From Scientific Distinctions to Global Commercialisation

Our previous article systematically examined the fundamental differences between the cell secretome and exosomes/small extracellular vesicles (sEVs) from the perspectives of scientific definition, molecular composition and quality control, while also considering how these product categories are currently positioned within China's evolving regulatory framework.
Building on this analytical framework, the present article broadens the discussion to global commercialisation practices. It examines how companies can approach technology selection across two distinct application settings — serious healthcare and non-serious healthcare — and draws practical insights for international expansion from commercial and regulatory examples in Indonesia, Taiwan, the United States, South Korea and Singapore.

Two Product Positioning Pathways: Strategic Distinctions Between Serious and Non-Serious Healthcare

Serious Healthcare: The Case for Highly Purified sEVs

In clinical medicine and other serious healthcare applications, products are subject to stringent regulatory scrutiny, clearly defined safety and efficacy endpoints, and requirements for reproducible manufacturing processes and consistent product quality. Within this context, highly purified and extensively characterised sEV products may offer a more clearly defined development pathway.
Several characteristics contribute to this positioning.
First, highly purified sEVs possess relatively well-defined physicochemical properties and can be systematically characterised using established analytical approaches, including nanoparticle tracking analysis (NTA), Western blotting and nano-flow cytometry. These methods can generate structured quality evidence to support regulatory evaluation.
Second, purification removes substantial quantities of soluble proteins, including potentially immunogenic components, which may simplify certain aspects of safety assessment.

Third, sEVs are small and exhibit favourable permeability characteristics. Their reported ability to cross biological barriers, including the blood–brain barrier, has attracted particular interest in translational research involving neurological and cardiovascular diseases (Na et al., 2026).
Clinical research worldwide is increasingly focused on MSC-derived sEVs, particularly those derived from umbilical cord MSCs. According to Na et al. (2026), who analysed therapeutic EV studies registered in ClinicalTrials.gov from China, more than 95% of therapeutic EV studies in China involve naturally derived stem-cell EVs, with MSC-derived EVs accounting for approximately 60%. Among MSC-derived EV studies, umbilical cord-derived MSCs (UC-MSCs) and adipose-derived MSCs (Ad-MSCs) account for approximately 44% and 12%, respectively. This distribution provides an indication of the current research preferences within the Chinese EV field.
The broader global clinical landscape also provides an important reference point for serious healthcare applications. By 2024, more than 200 EV-related clinical trials had been registered worldwide. Of these, 119 trials, or approximately 61%, were associated with China's NMPA, while 17% were associated with the US FDA. MSC-derived EVs accounted for approximately 80% of all EV-related trials (Mizenko et al., 2024).
A meta-analysis reported a serious adverse event (SAE) rate of approximately 0.7% in EV-related studies (Van Delen et al., 2024), suggesting a generally manageable safety profile within the populations and study settings evaluated. Nevertheless, no EV- or secretome-based therapeutic product has yet received formal marketing approval from either the FDA or EMA (Mizenko et al., 2024).
This regulatory gap remains a major challenge for developers. At the same time, the absence of an established global commercial precedent means that the field remains relatively open, creating opportunities for companies capable of establishing robust manufacturing, quality and clinical-development frameworks.

Non-Serious Healthcare: The Differentiated Value Proposition of the Secretome

Cosmetics, functional skincare and aesthetic medicine operate according to a substantially different product-development logic from medicinal products. In these settings, factors such as diversity of active components, skin compatibility, biological activity and formulation stability may be more central to product development than the clinical-grade evidence required for therapeutic medicines.
Within this context, the cell secretome (secretome/conditioned medium) may offer several differentiated advantages.
From a compositional perspective, the secretome contains a combination of growth factors, cytokines and extracellular vesicles, potentially providing broader coverage of biological functions associated with skin repair, inflammation modulation and collagen synthesis. This multi-component profile is broadly compatible with the multi-target approach commonly adopted in modern skincare formulations.

From a manufacturing perspective, secretome products generally do not require the extensive purification steps associated with highly purified sEV products. This can result in a comparatively simpler process and lower manufacturing costs, which may be particularly relevant to small and medium-sized businesses operating in the cosmetics sector.
Emerging human data also provide preliminary evidence supporting the potential of secretome-based products for topical applications. Lee et al. (2026) reported the first human pilot study investigating Wharton's jelly (WJ)-derived MSC secretome for skin rejuvenation. Following one week of topical treatment, 21 participants demonstrated significant improvements in skin hydration and elasticity (p < 0.0001). In a separate patch-test assessment involving 33 participants, no skin irritation was observed.
Proteomic analysis further identified ApoA4 and SERPINH1 as potentially traceable bioactivity-related quality-control markers. These findings provide preliminary human evidence for the topical activity of MSC secretome while also highlighting the practical importance of developing quantifiable activity markers for CMC control of cosmetic-grade secretome products.
However, before considering the commercial feasibility of secretome-based products in non-serious healthcare, an important regulatory distinction must be recognised: the regulatory status of exosomes and secretome-derived ingredients differs substantially between jurisdictions.

