# Exosomes in Hypertrophic Scars and Keloids: Mechanisms and Therapeutic Potentials—A Narrative Review

**Authors:** Mengke Wu, Jianfeng Zhang, Na Xiong, Yixiao Ma, Lingling Yong, Huaxu Liu, Qin Guo

PMC · DOI: 10.1111/jocd.70705 · Journal of Cosmetic Dermatology · 2026-01-30

## TL;DR

Exosomes may offer a new treatment for scars and keloids by regulating wound healing and fibrosis.

## Contribution

This review proposes exosomes as a multi-target therapy for pathological scars based on recent studies.

## Key findings

- Exosomes reduce inflammation and fibrosis in scar formation.
- They inhibit fibroblast transformation and regulate collagen synthesis.
- Exosomes modulate the TGF-β/Smad signaling pathway to suppress fibrosis.

## Abstract

Hypertrophic scars and keloids, types of pathological scars, arise from dysregulated wound healing, marked by abnormal fibroblast activation and excessive extracellular matrix (ECM) deposition. Current treatments have high recurrence rates and side effects, necessitating targeted therapies. Exosomes, extracellular vesicles mediating intercellular communication, offer multi‐target regulatory potential to address scar formation complexities.

This narrative review synthesizes in vitro and in vivo studies (2020–2025) from PubMed and Scopus on exosomes' role in regulating hypertrophic scars and keloids, proposing innovative therapeutic approaches.

Therapeutic exosomes attenuate inflammation, promote wound healing, inhibit fibrosis, and modulate the scar microenvironment. They suppress fibroblast‐to‐myofibroblast transformation, regulate collagen synthesis, and inhibit fibrotic pathways, particularly via the Transforming Growth Factor‐beta/Sma‐ and Mad‐related protein (TGF‐β/Smad) signaling pathway.

Exosomes are a promising cell‐free therapy for pathological scars due to their multi‐target regulatory capabilities. Future research should optimize large‐scale production, standardize protocols, and develop targeted delivery systems to enable clinical translation, with validation through clinical trials.

