Efficacy of Exosome-Based Therapies for Skin Rejuvenation: A Systematic Review of Human Studies
Julio César Flores Rodríguez, Luiz Eduardo Toledo Avelar, Kyuho Yi, Rodrigo Merino Arellano, Jesús Antonio López Rodríguez, Miriam Selene Garza Vargas
TL;DR
This review evaluates how well exosome-based treatments work for improving skin appearance in humans, finding some short-term benefits but calling for better research.
Contribution
A systematic review of human studies on exosome-based skin rejuvenation therapies, highlighting clinical outcomes and methodological gaps.
Findings
Exosome-based therapies improved skin hydration, elasticity, and appearance in the short term.
Most studies reported a positive safety profile for topical application.
Lack of randomized trials and follow-up limits the strength of the evidence.
Abstract
Exosomes are secreted tiny organelles that are single-membrane enclosed and can perform a broad spectrum of functions upon release, such as the reorganization of extracellular matrix and communication with other cells through the release of signals and chemicals, which play an important role in development, immunity, tissue homeostasis, cancer, and neurodegenerative diseases, among other aspects of human health and disease. This systematic review aimed to evaluate the clinical efficacy and safety of exosome-based therapies for skin rejuvenation in human populations and to identify gaps in the existing evidence. A methodological literature search was performed in databases such as PubMed, Scopus, Cochrane Library, and Web of Science with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Clinical experiments that were conducted on humans to…
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Figure 1
Figure 2| Database | Search strategy | Filters applied | Records retrieved |
| PubMed/MEDLINE | (("Exosomes"[MeSH Terms] OR exosome*[Title/Abstract] OR "extracellular vesicle*"[Title/Abstract]) AND ("Skin Aging"[MeSH Terms] OR "skin rejuvenation"[Title/Abstract] OR "skin aging"[Title/Abstract] OR "facial rejuvenation"[Title/Abstract] OR "aesthetic dermatology"[Title/Abstract]) AND (humans[MeSH Terms])) | Case reports; clinical study; clinical trial (phase I-IV); clinical trial protocol; comparative study; controlled clinical trial; multicenter study; observational study; randomized controlled trial; English; humans | 113 |
| Cochrane Library | (exosome* OR "extracellular vesicle*") AND ("skin rejuvenation" OR "skin aging" OR "facial rejuvenation" OR photoaging OR "aesthetic dermatology") AND (human* OR patient* OR clinical*) | No additional filters | 10 |
| Scopus | TITLE-ABS-KEY (exosome* OR "extracellular vesicle*") AND TITLE-ABS-KEY ("skin rejuvenation" OR "skin aging" OR "facial rejuvenation" OR photoaging OR "aesthetic dermatology") AND TITLE-ABS-KEY (human* OR patient* OR clinical) | No additional filters | 138 |
| Web of Science | TS=((exosome* OR "extracellular vesicle*" OR "small extracellular vesicle*" OR "exosome-derived") AND ("skin aging" OR "skin ageing" OR photoaging OR "photo-aging" OR photodamage OR rejuvenat* OR antiaging OR "anti-aging") AND (human* OR patient* OR clinical OR trial OR prospective OR randomized OR randomised OR volunteer* OR "in vivo")) NOT TS=(review OR "systematic review" OR meta-analysis OR "meta analysis" OR mouse OR mice OR rat OR murine OR rabbit* OR porcine OR bovine OR "guinea pig") | Excluded reviews and animal studies | 19 |
| Study | Country/setting | Design | Sample size (n) | Population (age/sex) | Indication | Exosome source/type | Delivery | Comparator/control | Follow-up duration | Key outcomes measured |
| Estupiñan et al. [ | USA; single outpatient dermatology clinical research center (NJ) | Non-randomized, investigator-blinded, split-face, non-inferiority trial | 15 enrolled (1 discontinued biopsy) | Age: 44-68; male & female; Fitzpatrick I-IV | Photoaged facial skin (mild-moderate photoaging) | Human adipose mesenchymal stem cell-derived exosomes (BENEV topical products; includes ADSC exosomes; EXO BALM contains ADSC + rose plant stem cell exosomes + other actives) | Topical application postradiofrequency microneedling (RFMN) to one hemiface | PRP/PRFM applied to the opposite hemiface post-RFMN (Selphyl PRFM system) | Photos and clinical grading at baseline, 3 months, 6 months; biopsies baseline/3/6 months in the first 10 | Wrinkling, dyschromia, erythema, texture, overall appearance, Griffiths photoaging scale, histology, collagen I/III, GAGs, safety/AEs |
| Kang et al. [ | Single-center clinical research organization (country not stated in excerpt) | Non-randomized prospective single-arm (pre-post) | 25 | 40-59 yrs; 18F/7M; mean 49.6±3.3; Fitzpatrick II–IV | Facial photoaging/anti-aging | Autologous blood-derived EVs (SEC isolation; NTA modal ~90 nm) | Single intradermal facial injection (33G; mid-to-deep dermis) | None (no control) | Day 5 and Week 3 | Wrinkles, lifting, hydration, TEWL, elasticity, tone/radiance, texture, pores, skin density, subjective satisfaction, AEs |
| Cho et al. [ | Single medical institution, South Korea | Retrospective chart analysis (case series) | 40 | Mean age 41.2±6.3; 32F/8M; Fitzpatrick II-IV | Facial aging/rejuvenation | Commercial exosome-containing skin booster (CUREDOC EXOSOME REPAIR Advanced Solution Skin Booster), 50 mcg/mL | Microneedling (0.25–1.0 mm; 3 passes) + topical/application of exosome booster (3 mL) + LED 5 minutes | None | Followed 8 weeks after the final session (treatment: 4 sessions every 2 weeks) | GAIS from photos, satisfaction (Likert + VAS), intention to repeat/recommend, adverse events |
| Park [ | South Korea; dermatology clinic follow-up after procedures done in non-medical settings (beauty salons/non-derm clinics) | Non-randomized case series | 4 | Adult women: 31, 33, 40, 42 (female only) | Aesthetic skin rejuvenation (off-label injection use) | “Exosome-containing formulation” (exact product/source not specified; unregulated) | Intradermal injection (performed outside medical supervision) | None | Persistent lesions; long course (some cases traced to injections in 2018, 2020, 2021) | Safety outcomes: erythema, nodules, persistent inflammation, scarring; treatment response |
| Shieh et al. [ | Taiwan (clinical evaluation; IRB NCKU HREC No. 113-182-2) | Prospective, single-arm, open-label | Hair: 30 (M/F) + Face: 30 (F) | 30-65 yrs; facial cohort females only | Skin rejuvenation and hair regrowth | Bio-Pulsed avian MSC-derived sEVs/EVs (primed with | Topical: scalp ampoule regimen 60 days; facial essence twice daily 28 days | No control group (single-arm) | Hair: 60 days (D0/D30/D60); Face: 28 days (multiple timepoints) | Hair: A/T ratio, telogen %, shedding, density, questionnaire. Face: wrinkle depth, pore size, firmness, collagen density, melanin/erythema, gloss, UV spots, irritation erythema model, questionnaires, AEs |
| Sileo et al. [ | Human cosmetic testing setting + lab safety assays | Non-randomized clinical | 20 (anti-wrinkle study); 20 (lenitive/redness study) | Anti-wrinkle: 41-69 y, both genders; Lenitive: 18-65 y, both genders (Caucasian) | Anti-aging, soothing/redness reduction, and safety | ADVs in a topical formulation (reported as 2% ADV-based formulation for efficacy tests) | Topical | Anti-wrinkle: no stated placebo control (pre-post); Lenitive: hydrocortisone acetate comparator area + irritant model | 60 days (anti-wrinkle); 60 minutes post-application (lenitive) | Wrinkle parameters (length/volume/roughness/depth), redness reduction, in vitro safety: genotoxicity, ocular toxicity, irritation/corrosion, sensitization |
