“There is tremendous philanthropic support for clinician scientists doing basic science and patient-oriented research, and that is critical if we are to make important discoveries,” says Dr. Armand Keating, a Scientist at the Krembil Research Institute and Director of University Health Network’s Cell Therapy Program. “Our ongoing research efforts in the Arthritis Program offer the potential to dramatically change current medical practice and improve the lives of millions worldwide.”
Specifically, the evolving field of regenerative medicine has been the focus of substantial investment in the Arthritis Program. Seeking to utilize the body’s own cells in developing treatments for disease, regenerative medicine may hold the key to changing the environment in which diseases such as osteoarthritis develop and worsen.
“Applying translational research in stem cells and cartilage biology to repair and replace damaged tissue at the source will allow treatments for arthritis to evolve from a reactive ‘one-size-fits-all’ approach towards a system of predictive, preventive, and precision care,” says Dr. Sowmya Viswanathan, an Affiliate Scientist at the Krembil Research Institute and a leading investigator of cell-based therapies for treatment of osteoarthritis. “Most importantly, the Krembil Research Institute has the requisite expertise to bring this science to the clinic, fundamentally altering the manner in which we treat and care for our patients.”
Harnessing the power of stem cells
In 2015, researchers launched the first stem cell trial in North America using autologous (autologous means the cells are obtained from the patient) bone marrow-derived mesenchymal stromal cells (MSCs) to reduce inflammation within an osteoarthritic joint. MSCs have the ability to make copies of themselves and turn into other kinds of cells (e.g., cartilage cells). These stem cells are harvested from a patient and expanded in the lab to large quantities over many weeks and then returned to the patient’s knee joint. Results of the trial thus far have been promising.
“We’re gaining excellent knowledge concerning the role MSCs play in potentially relieving symptoms related to inflammation of the joint,” says Dr. Viswanathan, co-principal investigator of the study. “Our main goal is to establish that the therapy is safe and to gather pilot data for future trials. Ultimately, we want to show that MSCs can repair cartilage and help generate new cartilage around the damaged joint.”
While the trial involving autologous MSCs is demonstrating feasibility, safety, and strong indications for clinical benefit, allogeneic (allogeneic means obtained from a donor other than the patient) MSC therapy may prove to be a better alternative for the treatment of osteoarthritis that is more logistically convenient than autologous MSC treatment. Allogeneic MSCs are obtained from healthy donors, expanded in the lab and used to treat large numbers of patients. As well, donor age and disease stage can also influence the proliferation and differentiation of autologous MSCs. Studies have shown that capacities of MSCs obtained from patients with osteoarthritis are reduced compared with those from healthy individuals.
“While autologous MSCs are an excellent therapeutic option for evaluating safety and developing protocols, it becomes challenging to grow the large number of MSCs needed for each patient, making the procedure slow and expensive,” says Dr. Keating. “Once we determine the optimal allogeneic source of MSCs, we can identify the most therapeutically active cells and manufacture them in large quantities, which is a more logistically sound choice.”
Identifying the optimal source of allogenic MSCs will be the next step – whether it be from bone marrow, synovium (soft tissue that lines a human joint), or umbilical cord blood. Once identified, Krembil researchers will isolate the cells with the most promising therapeutic capacity for cartilage regeneration and/or anti-inflammatory properties. Dr. Keating is optimistic that these research milestones are only just around the corner.
“I believe that within a year’s time we will find the suitable allogeneic properties and progress with clinical trials,” he says. “Funding will be critical to move these studies forward. Medical science has proven that when the right resources are provided, we can progress in the treatment, cure, and prevention of these types of chronic diseases.”
Reprogramming immune cells to reverse osteoarthritis
The immune system is an amazing network of cells that function from a very basic to highly complex level. When our immune system gets confused, it can mistakenly target normal tissue causing damage and disease. Ongoing research in Dr. Viswanathan’s laboratory is investigating the use of immune cells that are specifically associated with osteoarthritis inflammation.
“Our research has revealed that two major pools of immune cells are at work in osteoarthritis, both belonging to a class of cells known as macrophages,” says Dr. Viswanathan. “While one pool of immune cells appears to promote healing, the other drives inflammation, having an adverse effect on long-term function of the joint. By reprogramming a patient’s own immune cells, we can potentially reduce pain and even delay the progression of the disease.”
Dr. Viswanathan’s research will use animal models and take human cartilage samples from patients going through joint replacement surgery to try and understand how these different macrophage populations are related to osteoarthritic conditions. She will inject more of a specific immune cell – the type 2 macrophage – into the cartilage to see if it stops further degeneration. Together, the results from these studies will allow Dr. Viswanathan to better understand the role of immune cells in osteoarthritis and devise new treatment options.
“We have here an opportunity to make fundamental changes to the way we care for individuals with osteoarthritis,” says Dr. Viswanathan. “Significant disability and loss of function are associated with this disease, and its management is an enormous cost to our healthcare system. Support for our research gives us the capability to build a globally-renowned program that will have an enduring impact on individuals and families, and provide clinicians with better strategies for managing degenerative joint disease.”
It is also likely that new breakthroughs in stem cell treatments or immune cell therapy will lead to the development of companies that will be needed to bring these new treatments to patients. Although the primary goal of the research is to generate cures, the ability to generate research-intensive jobs is an important element of the Arthritis Program research strategy.
Funding this type of medical research is one of the best longterm investments donors to the Arthritis Program can make; offering hope to patients and their families, improving the health of all Canadians, while also acting as a catalyst for economic growth.
