Youlin Wu 1,2 & Chih-hung Huang 1
1. Institute of Chemical Engineering, National Taipei University of Technology, Taipei, Taiwan.
2. Prosperity Bio Co., Ltd., Taipei, Taiwan

Introduction: Exosomes as an Emerging Hotspot with Market Chaos

Since the 1990s, extracellular vesicles (EVs) were discovered to play immunological roles and to potentially mediate intercellular communication, which sparked a surge of related research [1]–[3]. In 2013, Rothman, Schekman, and Südhof were awarded the Nobel Prize in Physiology or Medicine for their work on the molecular mechanisms of vesicular trafficking, which indirectly raised global attention on EVs/exosomes [4]. Following this, resources and investments into this field rapidly expanded.

Nevertheless, our understanding of EVs and exosomes remains limited. The International Society for Extracellular Vesicles (ISEV), founded in 2011, has already updated its minimal information guidelines three times within a short period. MISEV2014 defined EVs and introduced the “three positive/one negative” protein characterization baseline [5]. MISEV2018 emphasized the unified terminology “EVs” and recommended enhanced methodological reporting [6], while MISEV2023 further incorporated advanced approaches, multimodal characterization, and reproducibility [7], [8].

Despite such rigor, commercial forces have advanced more quickly than the science or regulation. In recent years, exosomes have rapidly risen in both medical and cosmetic markets, being branded as a “next-generation cell therapy.” In Taiwan, the pace of commercialization has far outstripped the maturity of scientific and regulatory frameworks, leading to a proliferation of heterogeneous products, exaggerated claims, and lack of testing standards. In May 2025, the Taiwan Food and Drug Administration (TFDA) convened a workshop on exosome-related products, signaling regulatory agencies’ intention to intervene and restore market order.

This article therefore proposes, based on MISEV2023, a feasible framework for exosome product testing standards as a reference for academia, industry, and regulators.

I. Definitions and Classification: The International Consensus of MISEV2023

According to the latest ISEV guidelines (MISEV2023), exosomes should be considered within the broader category of EVs, and standardized terminology/classification is critical for both research and regulation [7], [8].

– Unified definition: Unless the subcellular origin is clearly demonstrated (e.g., multivesicular body release), terms like “exosome” or “microvesicle” should be avoided; the general term “EVs” is preferred.
– Classification: Based on size (e.g., small EVs < 200 nm), origin (cell type), and biochemical markers (CD9, CD63, TSG101), among other descriptors.
– New concepts: MISEV2023 also introduces “extracellular particles (EPs)” and “non-vesicular extracellular particles (NVEPs),” reflecting a more nuanced understanding of extracellular components [7], [8].

II. Analytical Methods: Imaging, Quantification, and Functional Assays

Testing methods for exosomes/EVs encompass purity, particle size, surface markers, and biological activity. Among these, imaging remains both critical and underdeveloped [10], [11].

1. Imaging methods:
   – TEM/SEM: Direct visualization of morphology and size distribution (qualitative).
   – Confocal microscopy with labeling: Detects specific markers.
   – Fluorescent nanoparticle tracking analysis (NTA): Quantitative analysis of EV subtypes.
   – Super-resolution microscopy (STORM, SIM, STED): Overcomes diffraction limits for precise molecular localization.
   – Cryo-EM: High-resolution structural visualization.

2. Particle size and concentration:
   – NTA: Widely used standard for size and concentration.
   – DLS: Useful for homogeneous samples, less reliable for heterogeneous EVs.

3. Biochemical analysis:
   – Western blot/ELISA for EV markers (CD63, TSG101).
   – Flow cytometry with nanoparticle platforms for quantitative assessment.

4. Functional assays:
   – Uptake and target-cell assays (migration, differentiation, immune responses).

III. Clinical Applications and Challenges: Promising but Immature

According to Nature Reviews Drug Discovery and the Journal of Extracellular Vesicles, as of September 2025, no exosome products have received formal drug approval from the U.S. FDA or the EMA [12]. The FDA has repeatedly stated that “there are currently no FDA-approved exosome products” and issued warnings against unlawful marketing [13], [14]. In the EU, clinical trial approvals and ATMP/orphan designations exist but do not yet constitute market authorization [19]–[22].

Ongoing investigational new drug (IND) trials focus on:
– Regenerative medicine (skin, cartilage repair)
– Immune modulation (autoimmune diseases)
– Oncology (adjunctive therapy)
– Neurodegenerative disease models

Most evidence of efficacy still stems from preclinical animal models. Mechanisms (e.g., RNA cargo, source-cell specificity) remain under debate, and consensus has not been reached [6]–[8].