n mainland China, for example, exosomes currently do not have an established legal basis for use as cosmetic ingredients. The Inventory of Existing Cosmetic Ingredient Names (2021 Edition) published by the National Medical Products Administration (NMPA) does not include “exosome”. Furthermore, as of the time of writing, no exosome-related new cosmetic ingredient has completed the relevant filing or registration process (NMPA, 2021).
The Safety and Technical Standards for Cosmetics (2015 Edition) also classify human-derived materials and their products as prohibited cosmetic ingredients. Consequently, human-derived exosomes fall outside the permitted ingredient framework (China Food and Drug Administration, 2015).
Plant- or non-human-animal-derived extracellular vesicles may present a different regulatory question, but genuine vesicular products that are not included in the relevant permitted ingredient lists may still face compliance issues. This distinction is particularly important because a product marketed as an “exosome” is not necessarily equivalent to a conventional botanical extract, and its regulatory status depends on the actual nature and composition of the material.

In addition, China's Cosmetics Supervision and Administration Regulation prohibits cosmetic products from explicitly or implicitly claiming medical effects (State Council, 2020). Marketing expressions such as “activating regeneration” or “stem-cell-level repair” may therefore raise regulatory concerns if they imply therapeutic effects.
For companies targeting the mainland Chinese cosmetics or aesthetic medicine markets, the current regulatory environment therefore presents significant compliance considerations, particularly for products containing human-derived exosomes or making therapeutic claims. These considerations are also an important part of the rationale for examining international market-entry strategies.

Safety considerations should likewise not be overlooked. In aesthetic injection settings, administration of exosome-containing products, including EV components within secretome preparations, has been associated with adverse reactions such as foreign-body granuloma (Choi et al., 2024). This highlights the importance of safety assessment even in non-serious healthcare applications, with particular caution warranted for injectable products.
More broadly, products of this type should not make disease-treatment claims unless they are being developed within the applicable medicinal-product framework, as such claims may trigger substantially more stringent regulatory requirements.

The Global Commercialisation Landscape: Regulatory Practices and Representative Market Examples

Indonesia: An Early Commercialisation Market for Cell Secretome

Indonesia represents one of the more developed examples of commercial activity involving cell secretome products in Southeast Asia. Its regulatory experience provides a useful reference for companies considering expansion into the region.
The Indonesian Food and Drug Authority (BPOM) has established a GMP certification framework, known as Cara Pembuatan Obat yang Baik (CPOB), covering stem-cell products and their metabolites, including secretome-related products.
PT Bifarma Adiluhung, part of the Kalbe Farma Group and operating under the Regenic brand, was an early participant in this market. In 2013, the company became the first Indonesian manufacturer to receive CPOB certification from BPOM for the production of clinical-grade stem-cell and secretome products (Bifarma Adiluhung, 2022).
According to company information published in 2022, Regenic reported a maximum production capacity of approximately 80 billion cells or 15,000 litres of secretome, equivalent to approximately 1,000 treatment doses (PT Kalbe Farma Tbk, 2022).
Its secretome products use umbilical cord-derived MSCs as the cellular source and contain a combination of growth factors, cytokines, chemokines and extracellular vesicles. These products have been applied in clinical-service settings involving areas such as orthopaedic conditions, autoimmune disorders and skin repair.
Another relevant example is PT Prodia StemCell Indonesia (ProSTEM), which also holds CPOB certification from BPOM and has obtained ISO 9001:2015 quality-management certification.

ProSTEM defines its secretome as the collection of biologically active molecules secreted by stem cells into the culture medium during cultivation, effectively corresponding to conditioned medium. This includes proteins such as growth factors and cytokines, as well as extracellular vesicles and exosomes. The company associates these components with potential roles in tissue regeneration and immune modulation (ProSTEM, 2025).
Together, these examples demonstrate that cell-secretome-based products can be incorporated into a GMP-regulated commercial framework, provided that appropriate manufacturing and quality systems are established.
In 2025, BPOM issued Regulation No. 8 of 2025 (Peraturan BPOM Nomor 8 Tahun 2025), further incorporating secretome and exosome products into its guidance for advanced therapeutic product evaluation. This represents a further development towards a more systematic regulatory framework for these emerging modalities (BPOM, 2025).

