Stem cell therapy
Cell-based therapies aim to return damaged or injured tissue to a more normal structure and function. An overarching goal in stem cell therapy is to protect and restore the articular surface, thereby preventing further joint degradation. We are harnessing the chondrogenic differentiation capabilities as well as the immunomodulatory properties of stem cells to address cartilage injury and global joint inflammation the ensues following trauma. By mitigating joint inflammation, we are hoping to prevent inflammation-driven degeneration of the joint.
Gene therapy also has the potential to bolster the weak healing response in articular cartilage and decrease joint inflammation. Dr. Ortved has demonstrated improved cartilage repair in large, full-thickness chondral defects created in the lateral trochlear ridge of the horse femur using autologous chondrocytes transduced ex vivo with an adeno-associated virus (AAV) vector overexpressing the anabolic protein IGF-I. We have also demonstrated the ability of the anti-inflammatory cytokine IL-10 to protect cartilage from degeneration and have shown that IL-10 can be safely overexpressed in vivo following direct injection of AAV-IL-10 into horse joints. We are now beginning to assess the effects of this therapy in vivo to determine if it can mitigate the post- traumatic inflammatory response that occurs following joint injury.
Dr. Ortved has also demonstrated that AAV vectors can be used to safely transduce equine articular cells in vivo with efficient, sustained expression of a therapeutic transgene. More recently, Dr. Ortved has been investigating AAV-mediated overexpression of interleukin-10 (IL-10), an immunomodulatory cytokine. She showed that L-10 overexpression downregulates expression of proinflammatory mediators in inflamed chondrocytes in vitro. We are now beginning to assess the effects of this therapy in vivo to determine if it can mitigate the post- traumatic inflammatory response that occurs following joint injury.
Post-traumatic Osteoarthritis (PTOA)
We are investigating changes in gene expression in cartilage, synovium, fat pad and meniscus in horses with PTOA, in order to understand how different pathways are affected by trauma. We are also developing an ex vivo model of PTOA to help understand the histologic, microscopic and molecular changes that occur post-traumatically.