An interview with Professor John E. Davies, University of Toronto.
By Hamideh Emrani
The second post, in my interview series with biomaterials experts, is with my Master’s supervisor, Professor John (JED) Davies. He is an internationally recognized leader in bone biomaterials, a serial entrepreneur, and a Professor at the University of Toronto’s Institute of Biomaterials and Biomedical Engineering (IBBME) and Faculty of Dentistry. He has won awards for teaching and was the recipient of the Clemson Award for Basic Research in 2000 for his contributions to the field of biomaterials. He is also the founding President and CEO of Tissue Regeneration Therapeutics (TRT Inc.), which now wholly owns his previous start-up company, BoneTec. Corp.
Before his research career, he practiced as a dental surgeon and saw many bone problems in his patients, which sparked his interest in this field. He and his team have developed OsteoScaf® a trabecular bone-like scaffold made out of PLGA (Poly-lactic-co-glycolic acid), a biodegradeable polymer commonly employed as suture material, but containing two separate biodegradable calcium phosphate phases. This internationally patented scaffold has a structure similar to human trabecular bone and has been successfully used in Southern America to treat alveolar bone defects in dental patients and alveolar bone clefts in underprivileged teenagers.
In 2002, Dr. Davies and his team discovered a novel source of human mesenchymal stromal (“stem”) cells (MSCs) in the perivascular tissue of the human umbilical cord. The cells isolated from this tissue are called HUCPVCs (human umbilical cord perivascular cells), and are being developed for a number of clinical trials since they possess potent immunomodulatory properties. Professor Davies is an avid horse rider and he and his veterinary colleagues in Guelph, Ontario, have employed similar cells derived from equine umbilical cords to treat tendon injuries in race horses.
With a long career under his belt studying bone regeneration and stem cells, he also has commercializing experience in both fields. I sat down with him and asked about his research and entrepreneurial work.
Your lab works on biomaterials in bone regeneration and stem cells. What especially attracts you to these subjects?
As an oral surgeon, I encountered many bone problems clinically and so I have had an interest in strategies for bone regeneration and biomaterials throughout my professional career. Interestingly, when I was starting my career, biomaterials was a relatively new discipline, but it rapidly evolved into the field of tissue engineering, which itself has become dominated by stem cell therapy. Combining all three disciplines was both a natural evolution and a progression in order to address real patient needs.
My lab in England was the first to focus on growing bone cells on artificial bone-substitute materials with the intention of trying to understand the mechanisms that drove those interactions. It was really the success of that work that brought me to Canada. I’ve been on the cellular side of biomaterials from the beginning. Now it’s just a part of the bigger field of regenerative medicine. So it all fits under the same umbrella.
Your latest start-up, TRT Inc., focuses on the commercial development of HUCPVCs. Can you tell us about these cells and how you discovered them?
HUCPVCs are mesenchymal stromal cells that have important immunomodulatory, angiogenic (can generate blood vessels), and anti-inflammatory properties. Initially, in my lab, we were trying to use human bone marrow cells to grow bone in our osteogenic cultures. But, we needed more cells than human bone marrow could provide.
I remember chatting over coffee with one of my PhD students, Morris Hosseini, about the different connective tissues of the body that would be able to provide us with the needed stem cells. We arrived at the umbilical cord and it was an important moment for us. This amazing tissue grows from nothing to almost 40 centimeters in the first trimester of pregnancy. It has a very important biological function: to transport blood from the mother to the baby. Fortunately, there’s a viscous connective tissue surrounding these vital blood vessels that prevents the vessels from kinking and allows continuous blood flow even though the cord is folded and curled during pregnancy. In order for this connective tissue to grow so rapidly, we hypothesized that there must be a local and rapidly proliferating source of MSCs to make the tissue. We looked for them around the vessels in the cord and discovered what has been described as the richest source of such cells ever reported.
It was with Rahul Sarugaser, a Master’s student in my lab at the time [Editor’s note: Dr. Sarugaser is the Director of Business Development at CCRM], that I dissected the first cord in 2002 and he isolated the first batch of HUCPVCs. Since MSCs are considered to be immune-privileged, the beauty of these cells is that you can use them allogeneically, meaning that there is no need for tissue matching.
TRT Inc. celebrated its 10th anniversary last summer and we now have a number of different world-leading clinical scientist groups who are using our cells with the drive to get them into clinical trials. In fact, we anticipate that the first clinical trial will start before the end of this calendar year – which will be an extremely important milestone event for us.
You have had many years of commercialization experience. Is there any advice that you would like to give to young biotech/biomaterials entrepreneurs?
Don’t be afraid of failure, as it is bound to happen sometime. Specifically in the field of biomaterials, there are so many competing great ideas out there and only a few are fortunate enough to not only raise the necessary funding, but also be developed commercially. A good idea is simply not good enough; it’s a very long road from the laboratory bench to the commercial market. With cell products, the regulatory environment is even more stringent and is thus more challenging than the medical devices arena.
An example is my attempt to commercialize “OsteoScaf®,” a bone scaffold that was generated in my lab after a long period of development. It works really well. It was being used clinically in South America, but it has still not entered the commercial market. One problem with the bone substitute market is that there are so many products out there that commercialization depends on finding a partner with the requisite market presence. Unfortunately, we have yet to be successful in this regard.
These difficulties have helped me devise a better strategy for our stem cell products, and we have been revenue-generating since our third year in operation.
What are the main challenges that you see in the field as a researcher?
In my opinion, the biggest challenge is to understand the mechanism of action of things, whether it is the biomaterial or cells. We’ve been working in the bone implant field for years trying to understand how bone grows on artificial materials and we have contributed a lot in that area. As a result, we now understand the importance of implant surface design, at the micron- and nano-scale, so that improved implant surfaces can now be generated that enhance early healing.
Similarly, in the MSC field we understand little of their mechanisms of action, but without the acquisition of this basic knowledge we will not be able to refine their use as therapeutics.
Hamideh Emrani is a freelance communicator specializing in scientific communications. She earned her B.Sc. in Cell and Molecular Biology at UC Berkeley and finished her M.Sc. at the University of Toronto (U of T), Faculty of Dentistry, the Bone Interface Lab. She was an intern at the Carnegie Institute at Stanford University, honours research student at UC Berkeley and has won awards for best podium and best poster presentations at the Faculty of Dentistry and IBBME at U of T. She is passionate about science and loves to talk and write about it. You can follow Hamideh on Twitter at @HamidehEmrani.