MSC KOL Interview: Tackling MSC EV Drug Delivery & Biomanufacturing Challenges with Steven Jay

Dr. Steven Jay is an associate professor in the Fischell Department of Bioengineering at the University of Maryland, whose research focuses on design and development of novel biotherapeutics, including extracellular vesicles. In his graduate years at Yale University under Rich Lee’s lab, he stumbled into the field of EVs and decided to pursue this area of research.

In this interview, we discussed the biggest advantages and challenges in utilizing EVs as a drug delivery vehicle. Given his long-time interest, Steven has explored various techniques to efficiently load DNA or mRNA cargo into EVs. In one study, exogenous linear DNA were loaded into EVs via electroporation, and his group found that the loading efficiency of DNA into EVs was dependent on DNA size [1]. More recently, Steven’s group also showed that loading of functional miRNA cargo can be enhanced by simply creating a pH gradient across EV membranes [2]. The loading efficiency accomplished using this method is comparable to methods like sonication and electroporation—but with the advantage of lowering potential damage to the cargo.

In addition to EV utility as a therapy, challenges in bioproduction of EVs such as batch-to-batch consistency, potential toxicity, and off-target effects are important to address in a developing therapeutic. A unique approach that Dr. Jay and his team took was published in this research report and article [3] [4], in which they produced mesenchymal stem cell (MSC)-derived and endothelial cell-derived EVs in a perfusion bioreactor. This work was done in collaboration with Dr. John Fisher, Univ of MD, who developed the 3D printed scaffolds. It shows that culture parameters can improve yields by impacting the dynamic nature of the cells’ health, like continuous perfusion to allow removal of waste by-products from the bioreactor environment. He also suggests that mechanobiology may play a role on MSCs, and may affect the production level of MSC EVs, however this is still not clear and requires more study.

As one who’s had a huge influence on others, Dr. Jay’s exposure to science was at an early age. He has always gravitated toward research and witnessing the impact that great teachers and mentors can have on peoples’ lives influenced his decision to go into academia. What drew him most to his current role as a professor was the lifelong learning component and intellectual freedom that academic life permits. And while this may be a scary notion for some of us, not knowing what you might end up doing in 10 years is a thrill for Steven.

As an academic who has been working closely with RoosterBio over the years, Dr. Jay is no stranger to the iterations of our highly productive MSC EV production system. In fact, Dr. Jay received a 2018 RoosterBio hMSC Development Award for his project to evaluate the production of RoosterBio’s MSC exosomes and EVs in a 3D printed scaffold perfusion bioreactor system. A key takeaway from this collaborative work was the importance of banking and starting with high quality MSCs and media. As paired systems, these can produce the expected high level of performance consistently through different experimental paradigms and readouts. Ease of use that requires minimal team training also improves overall lab productivity, generating more data for exiting new publications and a faster turnaround. RoosterBio is proud to serve as a catalyst for these “win-win” situations wherever and whenever it can.

 

References:

  1. Lamichhane et.al. Exogenous DNA loading into extracellular vesicles via electroporation is size-dependent and enables limited gene delivery. Mol Pharm. 2015. 12(10): 3650-57.
  2. Jeyaram et.al. Enhanced loading of functional miRNA cargo via pH gradient modification of extracellular vesicles. Molecular Therapy. 2020. 28(3): 975-85
  3. Patel et.al. Impact of cell culture parameters on production and vascularization bioactivity of mesenchymal stem cell-derived extracellular vesicles. AiChE Bioengineering & Translational Medicine. 2017. 2: 170-79.
  4. Patel et.al. Enhanced extracellular vesicle production and ethanol-mediated vascularization bioactivity via 3D-printed scaffold perfusion bioreactor system. Acta Biomaterialia. 2019. 95: 236-44.

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