Poster #063, UC Davis Health System
IL-10–“Expressing Mesenchymal Stem Cells as a Regenerative Therapy for Post-Traumatic Osteoarthritis
Mentors: Samhitha Tumkur; Gabriela Loots, Ph.D.
Post-traumatic osteoarthritis (PTOA) is a progressive joint disease that develops after a traumatic injury and is characterized by chronic inflammation, cartilage degeneration, pain, and reduced joint function. Current treatments include symptom management, but do not effectively prevent disease progression. Mesenchymal stem cells (MSCs) have emerged as a promising regenerative therapy because of their ability to affect inflammation and regeneration. Genetic engineering of MSCs to enhance anti-inflammatory cytokine expression may improve their efficacy and promote long-term joint preservation. In this study, genetically engineered MSCs expressing Interleukin-10 (IL-10) were evaluated in an anterior cruciate ligament (ACL) injury model of PTOA. IL-10 is an anti-inflammatory cytokine that modulates immune responses by inhibiting inflammatory signaling, making it a promising therapeutic target for reducing joint inflammation and slowing the progression of posttraumatic osteoarthritis. The MSCs were injected intraarticularly into the mouse knee following injury. Cell engraftment was evaluated through bioluminescent imaging, while joint inflammation was assessed using MMPsense fluorescence imaging to monitor matrix metalloproteinases (MMP) activity. Structural outcomes were analyzed using microCT to quantify osteophyte formation and subchondral bone loss following injury at both two weeks post injury and four weeks post injury. Cartilage degeneration will be evaluated using Safranin O and Fast Green histological staining. Two weeks post injury, mice treated with IL-10 expressing MSCs exhibited lower MMP activity than vehicle-treated controls, suggesting a reduction in early inflammatory response, although the difference was not statistically significant. Histological analysis showed similar severity of chondrolysis, osteolysis, erosions, and joint deformities in both groups. Overall, preliminary findings suggest that IL-10 expressing MSCs may reduce the inflammatory response following traumatic knee injury, supporting a potential therapeutic that could hinder or prevent the progression of PTOA.