Taiwan: A Defined Pathway for Human Cell-Derived Exosomes in Cosmetics

Taiwan provides an example of a jurisdiction that has established a specific regulatory mechanism for the use of human cell-derived exosomes as cosmetic ingredients.
In March 2024, the Taiwan Food and Drug Administration (TFDA) issued the Document Requirements for Individual Case Applications Concerning Cosmetic Products Containing Human Cell-Derived Exosome Ingredients. Under this framework, human cell-derived exosomes may be considered for cosmetic use through a case-by-case review process, subject to the submission of appropriate safety, quality-control and manufacturing information (Taiwan TFDA, 2024).
In 2024, Taiwanese biotechnology company ExoOne Bio, a subsidiary of TWi Biotechnology/associated with Dongsheng Pharmaceutical, became the first company in Taiwan reported to have received TFDA approval for the use of human cell-derived exosomes as a cosmetic ingredient. The company planned products including ampoules, serums, facial masks and hair-care products, with medical aesthetic clinics and e-commerce platforms identified as key commercial channels (Taiwan Healthcare+, 2024).
The product positioning reflects the intersection of regenerative medicine concepts and premium aesthetics, illustrating how exosome-related technologies can be positioned within the high-end beauty market when a defined regulatory route exists.
In February 2026, TFDA further refined the requirements by allowing certain long-term toxicity studies to be determined on a risk-assessment and case-by-case basis, rather than requiring every applicant to conduct the full set of long-term toxicological studies. This development may reduce application costs and regulatory uncertainty for some products (Personal Care Insights, 2026).
Taiwan therefore illustrates how a clearly defined safety-data framework combined with case-by-case regulatory assessment can provide a structured pathway for human cell-derived exosome ingredients in cosmetics.

United States: Market Flexibility and Regulatory Boundaries

In the United States, several functional skincare brands have entered the market using exosome- or secretome-related positioning.
Elevai Labs is one notable example. The company has positioned products around MSC-derived exosome technology within the premium anti-ageing skincare category and has described itself as an early commercial participant in the exosome skincare market.
However, examination of its publicly described manufacturing process indicates a process involving cell-bank establishment, cell expansion, supernatant collection, 0.22 μm filtration and formulation. Based on this process description, the resulting material is more consistent with a MSC-derived secretome/conditioned-medium preparation than with a highly purified exosome fraction.
The regulatory distinction is important. The US Food and Drug Administration (FDA) has not approved any exosome product for the treatment of diseases and has repeatedly issued consumer warnings concerning unapproved exosome products marketed for therapeutic purposes (FDA, 2024).
At the same time, exosome- or secretome-related materials used in cosmetic products are not subject to the same pre-market medicinal-product approval process, provided that the products remain within the applicable cosmetic framework and do not make disease-treatment claims.
This creates a market environment in which functional skincare products can reach consumers without undergoing the full drug-development pathway. However, the distinction between a cosmetic and a biological or medicinal product remains critical: if claims or intended uses move beyond the cosmetic boundary, FDA enforcement and significantly more demanding regulatory requirements may follow.

South Korea: Rapid Growth of Exosome Aesthetics and Emerging Safety Concerns

South Korea has become an important market for exosome-related aesthetic medicine and skincare applications.
The Korean Ministry of Food and Drug Safety (MFDS) has adopted a relatively open approach towards cosmetic products based on stem-cell conditioned-medium-derived materials, which are broadly consistent with the concept of the cell secretome. A number of skincare products containing human cell-derived conditioned-medium ingredients have entered the market through cosmetic registration channels.
At the aesthetic-clinic level, injectable exosome products have also been used in market practice for applications including skin rejuvenation and hair-loss treatment, although the precise regulatory classification of such products remains an evolving issue.
Importantly, peer-reviewed medical literature has documented cases of foreign-body granuloma following exosome injections at aesthetic clinics in South Korea (Choi et al., 2024).
This highlights a broader issue for the global industry: even when products are positioned outside conventional serious healthcare, the safety of exosome and secretome-based products cannot be treated as secondary. Establishing appropriate quality standards, manufacturing controls and usage protocols remains essential, particularly when products are administered by injection.

Singapore: A Practical Warning About Labelling and Regulatory Grey Areas

Singapore provides a different perspective on the commercialisation landscape.
A skincare product explicitly labelled as containing “Exosome” was observed on an open retail shelf in a Singapore shopping centre. However, examination of the ingredient list showed only various botanical extracts and did not identify an exosome or cell-derived ingredient using an apparent INCI-compatible nomenclature.
This example illustrates a broader challenge within the exosome skincare market: some brands may use the term “exosome” primarily as a technological or marketing concept, while the actual formulation may contain botanical extracts or ingredients positioned as having “exosome-like” activity rather than genuine extracellular vesicles. Whether such materials qualify scientifically as extracellular vesicles is a separate question from how they are marketed or labelled.
Singapore's Health Sciences Authority (HSA) relies primarily on a post-market regulatory approach for cosmetics, with comparatively limited pre-market assessment of cosmetic claims. This environment can create greater flexibility for market entry, but it also places greater importance on accurate product labelling and responsible claims.
As international regulatory standards for exosome-related cosmetic products become more clearly defined — with Taiwan already establishing a specific application pathway — the risks associated with inaccurate ingredient declarations or ambiguous claims may increase.

