ISCT 2023: MSCs & MSC-EVs Maturing Into a Mainstream Cell Therapy Topic

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RoosterBio at ISCT 2023

The 2023 annual meeting of the International Society of Cell and Gene Therapy (ISCT) commenced in Paris, France from May 31st until June 3rd. Over 51 countries were represented at the international event. There were an estimated >2000 attendees to the meeting, including 6 from RoosterBio. The exhibit hall was packed with >150 company exhibits, including a vibrant exhibit space provided by RoosterBio (pictured above). Due to the broader interest in the cell therapy field, many diverse company booths were represented, but the primary focus was upstream methods for cellular therapies.

Over 1300 posters were presented at the meeting, including 3 scientific posters contributed by RoosterBio, including: [1]

  • “Development of an End-to-End Scalable Purification Platform for Extracellular Vesicles” (presented in collaboration with Sartorius) [2]
  • “Development of Manufacturing Therapeutic Platform for Extracellular Vesicles Derived from Mesenchymal Stromal Cell (MSC-EVs) Using Scalable Manufacturing Clarification & Concentration Diafiltration System platforms, The Tangential Flow Depth Filtration (TFDF) & the Tangential Flow Filtration (TFF) with Hollow Fibers” (Presented in collaboration with Repligen) [3]
  • “A GMP-Compatible Process for the Efficient Transfection of MSCs with mRNA” [4]

Additionally, an oral presentation in the EV/Exosome session titled “Successful Development of a Scalable & Robust Process for MSC-EV Production” [5] was presented to showcase the large-scale capability of MSC-EV production at RoosterBio.

A Growing Representation of MSCs & EVs in Presentation & Discussion

Oral sessions kicked off with the Presidential Plenary, focused on cancer immunotherapy, the staple topic for ISCT in recent years. Dr. Bruce Levine (University of Pennsylvania) reminded the audience of the incredible successes in the commercialization of CAR-T therapies against blood cancers (>6 approvals since the first, Kymriah, in 2017). Because of this commercial success, many may think that CAR-T applications are restricted to applications against blood cancer, but Dr. Levine provided an update on the future of CAR-T therapies. The next-generation of CAR-T therapies are in development, with highlights including:

  • Therapies showing effectiveness against solid tumors.
  • A significant reduction in manufacturing time of autologous immunotherapy products.
  • More efficient therapies, thus lowering dose requirements (a significant cost driver).
  • Therapies to treat fibrosis and heart disease.

Technologies used to develop CAR-T products have been and continue to be applied to other cell types including natural killer (NK) cells. Accordingly, Dr. Mark Lowdell (INmuneBio, Inc.) shared an update on the promising Phase I success of primed-NK treatments against some cancers.

Despite the focus on immunotherapy for this plenary session, the RoosterBio team noticed an increasing trend at the meeting for spotlights on MSCs and MSC-EVs. Out of all scientific oral sessions, our team estimated ~30% were focused on MSCs or EVs. Several roundtable sessions also featured discussions on MSCs and/or EVs. Furthermore, a half-day Exosomes/EV education event took place on the final day of the conference.

In one roundtable session, “Exosome Therapeutics: Are MSCs now redundant?”, panelists discussed with the audience the relevance of microRNAs in EVs. Many believe that microRNAs are a critical content delivered by MSC-EVs to recipient cells for therapeutic action. However, some panelists believe that MSC-EVs exhibit their mechanism of therapeutic action not by uptake into target cells with subsequent cargo delivery, but probably by other means, including binding to the surface of target cells. The debate about the mechanism of action and the therapeutic relevance of RNAs within EVs continues to be featured at international conferences.

Additionally, in this session, the development of clonal MSCs was noted as being important for the field to overcome the challenge of heterogeneity between MSC batches. As mentioned by panelists, donor-to-donor variability likely will affect patient response. Furthermore, different MSC clones could be more or less relevant for different disease indications. At the very least, assays need to be developed to predict patient response to MSC therapies beforehand, and tying these assays to specific MSC clones would be significantly beneficial to successful translation.

For MSC-EVs, recent meetings have highlighted the need for a better understanding of potency and mechanism of action. CD73, a transmembrane protein recently being used as a target for enzymatic assays to show biological function of EVs, was proposed at this meeting as an active therapeutic component within EVs. This idea was strengthened later at the conference with results presented by Dr. Mario Gimona (Paracelsus Medical University).

The rise of lipid nanoparticles (LNPs) to deliver molecular payloads, most notably in vaccines against COVID-19, has led to a broader interest in LNPs for cell and gene therapy. Dr. Pieter Vader (UMC Utrecht) showed that EVs deliver cargoes more efficiently than LNPs. Their lab’s ability to synthesize hybrid EV-LNPs enables high-throughput generation of delivery vehicles with a greater delivery efficiency than LNPs alone. This concept will likely gain traction as delivery solutions continue to be explored for future therapies.

Out of the 1300 posters presented at the meeting, an estimated ~300 (23%) were focused on MSCs or EVs. Highlights included a poster from Tobias Tertel (University Hospital Essen) [6] showing that knockout of CD81 or CD73 on the EV surface decreases the immunomodulatory ability of MSC-EVs, suggesting that CD81 and CD73 are markers of functional EV immunomodulation. This idea can be leveraged for both process and analytical development, as methods can be developed to enrich EV populations for CD81+ or CD73+ EVs, which can then be evaluated for their therapeutically relevant contents.