## Full-text entities

- **Genes:** MIR19B1 (microRNA 19b-1) [NCBI Gene 406980] {aka C13orf25, MIR19B, MIRH1, MIRHG1, MIRN19B1, miR-19b-1}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, HSPG2 (heparan sulfate proteoglycan 2) [NCBI Gene 3339] {aka HSPG, PLC, PRCAN, SJA, SJS, SJS1}, TGFB3 (transforming growth factor beta 3) [NCBI Gene 7043] {aka ARVD, ARVD1, LDS5, RNHF, TGF-beta3}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, TGFB2 (transforming growth factor beta 2) [NCBI Gene 7042] {aka CAEND2, G-TSF, LDS4, TGF-beta2}, MIR7704 (microRNA 7704) [NCBI Gene 102465802] {aka hsa-mir-7704}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, TAC1 (tachykinin precursor 1) [NCBI Gene 6863] {aka Hs.2563, NK2, NKNA, NPK, TAC2}, COL1A1 (collagen type I alpha 1 chain) [NCBI Gene 1277] {aka CAFYD, EDSARTH1, EDSC, OI1, OI2, OI3}, MIR1246 (microRNA 1246) [NCBI Gene 100302142] {aka MIRN1246, hsa-mir-1246}, TAC4 (tachykinin precursor 4) [NCBI Gene 255061] {aka EK, HK-1, PPT-C}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, TYR (tyrosinase) [NCBI Gene 7299] {aka ATN, CMM8, OCA1, OCA1A, OCAIA, SHEP3}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, MIR126 (microRNA 126) [NCBI Gene 406913] {aka MIRN126, miRNA126, mir-126}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, VIPR1 (vasoactive intestinal peptide receptor 1) [NCBI Gene 7433] {aka HVR1, II, PACAP-R-2, PACAP-R2, RDC1, V1RG}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, SMAD3 (SMAD family member 3) [NCBI Gene 4088] {aka HSPC193, HsT17436, JV15-2, LDS1C, LDS3, MADH3}, BECN1 (beclin 1) [NCBI Gene 8678] {aka ATG6, VPS30, beclin1}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, MIR425 (microRNA 425) [NCBI Gene 494337] {aka MIRN425, hsa-mir-425, mir-425}, CXCR4 (C-X-C motif chemokine receptor 4) [NCBI Gene 7852] {aka CD184, D2S201E, FB22, HM89, HSY3RR, LCR1}, CD1D (CD1d molecule) [NCBI Gene 912] {aka R3, R3G1}, CD81 (CD81 molecule) [NCBI Gene 975] {aka CVID6, S5.7, TAPA1, TSPAN28}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, CALCB (calcitonin related polypeptide beta) [NCBI Gene 797] {aka CALC2, CGRP-II, CGRP2}, TLR9 (toll like receptor 9) [NCBI Gene 54106] {aka CD289}, TSG101 (tumor susceptibility 101) [NCBI Gene 7251] {aka TSG10, VPS23}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, NTF3 (neurotrophin 3) [NCBI Gene 4908] {aka HDNF, NGF-2, NGF2, NT-3, NT3}, KLRK1 (killer cell lectin like receptor K1) [NCBI Gene 22914] {aka CD314, D12S2489E, KLR, NKG2-D, NKG2D}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, TNFSF13 (TNF superfamily member 13) [NCBI Gene 8741] {aka APRIL, CD256, TALL-2, TALL2, TNLG7B, TRDL-1}, MIR215 (microRNA 215) [NCBI Gene 406997] {aka MIRN215, miRNA215, mir-215}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, SOX9 (SRY-box transcription factor 9) [NCBI Gene 6662] {aka CMD1, CMPD1, ENH13, SRA1, SRXX2, SRXY10}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, USP22 (ubiquitin specific peptidase 22) [NCBI Gene 23326] {aka USP3L}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, MIR17HG (miR-17-92a-1 cluster host gene) [NCBI Gene 407975] {aka C13orf25, LINC00048, MIHG1, MIRH1, MIRHG1, NCRNA00048}, CD63 (CD63 molecule) [NCBI Gene 967] {aka AD1, HOP-26, ME491, MLA1, OMA81H, Pltgp40}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290] {aka CCM4, CLAPO, CLOVE, CWS5, HMH, MCAP}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, MIR146A (microRNA 146a) [NCBI Gene 406938] {aka MIRN146, MIRN146A, miR-146a, miRNA146A}, TACR1 (tachykinin receptor 1) [NCBI Gene 6869] {aka NK1R, NKIR, SPR, TAC1R}, NRP2 (neuropilin 2) [NCBI Gene 8828] {aka NP2, NPN2, PRO2714, VEGF165R2}, MEG3 (maternally expressed 3) [NCBI Gene 55384] {aka FP504, GTL2, LINC00023, Lnc-DLK1-35, NCRNA00023, PRO0518}, NOTCH1 (notch receptor 1) [NCBI Gene 4851] {aka AOS5, AOVD1, TAN1, hN1}
- **Diseases:** itching (MESH:D011537), Hypertrophic (MESH:D002312), Inflammation (MESH:D007249), necrotic (MESH:D009336), skin diseases (MESH:D012871), Hypertrophic Scars (MESH:D017439), nerve damage (MESH:D000080902), ischemia (MESH:D007511), Hypoxia (MESH:D000860), contractures (MESH:D003286), fibrotic diseases (MESH:D004194), opportunistic infection (MESH:D009894), hypoxic (MESH:D002534), Fibrosis (MESH:D005355), thrombus (MESH:D013927), keloid scars (MESH:D002921), hepatic, renal, and pulmonary fibrosis (MESH:D011658), Keloids (MESH:D007627)
- **Chemicals:** H2O2 (MESH:D006861), ROS (MESH:D017382), oxygen (MESH:D010100), melanin (MESH:D008543), ADSC (-), glycosaminoglycans (MESH:D006025), Valproic acid (MESH:D014635), histamine (MESH:D006632), lipid (MESH:D008055)
- **Species:** Rosa x damascena (damask rose, species) [taxon 3765], Homo sapiens (human, species) [taxon 9606], Legionella sp. D (species) [taxon 66972], Lactobacillus delbrueckii (species) [taxon 1584]
- **Cell lines:** hiPSC — Homo sapiens (Human), Induced pluripotent stem cell (CVCL_C888), LD — Homo sapiens (Human), Plasma cell myeloma, Cancer cell line (CVCL_Y435)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12856728/full.md

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12856728/full.md

## References

109 references — full list in the complete paper: https://tomesphere.com/paper/PMC12856728/full.md

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Source: https://tomesphere.com/paper/PMC12856728