The Singapore example therefore illustrates an important commercial principle: for products based primarily on botanical extracts, using the “exosome” concept as a marketing device without demonstrating the presence and identity of genuine extracellular vesicles may create scientific and regulatory uncertainty.
Singapore's regulatory capabilities in other areas also demonstrate the country's broader regulatory maturity. HSA achieved the World Health Organization's highest maturity level for medicines regulation in 2022, and in 2026 Singapore became the first national regulatory authority to achieve Maturity Level 4 (ML4) in medical-device regulation.

Although specific regulatory guidance for exosome-based products remains limited, these developments indicate the broader regulatory capabilities of the Singapore system. Companies considering Singapore as a first market for serious healthcare applications should therefore assess the applicable product classification, evidence requirements and potential regulatory pathway carefully rather than assuming that relatively flexible cosmetic market-entry procedures extend to therapeutic products.

Strategic Implications for Chinese Companies: Building International Pathways on Scientific and Regulatory Foundations

Serious Healthcare: Establish a Strong Domestic Foundation While Preparing for International Development

For companies seeking to enter clinical medicine and serious healthcare, establishing a robust sEV quality system aligned with relevant NMPA requirements and international frameworks such as ISEV MISEV2023 is an important foundation for clinical translation and international collaboration.
Companies should also closely monitor the evolution of NMPA/CDE policies concerning advanced therapy medicinal products (ATMPs) and incorporate changes in the interpretation of cell components and cell-derived products into product-development strategies. Where appropriate, the feasibility of secretome-based products as candidates for clinical research pathways should also be evaluated.
Technology selection should ultimately be guided by the intended indication and biological mechanism, rather than by manufacturing complexity or cost alone.
Comparative studies by Li et al. (2022) and Vahed et al. (2025) suggest a useful conceptual distinction between precision and breadth.
For indications requiring relatively targeted delivery or specific biological activity — such as certain neurological disorders, where the ability of sEVs to cross biological barriers may be relevant, or engineered approaches in cancer immunotherapy — highly purified sEVs may provide a more clearly defined technological platform.
By contrast, for applications focused on broader tissue regeneration, including chronic wound healing, skin rejuvenation and osteochondral repair, secretome preparations retaining a broader soluble-factor profile may provide potential cost and functional advantages.
This “precision versus breadth” framework can therefore serve as one decision-making dimension when evaluating technology routes, alongside the indication, manufacturing requirements, regulatory environment and clinical-development strategy.

Non-Serious Healthcare: Multiple Technology Routes and Market-Specific Positioning

For companies targeting cosmetics and aesthetic medicine, technology selection should be closely matched to the regulatory and commercial characteristics of the intended market.
Plant-derived EVs/exosomes may offer an alternative route to human cell-derived materials because they avoid certain regulatory restrictions associated with human-derived biological materials. In jurisdictions where the relevant ingredients are recognised within established cosmetic frameworks, plant-derived vesicles may potentially enter the market through conventional cosmetic-ingredient pathways. Relevant INCI nomenclature and local ingredient requirements must nevertheless be assessed on a market-by-market basis.
For companies developing human cell-derived EVs or secretome products, international expansion may be considered in markets where regulatory pathways or commercial precedents have already emerged. These include Taiwan, where a case-by-case pathway for human cell-derived exosome cosmetic ingredients has been established; South Korea, where the market has relatively high consumer and clinical familiarity with secretome-related cosmetic applications; and Indonesia, where secretome-based regenerative medicine products have been incorporated into a GMP-regulated commercial environment.
Other emerging markets, including parts of the Middle East and Eastern Europe, may also warrant consideration as their regulatory frameworks for advanced biological and aesthetic technologies continue to develop.

The Singapore example, however, provides an important reminder that a relatively flexible market-entry environment does not eliminate the need for scientific substantiation. Products that rely primarily on the “exosome” concept for marketing while lacking demonstrable exosome or secretome content may face increasing compliance risks as regulatory standards mature.
For long-term commercial development, the more sustainable approach is therefore to establish a product's genuine scientific basis, maintain transparent ingredient declarations and ensure that marketing claims remain consistent with the actual composition and evidence supporting the product.

A Common Baseline: Scientific and Regulatory Compliance First

Regardless of the selected market or technology pathway, several principles should form the foundation of product development.
First, product composition and labelling claims should be consistent. Companies should avoid misleading ingredient declarations or marketing terminology that could create regulatory or legal exposure.
Second, even cosmetic and aesthetic products should be supported by an appropriate minimum safety and efficacy evidence package. The depth of evidence should reflect the product's intended use, route of administration and claims.
Third, companies should continuously monitor regulatory developments in their target markets. The regulatory environment for exosome- and secretome-based cosmetics and aesthetic applications is evolving rapidly worldwide. Regulatory foresight is therefore likely to become an increasingly important component of sustainable international commercialisation.

