RoosterBio had the honor to discuss MSCs and cell therapy with Dr. Christian van den Bos, founder and owner of Mares Ltd. Dr. van den Bos provided his perspective on lessons learned and challenges in addition to an overall understanding of MSCs in the regenerative medicine field. His expertise shines in this interview and explains why Mares Ltd has been requested by biotech and pharmaceutical companies to help in the commercialization of advanced therapies and technologies.
Mares Ltd is a consulting company based in Germany with most of their work in the EU and Britain. Mares Ltd helps companies in the commercialization of advanced therapies and uses innovation to address bottle necks. The services they provide are in the field of process development and quality, as well as regulatory. One quality service Mares Ltd provides in the EU is being a qualified person (QP). A QP is an individual responsible for maintaining quality of a released drug. Becoming a QP is not an easy task- requirements include being a licensed pharmacist, biologist, or chemist with knowledge and working experience in pharmaceutical operations, as well as a successful completion of an interview/examination.
Dr. Christian van den Bos’ explanation of the challenges and lessons learned of MSCs is intriguing. He explains one challenge as being that the expectations of MSCs were set too high when first discovered, e.g., extraordinary properties of alleged multipotency. “There’s not a single thing that isn’t being asked of these cells, and as a consequence, living up to these expectations is complex,” said Dr. van den Bos. Yet, now after 25 years, the benefits of MSCs finally highlight specific applications of cell and gene therapy that are very promising. MSCs’ clinical benefits are in accord with their prolific secretomes of bioactive ligands and ECM, making these cells very useful for tissue revascularization, graft versus host disease (GvHD), and orthopedics. Consequently, van den Bos asserted that readouts of MSCs’ paracrine potency (such as IDO secretion) should loom much larger in significance than costly, cumbersome, and non-quantitative tri-differentiation assays to validate MSC identity.
How does the future of MSCs look? Can COVID-19 inform their utility? Dr. Van Den Bos predicted that these could one day show benefit on account of their putative immune-modulatory, anti-inflammatory properties. Another “strong yes” for MSCs could be their uses as a “chassis” for cell engineering with synthetic gene programs due to their known safety in thousands of trial patients.
Dr. Christian van den Bos next pondered directly why after 25 years of development time, MSCs have not carried forth a major clinical breakthrough à la CAR-T’s example, a cell technology of similar age. He says he maintains lots of optimism for MSCs despite this, because nothing being done today is not sensible or lacking purpose. However, when developing a pharmaceutical based on MSCs, it’s important to leverage full control of the highly complex, end-to-end production process to know how these APIs are being handled until given to the patient. Also, he opined that one ought not neglect a careful cryopreservation method, since there’s a long span between a cell prep that is simply viable versus a high performing dose. There are many aspects that can be neglected if the sole focus is on the volume of cell output at the expense of quality. “If we do not address these points properly, we end up with clinical trials of mixed results,” he stated.
Later in the interview, Dr. van den Bos answered our question of differences between EU and USA regulations. One very obvious difference was that in the EU, all cellular material injected into patients needs to be made via full GMP, whereas in the USA, GMP requirement is not absolute for earlier, less clinically advanced trials. “With the FDA, in my experience, that’s a matter of negotiation,” he said, although these negotiations can sometimes be protracted. On the other hand, in both European and American geographies, there has been a concerted effort to crack down on unproven uses for stem cells, marketed as if they were snake oils by unscrupulous clinics.
Any final advice for new developers of cellular therapies? “If you want to avoid disappointments, stay quantitative and really rely on your facts.” RoosterBio would like to personally thank Dr. Christian Van Den Bos for taking the time to answer our questions and enlightening us on his company.