Joaquim Vives, PhD
Banc de Sang i Teixits
Extracellular vesicles (EV), a heterogeneous group of secreted vesicles of endosomal and plasma membrane origin, play a key role in cell-to-cell communication by transporting messenger RNA, miRNA and proteins (1). In addition to their clinical use as biomarkers, there’s a growing interest in exploring the therapeutic potential of EV because of the advantages over using living cells, such as limited immunogenicity and cytotoxicity, enhanced stability, and cell targeting properties (e.g. crossing the blood-brain barrier), among others. Consequently, ISCT created the Exosomes Committee to assist in the planning of the annual meeting scientific program, review the status of the EV field, identify major scientific obstacles, publish position papers and engage in scientific discourse to advance the field. Here in the Telegraft hub, EV were first featured in the inaugural issue of our section “Under the microscope” in Jan 2021 with an article authored by the Exosomes Committee chairs Drs. Sai Kiang Lim and Bernd Giebel. In this update we want to highlight the enormous activity that is currently underway in Europe in this field, as pioneered in the clinic by same Dr. Giebel in Germany, and Drs. Eva Rohde and Mario Gimona, in Austria.
This is a fascinating emerging field, offering new alternatives to parental cells in innovative therapies using product from cells. As of today, several bottlenecks still exist for scale up production and clinical translation, including the lack of standardized isolation and purification methods, limited drug loading efficiency (e.g. by genetic engineering approaches, chemical functionalization), insufficient clinical grade production yields, and the lack of harmonization of Quality Controls (QC). Some of these issues are common to the manufacture of cell- and gene-based therapeutics, but EV encounter yet additional challenges downstream in the production process and characterization of the drug substance. As any other medicinal product, reliable data on safety and consistent quality are key to ensure the success in their clinical translation. However, such fast-paced innovation requires developers and regulators to establishing new tools, standards, and approaches to adequately address these issues. Here is where scientific societies like ours play an essential role assisting all stakeholders involved providing guidance in key aspects along the development of novel therapeutics. The ISCT has been active in teaming up with other societies and the EV field is no exception. Together with the International Society for Extracellular vesicles (ISEV), white papers have been published recently to facilitate meeting best practice standards and pave the way for harmonization (2-4). Also, the end of most restrictions established worldwide during the pandemic is now offering new possibilities for face-to-face meetings that, according to a recent study, have been demonstrated to facilitate creative idea generation, better than videoconferencing (5). Particularly for EV, the return of in-person meetings is being productive as illustrated by a couple of examples, like the ISEV 2022 annual meeting (Lyon, France) in Europe, and the 30th ISCT Annual Meeting (San Francisco, CA) in North America, this way recovering channels of communication for learning and discussing on the progress of current EV research.
In the first case, the Banc de Sang i Teixits (BST)-Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP) collaborative group presented its approach to GMP-ize the scale up production of EV from Mesenchymal Stromal Cells, highlighting challenges (and proposed solutions) for consistent characterization of their identity, purity and potency. The 2022 ISCT meeting in San Francisco included a plenary session to discuss hot topics related to EV scale up manufacturing, set common criteria for characterization and development of EV-based product for clinical applications as a follow-up of last year’s plenary session on “First in Man” Trials, in New Orleans.
In-person meetings and workshops facilitate real-time interaction, improving social skills, organization, motivation, and accessibility. As EV serve cell-to-cell communication, with the end of the restrictions due to the pandemic we are somehow reducing the use of Zoom, Teams and alike, and we are back again to face-to-face interaction with our collaborators to explore together new avenues for progressing scientific and medical research. Hopefully we’ll have new opportunities to meet again and accelerate developments in this exciting emerging field arising from cell-based therapy!
- Yáñez-Mó M, Siljander PR, Andreu Z, Zavec AB, Borràs FE, Buzas EI, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066.
- Gimona M, Brizzi MF, Choo ABH, Dominici M, Davidson SM, Grillari J, et al. Critical considerations for the development of potency tests for therapeutic applications of mesenchymal stromal cell-derived small extracellular vesicles. Cytotherapy. 2021;23(5):373-80.
- Witwer KW, Van Balkom BWM, Bruno S, Choo A, Dominici M, Gimona M, et al. Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications. J Extracell Vesicles. 2019;8(1):1609206.
- Börger V, Weiss DJ, Anderson JD, Borràs FE, Bussolati B, Carter DRF, et al. International Society for Extracellular Vesicles and International Society for Cell and Gene Therapy statement on extracellular vesicles from mesenchymal stromal cells and other cells: considerations for potential therapeutic agents to suppress coronavirus disease-19. Cytotherapy. 2020;22(9):482-5.
- Brucks MS, Levav J. Virtual communication curbs creative idea generation. Nature. 2022;605(7908):108-12.