Professor James St John is Head of the Clem Jones Centre for Neurobiology and Stem Cell Research.
This Centre is within the Institute for Biomedicine and Glycomics at Griffith University, in Queensland, Australia. The Centre has 40 researchers who come from 19 different countries, and 60% are female and 40% male. James is a translational neuroscientist specialising in the creation and delivery of therapies to repair injuries and diseases of the nervous system. His three main areas of research are: spinal cord injury, peripheral nerve injury, and the role of microbes in neurodegeneration, with the major project of the Centre being the translation of a cell transplantation therapy to repair spinal cord injury. His expertise is in the biology of olfactory ensheathing cells, which are the glia of the olfactory nerve. These cells have numerous functions within the olfactory system which make them therapeutically suitable for transplantation into other regions of the nervous system. He has more than 100 publications in this field, with papers ranging from basic discovery research to translational research and therapeutic applications. In 2025, Professor St John is leading a Phase I clinical trial to test the transplantation of olfactory ensheathing cell nerve bridges for repairing chronic spinal cord injury.
SSN: What drove you to choose a career in medical research and spinal cord injury?
JSJ: My early background is completely different to my current research. I started my career in agricultural science and my PhD at The University of Melbourne was on carbohydrate metabolism in temperate pasture grasses. Despite my intention of continuing to work in agriculture, I was offered a job to work on how carbohydrates are involved in establishing the olfactory topographic map during development. In reality, while I was an expert on carbohydrates, I had little idea about the nervous system. However, this eventually gave me an advantage. Without having learnt the dogma about how the nervous system develops and regenerate, I came in with fresh eyes and crazy ideas. Some of those ideas did not work out, but others were highly successful.
My most memorable moment was when I started using live cell imaging to visualise living axons growing within a healthy zebrafish spinal cord. A select number of axons had been fluorescently labelled using a transgenic reporter, while all other cells were not visible. I could therefore watch individual growth cones on the end of axons as they navigated in three dimensions, with their long filopodia extending and retracting as it was seeking its path. But while seeing the axon move in vivo was absolutely fascinating, my curiosity was drawn to what I couldn’t see – the supporting glial cells of nervous system. So I switched focus from studying how axons grow to studying how the glia help neurons to grow. By using timelapse imaging of in vitro cultures of neurons and glia, it became apparent that in many circumstances the glia are the pathfinders while the axons often hitch a ride with the glia. Thus, to repair injuries of the nervous system I realised that the glia are the key to success. As an analogy, I often think about the spinal cord injury as a motorway in which a bridge has collapsed. The glia are the physical surface that form the bridge while axons are vehicles that need to traverse the bridge. To get the traffic to start flowing again, it is first necessary to clean up the damage and then repair the bridge. From that point on, my research has been to understand the therapeutic properties of glia can be used to treat spinal cord injury.
SSN: You are currently undertaking research looking into the translation of a cell transplantation therapy to repair spinal cord injury. Could you tell us more about it?
JSJ: My research in olfactory development and regeneration convinced me that the glia of the olfactory system are a potentially powerful therapeutic cell type. The glia, called olfactory ensheathing cells (OECs), have numerous roles within the olfactory nerve. Every day as part of its normal function, 1-3% of the primary olfactory sensory neurons are turned over because of their direct exposure to the environment within the nasal cavity. New neurons arise from stem cells that line the basal layer of the olfactory epithelium, with the neurons then extending axons up into the olfactory bulb within the cranial cavity where they find their appropriate topographic targets. The OECs are critical to the continual processes of regeneration thanks to their many functions. OECs are the main phagocytic cells that remove the axonal debris, they secrete growth factors and exosomes that stimulate neural growth, the provide a physical surface over which the axons can grow, and they ensheathe and support the axons. These numerous properties are what are needed to repair injuries elsewhere in the nervous system such as the spinal cord.
The therapeutic use of OECs to repair spinal cord injury has a long history with numerous research groups approaching it in various ways. The safety of OEC transplantation into human spinal cord injury was shown to be safe in research led by Professor Alan Mackay-Sim in 2002. Since then, groups around the world have continued to improve the therapy. Of note, was the Polish-UK trial in 2013 led by Dr Tabakow and Prof Geoffrey Raisman that demonstrated proof-of-principle efficacy in repairing chronic spinal cord injury with OEC transplantation. Despite these very encouraging outcomes, there were considerable technical difficulties in the use of OECs that limited its translation into the clinic.
