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Employing Transgenic Mouse Models to Study Cartilage Regeneration

Roman Krawetz

The wound healing response is one of most primitive and conserved physiological responses in the animal kingdom, as restoring tissue integrity/homeostasis can be the difference between life and death. However, the process by which wounds heal can be dramatically different between mammals and lower vertebrates. In many amphibians, wounds are healed through a regenerative process in which the healed area is indistinguishable from the original tissue, yet in mammals, a rapid repair response is observed in which the wound is closed with a fibrotic scar. Wound healing in mammals, typically proceeds via a set order of events: coagulation – inflammation – cellularization –tissue formation – matrix remodelling. Cartilage is one of the few tissues in the body that does not exhibit some level of endogenous repair, in part because of the apparent lack of stem/progenitor cells in this tissue.  However, the adjacent synovial membrane is abundant with mesenchymal progenitor cells capable of differentiating into cartilage both in vitro and in vivo.  Super-healer (MRL) mice have the unique ability to regenerate tissues (including articular cartilage) without scaring, yet the cellular mechanism behind this regenerative ability remains elusive. Our goal is to use transgenic models to determine which cell types (e.g. stem cells) and which pathways are responsible for this regenerative phenotype so that this ability can be transferred to humans suffering from chronic non-healing conditions such as Osteoarthritis.

 

 

About the speaker...

My laboratory studies stem cell biology and regenerative medicine with specific applications in joint injury and disease.  Most of my work focuses on developing novel therapies for patients suffering from a common form of arthritis called Osteoarthritis (OA). Osteoarthritis is a chronic degenerative disease that affects approximately 1 in 8 Canadians and about 400,000 Albertans.  At present, there is no definitive ‘cure’ for osteoarthritis and no known therapies that can slow the progression, or reverse this painful and debilitating disease. Therefore, it is essential to develop new therapies to combat the disease and give patients a higher quality of life so that they can resume their jobs and normal everyday activities without limited mobility and constant joint pain. My lab specializes in stem cells found within the joint, Stem cells are novel cells that under appropriate stimuli can be reprogrammed to replace and restore damaged tissue such as bone and cartilage in joints. Our research is focused on determining: 1). How these stem cells can be programmed to repair the joint in osteoarthritis patients, and 2.) Can we use these stem cells (or those from an unaffected joint in the body) as a potential treatment in osteoarthritis. This research is essential since a number of companies have emerged over the last 5 years promising stem cell ‘cures’ for diseases such as osteoarthritis. These companies deliver therapies with little to no research supporting their claims and in some cases do more harm than good.  My lab is passionate about providing Albertans and all Canadians with proven effective stem cell therapies based on high quality laboratory and clinical evidence.  


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