| Wan et al. [ | South Korea; private aesthetic clinic | Prospective case series (non-randomized) | 3 | 32–55 years; 1 male, 2 females; Fitzpatrick IV | Facial pore reduction, skin texture improvement | Stem-cell-derived exosomes (Exodew; pharyngeal stem cell origin) | Topical exosomes applied immediately after microneedling (0.5 mm) | None | 22 weeks | Pore size, skin texture, GAIS (clinician-rated), patient satisfaction, safety |
| Kang et al. [ | Korea (industry + university) | Non-randomized pre-post | 8 (human efficacy); 14 (microbiome substudy) | Human efficacy: females 40-60 (n = 8); Microbiome: females 20-39 (n = 14) | Skin rejuvenation/anti-photoaging | LAEs from | Topical toner (5% LAEs), twice daily | None stated (single arm) | 8 weeks (efficacy); 4 weeks (microbiome) | Wrinkles, hydration, redness, texture/roughness, pore area; microbiome diversity/composition; safety observations |
| Wyles et al. [ | USA (dermatology clinics) | Prospective non-randomized, | 56 | Mean age 54 y; adults (sex not specified) | Facial skin rejuvenation | Human platelet-derived extract (HPE) containing platelet exosomes | Topical serum, twice daily | None (single-arm) | 12 weeks | Pigmentation, luminosity, color evenness, collagen & elastin histology, safety |
| Svolacchia et al. [ | Italy | Non-randomized uncontrolled clinical evaluation | 72 | Female; 34-68 y (mean 48) | Facial chrono-/photoaging, wrinkles, furrows | ADSC-derived signaling vesicles/exosomes from adipose tissue; conditioned with Skin-B®; ultrafiltered (0.20 µm); “Jaluexos” | Injection (mesotherapy microinjections) into the dermis | None | Follow-ups reported at 15 & 30 days; some figures also show 90 days | Berardesca Scale (satisfaction), NRS (wrinkle/defect severity), VAS, Modified Vancouver Scale (stability/softness/hydration), safety, and flow cytometry markers (CD81/CD146) |
| Lu et al. [ | China (clinical + lab setting) | Non-randomized, single-arm clinical study | 31 | Females, 26-45 y | Skin anti-aging | Bovine milk-derived exosomes (MK-Exo) | Topical application (twice daily) | None (pre–post comparison) | 28 days | Skin hydration, elasticity, wrinkle count/area, safety |
| Nguyen et al. [ | Vietnam (clinical study + lab work; devices from South Korea/Ireland noted) | Non-randomized, prospective study | 3 | Adults 30-40 y; sex not clearly stated in excerpt | Skin rejuvenation and photoaging protection | Human adipose-derived stem cell small EVs (ADSC-sEVs) loaded with NR + NAD+ + resveratrol | Topical application on the dorsal hand (daily) | Placebo (0.9% saline) on the opposite hand | 8 weeks | Texture, hydration/moisture, elasticity, pore volume, pigmentation/redness/melanin, irritation/s |
| Chernoff [ | Not clearly stated (clinical aesthetic setting) | Prospective, non-randomized, multi-arm clinical study | 40 | 35F/5M; age 34-72 | Aesthetic skin quality/biostimulation | Placental MSC-derived exosomes (topical emulsion; 1 million in 1 cc stated) | Dermal infusion protocol (exfoliation + NO serum + ultrasound + emulsion + cavitating ultrasound + LED); sometimes followed by CaHA injection | Active comparators: CaHA alone groups (no dermal infusion) | 15 & 30 days (Quantificare mentioned; results shown at 30 days) | Quantifiable metrics (wrinkles/pores/evenness/vascularity/oiliness/pigment), satisfaction, AEs |
| Proffer et al. [ | USA; single center (Mayo Clinic, Rochester, MN) | Prospective, single-arm, non-randomized longitudinal study | 56 | Age 40-80 (mean 54 ± 11); 8M/48F; Fitzpatrick I-IV | Facial skin rejuvenation/photodamage & aging | Human platelet extract (HPE), platelet-derived exosome product (“plated” Intensive Repair Serum) | Topical application as part of a standardized twice-daily regimen | No control group (within-subject baseline vs 6 weeks) | 6 weeks (±4 days) | VISIA-CR/PRIMOS: wrinkles, erythema, brown spots, luminosity, color evenness, SHS, blinded surgeon photo scoring, participant questionnaires, AEs |
| Jo et al. [ | Korea; clinical testing site (Korea Dermatology Research Institute IRB) + in vitro lab work | Human: placebo-controlled study | 20 recruited; 16 completed (4 dropouts) | Human trial: Korean women, ~50s average (exact mean not provided) | Skin aging (wrinkles, elasticity, moisture, density, pigmentation) |
| Topical application by participants (agent mix; twice daily) | Mannitol 5% placebo vs mannitol 5% + LpEVs | 4 weeks (0, 2, 4 weeks) | Wrinkles (Antera 3D), elasticity (Cutometer), dermal density (ultrasound), skin imaging (MARK-Vu), moisture, pigmentation, and in vitro ECM gene/protein markers (MMP-1, COL1A1, FLG, HAS2) |
| Kerscher et al. [ | Germany: 6 clinical centers | Prospective, one-armed, multi-center interventional study | 95 | Women: 30-65 yrs (mean 50.2 ± 8.9) | Facial skin aging/firmness loss | Cell-free blood cell secretome (BCS/ACS) containing cytokines, growth factors, and exosomes | Intra-dermal injections (4 sessions at 0, 2, 4, 6 weeks) | None (no placebo/control arm) | 48 weeks | Skin firmness (R0), skin tiring (R3), FACE-Q™, GAIS, patient-perceived age, safety |
| Park & Shin [ | Korea; ACE Clinical Research Center (Seoul) | Non-randomized, single-arm pre-post study | Patch test 30; Efficacy 20 (1 dropout from 21) | Patch: adults 35-69 (mean 54); Efficacy: female, 34-63 (mean 50.7 ± 8.9) | Anti-aging skincare/skin rejuvenation |
| Topical ampoule twice daily | None (no placebo/control) | Patch: 24 h; Efficacy: 14 days | Patch irritation; pore parameters (Antera 3D); wrinkle depth (Antera 3D); layered hydration (MoistureMeter D; TDC); dermal density (ultrasound) |
| Wyles et al. [ | Single-center (Mayo Clinic IRB; Rochester, MN, USA) | Non-randomized prospective longitudinal single-arm | 20 | Mean age 54 (SD 11); 18F/2M; Fitzpatrick: mostly I–II | Skin rejuvenation/healthy skin aging | Human platelet extract (HPE) containing platelet-derived exosomes/EVs (allogeneic, leukocyte-depleted pooled platelets) | Topical HPE serum twice daily | None (no placebo/control) | 12 weeks | Senescence markers (p16INK4a, p21CIP1/WAF1); telomere-associated foci (TAF) & γH2AX; RNA-seq |
| Chang et al. [ | Taiwan (HungKuang University site) | Non-randomized clinical study | Treatment 20; Post-hoc placebo 10 | Treatment: mean age 36.5; 16F/4M (as stated). Placebo: mean age 40.1; 8F/2M | Facial skin rejuvenation/cosmetic anti-aging |
| Topical serum, 0.1 mL, twice daily for 28 days | EV-free identical base serum (post-hoc, non-concurrent placebo) | 28 days (Days 0, 7, 14, 21, 28) | Hydration, elasticity, melanin; wrinkles, redness, pores (VISIA), and irritation/safety |
| Study | Outcome domain | Measurement tool | Timepoints | Results (baseline → follow-up) | Between-group effect | Statistical significance (p/CI) | Authors’ conclusion |
| Estupiñan et al. [ | Global appearance + wrinkles + dyschromia + erythema + texture | Investigator-rated 5-point scale (0-5) using standardized photos (blinded) | Baseline; 3 months; 6 months | Overall average score baseline 2.12 both sides → PRP 2.70 (3 months), 3.04 (6 months) vs exosomes 2.68 (3 months), 3.14 (6 months) | The exosome side had a slightly greater improvement in wrinkling/erythema/texture; overall appearance & dyschromia were similar | No statistical tests for investigator clinical assessments (small n) | Both treatments improved photoaging features; exosomes were non-inferior clinically |