Firstly, it is technically challenging to obtain high purity OECs from the olfactory mucosa. Secondly, the typical method to transplant the cells was to use multiple micro-injections of cells into the healthy cord above and below the injury site, with the vast majority of cells not surviving more than a few days after transplantation.
Our team took on these challenges and have now solved them through two innovations that result in high purity OECs that are formed into three dimensional nerve bridges. With the cells forming stable cell-cell connections within the nerve bridges before transplantation there is considerably increased cell survival after transplantation. The nerve bridges also enable the surgeons to place them directly into the cavity at the injury site so the cells are implanted into the location where they are needed. With high purity cells that survive better and that are in the right location, we are hoping that it will lead to enhanced functional outcomes for patients. After transplantation, the OECs numerous functions will aid regeneration. The OECs will phagocytose cell debris within the injury site, secrete growth factors and exomes that act at a distance to stimulate the endogenous neurons to grow, and provide a permissive physical surface over which the axons can extend.
For the upcoming Phase I clinical trial, we will be testing the safety, feasibility and efficacy of transplanting the olfactory ensheathing cell nerve bridges into chronic spinal cord injuries. We will be starting with injuries that are at least 12 months old, but as interim safety is demonstrated we will recruit people as soon as 4 months after injury. We are looking for the types of injuries that respond versus those that do not respond so we will include injuries from C5 to thoracic. High level cervical injuries are excluded due to the risk of respiratory complications. We also have a particular focus on examining differences between females and males as we want to make sure the therapy is suitable across the sexes.
The cell transplantation is only part of the therapy. Once the OECs are implanted and the endogenous neurons start sprouting and growing across the injury site, intensive long-term rehabilitation is needed to help stimulate the neurons and reinforce connections. Participants in the trial will therefore do up to 3 hours of rehabilitation activities each day for 3-5 days per week for 8 months after transplantation. In addition, before transplantation, participants will do three months of “prehab” to prepare them for the surgery and get used to the post-surgery rehab program.
The first trial is limited to residents of Australia, but we are hoping to expand it internationally in future trials and we are seeking partners for the following trials.
SSN: What could your findings mean to help support the treatment of spinal cord injury and what will be the effect on patient experience?
JSJ: Currently, there are no curative treatments clinically available for spinal cord injury and patients face life-long loss of function and paralysis. OEC transplantation offers a potential biological repair of the injured spinal cord, but ultimately it may require a combinatorial approach that could include electrical stimulation, drug therapies and assistive devices.
While the current trial is for chronic injuries, we do think the therapy is suitable for acute injuries, but we need to demonstrate safety before we test acute injuries. Clearly, treating acute or sub-acute injuries would be more desirable and lead to better patient outcomes.
SSN: What is planned for the next stage of your research?
JSJ: The current clinical trial is testing version 1.0 of our olfactory ensheathing cell nerve bridges. Our research team is already working on combinatorial approaches, but we cannot incorporate them into the trial as we need to reduce the variables. We are also working on ways to make the implantation minimally-invasive to reduce risk and to facilitate repeat transplantation if that was appropriate.
SSN: How does the future look in the treatment of spinal cord injury?
JSJ: When I first started working in this field in the mid 1990s, repairing the injured spinal cord was just a dream. Thanks to the work of teams around the world, we now know that the spinal cord can be repaired but we need to make the therapy better. With so many potential treatments being developed, it seems that a combinatorial therapy can be developed, however the challenge is how we can speed up the delivery to the clinic. There is growing awareness and support for fast-tracking therapies particularly those with an urgent unmet need such as spinal cord injury so we hope that translation into the clinic will happen soon.
SSN: What’s the best part of your job?