Conclusion

The cell secretome and exosomes/sEVs should not be viewed as mutually exclusive alternatives. Rather, they represent different expressions of the same biological system at different levels of processing and purification, with distinct implications for product development and application.
From a scientific perspective, sEVs/exosomes represent a more defined vesicular fraction within the broader secretome. From a regulatory perspective, different jurisdictions are developing different approaches to cell-derived products, with some establishing specific pathways for EV- or secretome-based applications while others continue to operate within broader existing regulatory categories.

From a commercial perspective, global markets are gradually developing clearer — although still heterogeneous — approaches to these technologies. The opportunities available to developers therefore depend not only on the biological properties of the product, but also on the intended application, manufacturing strategy, regulatory classification and market-specific requirements.
For serious healthcare, highly characterised and quality-controlled sEV products may provide a more defined basis for clinical development, where identity, potency, safety, consistency and manufacturing controls are central considerations.
For non-serious healthcare, secretome-based products may offer broader biological activity and potentially lower manufacturing costs, although their greater compositional complexity also creates challenges in standardisation and quality control.
For companies seeking international expansion, the experiences of Indonesia, Taiwan, South Korea, the United States and Singapore illustrate that there is no single global pathway for secretome and exosome commercialisation. Instead, successful market entry requires technology and product positioning to be aligned with the regulatory framework, intended claims, manufacturing capabilities and evidence requirements of each target market.
For Chinese companies in particular, international expansion should therefore be approached not simply as a question of where a product can be sold, but of where its scientific definition, manufacturing process, evidence package and intended claims can be aligned with an appropriate regulatory pathway.
A scientifically substantiated product, transparent quality system and market-specific regulatory strategy provide the foundation for sustainable international development of secretome and exosome technologies.

