Background: The local immune response is an important pillar to consider when the aim is to enhance bone healing or regeneration. Although T lymphocytes are identified as positive regulators in fracture healing, it is not known whether they mediate their effects directly on osteoblast maturation. The goal of this study was to investigate the role of different T cell subsets on the osteogenesis of human mesenchymal stem cells (MSCs).
Methods: T cell populations were isolated from donor blood and activated. Naive T cells were polarised towards pro-inflammatory T helper 17 (TH17) or anti-inflammatory regulatory T (TREG) cells. The effect of T cell cytokines on osteogenesis of MSCs was studied in direct coculture or conditioned medium (CM) experiments. Alkaline phosphatase (ALP) activity and matrix mineralisation were measured as osteogenic markers. The role of cell-to-cell contact was studied in transwell culture assays. Moreover, cell proliferation was measured.
Results: T cells or their CM significantly increased the ALP activity in MSCs. In osteogenic medium, T cell CM enhanced their calcium deposition. CD4+T helper cells had the largest stimulatory effect on the osteogenic differentiation of MSCs. Inhibition of cell-to-cell contact did not change the T cell-mediated effects. An enrichment in the number of TREG cells had no additional effect on MSCs. In contrast, TH17 polarisation increased the stimulatory effects of the T cell CM. Strong pro-osteogenic effects were observed when studying TH17 cell-specific cytokines directly on MSCs.
Conclusion: The results of our experiments indicate that activated T cells are regulators of osteoblast maturation through the production of soluble factors. Moreover, individual T helper cell subsets differentially control MSC osteogenesis. We show that pro-inflammatory T lymphocyte populations, including the TH17 cells, are highly stimulatory for osteogenic differentiation. The occurrence of different T cells may be a predictive factor for bone healing in patients.
Disclosure: The authors declared no competing interests.