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SYSTEMATIC REVIEW OF EXOSOME TREATMENT IN HAIR RESTORATION: PRELIMINARY EVIDENCE, SAFETY, AND FUTURE DIRECTIONS

Abstract

Background

Exosomes are small extracellular vesicles with potential roles in modulating the hair growth cycle and are an emerging therapy for patients with alopecia. In recent years, researchers have made significant progress in deciphering the network of cellular interactions and signaling pathways mediated by the transfer of exosomes. This has opened the door to a wide range of potential therapeutic applications with an increasing focus on its application in precision medicine.

Aim

To evaluate current published evidence, both preclinical and clinical, on the use of exosomes for hair restoration.

Methods

In January 2023, a systematic search was conducted using PubMed, Embase, and the Cochrane Library. Records were identified, screened, and assessed for eligibility as per the PRISMA guideline.

Results

We identified 16 studies (15 preclinical and 1 clinical) showing varying degrees of efficacy using exosomes derived from sources including adipose-derived stem cells (ADSCs) and dermal papilla cells (DPCs). Applications of exosomes isolated from ADSCs (ADSC-Exo) and DPCs have shown early promising results in preclinical studies corroborated by results obtained from different model systems. Topical ADSC-Exo has been tried successfully in 39 androgenetic alopecia patients demonstrating significant increases in hair density and thickness. No significant adverse reactions associated with exosome treatment have been reported thus far.

Conclusions

Although current clinical evidence supporting the use of exosome treatment is limited, there is a growing body of evidence suggesting its therapeutic potential. Further studies are warranted to define its mechanism of action, optimize its delivery and efficacy, and to address important safety concerns.

1. INTRODUCTION

Hair loss attributed to non-scarring alopecia, such as androgenetic alopecia (AGA) or alopecia areata (AA), represents a significant source of disease and psychological burden to patients of all ages. There is a need for new and innovative therapies that offer sustained hair regrowth over extended durations with minimal side effects.

Previous studies have shown the potential efficacy of stem cell therapies derived from the adipose tissue in inducing significant hair growth in AGA and AA patients; similar results were also observed using extract of secreted proteins containing exosome and other extracellular vesicles (EVs).

Exosomes are small (30–150 nm) cargo-delivering EVs that mediate intercellular communications. They are characterized by a phospholipid bilayer with specific surface markers and cargos that affect cell signaling and gene expression (e.g., cytokines, growth factors and regulatory microRNAs [miRNAs]). Although its exact mechanism of action is unclear; it is suspected that exosomes, through modulations of paracrine signaling, can mediate the crosstalk between epithelial cells and mesenchymal cells during the hair growth cycle.

For example, exosomes derived from dermal papilla cells (DPCs; DPC-Exos) were shown to upregulate the Wnt/β-catenin pathway in outer root sheath cells (ORSCs), resulting in the telogen-to-anagen transition in mice.

The present review covers the current landscape of exosome treatment in hair restoration, with a focus on preclinical, clinical, and safety data reported thus far in the literature. Issues concerning the safety of exosome treatment, as well as future directions, are discussed.

2. MATERIALS AND METHODS

An electronic search was conducted in January 2023 using PubMed, Embase (Ovid), and the Cochrane Library, without date or language restrictions. We aimed to investigate published evidence pertaining to the use of exosomes for hair growth. Items identified using the following search/MeSH terms were combined: “exosome,” “alopecia,” “hair follicle,” “dermal papilla cell,” “root sheath,” and “Wnt pathway.” Reference sections of relevant review articles were screened for additional records. Deduplication and screening of identified records were performed using Rayyan (https://www.rayyan.ai/). Studies were excluded if a mixture of EVs was used, and if the observed effects could not be attributed to the exosome fraction. This review was designed in concordance with the PRISMA guideline.

3. RESULTS AND DISCUSSION

Following the initial identification of 255 search results, 16 articles were eligible for data extraction. Of the 15 preclinical studies, information on source, content and target of exosomes, as well as any observed genotypic and/or phenotypic effects are summarized in Table 1. Results from 1 clinical study of 39 patients are summarized in Table 2. No randomized or controlled trials were found.

3.1 Preclinical Evidence

Favorable effects have been observed using exosomes derived from a variety of cell types, including adipose-derived stem cells (ADSCs), which increase hair growth and dermis thickness in vivo, potentially through paracrine regulation of DPCs.