| Photoaging severity | Griffiths Photonumeric Photoaging Scale (0-8) | Baseline; 3 months; 6 months | Baseline 4.5 both sides → 3.1 (3 months) and 3.6 (6 months) both sides; reported % improvement vs baseline: 37% at 3 months, 22% at 6 months | No difference reported | Not reported (clinical scale comparisons descriptive) | Similar improvement with both arms | |
| Dermal regeneration | Histology: Collagen I/III stains; Alcian blue (GAGs); pathologist scoring + automated image analysis | Baseline; 3 months; 6 months (first 10 participants; 74 samples) | Increased collagen I and GAGs over time in both arms; collagen III total was not different, but stronger staining increased over time | No meaningful arm difference | Paired t-tests/t-tests were used for histology comparisons; there were no significant differences between arms (exact p-values were not provided in your excerpt) | Histology supports dermal remodeling with both; no superiority | |
| Safety | AE assessment (mild/mod/severe); monitored throughout | Each visit, post-procedure week | No adverse events; expected transient mild pain/erythema/edema/crusting resolved <1 week | N/A | N/A | Topical exosomes are well-tolerated; comparable to PRP side effects | |
| Kang et al. [ | Wrinkles | Antera 3D CS | Baseline, Day 5, Week 3 | Periorbital wrinkle depth: -19.05% at Week 3; nasolabial wrinkle depth: -19.68% at Week 3 | N/A (single-arm) | p < 0.05 (Wilcoxon; per caption) | EVs improve wrinkles over 3 weeks |
| Lifting/firmness | Antera 3D lifting index/lift volume | Baseline, Day 5, Week 3 | Periorbital lift volume -17.55%, Nasolabial lift volume -29.38% at Week 3 | N/A | p < 0.05 | Improved firmness/lifting | |
| Hydration | Corneometer CM 825 | Baseline, Day 5, Week 3 | +22.65% (Day 5), +34.52% (Week 3) | N/A | p < 0.05 | Increased hydration | |
| Barrier function | TEWL via Tewameter TM 300 | Baseline, Day 5, Week 3 | TEWL -16.17% (Day 5), -25.85% (Week 3) | N/A | p < 0.05 | Improved barrier | |
| Elasticity | Cutometer (R2) | Baseline, Day 5, Week 3 | R2 +17.81% (Day 5), +29.76% (Week 3) | N/A | p < 0.05 | Increased elasticity | |
| Texture | Antera 3D (Ra roughness) | Baseline, Day 5, Week 3 | Ra -17.11% at Week 3 | N/A | p < 0.05 | Smoother texture | |
| Pores | Antera 3D (pore area/volume) | Baseline, Day 5, Week 3 | Pore area: -32.35% (Day 5), -46.80% (Week 3); Pore volume: -36.16% (Day 5), -50.62% (Week 3) | N/A | p < 0.05 | Pore refinement | |
| Tone/radiance | VISIA-CR (L-value, radiance intensity) | Baseline, Day 5, Week 3 | Tone and radiance significantly improved at Day 5 and Week 3 (exact values not in the excerpt). | N/A | p < 0.05 | Brighter/radiant skin | |
| Dermal regeneration proxy | 22 MHz ultrasound skin density | Baseline, Day 5, Week 3 | Skin density +10.43% at Week 3 | N/A | p < 0.05 | Increased density/compactness | |
| Cho et al. [ | Global aesthetic improvement | GAIS (3 independent evaluators from photos) | Baseline → follow-up (8 weeks after final treatment) | 40% very much improved, 45% much improved, 12.5% improved, 2.5% no change → 97.5% improved overall | N/A | Not reported in excerpt | Combination therapy improved facial aging |
| Patient satisfaction | Likert + VAS + willingness items | Follow-up | Overall satisfaction: 87.5%; 82% would repeat; 85% would recommend | N/A | Not reported | High acceptance and satisfaction | |
| Texture/tone (qualitative) | Clinical photos (descriptive) | Follow-up | Photos show improvement in texture/tone (no numeric device outputs provided) | N/A | Not reported | Visible improvements reported | |
| Kang et al. [ | Safety/adverse events | Clinical observation and photos; treatment records | After injection → dermatology presentation → post-treatment course | 4/4 developed persistent inflammatory reactions (erythema, nodules; incomplete resolution; residual scarring common) | N/A | N/A | Off-label intradermal injection of unapproved exosome formulations may cause serious, persistent cutaneous complications; regulation and education are needed |
| Shieh et al. [ | Wrinkles | Antera 3D | Day 0, 7, 14, 28 | Wrinkle depth ↓ (reported ~7.5% at Day 28) | N/A | Day 14: p = 0.0288; Day 28: p < 0.0001 | Topical Bio-Pulsed AMSC-sEVs improved facial aging markers |
| Firmness/elasticity | DermaLab Combo (elastometry) | Day 0, 7, 14, 28 | Firmness ↑ 14.0% by Day 28 | N/A | Day 14 p < 0.0001; Day 28 p < 0.0001 | Improved dermal mechanical properties | |
| Collagen/dermal regeneration | DermaLab Combo (20 MHz ultrasound) | Day 0, 7, 14, 28 | Collagen density ↑ 18.2% at Day 28 | N/A | p < 0.0001 | Suggests dermal matrix improvement | |
| Pores | Antera 3D | Day 0, 7, 14, 28 | Pore area ↓ 8.5% at Day 28 | N/A | p < 0.0001 | Reduced pore size | |
| Pigmentation | Mexameter MX18; Antera 3D; VisioFace RD | Day 0 → Day 28 | Melanin index ↓ 6.5%; pigmented spots ↓ 5.3%; UV spots ↓ 5.3% | N/A | p < 0.0001 for these reported endpoints | Improved tone/brightness | |
| Erythema/redness | Antera 3D; irritation model (Chromameter a-value) | Baseline → Day 28; irritation follow-up | Erythema index ↓ 3.9% at Day 28 (p = 0.0101). Irritation model: redness reduction 14.2% vs 9.4% control at 60 min | Internal untreated control in the irritation model only | p < 0.0001 (irritation model); p = 0.0101 (facial erythema) | Mild but significant soothing/anti-inflammatory effect | |
| Hair outcomes (supportive) | Scalp analyzer, comb test, imaging | D0/D30/D60 | A/T ratio ↑ (1.32→1.97); telogen % ↓; shedding ↓ (8.60→4.60 hairs) | N/A | Multiple significant comparisons were reported | Improves hair cycling and reduces shedding | |
| Sileo et al. [ | Wrinkle length | Antera 3D | T0, T30, T60 | Reduced over time (exact baseline values not provided in your excerpt; Table | No placebo stated | p < 0.05 (reported as significant reduction) | ADV formulation improved wrinkle appearance |
| Wrinkle volume | Antera 3D | T0, T30, T60 | Reduced over time (Table | No placebo stated | p < 0.05 | Reduced wrinkle volume | |
| Roughness (Ra) | Antera 3D | T0, T30, T60 | Improved (decreased roughness) by T60 (Table | No placebo stated | p ≤ 0.05 | Smoother skin surface | |
| Wrinkle depth | Antera 3D | T0, T30, T60 | Small change (Table | No placebo stated | Not significant (as described) | Depth not meaningfully changed | |
| Skin redness (soothing/lenitive) | Instrumental redness probe | 15, 30, 60 minutes after the product | Redness reduced at 60 minutes vs irritant baseline | Compared with the hydrocortisone area (faster effect) | p < 0.05 at 60 min | ADV cream reduces irritation-related redness (slower than hydrocortisone but effective) | |
| Wan et al. [ | Pore size | Standardized clinical photography; GAIS | Baseline; 12 & 22 weeks | Visible reduction in pore size in all patients; GAIS 4-5 (“very much improved”) | Not applicable | Not reported | Combination therapy improved pore appearance |
| Skin texture | GAIS; photographic assessment | Baseline; 12 & 22 weeks | Smoother skin texture observed across the nose and cheeks | Not applicable | Not reported | Enhanced skin texture with sustained improvement | |
| Patient satisfaction | Self-reported 4-point scale | 12 & 22 weeks | High satisfaction (scores 2-3 across all cases) | Not applicable | Not reported | Patients are satisfied with the cosmetic outcome | |
| Safety | Adverse-event monitoring | Throughout study | No serious adverse events reported | Not applicable | Not applicable | Treatment well-tolerated | |
