Abstract
BackgroundRecent 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.MethodsEight-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.ResultsAt 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.ConclusionsvIL-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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0331-2) contains supplementary material, which is available to authorized users.
Highlights
Recent efforts in osteoarthritis (OA) research have highlighted synovial inflammation and involvement of immune cells in disease onset and progression
adenoviral vectors expressing vIL-10 (AdIL-10)-transduced human mesenchymal stem cell (hMSC) are immunomodulatory and not immunogenic towards murine lymphocytes To confirm the immunomodulatory potential of a xenogeneic source of mesenchymal stem cell (MSC), the ability of untransduced, AdNull-transduced and AdIL-10-transduced hMSCs to suppress the proliferation of stimulated C57BL/6 lymphocytes in vitro was determined
Untransduced, AdNull-transduced and AdIL-10-transduced hMSCs significantly reduced the proliferation of stimulated lymphocytes compared with untreated cells (Fig. 1a; p < 0.001, n = 3)
Summary
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 collagenaseinduced 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. Farrell et al Stem Cell Research & Therapy (2016) 7:74 In addition to their multipotent nature, MSCs may enhance intrinsic tissue repair through the release of trophic factors which act to modulate inflammatory processes or recruit endogenous progenitor cells [8, 9]. Intra-articularly delivered adipose-derived stem cells have been reported to migrate to the synovium, reduce synovial lining thickness and decrease cartilage damage in a murine collagenase-induced OA model [15], the ability of bone marrow-derived hMSCs to alter the inflammatory environment in OA and subsequently delay disease progression requires further investigation
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