Similar functions were observed for DPC-Exos, including induction of human hair follicle growth and acceleration of the telogen-to-anagen transition in mice, potentially through upregulation of fibroblast growth factor and β-catenin pathways.

DPCs may function as a paracrine regulator of hair follicle stem cells (HFSCs) and ORSCs. Interestingly, exosomes from ORSCs exhibited reciprocal effects on DPCs.

Other sources include myeloid-derived suppressor cells and amniotic fluid stem cells. Platelet-derived exosomes (PRP or platelet lysate) showed limited efficacy in some studies. Delivery systems such as microneedle patches may improve efficacy.

miRNAs within exosomes play a key role in regulating hair growth. Some miRNAs promote hair growth (e.g., miR-181a-5p, miR-218-5p), while others inhibit it (e.g., miR-22-5p).

3.2 Clinical Evidence

Exosomes are not currently approved by the U.S. FDA for hair disorders. A case series of 39 AGA patients treated with ADSC-derived exosomes showed improvements in hair density and thickness after 12 weeks of topical treatment using microneedle rollers.

However, randomized controlled trials are lacking. Another case series using EV mixtures showed partial hair growth in 64.5% of patients, but effects could not be attributed specifically to exosomes.

3.3 Safety

Limited safety data exist. No serious adverse reactions were reported in AGA patients treated with topical ADSC-derived exosomes. Mild side effects such as injection site reactions, erythema, edema, dryness, and mild hyperpigmentation were observed in some studies.

Subcutaneous MSC-derived biologics containing EVs also showed no major adverse effects.

Preclinical studies indicate that exosomes may localize in organs such as liver, kidneys, brain, and lungs without major toxicity, although immunological changes (e.g., elevated immunoglobulins and CD8+ T cells) were observed.

Long-term risks such as tumorigenesis and metastasis remain unclear.

3.4 Regulatory Concerns

The U.S. FDA has issued alerts against exosome products. Exosomes are regulated as drugs and biologics, but no approved marketed exosome therapies exist.

Challenges include:

  • Lack of standardization in isolation and characterization
  • Heterogeneity of exosome populations
  • Limited detection methods for functional components (e.g., miRNAs)
  • Manufacturing and contamination risks (e.g., Mycoplasma)

Good Manufacturing Practice (GMP) compliance is essential.

3.5 Future Directions

Future improvements may include:

  • Optimizing formulation, dosing, and delivery
  • Use of topical formulations to improve compliance
  • Combination therapies (e.g., minoxidil, PRP, stem cells)
  • Advanced delivery systems such as microneedles and ultrasound
  • Enhancing exosome production (e.g., phototherapy, plant extracts, engineered vesicles)
  • Exploring alternative sources (e.g., bovine colostrum, plant-derived vesicles)

Microneedle patches and nanovesicle technologies show promise in improving delivery and efficacy.

Conclusion

Exosome-based therapies show promising potential for hair restoration, supported by preclinical and limited clinical evidence. However, significant challenges remain in terms of safety, standardization, regulatory approval, and large-scale clinical validation. Further research and clinical trials are required to establish their role in routine treatment of alopecia.

link:

https://onlinelibrary.wiley.com/doi/10.1111/jocd.15869

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Mrs Reshma successfully completed her Bachelor of Science degree in nursing from Kerala University of Health Science, India in 2016. She has more than 7 years of experience in the field of nursing. She has successfully participated in a workshop on objective structured clinical examination at a national level and she has successfully published a research study in knowledge of mothers in the weaning process during her undergraduate degree. Mrs Reshma has served as a medical intensive care nurse at Dr Moopen’s WIMS Medical college (ASTER) in Kerala soon after graduation for a total of three years. She then progressed to serve as a medical surgical nurse at Aspel health care in 2020 for 12 months after which she moved to Dubai, where she started working for two years at One call Doctor Home Health Care in Al Qusais as a registered nurse and medical director. In November 2023, Mrs Reshma joined our team at the Al Rubaie Dermatology Center as registered nurse, and she has done fantastically well in her first year with great feedback from many patients.

