vIL-10-overexpressing human MSCs modulate naïve and activated T lymphocytes following induction of collagenase-induced osteoarthritis

Farrell, Eric, Fahy, Niamh, Ryan, Aideen E., Flatharta, Cathal O., O’Flynn, Lisa, Ritter, Thomas, & Murphy, J. Mary. (2016). vIL-10-overexpressing human MSCs modulate naïve and activated T lymphocytes following induction of collagenase-induced osteoarthritis. Stem Cell Research & Therapy, 7(1), 74. doi: 10.1186/s13287-016-0331-2

Abstract

Recent efforts in osteoarthritis (OA) research have highlighted synovial inflammation and involvement of immune cells in disease onset and progression. We sought to establish the in-vivo immune response in collagenase-induced OA and investigate the ability of human mesenchymal stem cells (hMSCs) overexpressing viral interleukin 10 (vIL-10) to modulate immune populations and delay/prevent disease progression. Eight-week-old male C57BL/6 mice were injected with 1 U type VII collagenase over two consecutive days. At day 7, 20,000 hMSCs overexpressing vIL-10 were injected into the affected knee. Control groups comprised of vehicle, 20,000 untransduced or adNull-transduced MSCs or virus alone. Six weeks later knees were harvested for histological analysis and popliteal and inguinal lymph nodes for flow cytometric analysis. At this time there was no significant difference in knee OA scores between any of the groups. A trend toward more damage in animals treated with hMSCs was observed. Interestingly there was a significant reduction in the amount of activated CD4 and CD8 T cells in the vIL-10-expressing hMSC group. vIL-10-overexpressing hMSCs can induce long-term reduction in activated T cells in draining lymph nodes of mice with collagenase-induced OA. This could lead to reduced OA severity or disease progression over the long term.

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