References

Bifarma Adiluhung. (2022, September 30). Stem cell processing facility of Kalbe received a visit from the Ministry of Health, BPOM, BRIN, and KPSPS. PT Kalbe Farma Tbk. https://www.bifarma.co.id
Badan Pengawas Obat dan Makanan (BPOM). (2025). Peraturan BPOM Nomor 8 Tahun 2025 tentang pedoman penilaian produk terapi advanced [Regulation No. 8 of 2025 on guidelines for the evaluation of advanced therapy products]. Indonesian Food and Drug Authority.
Choi, H., Kwak, J. H., Shin, B. S., Na, C. H., & Kim, M. S. (2024). Foreign body granuloma caused by an injection of exosomes. JAAD Case Reports, 47, 67–69. https://doi.org/10.1016/j.jdcr.2024.03.026
Gould, S. J., & Raposo, G. (2013). As we wait: Coping with an imperfect nomenclature for extracellular vesicles. Journal of Extracellular Vesicles, 2, 20389. https://doi.org/10.3402/jev.v2i0.20389
Gollihue, J. L., & Rabchevsky, A. G. (2017). Prospects for therapeutic mitochondrial transplantation. Mitochondrion, 35, 70–79. https://doi.org/10.1016/j.mito.2017.05.007
Kalluri, R., & LeBleu, V. S. (2020). The biology, function, and biomedical applications of exosomes. Science, 367(6478), eaau6977. https://doi.org/10.1126/science.aau6977
Mathieu, M., Martin-Jaular, L., Lavieu, G., & Théry, C. (2019). Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nature Cell Biology, 21(1), 9–17. https://doi.org/10.1038/s41556-018-0250-9
Na, T., Zhang, K., Zhao, L., Yao, X., Xu, C., Zhang, Y., Wang, L., Xu, M., Zhang, H., & Meng, S. (2026). Quality evaluation considerations for stem cell-derived extracellular vesicles-based therapeutic products in China. Journal of Extracellular Vesicles, 15, e70297. https://doi.org/10.1002/jev2.70297
Personal Care Insights. (2026, February 6). Taiwan's exosome policy shift signals more predictable approval path for cosmetics. https://www.personalcareinsights.com/news/taiwan-exosome-cosmetics-regulation.html
ProSTEM. (2025, December 4). Pengembangan secretome ProSTEM untuk hasil terapi lebih efektif [Development of ProSTEM secretome for more effective therapeutic results]. PT Prodia StemCell Indonesia. https://prostem.co.id
PT Kalbe Farma Tbk. (2022, September 30). Stem cell processing facility of Kalbe received a visit from the Ministry of Health, BPOM, BRIN, and KPSPS. PublicNow. https://www.publicnow.com/view/4710B5F98AE16AA9661C57A97DAD4AD79C986863
Ranganath, S. H., Levy, O., Inamdar, M. S., & Karp, J. M. (2012). Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell, 10(3), 244–258. https://doi.org/10.1016/j.stem.2012.02.005
Taiwan Healthcare+ B2B. (2024, April 25). ExoOne has been granted approval by the Ministry of Health and Welfare to use human-derived exosomes as cosmetic ingredients, marking the first case in Taiwan. https://www.taiwan-healthcare.org
Taiwan Food and Drug Administration (TFDA). (2024). 化妆品含人类细胞来源外泌体成分个案申请文件要求 [Documentation requirements for case-by-case applications for the use of exosomes derived from human cells in cosmetics]. Ministry of Health and Welfare, Taiwan.
Théry, C., Witwer, K. W., Aikawa, E., Alcaraz, M. J., Anderson, J. D., Andriantsitohaina, R., Bhatt, D. L., Bhattacharyya, S. N., Bhattacharya, A., Blenkiron, C., & Zucchetti, A. E. (2018). Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. Journal of Extracellular Vesicles, 7(1), 1535750. https://doi.org/10.1080/20013078.2018.1535750
U.S. Food and Drug Administration (FDA). (2024). Public safety notification: Exosome products. U.S. Department of Health and Human Services. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/public-safety-notification-exosome-products
van Niel, G., D'Angelo, G., & Raposo, G. (2018). Shedding light on the cell biology of extracellular vesicles. Nature Reviews Molecular Cell Biology, 19(4), 213–228. https://doi.org/10.1038/nrm.2017.125
Welsh, J. A., Goberdhan, D. C. I., O'Driscoll, L., Buzas, E. I., Blenkiron, C., Bhattacharyya, S. N., Dasgupta, S., De Wever, O., Drummen, G. P. C., Ghiran, I. C., Hendrix, A., Hill, A. F., Klingeborn, M., Lewandrowski, U., Lötvall, J., Prabhakar, S., Sahoo, S., Tahara, H., Théry, C., & Witwer, K. W. (2024). Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. Journal of Extracellular Vesicles, 13(2), e12404. https://doi.org/10.1002/jev2.12404
Witwer, K. W., & Théry, C. (2019). Extracellular vesicles or exosomes? On the pros and cons of various nomenclatures. Journal of Extracellular Vesicles, 8(1), 1648167. https://doi.org/10.1080/20013078.2019.1648167
Yáñez-Mó, M., Siljander, P. R., Andreu, Z., Zavec, A. B., Borras, F. E., Buzas, E. I., Buzas, K., Casal, E., Cappello, F., Carvalho, J., Colás, E., Cordeiro-da Silva, A., Fais, S., Falcon-Perez, J. M., Ghobrial, I. M., Giebel, B., Gimona, M., Graner, M., Gursel, I., … De Wever, O. (2015). Biological properties of extracellular vesicles and their physiological functions. Journal of Extracellular Vesicles, 4(1), 27066. https://doi.org/10.3402/jev.v4.27066