Mrs Cruz is one of the most experienced members of our staff with more than 25 years of experience, working in the field of nursing. She is a graduate of St. Paul University Dumaguete in 1997, with a degree of Bachelor of Science in Nursing (BSc Nursing). Soon after graduation, Mrs Cruz took up a post as a junior nurse in the Provincial Hospital located in Dumaguete. She relocated to Dubai in 1999, where she started working at Gulf Medical Center for 3 years and then took up a post at Dr Salah Al-Rubaie Dermatology and Venereology Clinic (now known as Al Rubaie Dermatology Center) in 2003. She is a licensed LASER technician and operates many machines unsupervised including IPL Quantum by Lumenis, Splendor X by Lumenis and Radiofrequency microneedling. Her areas of interest include LASER hair removal, cosmetic and aesthetic dermatology. She is well familiar with all treatments provided at our Center including biological medications used to treat atopic dermatitis, psoriasis and alopecia areata. She is also responsible for provided phototherapy to our patients including through Ultraviolet A, Ultraviolet B and Excimer.

Originally, a dentist by trade, Dr Abeer completed his Bachelor of Dental Surgery (BDS) at the University of Alexandria, Egypt in 1973 before being awarded with the Doctor of Philosophy (PhD) degree in fixed dental prostheses and bridge procedures in 1987. He is the man behind the scenes, ensuring that our services are running up to the standards required and that everyone attending our healthcare facility is leaving with a smile on their face. Dr Abeer has played an important role in developing our new clinic in Jumeirah, as he has applied the final touches to the general design of the facility as well as being instrumental in securing our partnership deals with Esaad and Avène.
Dr Al-Rubaye finished his medical training at the well-known Royal College of Surgeons of Ireland (RCSI-MUB) University in 2015. He has since completed an IHO year at Dubai Health Authority and then started working as a Senior House Officer in core medical specialties at the Royal Wolverhampton NHS Trust where he completed 2 years before achieving Membership of the Royal College of Physicians of the United Kingdom (MRCP-London). He has then served 4 years as a dermatology registrar rotating in New Cross Hospital, Walsall Manor Hospital and Cannock Chase Hospital in the West Midlands during which he completed the Specialty Certificate Examination in Dermatology. Dr Al-Rubaye worked as a senior specialist dermatologist at Health Harmonie Group – Birmingham, regularly doing medical dermatology and surgical dermatology clinics in Birmingham, Stoke and Shrewsbury. He holds a post graduate diploma in clinical dermatology (PGDip-Clinical Dermatology) with Merit from Queens Mary University in London and he has a master’s in clinical dermatology (MSc Clinical Dermatology) with distinction from Cardiff University during which he finished as one of the top students in his class. Dr Al-Rubaye holds the American Board of Aesthetic Medicine and is an expert in LASER treatments, Radiofrequency, BOTOX and non-surgical lip enhancements and facial contouring. He has published more than 15 review articles in international and peer reviewed journals. Dr Al-Rubaye is a regular attender of national and international conferences, and he is a regular presenter at the Dubai World Dermatology and LASER Conference & Exhibition (DUBAI DERMA).

Dr Salah is one of the most distinguished and famous dermatologists in Dubai and highly regarded as the go to skin specialist for complicated cases in this city. He has served as a consultant dermatologist at Rashid Hospital for 20 years during which he trained hundreds of aspiring physicians and dermatologists, many of which continued their careers successfully in the country and internationally. A University of Baghdad graduate originally, Dr Salah continued his career in Egypt where he achieved a diploma in clinical dermatology with distinction followed by a masters in dermatology and an MD Doctorate in dermatology at Cairo University (Kasr Al-Ainy) School of Medicine. He then continued his medical career in New York where he completed a fellowship in dermatopathology at the world renown New York University (NYU) and affiliated hospital. He has published more than 70 different clinical research papers both locally and internationally, as well as hundreds of oral presentations in the United Arab Emirates, France, China, Italy, and the United Kingdom. His areas of interest include biological medications in the treatment of Atopic Dermatitis, Psoriasis and Alopecia Areata. His oral presentations and talks have covered many different topics including LASER’s and genodermatosis as well as chronic dermatological diseases such as Acne vulgaris, Atopic dermatitis, Hair loss, and Psoriasis. Dr Salah has been recognised on an international level and he has been chosen as the “Man of the Year” by the Marquis Who’s Who in the World in 1999 and “Man of the Year” by the Marquis Who’s Who in Science and Engineering from 2000-2001. Dr Al-Rubaie opened the doors to his private practice in Dubai in 2003 and has relocated in 2023 to Jumeirah. He is an active member of the American Academy of Dermatology from 1985 – present and his 3 decades of membership have been valued and rewarded as he is a fellow of the American Academy of Dermatology (FAAD). He has also been a member of the European Academy of Dermatology and Venereology (EADV) for almost 3 decades.