| Kang et al. [ | Wrinkles | Antera 3D | Up to 8 weeks | Frontal eye: -11.49%; lateral eye: -20.23%; nasolabial fold: -11.43% by 8 weeks | N/A | Reported as significant for most wrinkle types after 2 weeks (except nasolabial folds) | LAEs improve multiple facial wrinkles |
| Hydration | Corneometer | Up to 8 weeks | Improved; plateau noted after ~4 weeks | N/A | Not fully specified in excerpt (improvement described as significant after 4 weeks) | LAEs improve skin hydration | |
| Redness (inflammation proxy) | Chromameter + Antera 3D | Up to 8 weeks | Redness: -7.18% by 8 weeks; slight early increase, then decrease | N/A | Not fully specified in the excerpt | After acclimation, LAEs may soothe skin | |
| Texture/roughness | Chromameter + Antera 3D | 2 weeks; 8 weeks | -3.78% at 2 weeks; -11.79% at 8 weeks | N/A | Significant improvements stated | LAEs improve texture | |
| Pore area | Antera 3D | 2 weeks onward | Significant decrease after the first 2 weeks | N/A | Significant stated | LAEs reduce pore area | |
| Pigmentation/color evenness | VISIA-CR, PRIMOS 3D | Baseline → 12 weeks | 87.3% subjects reported visible improvement | N/A | p ≤ 0.001 | Topical HPE improves facial skin appearance | |
| Luminosity/skin quality | Participant questionnaires and imaging | Baseline → 12 weeks | Sustained improvement at 12 week | N/A | p ≤ 0.001 | Cosmetic benefit maintained | |
| Collagen remodeling | Masson’s Trichrome + EM | Baseline → 12 weeks | Significant increase in collagen fibril thickness | N/A | p ≤ 0.0001 | HPE enhances dermal collagen structure | |
| Elastin formation | Verhoeff-Van Gieson stain | Baseline → 12 weeks | Increased elastin density | N/A | Reported significant | Supports dermal regeneration | |
| Wyles et al. [ | Wrinkles/skin aging | VISIA-CR 3D, PRIMOS imaging | Baseline, 12 weeks | Visible improvement in facial skin aging parameters; increased luminosity and color evenness | Not applicable (single-arm study) | p ≤ 0.001 | Topical HPE improved overall facial skin appearance after 12 weeks |
| Pigmentation | VISIA-CR 3D photography | Baseline, 12 weeks | Sustained reduction in facial pigmentation reported by 87.3% of participants | Not applicable | p ≤ 0.001 | HPE demonstrated pigment-reducing effects | |
| Texture/elasticity (indirect) | Participant questionnaires and imaging | Baseline, 12 weeks | Subject-reported improvement in texture, luminosity, and color uniformity | Not applicable | p ≤ 0.001 | Participants perceived a meaningful cosmetic improvement | |
| Dermal regeneration (collagen) | Histology (Masson’s trichrome), electron microscopy | Baseline, 12 weeks | Significant increase in collagen fibril thickness | Not applicable | p ≤ 0.0001 | Topical HPE promoted dermal collagen remodeling | |
| Safety/tolerability | Clinical monitoring | Throughout study | No serious adverse events; well-tolerated | Not applicable | Descriptive | HPE is safe for topical facial use | |
| Svolacchia et al. [ | Patient satisfaction/skin firmness & cutaneous relief | Berardesca Scale (0-4) | D0 → D30 (and D90 shown in figure) | Improvement vs baseline (direction: ↑ satisfaction) | N/A | p < 0.0001 (one-way ANOVA) | Treatment improves visible aging signs |
| Wrinkle/defect severity | NRS (0-10) | D0 → follow-up (figure indicates improvement during follow-up) | Severity reduced vs baseline (direction: ↓) | N/A | p < 0.05 and p < 0.0001 reported | Exosome nanofiltrate reduces wrinkle/defect severity | |
| Global skin appearance (stability/softness/hydration) | Modified Vancouver Scale (MVS) | D0 → D15/D30 | Improvement vs baseline (direction: ↑) | N/A | p < 0.0001 (one-way ANOVA) | Skin quality improves after treatment | |
| Biological confirmation of vesicles | Flow cytometry (EV kit; CD81/CD146) | Post-processing verification | Reported ~450 million CD81+ secretory vesicles (standardized sampling) | N/A | Not stated | Protocol yields vesicles with exosomal markers | |
| Lu et al. [ | Skin hydration | Corneometer CM825 | Day 2, 14, 28 | +5.6% at Day 28 (overall); +7.96% in age 36-45 | Not applicable | p < 0.05 | MK-Exo improves skin moisturization |
| Elasticity | Cutometer (F3/F4, R2) | Day 14, 28 | F3/F4 +6.33%; R2 +7.24% at Day 28 | Not applicable | p < 0.01 | Improved skin elasticity | |
| Wrinkle count | PRIMOS CR | Day 14, 28 | -4.99% at Day 28 | Not applicable | p < 0.001 | Reduced wrinkle number | |
| Wrinkle area | PRIMOS CR | Day 14, 28 | -9.59% at Day 28 | Not applicable | p < 0.001 | Reduced wrinkle severity | |
| Nguyen et al. [ | Photoaging protection (oxidative stress) | DCFDA ROS assay in UVB-exposed HaCaT | After an hour of treatment + UVB | Loaded sEVs reduced ROS by 38.3% vs sEVs 13.3% vs compounds 18.5% | Not applicable (in vitro arms) | p < 0.05 stated generally | Loaded sEVs show synergistic protection |
| Hydration/moisture | GPSkin Barrier + API-100 | Every 2 weeks, endpoint 8 weeks | Hydration/moisture improved (reported +104% hydration and elasticity-see below note) | The placebo hand had minimal change | p < 0.05 (t-test reported) | Skin hydration improved | |
| Elasticity | API-100 Skin Analyzer | Every 2 weeks, endpoint 8 weeks | Elasticity increased by 104% | Placebo minimal change | p < 0.05 (reported) | Elasticity improved | |
| Texture/pore | Antera 3D + API-100 | Every 2 weeks, endpoint 8 weeks | Texture smoother; mean pore volume reduced 51% | Placebo minimal change | p < 0.05 (reported) | Rejuvenation effect on texture/pore | |
| Pigmentation/redness/melanin | Antera 3D + API-100 | Every 2 weeks, endpoint 8 weeks | Less pigmentation/redness (qualitative); melanin decreased by API-100 but inconsistent vs Antera | Unclear | Mixed/inconsistent | Whitening effect uncertain | |
| Chernoff [ | Wrinkles, pores, evenness, vascularity, oiliness, pigment, texture | Quantificare 3-D photo documentation/skin analysis | Baseline → 15 days → 30 days | Improved in all groups (dermal infusion alone and CaHA alone) | Dermal infusion “primer” + CaHA appeared faster/more enhanced than CaHA alone (qualitative claim) | Not reported | Dermal infusion improves absorption; adding CaHA after priming yields faster enhanced skin quality |
| Proffer et al. [ | Global skin health | Skin Health Score (SHS; composite) | Baseline vs 6 weeks | Mean delta +224.2 ± 112.8 (top quartile responders n = 14) | N/A (single-arm) | p ≤ 0.0001 | Topical platelet exosomes improved overall skin health at 4-6 weeks |
| Redness/erythema | VISIA-CR RBX erythema fractional area | Baseline vs 6 weeks | -2.39 ± 2.68 (top quartile n = 14) | N/A | p = 0.005 | Reduced redness | |
| Pigmentation/brown spots | VISIA-CR brown spot fractional area | Baseline vs 6 weeks | -0.0161 ± 0.005 (top quartile n = 14) | N/A | p ≤ 0.0001 | Reduced melanin/brown spots | |
| Luminosity | VISIA-CR luminosity (relative units) | Baseline vs 6 weeks | +5.42 ± 1.36 (top quartile n = 14) | N/A | p ≤ 0.0001 | Improved brightness | |
| Color evenness | VISIA-CR color evenness (relative units) | Baseline vs 6 weeks | +0.071 ± 0.03 (top quartile n = 14) | N/A | p ≤ 0.0001 | Improved evenness | |
| Wrinkles (forehead) | VISIA-CR 3D PRIMOS wrinkle fractional area | Baseline vs 6 weeks | -0 | ||||
| Jo et al. [ | Wrinkles (periocular) | Antera 3D (indentation index, A.U.) | 0, 2, 4 weeks | -8.9% at 2 weeks; -15.89% at 4 weeks vs baseline (LpEV group); no change in placebo | Placebo shows no meaningful change (reported descriptively) | p-values not clearly provided in the excerpt for this endpoint | LpEVs suppress wrinkle formation |
