Peer-Reviewed Journal Details
Mandatory Fields
Lohan, P,Treacy, O,Lynch, K,Barry, F,Murphy, M,Griffin, MD,Ritter, T,Ryan, AE
2016
March
Osteoarthritis And Cartilage
Culture expanded primary chondrocytes have potent immunomodulatory properties and do not induce an allogeneic immune response
Published
()
Optional Fields
Primary chondrocyte Mesenchymal stromal cell Osteoarthritis Immunosuppression Immune response Immunogenic MESENCHYMAL STEM-CELLS ARTICULAR-CARTILAGE EXPERIMENTAL OSTEOARTHRITIS OSTEOCHONDRAL ALLOGRAFTS STROMAL CELLS TRANSPLANTATION DIFFERENTIATION DEFECTS HYPOXIA MACROPHAGES
24
521
533
Objective: Allogeneic cell therapies, such as mesenchymal stromal cells (MSC), which have potent regenerative and anti-inflammatory potential are being investigated as a therapy for osteoarthritis (OA) and cartilage injury. Here we describe another potential source of regenerative and anti-inflammatory allogeneic cells, culture expanded primary chondrocytes (CEPC). In direct comparison to allogeneic MSC, we extensively assess the immunological interactions of CEPC in an allogeneic setting.Methods: Chondrocytes were isolated from rat articular cartilage and cultured in normoxic or hypoxic conditions. In vitro co-culture assays with allogeneic lymphocytes and macrophages were used to assess the immunomodulatory capacities of the chondrocytes, followed by immune response analysis by flow cytometry, ELISA and qPCR.Results: CEPC showed reduced induction of proliferation, activation and cytotoxic granzyme B expression in allogeneic T cells. Importantly, exposure to pro-inflammatory cytokines did not increase CEPC immunogenicity despite increases in MHC-I. Furthermore, CEPC had a potent ability to suppress allogeneic T cell proliferation, which was dependent on nitric oxide production. This suppression was contact independent in hypoxia cultured CEPC. Finally, chondrocytes were shown to have the capacity to modulate pro-inflammatory macrophage activity by reducing MHC-II expression and TNF-alpha secretion.Conclusion: These data indicate the potential use of allogeneic chondrocytes in OA and cartilage defects. The lack of evident immunogenicity, despite exposure to a pro-inflammatory environment, coupled with the immunomodulatory ability indicates that these cells have the potential to evade the host immune system and suppress inflammation, thus potentially facilitating the resolution of OA induced inflammation and cartilage regeneration. (C) 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
10.1016/j.joca.2015.10.005
Grant Details
PRTLI, Science Foundation Ireland (SFI), Irish Research Council (IRC)
The authors are supported by research grants from Science Foundation Ireland (grant number 09/SRC/B1794 to TR, MG and MM). PL is funded by a PhD fellowship in Biomedical Engineering and Regenerative Medicine from the Higher Education Authority of Irelandís PRTLI-5 programme. TR is funded by Science Foundation Ireland Principal Investigators grant 12/IA/1624. AER is funded through a Research Fellowship from Irish Cancer Society grant number CRF12RYA. MM is funded by European Unionís 7th Framework
Publication Themes
Biomedical Science and Engineering