Table 1.
Summary of evidence on mesenchymal stem cell exosomes for repairing skin barrier functions
| Skin Barrier |
Exosome Source | Key Findings | Study Model & Design | Evidence tier | Implications | Limitations |
|---|---|---|---|---|---|---|
| Physical barrier | hASCs | Repairs barrier: ↓TEWL, ↑hydration, ↑ceramide synthesis [48] |
SKH-1 mouse chronic oxazolone AD; RCT, multi-dose + control |
High (Preclinical) | Novel dual “barrier-immune” repair strategy | Model simplifies human AD; s.c. route unproven; active components unknown |
| Heals wounds: ↑Type III collagen ratio (↓scar width); additive benefit of topical + IV delivery [49] | ICR mouse, full-thickness wound; RCT | Medium–High (Preclinical) | Validates topical therapy; combined strategy shows synergy | Mouse scarring mechanism differs from humans (e.g., hypertrophic scars) | ||
| hAECs |
Enhances repair: ↑fibroblast migration/proliferation, modulates ECM, ↑orderly collagen alignment [50] |
SD rat full-thickness wound; human dermal fibroblasts (in vitro) | Medium–High (Preclinical) | New candidate for scar-minimizing therapy | “Scarless healing” is model-specific, not directly translatable | |
| iPSC-iMSCs | Boosts keratinocytes: iMSC-exos > MSC-exos via ERK1/2; s.c. exosomes internalized in vivo [51] | In vitro: HaCaT & fibroblasts; In vivo: s.c. tracer (mice) | Medium (Preclinical) | iPSCs as a scalable, standardized exosome source | Lacks functional wound model; caution extrapolating cell-line data | |
| Pigmented barrier | hAMSC | Lightens pigmentation: Inhibits melanogenesis (α-MSH/UVB) & promotes melanosome degradation via autophagy; key effector miRNAs: -181a-5p, -199a [52] | Models: B16F10 cells; mouse ear UVB model; 3D human skin substitute | Medium–High (Preclinical) | Dual-pathway (“block synthesis + clear”) strategy with defined molecular targets (miRNAs) | Exosome-only efficacy data needed; mouse model differs from complex human conditions (e.g., melasma) |
| Microbial barrier | eMSCs | Fights infection: Equine MSC-CM directly disrupts MRSA biofilm; CCL2 within CM ↑ keratinocyte AMPs to enhance innate immunity [53] | Ex vivo: Equine skin explant (MRSA biofilm); In vitro: primary equine keratinocytes | Medium (Preclinical) | Novel “direct + host-directed” strategy against drug-resistant wound infections | Species-specific (equine); active components are in CM, not purified exosomes. microenvironment; the effective substance is a CM, not purified exosomes |
| Nerve barrier | hUC-MSCs | Relieves sensitive skin: Improves objective symptoms & repairs epidermal barrier; safe in 28-day trial (no SAEs) [54] | Human trial: Single-arm, self-controlled pilot study | High (Clinical) | Direct proof of safety & efficacy for topical use in humans | Small, homogeneous cohort; short follow-up; mechanism of action unclear |
| Immune barrier | hASCs | Combats AD: ↓clinical score, ↓serum IgE/eosinophils, ↓skin inflammation (multiple cytokines) [55] | Model: NC/Nga mice, house dust mite-induced AD; Design: Multi-dose, IV/SC | High (Preclinical) | Validates efficacy in a mainstream model; demonstrates multi-target (Th2/IL-23/IL-31) potential | Donor variability; long-term safety unknown |
| hT-MSCs | Tames mast cells: Inhibits activation (TLR7-mediated) & skin inflammation; exosomal miRNAs target M-CSF/IL-8 [56] | Models: TLR7-stimulated human mast cell line; mouse imiquimod model (s.c.) | Medium–High (Preclinical) | Novel rationale for TLR7-driven disorders (e.g., psoriasis subtypes, pruritus) | miRNA-phenotype link is correlative; lacks causal functional validation | |
| hUC-MSCs | Ameliorates psoriasis: Improves phenotype, inhibits IL-23/IL-17 axis & dendritic cell activation [57] | Model: Imiquimod-induced mouse dermatitis; Validation: HaCaT & dendritic cells in vitro | Medium–High (Preclinical) | Novel cell-free strategy targeting the core therapeutic axis of psoriasis | Acute chemical model differs fundamentally from chronic human disease | |
| cASCs | Works across species: Canine MSC-exos repair barrier & modulate itch signaling in a mouse AD model [58] | Model: DNCB-induced mouse AD, for cross-species assessment | Medium–High (Preclinical) | A promising cell-free candidate for veterinary use (canine AD) | Preclinical study aimed at veterinary translation | |
| eMSCs | Induces immune tolerance: Mediates antigen-dependent suppression of GVHD & improves survival [59] | Models: Mouse CD4 + T cells in vitro; humanized mouse GVHD model in vivo | High (Preclinical) | Reveals critical prerequisite (antigen presentation) for precise immunotherapy | GVHD model differs immunologically from common skin diseases | |
| Antioxidant barrier | hUC-MSCs | Shields from photo-damage: Activates NRF2 pathway to resist oxidative stress & boost antioxidant capacity [60] | Model: UV-induced damage in wild-type vs. Nrf2-knockout mice | High (Preclinical) | Strategy to combat photoaging by boosting endogenous NRF2 defense | Acute model ≠ chronic photoaging; vs. conventional antioxidants (e.g., Vit C/E) unknown; active component unclear |
To clearly present the evidence strength and translational potential of the included studies, the key mechanistic research discussed in the text is summarized in this table. It details the study models, evidence levels, and major limitations for clinical translation, aiming to help readers critically assess the findings. The evidence levels were rated with reference to the GRADE framework, integrating the rigor of study design, clinical relevance of the models, and depth of mechanistic exploration: High = rigorous animal/clinical study; Medium–High = systematic animal study; Medium = in vitro or preliminary animal study [61, 62]
Human Adipose-derived Stem Cells (hASCs);Human Amniotic Epithelial Stem Cells (hAECs)
Induced Pluripotent Stem Cell-derived MSCs (iMSCs);Human Tonsil-derived MSCs (hT-MSCs)
Human Umbilical Cord MSCs (hucMSCs);Canine Adipose-derived Stem Cells (cASCs);Equine MSCs (eMSCs)