Enhances mitochondrial function - Upregulates SIRT3 and SOD2, downregulates acetylated SOD2 | - Promoted angiogenesis and wound closure in diabetic wounds - Protected endothelial cells under high-glucose conditions | [67] | ||
- miR-29a inhibits fibroblast proliferation, migration, and collagen deposition - Activates the TGF-β2/Smad3 signaling pathway | - Reduced hypertrophic scar formation - Improved wound healing and dermis repair in thermal injury model | [38] | ||
- Sustained exosome release (95% in 72 h) from thermosensitive ECM hydrogel - Promotes fibroblast migration, collagen synthesis, and tube formation | - 92% wound closure in diabetic ulcers - Enhanced wound regeneration in both diabetic and normal wound models | [74] | ||
iPSC -derived exosomes | In vitro and in vivo | - Enhances fibroblast proliferation and migration (from diabetic mice) - Exhibits low immunogenicity (no HLA-ABC/DR expression) | - Accelerated wound closure in diabetic mice - Increased vessel density by day 7 post-treatment | [83] |
- Enhances fibroblast proliferation and migration - Proposed to mediate anti-aging effects | - Improved cell viability following UV-induced damage | [87] | ||
hUCMSC, derived exosomes | In vitro and in vivo | - Wnt4 expression activates Wnt/β-catenin signaling - Protects HaCaT cells and fibroblasts from heat stress-induced apoptosis | - Enhanced re-epithelialization and tissue remodeling in second-degree burn wounds - Increased collagen I/III ratio - Improved fibroblast proliferation post-heat stress | [97] |
HF-MSC derived exosomes | In vitro and in vivo | - lncRNA H19 modulates NLRP3 inflammasome-mediated pyroptosis - Promotes fibroblast proliferation, migration, and anti-apoptosis | - Improved wound healing in diabetic mouse skin (thicker granulation tissue, fewer inflammatory cells) - Downregulated caspase-1, IL-1β, TNF-α (reduced inflammation) | [98] |
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Jo, C.; Choi, Y.J.; Lee, T.-J. Therapeutic Potential of Stem Cell-Derived Exosomes in Skin Wound Healing. Biomimetics 2025, 10, 546. https://doi.org/10.3390/biomimetics10080546
Jo C, Choi YJ, Lee T-J. Therapeutic Potential of Stem Cell-Derived Exosomes in Skin Wound Healing. Biomimetics. 2025; 10(8):546. https://doi.org/10.3390/biomimetics10080546
Chicago/Turabian StyleJo, ChanBee, Yun Ji Choi, and Tae-Jin Lee. 2025. "Therapeutic Potential of Stem Cell-Derived Exosomes in Skin Wound Healing" Biomimetics 10, no. 8: 546. https://doi.org/10.3390/biomimetics10080546
APA StyleJo, C., Choi, Y. J., & Lee, T.-J. (2025). Therapeutic Potential of Stem Cell-Derived Exosomes in Skin Wound Healing. Biomimetics, 10(8), 546. https://doi.org/10.3390/biomimetics10080546