IV. Taiwan Market Status: Urgent Need for Regulation and Standards

Products labeled with “exosomes” in Taiwan mainly include:
– Cosmetics/skincare: Often without concentration/source labeling.
– Medical devices with injectable solutions: Sometimes derived from stem cell culture supernatants.
– Health supplements: Largely marketing-driven, lacking scientific validation.

Most lack GMP-grade manufacturing, standardized quality control, or validated assays, undermining both consumer trust and industry credibility.

V. Recommendations and Outlook

1. For regulators:
   – Establish definition and testing standards for exosome products (e.g., size, markers, purity based on MISEV2023).
   – Implement tiered regulation (cosmetic vs. medical device vs. therapeutic).

2. For industry:
   – Select partners with validated EV sources and GMP-compliant manufacturing.
   – Track TFDA/ICH regulatory updates and invest in lab-level QC capacity.
   – Join ISEV and other standardization groups for technical support.

3. For researchers:
   – Employ multimodal validation (imaging, functional, molecular).
   – Focus on translational models with potential for early clinical entry.

Conclusion

The exosome market is booming, yet exosomes remain highly heterogeneous and incompletely understood. Without clear testing standards and regulatory systems, sustainable development will be difficult. Taiwan should seize this critical moment to establish comprehensive and credible industry norms through joint efforts across academia, industry, and government.

References

[1] G. Raposo et al., “B lymphocytes secrete antigen-presenting vesicles,” J. Exp. Med., vol. 183, pp. 1161–1172, 1996.

[2] L. Zitvogel et al., “Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell derived exosomes,” Nat. Med., vol. 4, pp. 594–600, 1998.

[3] H. Valadi et al., “Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells,” Nat. Cell Biol., vol. 9, pp. 654–659, 2007.

[4] Nobel Prize, “The Nobel Prize in Physiology or Medicine 2013—Press Release,” NobelPrize.org, 2013.

[5] J. Lötvall et al., “Minimal experimental requirements for definition of extracellular vesicles and their functions: A position statement from ISEV,” J. Extracell. Vesicles, vol. 3, 26913, 2014.

[6] C. Théry et al., “MISEV2018: Minimal information for studies of extracellular vesicles,” J. Extracell. Vesicles, vol. 7, 1535750, 2018.

[7] ISEV, “About the MISEV Guidelines (2014, 2018, 2023),” 2024.

[8] J. A. Welsh et al., “MISEV2023: From basic to advanced approaches,” J. Extracell. Vesicles, vol. 13, e12451, 2024.

[9] J. Van Deun et al., “EV-TRACK: Transparent reporting and centralizing knowledge in EV research,” Nat. Methods, vol. 14, pp. 228–232, 2017.

[10] Nobel Prize, “The Nobel Prize in Chemistry 2014—Press Release (super-resolution microscopy),” 2014.

[11] Nobel Prize, “The Nobel Prize in Chemistry 2017—Popular information (cryo-EM),” 2017.

[12] U.S. FDA, “Public Safety Notification on Exosome Products,” Dec. 2019.

[13] U.S. FDA, “Consumer Alert on Regenerative Medicine Products, including stem cells and exosomes,” Jul. 2020.

[14] CDC, “Stem Cell and Exosome Products—Safety Information,” Dec. 2019.

[15] Bio-Techne/Exosome Diagnostics, “FDA Grants Breakthrough Device Designation to ExoDx Prostate (EPI),” Press Release, Jun. 17, 2019.

[16] Exosome Diagnostics, “Press Releases / Product Page—ExoDx Prostate Test,” 2019–2024.

[17] Urology Times, “The Role of the ExoDx Prostate Test in Early Detection…,” 2021.

[18] A. McKiernan et al., “Clinical performance of the ExoDx (EPI) Prostate Test…,” Prostate Cancer Prostatic Dis., 2022.

[19] EXO Biologics, “First EMA-approved MSC-exosome clinical trial (news update),” Jun. 24, 2024.

[20] EMA/CAT, “Scientific recommendations on classification of ATMPs,” European Medicines Agency, 2025.

[21] EMA, “EU/3/21/2508 Orphan designation—BPD prevention,” Oct. 2021.

[22] NurExone, “EMA grants Orphan Designation for ExoPTEN,” Nov. 2024.

[23] Allure, “FDA: ‘There are currently no FDA-approved exosome products for any use’,” 2024.

[24] The Guardian, “Beauty clinics in UK offering banned human-cell–derived exosome treatments,” Mar. 29, 2025.