Al-Sharabi, N., Gruber, R., Sanz, M., Mohamed-Ahmed, S., Kristoffersen, E. K., Mustafa, K., & Shanbhag, S. (2023). Proteomic analysis of mesenchymal stromal cells secretome in comparison to leukocyte- and platelet-rich fibrin. *International Journal of Molecular Sciences*, *24*(17), 13057. https://doi.org/10.3390/ijms241713057
Bari, E., Perteghella, S., Di Silvestre, D., Sorlini, M., Catenacci, L., Sorrenti, M., Torre, M. L., & Farraro, F. (2023). Towards the standardization of mesenchymal stem cell secretome-derived product manufacturing for tissue regeneration. *International Journal of Molecular Sciences*, *24*(16), 12594. https://doi.org/10.3390/ijms241612594
Chinnadurai, R. (2023). Advanced technologies for potency assay measurement. In *Mesenchymal Stromal Cells: Biology, Manufacturing and Clinical Use* (pp. 145-168). Springer. https://doi.org/10.1007/978-3-031-30040-0_6
Dangerfield, J. A., & Metzner, C. (2026). Collecting eggs, not killing chickens: Why stem cell secretome and exosomes are redefining regenerative medicine for healthspan extension. *Biomedicines*, *14*(4), 854. https://doi.org/10.3390/biomedicines14040854
Drobiova, H., Sindhu, S., Ahmad, R., Haddad, D., Al-Mulla, F., & Al Madhoun, A. (2023). Wharton's jelly mesenchymal stem cells: A concise review of their secretome and prospective clinical applications. *Frontiers in Cell and Developmental Biology*, *11*, 1211217. https://doi.org/10.3389/fcell.2023.1211217
Foo, J. B., Looi, Q. H., Chong, P. P., Hassan, N. H., Yeo, G. E. C., Ng, C. Y., Koh, B., How, C. W., Lee, S. H., & Law, J. X. (2021). Comparing the therapeutic potential of stem cells and their secretory products in regenerative medicine. *Stem Cells International*, *2021*, 2616807. https://doi.org/10.1155/2021/2616807
Han, Y., Yang, J., Fang, J., Zhou, Y., Candi, E., Wang, J., Hua, D., Shao, C., & Shi, Y. (2022). The secretion profile of mesenchymal stem cells and potential applications in treating human diseases. *Signal Transduction and Targeted Therapy*, *7*(1), 92. https://doi.org/10.1038/s41392-022-00932-0
Humbert, C., Cordier, C., Drut, I., Churlaud, G., Chabriat, S., Joanne, P., Agbulut, O., Blons, H., Mooney, N., Magalon, J., Wilson, M. C., Pidial, L., Bellamy, V., Vanneaux, V., Larghero, J., Arock, M., Gnocchi, M., Da Silva, C. C., Planat-Benard, V., Carvalho, J., Planat, V., Baroukh, N., Torregrossa, R., Amouroux, R., Silvestre, J. S., Hulot, J. S., Sanchez, E., Menasche, P., & the Vesicard Consortium. (2025). GMP-Compliant process for the manufacturing of an extracellular vesicles-enriched secretome product derived from cardiovascular progenitor cells suitable for a phase I clinical trial. *Journal of Extracellular Vesicles*, *14*(8), e70145. https://doi.org/10.1002/jev2.70145
Kalluri, R., & LeBleu, V. S. (2020). The biology, function, and biomedical applications of exosomes. *Science*, *367*(6478), eaau6977. https://doi.org/10.1126/science.aau6977
Knecht, S., Eberl, H. C., Kreisz, N., Ugwu, U. J., Starikova, T., Kuster, B., & Wilhelm, S. (2023). An introduction to analytical challenges, approaches, and applications in mass spectrometry-based secretomics. *Molecular & Cellular Proteomics*, *22*(9), 100636. https://doi.org/10.1016/j.mcpro.2023.100636
Kugeratski, F. G., Hodge, K., Lilla, S., McAndrews, K. M., Zhou, X., Hwang, R. F., Zanivan, S., & Kalluri, R. (2021). Quantitative proteomics identifies the core proteome of exosomes with syntenin-1 as the highest abundant protein and a putative universal biomarker. *Nature Cell Biology*, *23*(6), 631-641. https://doi.org/10.1038/s41556-021-00693-y
Lee, Y. J., Shin, K. J., & Chae, Y. C. (2024). Regulation of cargo selection in exosome biogenesis and its biomedical applications in cancer. *Experimental & Molecular Medicine*, *56*, 877-889. https://doi.org/10.1038/s12276-024-01209-y
Lee, N. E., Hwang, J. I., Bang, C. Y., Kim, E. H., & Bang, O. Y. (2026). Wharton's jelly mesenchymal stem cell-secretome enhances skin rejuvenation via ApoA4 and SERPINH1. *Regenerative Therapy*, *25*, 1-15. https://doi.org/10.1016/j.reth.2026.101071
Leñero, C., Kaplan, L. D., Best, T. M., & Kouroupis, D. (2022). CD146+ endometrial-derived mesenchymal stem/stromal cell subpopulation possesses exosomal secretomes with strong immunomodulatory miRNA attributes. *Cells*, *11*(24), 4002. https://doi.org/10.3390/cells11244002
Li, C., Wang, Y., Li, Y., Zhao, Y., Xu, J., Li, X., Li, M., Mei, Q., Zhang, L., & Wang, Z. (2022). Comparison of two cell-free therapeutics derived from adipose tissue: small extracellular vesicles versus conditioned medium. *Stem Cell Research & Therapy*, *13*, 18. https://doi.org/10.1186/s13287-021-02635-9
