Therapeutic potential of stem cell-derived exosomes in hair regeneration: A systematic review

Table 2 Summary of the main findings of included pre-clinical studies involving exosomes for hair regeneration

Ref.	Title	Country	Sources of exosomes	Treatment groups	Main study outcomes
Rosalina et al[75], 2023	Placenta extract-loaded novasome significantly improved hair growth in a rat in vivo model	Indonesia	Bovine PE-loaded novasomes	Control group: No treatment	Hair growth acceleration: The PE-novasome group showed earlier and more even hair growth compared to other groups. By day 14, the control group still had incomplete hair coverage, while all the treatment groups had full coverage. Hair length & diameter: At week 4, the PE-novasome group had the longest hair (14.19 mm), followed by PE-liposome (12.54 mm), minoxidil (12.05 mm), and control (8.50 mm). Hair diameter was significantly thicker in the PE-novasome group (120.68 μm) compared to PE-liposome (90.06 μm), minoxidil (49.98 μm), and control (38.59 μm). Anagen-telogen ratio: PE-novasome group had the highest anagen/telogen ratio (4.25), followed by PE-liposome (3.41), minoxidil (2.66), and control (1.88). Hair weight evaluation: Hair weight on day 28 was highest in the PE-novasome group (128.6 mg), significantly greater than PE-liposome (110.7 mg), minoxidil (104 mg), and control (83.4 mg). Novasome characterization & stability: PE-loaded novasomes had 155.0 nm particle size, polydispersity index of 0.139, and entrapment efficiency of 79.60%. Transmission electron microscopy confirmed non-aggregating, oligolamellar nanovesicles. Stable at 4 °C for 90 days with minimal changes in size and entrapment efficiency
				Minoxidil group: Treated with 2% minoxidil solution
				PE-liposome group: Treated with PE-loaded liposomes
				PE-novasome group: Treated with PE-loaded novasomes
Zöller et al[39], 2018	Immunoregulatory effects of myeloid-derived suppressor cell exosomes in mouse model of autoimmune alopecia areata	Germany	MDSCs isolated from bone marrow cells of healthy donor mice	Control group: Mice with alopecia areata receiving no treatment	Hair growth acceleration: MDSC-Exo-treated mice showed partial hair regrowth, preventing the progression of alopecia areata. MDSC-Exo homing was the strongest in activated immune cells. Live imaging confirmed exosome uptake in skin-draining lymph nodes and near hair follicles. Histological analysis: H&E staining showed increased Treg infiltration in MDSC-Exo-treated mice. T helper cell proliferation was significantly reduced, and cytotoxic T-cell activity was suppressed. Immunomodulation & gene expression: FoxP3 (Treg marker) and arginase 1 mRNA levels increased in MDSC-Exo-treated mice. Treg expansion was a dominant feature, supporting immune tolerance in AA. Cytotoxic activity of T cells was suppressed, reducing inflammation. Exosome characterization & targeting: MDSC-Exo were 30-100 nm in diameter, confirmed via transmission electron microscopy. Flow cytometry showed that MDSC-Exo preferentially targeted Tregs, macrophages, and NK cells. Exosome uptake exceeded the binding of MDSCs themselves, suggesting stronger immunoregulatory effects. In vivo distribution & effects: MDSC-Exo were detected in lymphoid tissues and near hair follicles 8-48 hours after injection. Repeated MDSC-Exo injections reduced inflammatory cytokines (IL-1β, IL-6) and increased IL-10 expression
				MDSC-Exo group: AA mice treated with MDSC-derived exosomes
				MDSC group: AA mice treated with MDSCs
				SADBE group: AA mice treated with squaric acid dibutylester, a known therapeutic agent for AA
				MDSC group: AA mice treated with MDSCs
Mao et al[46], 2024	Exosomes derived from umbilical cord mesenchymal stem cell promote hair regrowth in C57BL6 mice through upregulation of the RAS/ERK signaling pathway	China	Umbilical cord mesenchymal stem cells	Blank group: No treatment	Hair growth acceleration: Model group had significantly shorter and thinner hairs compared to the blank group. Exosome hydrogel-treated mice showed longer hair length, greater hair diameter, and more hair follicles than the model group. Histological analysis: H&E staining revealed increased hair follicle number and size in the exosome group compared to the model group. AR expression: Model group exhibited significantly higher AR mRNA and protein levels, which were reduced in the exosome hydrogel group. HFSC markers: K15 and CD200 expression increased in the exosome group, indicating improved stemness of HFSCs. PCNA expression (a marker of proliferation) was significantly upregulated in exosome-treated mice. Molecular mechanism (transcriptomics & pathway analysis): KEGG analysis identified the RAS/ERK pathway as significantly activated in the exosome group. Exosome treatment upregulated p-Raf, p-MEK1/2, p-ERK1/2, and RAS expression, confirming ERK/MAPK pathway activation. Western blot showed reduced expression of AR and increased expression of MAPK-related proteins in exosome-treated mice
				Model group: Injected with dihydrotestosterone solution (AGA induction)
				Positive control group: Treated with 5% minoxidil solution
				Exosome hydrogel group: Treated with hUCMSC-derived exosome hydrogel

PE: Placenta extract; MDSCs: Myeloid-derived suppressor cells; hUCMSCs: Human umbilical cord mesenchymal stem cells; Treg: Regulatory T-cell; AR: Androgen receptor; HFSC: Hair follicle stem cell; PCNA: Proliferating cell nuclear antigen; H&E: Hematoxylin and eosin; NK: Natural killer; IL: Interleukin; KEGG: Kyoto Encyclopedia of Genes and Genomes; ERK: Extracellular signal-related kinase; MAPK: Mitogen-activated protein kinase.