| Elasticity | Cutometer MPA 580 | 0, 2, 4 weeks | +14.76% at 2 weeks; +27.07% at 4 weeks (LpEV) | Placebo not improved as much (direction reported) | Not clearly shown here | LpEVs improve elasticity | |
| Moisture/hydration | (Instrument not fully named in excerpt) | 0, 2, 4 weeks | +10.79% at 2 weeks; +21.40% at 4 weeks (LpEV); placebo “no significant effect” | LpEV better than placebo | Not clearly shown here | LpEVs increase moisture | |
| Dermal density | Ultrasound (DermaLab Skin) | 0, 2, 4 weeks | Density increased in both: LpEV +39.30% vs placebo +15.19% (rate) | LpEV greater increase | Not clearly shown here | LpEVs enhance skin density | |
| Pigmentation | MARK-Vu imaging and visual reading | 0, 2, 4 weeks | Pigmentation decreased at 2 weeks & 4 weeks in LpEV; the placebo had less/no change (reported) | LpEV better | Not clearly shown here | LpEVs reduce aging-related pigmentation | |
| Kerscher et al. [ | Skin firmness | Cutometer® (R0) | 0, 12, 24, 48 weeks | 0.40 → 0.36 mm (Week 24); 0.37 mm (Week 48) | N/A | p < 0.0001 (Week 24) | BCS significantly improves skin firmness |
| Skin tiring | Cutometer® (R3) | 0, 12, 24, 48 weeks | 0.45 → 0.40 mm (Week 24); 0.41 mm (Week 48) | N/A | p < 0.0001 (Week 24) | BCS increases resistance to skin fatigue | |
| Patient-reported skin satisfaction | FACE-Q™ | 0, 12, 24, 48 weeks | 39.6 → 59.8 (Week 12); sustained to Week 48 | N/A | p < 0.0001 | Sustained improvement in perceived skin quality | |
| Facial appearance/psychosocial | FACE-Q™ | 0, 12, 24, 48 weeks | Significant improvement across domains | N/A | p < 0.0001 | Improved facial satisfaction & well-being | |
| Global aesthetic improvement | GAIS (physician & patient) | 6-48 weeks | 90.5% physician-rated improvement (Week 6) | N/A | p < 0.001 | Objective and subjective improvement | |
| Perceived age | FACE-Q™ Age appraisal | 0, 24, 48 weeks | 1.68 years younger at Week 48 | N/A | p < 0.0001 | Patients perceive a younger facial age | |
| Park & Shin [ | Pores | Antera 3D | Day 0 → Day 1 (single use) | Mean pore area 0.1378 → 0.1131 mm² (-17.9%); pore density 32.83 → 24.00 ea/cm² (-26.9%); total pore volume 0.8350 → 0.5005 mm³ (-40.1%) | N/A | p < 0.05 | Rapid pore-refining effects after a single application |
| Texture/roughness | 3D imaging output | Day 0 → Day 14 | Surface roughness -9.0% | N/A | p < 0.05 | Improved skin surface texture | |
| Wrinkles | Antera 3D | Day 0 → Day 14 | Wrinkle depth reduction 7.8-18.8% (forehead -7.8%; glabella -11.3%; crow’s feet -11.7%; nasolabial folds -18.8%; neck -9.5%) | N/A | p < 0.05 | Significant multisite wrinkle reduction after 2 weeks | |
| Hydration (layered) | MoistureMeter D (TDC) | Day 0 → Day 1 (single use) | +7.9% at 0.5 mm (40.4 → 43.5); +6.5% at 1.5 mm (37.3 → 39.8); +4.5% at 2.5 mm (32.3 → 33.77) | N/A | p < 0.05 | Significant hydration gains across depths | |
| Dermal regeneration/structure | Ultrasound (reported as dermal density) | Day 0 → Day 14 | Dermal density 21.31 → 24.01 (+12.67%) | N/A | p < 0.05 | Increased dermal density after 2 weeks | |
| Wyles et al. [ | Senescence signaling | IHC + digital quantification (Aperio/QuPath) for p16INK4a, p21CIP1/WAF1 | Baseline → 12 weeks | High-baseline subgroup: reduction in high p16INK4a dermal senescent cells | N/A | p = .02 | Topical HPE reduces senescence signaling, especially in high-senescence baseline individuals |
| Telomere damage/genomic instability | Immuno-FISH for TAF (telomere + γH2AX overlap), ImageJ quantification | Baseline → 12 weeks | Decrease in TAF per nucleus | N/A | p = .03 | Topical HPE reduces senescence-associated telomere damage | |
| Inflammation (SASP) | RNA-seq (DESeq2 + GSEA), subgroup analysis | Baseline → 12 weeks | In high-senescence baseline patients: ~40% reduction in proinflammatory SASP (reported as reduction) | N/A | Not clearly specified in excerpt (RNA-seq uses FDR q < 0.25 for pathway-level GSEA) | Suggests modulation of proinflammatory senescence phenotype | |
| Dermal regeneration/ECM remodeling | RNA-seq pathway enrichment (Reactome/GSEA) | Baseline → 12 weeks | Upregulation of ECM remodeling pathways (collagen, proteoglycans, elastic fibers) and keratinization pathways | N/A | Pathway significance by FDR q < 0.25 (GSEA threshold described) | Suggests a proregenerative remodeling response | |
| Chang et al. [ | Hydration | Corneometer® CM825 | Day 0, 7, 14, 21, 28 | ↑ 14.6-21.2% improvement by Day 28 (range across regions) | Treatment improved; placebo, no significant change | Within-group: p < 0.0001; treatment vs. placebo on Day 28 significant for most regions | Cica EV serum improved facial hydration over 28 days |
| Elasticity (R²) | Cutometer® (Dual MPA580) | Day 0, 7, 14, 21, 28 | ↑ 12.0-12.5% by Day 28 (across regions) | Treatment > placebo | Within-group: p < 0.001/p < 0.0001; vs placebo significant on Day 28 | Cica EV serum improved elasticity | |
| Pigmentation (melanin) | Mexameter® MX18 | Day 0, 7, 14, 21, 28 | ↓ 9.2-11.3% melanin by Day 28 (lower scores = less melanin) | Treatment > placebo | Within-group: p < 0.0001; vs placebo significant Day 28 | Cica EV serum reduced melanin measures | |
| Wrinkles | VISIA® (percentile/score approach | Day 0, 7, 14, 21, 28 | ↑ 32.9-34.8% “wrinkle improvement” by Day 28 | Treatment > placebo | Within-group: p < 0.001/p < 0.0001; vs placebo Day 28 significant | Cica EV serum reduced wrinkles (instrumental) | |
| Redness | VISIA® RBX | Day 0, 7, 14, 21, 28 | ↑ 26.3-34.0% “redness improvement” by Day 28 | Treatment > placebo | Within-group: p < 0.001/p < 0.0001; vs placebo Day 28 significant | Cica EV serum reduced redness | |
| Pores | VISIA® | Day 0, 7, 14, 21, 28 | ↑ 40.6-41.3% “pore improvement” by Day 28 | Treatment > placebo | Within-group: p < 0.0001; vs. placebo, Day 28 significant | Cica EV serum reduced pores |
| Study | Total AEs (n/%) | Local reactions (erythema/edema/pain) | Serious AEs | Dropouts due to AEs | Infection/immune reactions | How AEs were collected | Safety conclusion |
| Estupiñan et al. [ | 0 AEs reported | Expected transient mild pain, erythema, edema, light crusting; resolved within 1 week | None | None (1 withdrew consent for biopsies, not AE) | None reported | The investigator assessed/documented at visits; periodic review for study continuation | Both arms were well-tolerated; topical exosomes appear safe in this setting |
| Kang et al. [ | 0/0% reported | None clinically significant reported | None | None | None reported | Dermatologist assessment each visit + participant questioning (active follow-up) | Considered safe over 3 weeks in this sample |
| Cho et al. [ | Not reported as total count; AEs described | Erythema 85% (resolved 24-48 hours); edema 65% (resolved within an hour); pain VAS 3.2 ± 1.1 | None | Not reported | None reported | Chart documentation + clinician observation | Transient, mild AEs; no serious reactions |
| Park [ | 4/4 (100%) severe local AEs | Persistent erythema, swelling/warmth, nodules, suspected granulomatous inflammation, residual scarring; some developed atrophic scarring after steroid injections | No systemic SAEs reported; clinically severe local complications requiring repeated procedures | 1 case discontinued treatment and self-managed | Immune/inflammatory mechanism suspected; product contamination/excipients discussed as possible contributors (no histology) | Retrospective case documentation from dermatology clinic; patient history of off-site injection; photos | Intradermal injection of cosmetic exosome products (unregulated/off-label) can cause serious and persistent skin complications |