JSJ: The clinical trial that we are launching is truly a community effort and that is what makes it so enjoyable. The therapy has been co-designed with a panel of consumers who have been advising us for several years. They are familiar with the research and have helped design and revise the participant journey on the trial so that it meets their expectations. We have also hosted numerous tours through the laboratories to show members of the spinal cord injury community, potential donors, and politicians the research first-hand, with over 1200 people coming through in the last five years. The questions they ask us on the tours have also helped us design the trial and have really encouraged our research team to strive toward delivering the therapy. We have had extensive funding support from the Motor Accident Insurance Commission, the Clem Jones Foundation and the Perry Cross Spinal Research Foundation and all these funders have a strong interest in ensuring our success. The Motor Accident Insurance Commission has enabled us to fast-track the preclinical research to get to the point of clinical trial. The Clem Jones Foundation’s high profile and extensive network has brought in more support and enabled us to leverage funding. Mr Perry Cross, who lives with high level injury and is ventilated, and is founder of his foundation that supports research has an enormous supporter base who we regularly meet with and communicate with through social media.
The clinical and nursing team and the rehabilitation specialist providers are critical to success and it is exciting to work with such keen people who truly want to make a difference to patients. It is one thing to do preclinical research, but to see the healthcare providers take it to the stage of a human therapy is wonderful. As scientists, we are learning so much from them and vice versa, and everyone respects each person’s expertise. In addition to that, there are the numerous administrators within the hospital and university who are providing critical support for the therapy, including ethics and research governance approval, finance, contracts and legal support, philanthropic engagement, research grant support, commercialisation, marketing and communication, and external contract research organisation support. We are yet to add up how many people how many people are directly involved in the trial, but it is certainly in the hundreds and if we include all the donors there must be over a thousand people. The team work is just brilliant and this is what makes the work so enjoyable.
SSN: … and the worst?
JSJ: Our aim is to help people with spinal cord injury as soon as we can and technological advances are now making many analyses much faster and more powerful in ways that we couldn’t have imagined even five years ago. However, wet-lab research using primary cells which are obtained from biopsies (rather than cells lines) can be quite slow, and this can be exacerbated by equipment failure, technical difficulties and unexpected results. Knowing that we may have a therapy that might help, but not being able to translate it to the community fast enough is certainly the most frustrating part of the job.
SSN: What has been the highlight of your career so far?
JSJ: Working with the community is by far the highlight. So many people have inspired us and encouraged us by sharing their stories of their injuries, the impact on their lives and what a therapy might mean to them. This makes our research real.
SSN: Are you planning to attend or speak at any medical conferences or events in 2025?
JSJ: I am speaking at the Auckland Spinal Cord Symposium in February. Beyond that I only just now thinking of planning 2025 but will most likely attend the International Spinal Cord Symposium in Gothenburg in October.
SSN: If you didn’t work in the health industry, what would you be?
JSJ: I would go back to my roots and work in agriculture. Producing food and fibre in a sustainable and profitable way while reducing the impact on the climate is critical to our future. I love being outdoors and perhaps one day I may do this.
SSN: What would you tell your 21-year-old self?
JSJ: Have a vision, know what the end user wants, be a risk taker and make it happen. These are the keys to successfully making an impact. Griffith University’s motto is “Make it Matter”. Thanks to spinal cord injury community who want us to get the therapy working faster, I take the liberty of expanding upon that: we need to make it matter, make it happen and make it happen faster. The best way of doing that is to work closely on the shared vision with patients, families, friends, carers, clinicians, industry, government and other researchers.
SSN: If you were Health Minister for the day, what changes would you implement?
JSJ: Give more time to clinicians to work with researchers and participate in clinical trials to help speed up translation of potential therapies into the clinic. The clinical and allied health professionals are keen to work with scientists to create new therapies, but their heavy workloads, particularly in public hospitals, can limit their involvement. While the cost of giving clinicians more time for research activities will increase the health budget, the outcomes to the community through cost-saving therapies that improve quality of life will outweigh the budget increase.
SSN: How do you think the future looks within the field of spinal surgery and treatments and what are your predictions for 2025 and the next decade?
JSJ: While there are some very clever brain and electrical stimulation therapies are being tested, the feedback we have had from spinal cord injury community is that they would prefer to not have such artificial therapies. Instead they would prefer a biological repair that restores their natural functions. While biological repair therapies are being developed and improved over the next decade, such as our olfactory ensheathing cell transplantation therapy, I expect that the assistive technology therapies will provide interim treatment options which can then be combined with the biological therapies.
Image: Credit: Griffith University Media and Communication.