Liangsupree, T., Multia, E., & Riekkola, M. L. (2021). Modern isolation and separation techniques for extracellular vesicles. *Journal of Chromatography A*, *1636*, 461773. https://doi.org/10.1016/j.chroma.2020.461773
Mathieu, M., Martin-Jaular, L., Lavieu, G., & Thery, C. (2019). Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. *Nature Cell Biology*, *21*(1), 9-17. https://doi.org/10.1038/s41556-018-0250-9
Mizenko, R. R., Feaver, M., Bozkurt, B. T., Lowe, N., Nguyen, B., Huang, K. W., Wang, A., & Carney, R. P. (2024). A critical systematic review of extracellular vesicle clinical trials. *Journal of Extracellular Vesicles*, *13*(10), e12510. https://doi.org/10.1002/jev2.12510
Niada, S., Giannasi, C., Magagnotti, C., Andolfo, A., & Brini, A. T. (2021). Proteomic analysis of extracellular vesicles and conditioned medium from human adipose-derived stem/stromal cells and dermal fibroblasts. *Journal of Proteomics*, *232*, 104069. https://doi.org/10.1016/j.jprot.2020.104069
Reis, M., Sobreira, G. M., Vasques, J. F., Oliveira, M. D. F., Ramalho, L. R. Z. P., & Rodrigues, M. C. (2025). MSC-derived secretome and exosomes in dermatology: Mechanisms, applications, and translational barriers. *Journal of the European Academy of Dermatology and Venereology*, *39*(3), 435-452. https://doi.org/10.1111/jdv.20116
Shin, S., Lee, J., Kwon, Y., Park, K.-S., Jeong, J.-H., Choi, S.-J., Bang, S. I., Chang, J. W., & Lee, C. (2021). Comparative proteomic analysis of the mesenchymal stem cells secretome from adipose, bone marrow, placenta and Wharton's jelly. *International Journal of Molecular Sciences*, *22*(2), 845. https://doi.org/10.3390/ijms22020845
Vahed, S. Z., Hejazian, S. M., Bakari, W. N., Landon, R., Gueguen, V., Meddahi-Pelle, A., Anagnostou, F., Barzegari, A., & Pavon-Djavid, G. (2025). Milking mesenchymal stem cells: Updated protocols for cell lysate, secretome, and exosome extraction, and comparative analysis of their therapeutic potential. *Methods*, *238*, 40-60. https://doi.org/10.1016/j.ymeth.2025.03.004
Van Delen, M., Derdelinckx, J., Wouters, K., Nelissen, I., & Cools, N. (2024). A systematic review and meta-analysis of clinical trials assessing safety and efficacy of human extracellular vesicle-based therapy. *Journal of Extracellular Vesicles*, *13*(7), e12458. https://doi.org/10.1002/jev2.12458
Visan, K. S., Lobb, R. J., Ham, S., Lima, L. G., Palma, C., Edna, C. P. Z., Wu, L. Y., Gowda, H., Datta, K. K., Hartel, G., Salomon, C., & Moller, A. (2022). Comparative analysis of tangential flow filtration and ultracentrifugation, both combined with subsequent size exclusion chromatography, for the isolation of small extracellular vesicles. *Journal of Extracellular Vesicles*, *11*(9), e12266. https://doi.org/10.1002/jev2.12266
Wang, C. K., Tsai, T. H., & Lee, C. H. (2024). Regulation of exosomes as biologic medicines: Regulatory challenges faced in exosome development and manufacturing processes. *Clinical and Translational Science*, *17*(8), e13904. https://doi.org/10.1111/cts.13904
Wei, D., Zhan, W., Gao, Y., Huang, L., Gong, R., Wang, H., Zhang, S., Zhu, Q., Zeng, Z., Cheng, J., Fu, Q., Yang, X., Yuan, W., Peng, S., Jiang, M., Lin, X., Lou, Y., Yan, Q., Xing, R., Xu, M., Nie, Y., Wang, X., Shao, Z., Wang, P., Zhang, Y., Li, Z., Chen, L., Huang, W., Wu, K., Wang, X., Fan, D., & Zhang, H. (2021). RAB31 marks and controls an ESCRT-independent exosome pathway. *Cell Research*, *31*(2), 157-177. https://doi.org/10.1038/s41422-020-00409-1
Welsh, J. A., Goberdhan, D. C. I., O'Driscoll, L., Buzas, E. I., Blenkiron, C., Bussolati, B., Cai, H., Di Vizio, D., Driedonks, T. A. P., Erdbrugger, U., Falcon-Perez, J. M., Fuhrmann, G., Gho, Y. S., Haro, M., de Junjaras Javornik, U., Kestens, V., Kibria, G., Kong, A. T., Kruger, A. E., Kuypers, S., Lacroix, R., Lasser, C., Lener, T., Llorente, A., Lorenowicz, M. J., Mateescu, B., van der Meel, R., Moeller, A., Nazarenko, I., O'Driscoll, R., Olivotto, M., Perez-Pozo, M. E., Pluchino, S., Reekmans, R., Rider, M. A., Russell, A. E., Salinas, J. L., Sandau, U., Scott, A., Scott, R., Selderslaghs, I., Shekari, F., Spragg, J., Thalmann, C., Thietart, S., Tu, M., van der Vlist, E. J., Vukman, K. V., Wang, J., Welton, J. L., Witwer, K. W., Yan, I., Yuana, Y., Zhou, W., Zuniga, P., Vader, P., & Witwer, K. W. (2024). Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. *Journal of Extracellular Vesicles*, *13*(2), e12404. https://doi.org/10.1002/jev2.12404
国家食品药品监督管理总局. (2015). 化妆品安全技术规范（2015年版）. 国家食品药品监督管理总局. https://www.nmpa.gov.cn/hzhp/hzhpggtg/hzhpqtgg/20151223120001986.html
国家药品监督管理局. (2021). 已使用化妆品原料目录（2021年版）. 国家药品监督管理局. https://www.nmpa.gov.cn/hzhp/hzhpggtg/hzhpqtgg/20210401153847195.html
国务院. (2020). 化妆品监督管理条例（国务院令第727号）. 中华人民共和国中央人民政府. http://www.gov.cn/zhengce/content/2020-06/29/content_5522593.htm
国家卫生健康委员会. (2024). 细胞组分及衍生物治疗新技术临床研究备案指引（第一版）. 国家卫生健康委员会.