Dear Sir,
We read with great interest the comprehensive review by Lee et al.1 examining the emerging role of exosome-based therapies in androgenetic alopecia, alopecia areata, and chemotherapy-induced alopecia. The authors provide a timely and well-structured synthesis of preclinical mechanisms and early clinical data, highlighting key signaling pathways—including Wnt/β-catenin, PI3K/AKT, VEGF, and TGF-β modulation—that underpin the regenerative potential of extracellular vesicles (EVs). Their work represents an important contribution to a rapidly expanding translational frontier within reconstructive and aesthetic surgery.
As enthusiasm for exosome therapeutics accelerates, however, the field now stands at a critical inflection point: the transition from biologic plausibility to disciplined clinical integration. We believe that the next decisive step is the establishment of a standardized translational framework capable of ensuring reproducibility, safety, and scientific credibility.
Exosomes are not uniform pharmacologic agents but biologically dynamic vesicles whose cargo composition, potency, and downstream effects vary substantially according to cell source, culture conditions, isolation methodology, storage parameters, and delivery technique. Foundational investigations into EV biology have underscored that variability in characterization directly influences biological interpretation and therapeutic reproducibility.2 International consensus guidelines, most notably the MISEV2018 recommendations, were developed precisely to mitigate these inconsistencies by defining minimal requirements for EV identification, quantification, and reporting.3 Yet, as reflected in the studies summarized by Lee et al.,1 standardized reporting of particle concentration, size distribution, and molecular markers remains inconsistent within trichology literature.
This heterogeneity has practical implications for reconstructive and aesthetic surgeons. Encouraging improvements in hair density and shaft thickness have been reported across predominantly Level II–IV studies,1 but dosing is frequently described in volumetric terms rather than particle-based metrics. Without harmonized quantification and potency assessment, inter-study comparison—and by extension, evidence synthesis—remains inherently constrained. In an era where exosome-based products are increasingly marketed within private practice settings, the absence of uniform characterization risks widening the gap between regenerative innovation and evidence-based medicine.
Equally important is the question of long-term biologic safety. Exosomes exert multifaceted effects on angiogenesis, immune modulation, and proliferative signaling.2,4, 5. While regenerative applications are distinct from oncologic contexts, extensive oncology literature demonstrates the capacity of EVs to influence cellular microenvironments in context-dependent ways.4 These observations do not contraindicate therapeutic exploration; rather, they reinforce the necessity of rigorous longitudinal safety monitoring, particularly when biologically active vesicles are administered repeatedly to highly vascularized scalp tissue.
To advance the field responsibly, we propose that future clinical investigations and translational protocols incorporate a minimal reporting and safety framework that includes:
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Transparent disclosure of cellular origin and manufacturing conditions, including donor screening and culture parameters;
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Standardized vesicle characterization consistent with international consensus guidelines³ (particle size distribution, concentration, and molecular markers);
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Dose reporting in particle-based or protein-normalized units, facilitating reproducibility and inter-study comparability;
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Objective, standardized outcome measures, including blinded trichoscopic density and shaft diameter analysis;
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Structured adverse-event reporting with extended follow-up, ideally through multicenter registries.
Such measures would not impede innovation but instead elevate the scientific rigor necessary for durable clinical adoption. By aligning trichologic applications with broader regenerative medicine standards, the specialty can ensure that therapeutic enthusiasm is matched by methodological precision.
Lee et al.1 have provided a valuable synthesis that both documents promise and acknowledges present limitations. Building upon their work with structured translational safeguards may help ensure that exosome therapy evolves not as a transient aesthetic trend, but as a reproducible and evidence-driven modality within plastic, reconstructive, and aesthetic surgery.
We commend the authors for stimulating this important dialogue and hope that continued methodological refinement will support the responsible integration of extracellular vesicle therapeutics into clinical practice.
References
- 1.Lee K.W.A., Sydorchuk O., Song J.K., et al. Exosomes in trichology: a literature review. JPRAS Open. 2026;48:567–584. doi: 10.1016/j.jpra.2025.11.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Kalluri R., LeBleu V.S. The biology, function, and biomedical applications of exosomes. Science. 2020;367(6478):eaau6977. doi: 10.1126/science.aau6977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Théry C., Witwer K.W., Aikawa E., et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018) J Extracell Vesicles. 2018;7(1) doi: 10.1080/20013078.2018.1535750. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Kalluri R. The biology and function of exosomes in cancer. Nat Rev Cancer. 2016;16:453–463. doi: 10.1038/nrc.2016.73. [DOI] [PubMed] [Google Scholar]
- 5.Hong P., Yang H., Wu Y., et al. The functions and clinical application potential of exosomes derived from adipose mesenchymal stem cells: a comprehensive review. Stem Cell Res Ther. 2019;10:1–12. doi: 10.1186/s13287-019-1358-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
