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

Table 4 Summary of the main findings of included clinical studies involving exosomes for hair regeneration

Ref.	Title	Country	Sources of exosomes	Groups in study	Results/key outcomes
Gentile et al[29], 2015	The effect of platelet-rich plasma in hair regrowth: A randomized placebo-controlled trial	Italy, India, Turkey (multicentric study)	Autologous micrografts containing EVs derived from human follicle mesenchymal stem cells	MPHL group: 40 males (Norwood-Hamilton stages I-III vertex); FPHL group: 20 females (Ludwig stages I-II)	HD increase: FPHL group: HD increased by 28 ± 4 hairs/cm2 after 12 months (P = 0.0429). MPHL group: HD increased by 30 ± 5 hairs/cm2 after 12 months (P = 0.0012)
					Trichoscopic analysis: Baseline HD (T0): 114 ± 5 hairs/cm2 (FPHL), 108 ± 3 hairs/cm2 (MPHL). Post-treatment HD (T4, 12 months): 142 ± 4 hairs/cm2 (FPHL), 138 ± 4 hairs/cm2 (MPHL). No significant changes in vellus HD, hair thickness, or anagen/telogen ratio
					Physician’s global assessment: 70% of patients (42/60) reported improved global scalp coverage (P = 0.045)
					Patient satisfaction: 80% of patients (48/60) reported a good level of satisfaction (P = 0.021)
					In vitro exosome analysis: EVs were 95.9-123.2 nm in size, with concentrations ranging from 108 to 1010 particles/mL
					Transmission electron microscopy confirmed lipid bilayer vesicle morphology. Fluorescence microscopy showed EV uptake by fibroblasts, confirming cellular interaction
Lee et al[51], 2024	The efficacy of adipose stem cell-derived exosomes in hair regeneration based on a preclinical and clinical study	South Korea	Adipose stem cell derived exosomes	In-vitro groups: HDPCs treated with ASC-exosomes (8 μg or 40 μg); ex-vivo groups: Human hair follicles treated with ASC-exosomes (8 μg or 40 μg) or 20 μmol/L minoxidil; clinical groups: 30 patients with androgenetic alopecia treated with ASC-exosomes (ASCE + HRLV®) over 24 weeks	In vitro & ex vivo findings: (1) hDPC proliferation: ASC-exosomes increased hDPC proliferation in a concentration-dependent manner (P < 0.05) compared to controls; (2) Hair follicle growth: Hair shaft elongation was significantly greater in the ASC-exosome 40 μg group than in controls (P = 0.03); (3) Gene & protein expression: ALP, VCAN, β-catenin, and LEF-1 mRNA levels were upregulated in ASC-exosome-treated hDPCs (P < 0.05). Western blot confirmed increased β-catenin and phosphorylated GSK3β, indicating Wnt/β-catenin pathway activation; and (4) Immunostaining: Ki67 and β-catenin expression was highest in ASC-exosome-treated follicles, suggesting enhanced cell proliferation
					Clinical findings: (1) HD increase: Baseline: 158.03 ± 16.48 hairs/cm2. Week 12: 161.90 ± 17.78 hairs/cm2 (P = 0.033). Week 24: 166.14 ± 19.57 hairs/cm2 (P < 0.001); (2) Global photographic assessment: Week 12: 31.03% of patients showed slight improvement, 3.45% showed marked improvement (P = 0.023). Week 24: 41.38% had slight improvement, 10.34% had marked improvement (P = 0.004); (3) Subjective satisfaction: 52.72% of patients reported improved HD (P < 0.001). 55.17% noted reduced daily hair loss (P = 0.003). 58.62% reported thicker hair strands (P < 0.001); and (4) Adverse reactions: Mild scalp tingling and erythema were observed but resolved quickly. No severe adverse effects reported
Lueangarun et al[81], 2024	Rose stem cell-derived exosomes for hair regeneration enhancement via noninvasive electroporation in androgenetic alopecia	Thailand, South Korea	RSCEs	Single case study: 54-year-old male with Norwood-Hamilton scale V androgenetic alopecia	Hair growth improvement: After three treatment sessions, the patient showed increased HD and thickness. Significant regrowth observed by the 6th and 12th sessions, with continued improvement three months post-treatment
					Dermoscopy & clinical evaluation: Dermoscopic images showed increased HD and shaft thickness after six and twelve treatment sessions
					Exosome characterization: RSCEs were 100-200 nm in diameter, confirmed by nanoparticle tracking analysis and cryo-electron microscopy. Proteomic analysis identified 206 proteins, including cell membrane components, enzymes, and RNA-binding proteins. RSCEs contained Let-7 family miRNAs, miR-8485, miR-574-5p, and miR-1246, which are linked to cell proliferation and inflammation regulation
					Mechanism of action: RSCEs activated the Wnt/β-catenin signaling pathway, promoting dermal papilla proliferation and follicular development. Reduced inflammation and oxidative stress, supporting hair regeneration
					Treatment protocol: 5 mL of lyophilized RSCEs (20 mg) applied via electroporation every 3 weeks for 12 sessions. Electroporation enhanced exosome penetration, avoiding the need for invasive injections
					Adverse events & safety: No serious adverse effects reported

EVs: Extracellular vesicles; RSCEs: Rose stem cell-derived exosomes; MPHL: Male pattern hair loss; FPHL: Female pattern hair loss; hDPCs: Human dermal papilla cells; ASCs: Adipose-derived stem cells; HD: Hair density; ALP: Alkaline phosphatase; VCAN: Versican; LEF-1: Lymphoid enhancer-binding factor 1; GSK3β: Glycogen synthase kinase-3β; miRNAs: MicroRNAs.