Dr. Rod Bremner
Lunenfeld-Tanenbaum Research Institute
Stimulating Endogenous Regeneration of Photoreceptors as a Potential Cure for Blindness (2015-2018)
A project funded in partnership with Brain Canada
Most diseases that cause blindness result from gradual death of photoreceptors (cells in the retina that translate light into neural signals). The goal of many researchers is to replace or regenerate these cells by transplanting stem cell derived photoreceptors. This strategy, however, can be inefficient as it depends on the cells successfully integrating and surviving following transplantation. Dr. Bremner and his team are exploring alternative strategies to replace photoreceptors, and restore vision. Rather than injecting new cells into the eye, Dr. Bremner and his team propose to harness the regenerative potential of cells that are already present within the retina. Because the regenerative potential in mammalian eyes is inefficient. Dr. Bremner plans to use combinatorial strategies to stimulate photoreceptor regeneration. The overall goal of this work is to identify mechanisms that will eventually lead to therapies that will ultimately restore vision.
Dr. Gordon Keller
McEwen Centre for Regenerative Medicine
Pluripotent Stem Cell-Derived Chondrocytes and Cartilage for Joint Repair and Disease Modeling (2012-2015)
After injury, or during aging, degeneration of cartilage in the joints can lead to osteoarthritis, a debilitating disease causing pain and inflammation that severely affects mobility. Because cartilage can’t readily repair or replace itself, it is difficult to reverse damaged cartilage. Therapies that can replace or regenerate cartilage are an emerging approach to treat cartilage degeneration associated with osteoarthritis. Human pluripotent stem cells are an ideal source because in the right environment they can be coaxed into becoming specific types of cells. Dr. Keller and his team are developing methods to make cartilage-forming cells (chondrocytes) and cartilage from human pluripotent stem cells in the Petri dish. Their goal is to demonstrate that newly generate chondrocytes and/or cartilage can be used to treat joint disease in large animals, as well as to model the earliest stages of osteoarthritis. The ability to recreate osteoarthritis in a Petri dish will provide a novel method for identifying and testing new drugs to treat this disease.
Past Grant: Human T cell Development (2007-2013)
Dr. Juan Carlos Zúñiga-Pflücker
Sunnybrook Research Institute
Rebuilding the Human Immune System (2014-2016)
T cells are an important component of our immune system that recognize, remember, and attack foreign antigens. If our T cell population becomes depleted (for example after chemotherapy, during aging, or due to HIV) we become susceptible to infection and sickness. The thymus supports the development of T cells from incoming bone marrow derived progenitor cells. Without the thymus, T cells do not develop. Dr. Zuniga-Pflucker was the first to create a thymic environment in a dish in order to coax bone marrow derived progenitor cells to become T cells in vitro. This transformative research led to a cell line and protocol to generate T cells that are being used by hundreds of labs around the world. Since then, the Krembil Foundation has had a long-standing commitment to the overarching goal of Dr. Zuniga-Pflucker’s research which is to understand the basic development of T cells, generate human T cells from stem cells in vitro, and translate this to clinical practice for immune-regeneration.
Dr. Michael Fehlings
Toronto Western Research Institute
Repair and Regeneration of the Injured Cervical Spinal Cord (2015-2018)
Spinal cord injury results in devastating motor and sensory impairments, and patients are left with few treatment options. The most common form of spinal cord injury occurs in the neck (or cervical) region, and causes the most severe consequences for patients. Although the path toward clinical translation of regenerative stem cell therapies for spinal cord injury has commenced, there are several major challenges that need to be studied at pre-clinical stages. These include the need for a better understanding of cervical spinal cord injury, the use of non-donor matched cells, and the negative influence of the glial scar that limits the survival and integration of stem cells. Dr. Fehlings has assembled a specialized team with a range of expertise in neural surgery and repair, stem cell biology, and tissue engineering to address these limitations. Together, the team will characterize a model of cervical spinal cord injury, optimize methods to generate specific cell types, determine the efficacy of both exogenous and endogenous stem cell mediated recovery, and finally, develop a combinatorial strategy to reduce glial scarring. The overall goal of this research project is to optimize stem cell therapies so that they have the greatest chance of promoting recovery following injury.
* Not all grants have been displayed
Past Grants: Spinal Cord Injury New Emergin Team Regeneratice Medicine Project (2011-2013)
Regenerative Medicine Strategies for Spinal Cord Injury Repair (2006-2010)
Surgical Timing in Acute Spinal Cord Injury Study (STASCIS) (2002-2004)
Dr. Rajiv Gandhi, Toronto Western Research Institute
Dr. Penney Gilbert, Institute of Biomaterials and Biomedical Engineering
Mesenchymal Stem Cell Therapy: Pioneering Treatment for Osteoarthritis (2014-2015)
Osteoarthritis is a debilitating inflammatory disorder with no effective therapy to reverse joint damage. A higher proportion of patients with osteoarthritis are female, and this may be due to gender-specific differences in metabolically active fat that resides in the joints. Metabolically active fat releases inflammatory factors, and recent studies have identified gender-specific correlations between these factors and the extent of damage to joints. The gender-specific differences may not only affect the progression of osteoarthritis, but also impact the efficacy of treatments. Clinical trials using mesenchymal stromal cells (MSC) for the treatment of osteoarthritis have already begun at the University of Toronto, but the mechanisms underlying their effectiveness is unclear. Drs. Gandhi and Gilbert plan to study the gender-specific metabolic climate in samples of synovial fluid taken from osteoarthritic joints. By adding MSCs to samples from each gender, they will study the differential responses to MSCs and determine whether they can restore the metabolic environment. In doing so they will inform future clinical trials by identifying patient candidates who are most likely to benefit from MSC treatment.
Last updated 14/12/2018
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