| Shieh et al. [ | None reported | None reported | None | None reported | None reported | “Monitored throughout”; compliance and AE monitoring stated (details limited) | Appears well-tolerated in these cohorts |
| Sileo et al. [ | Not reported for the 60-day anti-wrinkle use in your excerpt | Not reported | Not reported | Not reported | Not reported | Not clearly stated for human use | Human AE reporting is unclear in the excerpt |
| Wan et al. [ | In vitro safety battery | No genotoxicity (Ames negative); no corneal toxicity; non-corrosive; non-irritant; non-sensitizing (THP oSens described) | N/A | N/A | N/A | OECD guideline assays | ADVs show a strong preclinical safety profile for topical use |
| Kang et al. [ | 0/0% | Mild, transient erythema, edema, and minor bleeding (resolved within 24-72 hours) | None | None | None reported | Active monitoring during and after each session | Combined microneedling and exosome therapy appears safe and well-tolerated |
| Wyles et al. [ | Not clearly quantified in the excerpt | Mild transient redness increase early possible; no severe adverse effects reported | None reported | Not reported | None reported; authors mention possible rare mild reactions to non-human derivatives | Not clearly specified (likely active monitoring during visits + questionnaire) | Appears generally safe in small short-term topical use; AE reporting detail is limited |
| Svolacchia et al. [ | Not specifically quantified | Mild, transient topical reactions only | None | None | None reported | Active monitoring + participant questionnaires | Well-tolerated; no serious safety concerns |
| Lu et al. [ | Not quantified; stated none recorded | Not detailed | None reported | Not reported | None reported | Unclear (appears to be clinical follow-up; not explicitly “active AE surveillance”) | Reported as extremely safe, but AE capture/reporting lacks detail |
| Nguyen et al. [ | 0/0% | None reported | None | 0 | None observed | Active monitoring and patch testing | MK-Exo demonstrated good cutaneous safety |
| Chernoff [ | 0 reported | No itching/redness/swelling/rash/blisters/peeling, etc. in 3 volunteers | None reported | 0 | None reported | Active checks at baseline, days 1/3/7 first week, then every 2 weeks | Topically loaded ADSC-sEVs appeared safe in this small sample |
| Proffer et al. [ | 0 reported | None reported | None | 0 lost to follow-up | None reported (no hypersensitivity/allergic events) | Not clearly specified | Appears well-tolerated in short follow-up (≤30 days) |
| Jo et al. [ | 12/56 (21.4%) reported side effects | Dryness 9/56 (16.1%), most common; also monitored redness/irritation/pain/swelling | None reported | 0 | No allergic or irritant contact dermatitis reported | Monitoring at baseline & 6-week visit + participant reporting | Safe and well-tolerated over 6 weeks; mostly mild dryness |
| Kerscher et al. [ | Not clearly reported in the excerpt | Not clearly reported | Not stated | 4 dropouts (reason not provided here) | Not stated | Not stated | Safety reporting is insufficient in the provided text (needs a full AE section/details) |
| Park & Shin [ | 36/380 injections (9.5%) | Hematoma, redness, swelling, pain, urticaria (mostly mild) | None | 0 | None reported | Active monitoring throughout the study | BCS injections were safe and well-tolerated |
| Wyles et al. [ | Patch test: 0/30 irritation (index 0.00). Efficacy: no adverse reactions reported/observed | None in patch test; none reported during 2-week use | None reported | 0 (one dropout due to noncompliance, not AE) | None reported | Dermatologist grading at 30 minutes & 24 hours post patch removal; monitoring during use | Product classified as non-irritant and well-tolerated |
| Chang et al. [ | Not reported in excerpt | Not reported | Not reported | Not reported | Not reported | Not reported | Safety conclusions cannot be fully extracted from the provided text (article may report elsewhere) |
| 0 reported | Patch test negative; no irritation/allergy reported | 0 | 0 | Not reported/none indicated | Patch test screening and ongoing monitoring during visits | Well-tolerated over 28 days; no safety signals reported |
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Taxonomy
TopicsDermatologic Treatments and Research · Advancements in Transdermal Drug Delivery · Skin Protection and Aging
Introduction and background
Skin is a highly specialized organ that consists of several structurally and functionally different layers, which, together, offer protection, sensory sensation, and homeostatic control [1]. The development of histological and imaging procedures enhanced the study of the skin's architecture and demonstrated that there is a complicated spatial organization among the keratinocytes, fibroblasts, melanocytes, vascular networks, and immune cells [2]. This complex structure allows the dynamically responsive skin to respond to environmental stressors and trauma. Normal repair mechanisms may, however, be impaired by interference with this well-regulated structure due to trauma, inflammation, or aging [3]. Consequently, structural damage tends to take the form of scarring, changes in pigmentation, or early aging, all of which have functional and psychosocial implications.
Wound healing is a highly controlled biological process that requires inflammation, proliferation, and remodeling of the underlying structure of normal skin. In case of the situation descending to dysregulation, pathological scarring may develop, such as hypertrophic scars, keloids, or atrophic lesions [4]. There is experimental and clinical evidence that the primary cause of abnormal scar formation is failure to restore the normal architecture of the extracellular matrix. In addition, continuing fibroblast stimulation and collagen deposition also worsen tissue hardening and mutilation. In that regard, the molecular determinants of scarless and pathological healing are still a top research focus of dermatologic and regenerative studies [5].
Pigmentary disorders and aging of the skin are other effects of broken cutaneous homeostasis besides scarring. Hypertrophic pigmentation results from the disrupted activity of melanocytes and melanosome distribution and commonly relates to inflammation, exposure to UV radiation, and hormonal factors [6]. Simultaneously, intrinsic and extrinsic aging result in the accumulation of oxidative stress, collagen degradation, and dermal loss of elasticity, which also cause wrinkles and changes in texture [7]. This has led to an increased interest in cell-free therapeutic approaches and regenerative approaches.
Exosomes have become important therapeutic mediators of intercellular communication during the last few years. These nanosized extracellular vesicles (EVs) contain bioactive cargo (proteins, lipids, and nucleic acids) that have the ability to regulate the behavior of the recipient cell [8]. Notably, cellular origin plays a major role in determining the biological activity of exosomes. While exosomes released by stressed or diseased cells can propagate inflammation or endothelial dysfunction [9], exosomes released by mesenchymal stem cells (MSCs) have anti-inflammatory, proregenerative, and immunomodulatory effects.
