Dr. Viswanathan’s research program is focused on developing novel cell based therapies for Osteoarthritis. Her research has dual foci: i) understanding inflammation and immune cell interactions that drive joint inflammation and cartilage degradation in osteoarthritis (OA), and ii) using advanced engineering/manufacturing solutions to develop more potent and stable anti-inflammatory cellular therapies for treating OA. One of the aims is focused on the role of monocytes/macrophages in joint inflammation and degradation, to identify molecular and cellular metabolic regulators of monocyte/macrophage dysregulation, which contributes to this pathology. This will improve our understanding of OA pathology and enable the development of monocyte/macrophage-based therapies.
Mesenchymal stromal cells (MSCs) with anti-inflammatory and immunomodulatory properties are emerging as promising symptom- and potentially disease-modifying treatments. Dr. Viswanathan has successfully driven the clinical translation of a first-in-Canada and made-in-Canada MSC trial in knee Osteoarthritis. Dr. Viswanathan is proposing to use engineering/manufacturing solutions to “boost” MSCs and improve their anti-inflammatory and immunomodulatory potential in the context of OA. She is evaluating these enhanced next-generation MSCs in OA explant and animal models prior to clinical trials.
Stromal cell therapy for patients with knee osteoarthritis
Study Status: active
Institute: Krembil Research Institute
Study Purpose: To better understand how stromal cells work in the context of osteoarthritis.
Background: Osteoarthritis (OA) is the most common cause of disability in people over the age of 50. OA involves loss of cushioning cartilage in the joint, changes in bone and inflammation. OA is becoming more prevalent as our population ages with 1 in 4 Canadians predicted to have OA by 2040. There are direct and indirect healthcare and socio-economic costs, over 2% of our GDP. Although many drugs have been developed, there is no treatment. Patients typically get steroid or other biologics to help manage their pain and symptoms; ultimately patients have to resort to joint-replacement surgery. Stromal cell therapy has recently emerged as a promising therapy, with evidence that it improves patients’ pain and function. My own lab has conducted Canada's first stromal cell therapy trial in 12 patients with knee OA, and we reported improvements in pain, symptoms and joint stiffness. We also saw that stromal cells were reducing inflammation. Our working hypothesis is that stromal cells are reducing inflammation in the joint through their interactions with immune cells known as macrophages. We want to better understand how stromal cells work in the context of OA.
Study Methods: This is important to understand before we undertake a larger, more expensive clinical trial, because if we know how the stromal cells work, we can design more effective clinical trials. This includes screening stromal cells from different donors to pick the ones that are going to be most effective in treating OA; choosing patients who will best respond to stromal cell therapy, and modifying the stromal cells using genetic engineering tools such that they are really good at treating OA (likely by reducing joint inflammation, and therefore pain). Our study results will help make stromal cell therapy for OA effective, which is needed if this treatment is to receive approval by the regulators. Only then can stromal cell therapy become a routine clinical treatment available to Canadian patients.
Health Conditions:
Arthritis
Dr. Viswanathan is a Scientist at the Osteoarthritis Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute and the Krembil Research Institute (University Health Network) and an Associate Professor at the Institute of Biomedical Engineering and at the Division of Hematology, Department of Medicine (University of Toronto).
Dr. Viswanathan’s research is focused on using anti-inflammatory approaches to target osteoarthritis (OA), including i) using proprietary enhanced mesenchymal stromal cells (MSCs) to modulate inflammatory responses and ii) reprograming monocytes/macrophages to more inflammation resolving subtypes using small molecules and gene edited iPSCs. Dr. Viswanathan’s lab is translation of cellular and immunotherapies into clinical investigations. Dr. Viswanathan is a co-Principal Investigator of a recently completed trial using autologous MSCs to treat OA patients, a North American first. Dr. Viswanathan’s publication was cited as the most downloaded paper in Stem Cells Translational Medicine in 2019, and also garnered The Arthritis Society’s Top 10 Research Advances in 2019.
Dr. Viswanathan is also investigating the role of synovium and monocytes/macropahges in osteoarthritis pathogenesis, with the intention of developing a macrophage-based adoptive transfer immunotherapy. Dr. Viswanathan is the recipient of the Biologics Association’s Summit Research Award (2021) for research in this area. An in vitro model developed in the lab demonstrates the role of synovium on cartilage degradation and was cited as one of the Top 10 Research Advances of The Arthritis Society in 2021.
Dr. Viswanathan is leading international efforts to standardize MSC nomenclature and create reference materials for MSC research. Dr. Viswanathan sits on the Standard Council of Canada’s Mirror Committee for International Organization for Standardization (ISO TC276) on Analytical Methods and Bioprocessing, and is on the steering and working committee of an international Standards Coordinating Body (SCB). Dr. Viswanathan is a formal liaison between ISO TC276 and the International Society of Cell and Gene Therapy (ISCT). Dr. Viswanathan is Associate Editor of Cytotherapy, the official journal for ISCT.
As a translational scientist, Dr. Viswanathan serves as a national regulatory and cell manufacturing consultant for projects across Canada. At the Cell Therapy Program at the University Health Network, Dr. Viswanathan has overseen clinical translation of over 13 cell-based therapies into Health Canada approved clinical investigations; these include immunotherapies, therapies for lysosomal storage disorders and acute kidney failure. Dr. Viswanathan chaired the Cell Therapy Stakeholder Group, a bilateral group that engages Health Canada on cell therapy related policy issues from 2015-2021.
- Scientist, Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute, UHN
- Assistant Professor, Division of Hematology, Department of Medicine, University of Toronto
- Cross Appointed Faculty, Institute of Biomedical Engineering, University of Toronto
- North American VP-Elect, International Society for Cell & Gene Therapy (ISCT)