Expanding Scope of MSC & MSC-EV Translation as Therapies

Manufacturing commercialized MSC-based cell therapies is clearly possible, as represented by Dr. Tony Lee and MEDIPOST with their commercialized allogeneic MSC therapy, Cartistem. This therapy treats defects in knee cartilage including osteoarthritis and includes administration of cells along with a gel-like excipient. Cartistem has been on the market in South Korea for over 10 years, with 4000-5000 patients receiving the treatment every year. This real-world example demonstrates the possibility of translating and commercializing allogeneic MSC therapies.

Other, more novel applications of MSCs are beginning to see success in Phase I clinical trials. Professor

Samuel Janes (University College London) featured a technology wherein MSCs are genetically engineered to express TRAIL, an apoptosis inducing ligand that can be used to kill cancer cells. For lung cancer applications, they show that TRAIL-MSCs home to sites of tumors and cause a reduction of lung cancer metastases. This therapy can be used with existing treatments concurrently and is currently generating results in Phase I clinical trials. Dr. Massimo Dominici (Evotec) similarly demonstrated an application using adipose-derived MSCs genetically modified with TRAIL. In contrast to systemically administered MSCs, this treatment involves application directly to the site of the tumor. Critically, these therapies do not trigger allorecognition, and therefore are candidates for translation as an allogeneic cell therapy. These examples clearly demonstrate that the future for MSC therapies likely will include effective treatments against a range of cancers.

Drs. Mario Gimona and Eva Rohde (Paracelsus Medical University) showed promising preclinical results in a sheep model of fibrosis (rotator cuff) using EVs naturally secreted from umbilical cord-derived MSCs. Dr. Gimona expanded on applications to generate cell-derived vesicles (CDVs) by membrane extrusion of MSCs. Although formed by cell obliteration (versus natural secretion), these MSC-CDVs exhibit a membrane topology and size similar to EVs, though CDVs predictably have a greater amount of cytoplasmic material. Their team is working to show similarity in effect of CDVs in their preclinical studies, which will further enable translation of MSC therapeutics, since manufacturing of CDVs is likely more easily scalable than EVs.

Dr. Rohde pointed to their impressive number of 6 ongoing preclinical efforts involving MSC-EVs, including a Phase I study for application in cochlear implantation. Dr. Rohde also provided a compelling anecdote where MSC-EVs were administered to a patient with severe pain due to neuropathy stemming from oral surgery – a unique condition, but MSC-EVs showed efficacy for this otherwise untreatable situation. These examples highlight leading efforts to translate MSC-EVs from the preclinical to the clinical stage. Based on conversations at the conference, the team expects to see significantly more applications for MSC-EVs to jump from preclinical to clinical stages in the coming years.


ISCT 2023 added yet another chapter in cell therapy communication by sharing with the broader field that despite predictable challenges, significant advancements are truly mobilizing cell therapy toward progress.

Dr. Thomas Peterson (United Therapeutics [UT]) provided a clear narrative of how dedicated efforts toward developing cell therapies at all levels within a single company can lead to field-defining advancements. UT originally started by using MSC-EVs to treat pulmonary arterial hypertension. Their experience has propelled them to be a leader in the cell therapy field. Now, UT is pioneering the development of transplantable lungs derived from porcine tissue, populated with human cells (including stromal cells) in their own “organ culture bioreactors”. In the future, UT is moving towards 3D-printed lung scaffolds, which can be cellularized in bioreactors starting from standardizable iPSC sources.

This example shows that progress in cell therapy is driven by action. To drive further progress for MSCs and MSC-EV therapies, it is critical to supply the field with scalable products and processes that can enable immediate action. In the manufacturing process, every minor improvement matters – this point was echoed throughout the conference by industry giants such as Dr. Katy Spink and Geoff MacKay — and the sum of these process improvements really makes a difference to the availability of cell therapies. This fact speaks to the importance of process development and engineering in cell therapy, an effort which is consistently led by RoosterBio for MSCs and MSC-EVs.


  1. RoosterBio. Upstream, Downstream, & In Between: RoosterBio Collaborations Featured at May 2023 Conferences (ISEV, ISCT, & ASGCT). (2023).
  2. Jadhav S, Patel G, Gupta P, Dehgani M, Staubach S, Teshome B, et al. Exosomes/EVs: DEVELOPMENT OF AN END-TO-END SCALABLE PURIFICATION PLATFORM FOR EXTRACELLULAR VESICLES. Cytotherapy. 2023;25(6):10.1016/S1465-3249(23)00338-9
  4. Doolin M, Willstaedt T, Boychyn M, Rowley J. Gene Editing/Gene Therapies: A GMP-COMPATIBLE PROCESS FOR THE EFFICIENT TRANSFECTION OF MSCS WITH mRNA. Cytotherapy. 2023;25(6):S272; 10.1016/S1465-3249(23)00671-0.
  5. Lenzini S, Jung J, Patel G, Jadhav S, Gupta P, Ladi R, et al. Exosomes/EVs: SUCCESSFUL DEVELOPMENT OF A SCALABLE AND ROBUST PROCESS FOR MSC-EV PRODUCTION. Cytotherapy. 2023;25(6):S22; 10.1016/S1465-3249(23)00164-0.

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