Exosomes are a specific subtype of EVs, typically ranging from 30 to 150 nm in diameter, formed through the endosomal pathway and released upon fusion of multivesicular bodies with the plasma membrane. In contrast, EVs represent a broader category that includes exosomes, microvesicles, and apoptotic bodies, which differ in size, biogenesis, and biological function. For clarity and consistency, this review uses the term “exosome” when referring specifically to vesicles of endosomal origin, while acknowledging the broader EV classification in accordance with current Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines [8,9].
When applied to clinical dermatology, the results of stem cell-derived exosome studies suggest that they can be beneficial across a wide range of aesthetic and therapeutic indications, based on their biological characteristics. It has been found that clinical studies benefit from acne scars, skin texture, and photoaging using exosomes as either a single modality or together with energy-based devices and microneedling [10,11]. The new findings can prove that some of them are effective for skin lightening and healing the wound without safety issues, such as live cell therapies [12]. However, inconsistency in isolation procedures, characterization criteria, and reporting of outcomes still hampers cross-study comparability.
Considering such a growing yet diversified body of evidence, a synthesis of research must be conducted rigorously. Standardized methods of reporting and bias assessment are systematic review methodologies, an excellent approach to the evaluation of clinical effectiveness and safety [13]. Additionally, the use of the accepted instruments to evaluate both randomized and non-randomized studies contributes to the validity of the findings comparing the conclusions made based on different design types of studies [14-16].
Given the usage of exosome-based dermatologic regimens in practice, it is of utmost importance that a comprehensive exercise be undertaken to provide clear, methodologically sound, and clinically relevant information that can essentially be utilized to develop an informed practice. In order to assess the effectiveness of therapy regimens, an understanding of the previous body of research in the context of standardized reporting methodologies is vital, ultimately having direct implications for the efforts being undertaken to elucidate the subject as well as provide clear directions regarding how to make such an exercise clinically relevant in terms of the decisions being taken for the treatment of a regenerative intervention. This systematic review aimed to evaluate the clinical efficacy and safety of exosome-based therapies for skin rejuvenation in human populations and to identify gaps in the existing evidence.
Review
Methodology
Study Design and Reporting Framework
This systematic review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines for systematic review and meta-analysis. Following the PRISMA 2020 guidelines helped to systematically find, evaluate, and combine the available clinical evidence on exosome-based therapies for skin rejuvenation.
Eligibility Criteria
The population, intervention, comparison, and outcome (PICO) framework was used to make sure that the qualifying criteria were clear, methodical, and repeatable: population (human adults undergoing aesthetic or dermatologic skin rejuvenation), intervention (exosome-based therapies utilized independently or as supplementary treatments to dermatological procedures), comparator (none, placebo, standard care, or alternative rejuvenation interventions), outcomes (the results showed improvements in wrinkles, elasticity, texture, pigmentation, and safety outcomes). A priori criteria of eligibility were based on a population, intervention, and outcome framework. The inclusion criteria were that the studies had to include human subjects who were undergoing aesthetic or dermatologic skin rejuvenation treatments. Qualified interventions included exosome-based treatments to be used as either individual protocols or as a supplement to other dermatological treatments. Eligible study designs included randomized controlled trials and various types of non-randomized studies involving humans, such as split-face trials, single-group studies looking at results before and after treatment, case series, studies comparing treatments with a placebo, and multigroup non-randomized studies. Only peer-reviewed full-text articles in English were considered. Only studies that were animal or in vitro studies, reviews, editorials, letters, conference abstracts, case reports, or single-patient studies were excluded. Also, we eliminated papers dedicated only to wound healing or scar management without focusing on intended outcomes, as well as commercially driven promotional studies that lacked transparency in their methods, to ensure clinical relevance and scientific rigor.
Information Sources and Search Strategy
An extensive literature review was conducted in several electronic databases, such as PubMed, Scopus, the Web of Science, and the Cochrane Library. The databases were systematically searched for studies published between January 1, 2000, and December 31, 2025, with the final search performed on January 15, 2026. It was a combination of controlled vocabulary and free text keywords on exosomes, skin rejuvenation, aesthetic dermatology, and clinical outcomes. Each database had detailed search strings recorded in it, which are presented in Table 1 to promote reproducibility and transparency.
Study Selection
The selection of studies was done in two phases. First, titles and abstracts obtained in the database searches were filtered independently by two reviewers to adhere to possible eligibility. Full-text articles were then acquired on studies that met the inclusion criteria or were ambiguous on the aspect of eligibility. The same reviewers engaged in full-text screening. Any differences that arose during the screening steps were resolved through discussion and agreement, and when agreement could not be reached, a third reviewer was consulted. This process of selecting studies in general was recorded via a PRISMA flow diagram that is listed in Figure 1.
PRISMA flow diagramPRISMA: Preferred Reporting Items for Systematic Reviews and Meta-AnalysesRecords were identified through database searching (2000-2025; final search on January 15, 2026). Duplicate records were removed using EndNote (Clarivate Analytics), and articles were excluded during title and abstract screening according to predefined eligibility criteria. The diagram was adapted from the official PRISMA 2020 template and manually completed by the authors
Data Extraction and Quality Appraisal
The data extraction was carried out with the help of a standardized data extraction form. Data obtained were research design, sample size, demographics of study population, nature and source of exosome intervention, treatment regimen, measures of outcomes, duration of follow-up, and any adverse effects described. The inclusion criteria were satisfied by 19 studies, and they were incorporated in the final synthesis. Two reviewers extracted data independently to reduce errors and discrepancies. The methodological quality and risk of bias were assessed at the level of the study. The Cochrane Risk of Bias in Non-randomized Studies (ROBINS-I) was used to evaluate randomized controlled trials. The ROBVIS software was used to draw an illustration of the ROBINS-I ROB summary plot.
Data Synthesis
Quantitative meta-analysis was not done because of the expected heterogeneity in the study designs, intervention protocols, outcome measures, and follow-up periods. Instead, the findings were summarized in a written format, where the results were grouped by the type of intervention and the clinical outcomes reported, making them easier to understand.
Results
The evidence base was generally non-randomized, with most studies having single-arm pre-post, split-face comparisons, or uncontrolled clinical assessments. The sample sizes varied between 3 and 95, and those studied were normally middle-aged adults, and in some cases, only women were enrolled in the study. The indicators were mainly facial rejuvenation and photoaging, which aimed to treat wrinkles, texture, pores, hydration, pigmentation, and general aesthetic enhancement. There were many different ways the treatments were made, including exosomes from human fat cells, exosomes from platelets with extracts, exosomes from placental stem cells, EVs from a person's own blood, and vesicles from non-human sources like cow's milk, Lactobacillus, and plants like Cent. The delivery methods included creams or lotions applied once or twice a day, injections into the skin, and mesotherapy, along with additional treatments after microneedling or radiofrequency microneedling (Table 2).
In imaging and biophysical devices such as VISIA (Canfield Scientific, Inc., Parsippany, NJ, USA), PRIMOS (GFMesstechnik GmbH; Teltow, Germany), and Antera 3D (Miravex Limited; Dublin, Ireland), as well as in corneometers, cutometers, tewameters, and ultrasounds, the majority of studies show improvements in hydration, elasticity, wrinkle measurements, pore measurements, and skin texture at baseline over a short follow-up period of 2-12 weeks. Split-face data indicated that topical exosome treatments and platelet-rich plasma had similar effects after radiofrequency microneedling, but there wasn't much formal statistical analysis because the number of participants was small. Other studies also found helpful signs or tissue changes that matched with skin improvement or fewer aging signs, but these couldn't be compared because they looked at different outcomes, times, and quality of reporting (Table 3).
The majority of managed clinical trials did not report any severe adverse effects and only reported temporary local reactions like erythema, edema, dryness, or mild discomfort, especially during such procedures as microneedling or injections. On the other hand, one case study found that using unregulated intradermal injections of poorly defined exosome products led to long-lasting lumps and scars, which points to the risks when the product quality and medical supervision are not good enough (Table 4).
Figure 2 illustrates the bias risk for each included domain in the research. Most studies showed a moderate to high risk of bias, mainly due to factors that could confuse the results and how participants were chosen, but bias in how interventions were classified, and outcomes measured was usually low. The overall quality of the methods varied, indicating that the current clinical evidence has certain limitations.
