Immunosuppressive effect of mesenchymal stem cells in collagen-induced arthritis

Background and objective

Mesenchymal stem cells (MSCs) are bone marrow-derived progenitor cells, widely investigated for their potential for differentiation towards multiple lineages, such as osteocytes and chondrocytes. Recently, we and other workers showed that MSCs exhibit immunosuppressive properties inducing in vivo tolerance of T lymphocytes towards allogeneic cells. Moreover, these cells can be easily genetically modified to express ectopic molecules, such as anti-inflammatory cytokines. Here, we investigate whether naive and IL-10-expressing MSCs could display an inhibitory effect towards self-reactive T lymphocytes in vitro, and could have a biological effect in the murine model of collagen-induced arthritis (CIA).

Methods

We used the murine C3H10T1/2 cell line (C3 MSCs) and we derived cell clones stably expressing vIL10 (C3-IL10 MSCs). Secretion of IL-10 was measured in cell culture supernatants by ELISA, and its immunosuppressive effect was evaluated on the proliferation of T lymphocytes in a mixed lymphocyte reaction. In the CIA model, C3 MSCs or C3-IL10 MSCs (106 cells) were intravenously injected on the day of immunization with collagen, and secretion of vIL10 was monitored in the mouse sera during the overall experimental period.

Results

First, we tested in vitro the functionality of C3-IL10 MSC clones. Secretion of vIL10 by C3-IL10 MSCs was up to 500pg/106 cells per 24 hours, and the antiproliferative activity of these MSCs on alloreactive T lymphocytes was twofold higher than C3-MSCs. Second, we evaluated the potential immunosuppressive role of MSCs in the CIA murine model. Using both clinical, radiological and histological analysis, we showed that disease progression was reduced when MSCs were injected.

Conclusion

In this study, we demonstrate that the immunosuppressive role of MSCs might be of therapeutic value in CIA, and that MSCs may be used to systemically express anti-inflammatory cytokines