Searching for New Cell-Therapy Innovations in Rotator Cuff Repair
The HSS Research Institute is dedicated to identifying mechanisms and developing effective approaches for the prevention, diagnosis and treatment of orthopaedic and rheumatic conditions. This week, I discussed innovations in rotator cuff repair, specifically the role of cell therapy, at the American Academy of Orthopaedic Surgeons 2022 Annual Meeting. I outlined what’s currently available, what questions we are currently investigating and what the future looks like.
Rotator cuff tears are one of the most common musculoskeletal conditions, becoming more prevalent as people age. While most tears need to be treated surgically, healing is an imperfect and slow process. The surgery itself does not reverse the muscle atrophy (thinning or loss of muscle tissue) but involves re-attaching tendon to the bone. Up to 15 to 20 percent of patients may have incomplete or failed healing. The most common issues post-surgery are pain and weakness. To date, there is no approved biologic therapy to improve rotator cuff repair.
There is a real unmet clinical need to raise the success rate of this repair. More and more older individuals want to get back to an active lifestyle through activities such as tennis and swimming, which put strain on the shoulder. Approximately 200,000 to 250,000 rotator cuff repairs are done each year, with over 1,000 performed at HSS.
The HSS Center for Regenerative Medicine, of which my lab is a part, has a robust research program that investigates the basic cellular and molecular mechanisms of healing damaged tissue. Our multidisciplinary group of scientists and clinicians are trying to understand the underlying reasons why tendons tear and why they don’t heal. We carry out basic science models of tendon repair for conditions including overuse tendonitis and rotator cuff tears.
Cell therapy has tremendous potential to regenerate tissue. We know that tendons are not highly cellular. We need to determine how to stimulate cells that are intrinsic in tissues or inject a cell population to jumpstart healing. The term “stem cell” is often used, but a more accurate description is a “connective-tissue progenitor cell”, which is a bit more limited in its ability to regenerate tissue. A true stem cell is a rare and highly specialized cell, and we know that true stem cells are present in many tissues. We have discovered that stimulation of these intrinsic stem cells can improve tissue healing and regeneration. Learning how to best leverage these existing cells may greatly improve the healing of rotator cuff tears.
Additionally, we are continuing to identify ways to characterize cell populations. The cells we can use currently derive from fat or bone marrow and are heterogeneous and highly variable. If we are able to sort them, we can culture only the desired cells and remove undesired cells. This would be a big breakthrough in cell therapy research.
We need to know which cells are best, where they should be sourced from and what doses to use. I believe there also needs to be changes in the regulatory environment so relevant clinical trials can occur.
At HSS, it is important that our lab research mirrors clinical work so that we can bring our findings directly to patients. The HSS Center for Regenerative Medicine evaluates a range of cell therapies that seek to heal tissue that has been damaged by injury or disease in order to improve effectiveness of new treatment options.
We are currently running two clinical trials testing cell therapy for patients undergoing rotator cuff repair. One is a Phase 1B clinical trial that evaluates the safety and feasibility of injecting E-CEL UVEC cells at the end of the operation; these are proprietary allogeneic human umbilical vein endothelial cells produced under cGMP and cGTP regulations. Angiocrine Bioscience is providing support for this study. The other is a Phase II interventional clinical trial that has a similar design except surgeons take adipose tissue from the abdomen at the beginning of the operation, isolate stromal vascular fraction cells (SVFCs) from this tissue, and then inject it into the tendon and muscle after rotator cuff repair. This trial will determine if the use of these cells can enhance outcomes for patients undergoing rotator cuff repair.
The marketing for stem cells continues to stay ahead of the science. It is my hope that our research will help make cell therapy a viable reality for patients.
- Scott A. Rodeo, MD, sports medicine surgeon, Vice Chair of Orthopaedic Research and Co-director of the Orthopaedic Soft Tissue Research Program at HSS, Director of HSS Center for Regenerative Medicine