ROBINS-I quality appraisal robvisROBINS-I: risk of bias in non-randomized studies-of interventions; robvis: risk-of-bias visualizationAdapted/reproduced from [17-35], with permission
Discussion
Main Findings
This systematic review has summarized current human clinical data on exosome-based skin rejuvenation treatments and found consistent short-term benefits for different beauty aspects. In the studies included, using exosomes as part of skin treatments was associated with better results in hydration, elasticity, wrinkles, pore size, skin color, and overall skin quality. These effects were the most common during the two- to 12-week follow-up, and they were assessed by a combination of validated imaging platforms, biophysical instruments, and investigator-rated scales. Importantly, studies that looked at both sides of the face found that treatments using exosome-containing products worked just as well as traditional methods like platelet-rich plasma when combined with microneedling.
In terms of safety, the majority of regulated clinical studies depicted excellent tolerability rates, and the adverse events were mild, transient local reactions. Nevertheless, the review also found clinically significant complications associated with the off-label, intradermal injection of ill-defined exosome products delivered without medical guidance, illustrating the significance of product standardization and clinical governance. Generally, the results indicated that exosome-based interventions were an exciting but immature modality in aesthetic dermatology; their emerging results were promising but limited by methodological heterogeneity, a lack of long-term data, and a lack of uniformity in reporting standards across studies.
Comparison With Previous Literature
The overall results of this review supported earlier studies that showed the healing benefits of exosomes from mesenchymal stem cells for skin use. Enhanced wound healing and skin quality after topical application of human MSC-derived exosomes in the aftermath of the aesthetic sector have been reported in clinical case series and small prospective studies in the past, supporting the role of paracrine-mediated repair in this review [36]. Likewise, split-face trials using adipose-derived stem cell exosome solutions with microneedling have shown significant improvements in wrinkles, elasticity, and texture compared to baseline and placebo-treated sites, which is consistent with the outcome patterns observed [11].
Evidence from acne scar and pigmentation-focused studies further facilitated the applicability of exosome therapies to a wider range of dermatology indicators. Exosomes made from mesenchymal stem cells might be a beneficial alternative to cell-based treatments for acne scars because they can help regenerate skin with fewer side effects than other types of cell implants [37]. At the same time, studies that randomly tested adipose-derived exosomes on one side of the face showed significant improvements in skin brightness and evenness of tone, which were better than the pigmentation results found in other research included in this review [38].
These clinical observations have been supported by mechanistic evidence in preclinical systematic reviews and meta-analyses. The animal studies show that small EVs made from MSCs help wounds heal better by increasing collagen production, improving blood vessel growth, and adjusting the immune response, which results in better tissue quality and less scarring [39,40]. These biological effects are also seen in other types of tissue, like corneal scarring, where MSC exosomes help reduce inflammation and adjust the immune system, promoting tissue healing [41].
Simultaneously, the exosome literature echoed the methodological issues articulated in the review. The amount, cleanliness, and effectiveness of vesicles can vary depending on the method used for their isolation, such as tangential flow filtration, ultracentrifugation, and size exclusion chromatography, leading to different outcomes in clinical settings [42-44]. Cross-study comparisons are even more complicated due to differences in characterization and quantification techniques, including nanoparticle tracking analysis [45,46]. All these reasons point to the need for consistent methods in making, testing, and reporting exosomes to ensure that the positive effects of exosome-based skin rejuvenation treatments can be reliably repeated and used in everyday medical practice.
Implications of the Findings
The results of this systematic review had significant clinical and research implications for aesthetic and regenerative dermatology. All the evidence showed that a treatment using exosomes could be a useful, non-cell method to improve various skin qualities, like moisture, flexibility, color, and the look of wrinkles. In clinical settings, using topical exosome preparations along with microneedling or energy-based systems appeared to have strong short-term benefits and a good safety record when done in a controlled way. Exosome-based products could complement existing aesthetic procedures, but they shouldn't take their place. The review also pointed out the important role of treatment context, product characterization, and delivery mode in influencing outcomes. To the clinicians, the findings have highlighted the importance of selecting patients carefully, following certified formulations, and avoiding off-label injectable use. The results showed that paracrine signaling plays a key role in skin regeneration and pointed out the chance to standardize exosome-based treatments in beauty practices.
Limitations and Future Recommendations
When interpreting the findings of this review, it is important to consider several limitations. To start, most of the studies included were not randomized and only looked at one group with small numbers of participants, which made it challenging to draw clear cause-and-effect conclusions and increased the chances of bias in the research. Secondly, the studies varied greatly in where the exosomes came from, how they were isolated and prepared, the amounts used, how they were given, what results were measured, and how long they followed up, which made it impossible to combine the results for a thorough analysis. Third, the way outcomes were reported varied a lot, as most studies used short-term indicators, personal satisfaction ratings, or simple comparisons of results without proper statistical analysis. The reporting on safety was inconsistent; many studies vaguely reported adverse events and lacked active surveillance methods. Notably, long-term safety and durability are not adequately defined.
Future studies are encouraged to conduct more effective randomized controlled trials with sufficient sample sizes, standardized outcome measures, and extended follow-up periods to determine durability and delayed adverse events. The exosome manufacturing, characterization, and reporting standards have to be harmonized to enhance reproducibility. It is also suggested that comparative trials with proven regenerative modalities, such as platelet-based therapies, be done. Lastly, regulatory control and clinician training ought to be intensified in order to curb the risks related to unregulated or off-label injectable exosome products.
Conclusions
Overall, this systematic review revealed that exosome-based treatment had promising short-term effects in various areas of skin rejuvenation, such as hydration, elasticity, texture, pigmentation, and wrinkle appearance. Topical utilization or interventions as adjuncts during conventional aesthetic practice proved to be tolerable in most cases in controlled clinical environments. However, methodological heterogeneity, limited follow-up, and unstable safety reporting still constrain the existing clinical evidence. Although exosome-based skin rejuvenation is a fast-moving and potentially transformative area of research, it will be premature until strong clinical trials and standardized frameworks are established before mass clinical adoption can be supported.
The reference list from the paper itself. Each links out to its DOI / PubMed record.
- 1Structure and function of the skin Rook’s Textbook of Dermatology Mc Grath JA Uitto J 150Hoboken, NJ Wiley & Sons 2023
- 2Progress on three-dimensional visualizing skin architecture with multiple immunofluorescence staining and tissue-clearing approaches Histol Histopathol Wang Y Bai W Wang X 6456514020253939089210.14670/HH-18-815 · doi ↗ · pubmed ↗
- 3From reactive species to disease development: effect of oxidants and antioxidants on the cellular biomarkers J Biochem Mol Toxicol Curieses Andrés CM Pérez de la Lastra JM Andrés Juan C Plou FJ Pérez-Lebeña E 037202310.1002/jbt.2345537437103 · doi ↗ · pubmed ↗
- 4An update on molecular mechanisms of scarring-a narrative review Int J Mol Sci Kohlhauser M Mayrhofer M Kamolz LP Smolle C 115792520243951913110.3390/ijms 252111579 PMC 11546163 · doi ↗ · pubmed ↗
- 5Toward understanding scarless skin wound healing and pathological scarring F 1000 Res Karppinen SM Heljasvaara R Gullberg D Tasanen K Pihlajaniemi T 7878201910.12688/f 1000 research.18293.1PMC 655699331231509 · doi ↗ · pubmed ↗
- 6Multimodality management of skin hyperpigmentation Aesthetic Plast Surg Almansory AS Alhamdany ZS 377637844920254030120010.1007/s 00266-025-04866-0PMC 12310902 · doi ↗ · pubmed ↗
- 7Focus on the contribution of oxidative stress in skin aging Antioxidants (Basel) Papaccio F D Arino A Caputo S Bellei B 11211120223574001810.3390/antiox 11061121 PMC 9220264 · doi ↗ · pubmed ↗
- 8The biology, function, and biomedical applications of exosomes Science Kalluri R Le Bleu VS 6977367202010.1126/science.aau 6977 PMC 771762632029601 · doi ↗ · pubmed ↗