The capacity of mesenchymal stem cells (MSCs) to differentiate into intervertebral disc (IVD)-like cells has been well described, but their ability to modulate the inflammatory processes in the IVD remains unclear. We found that tissue obtained by discectomy of degenerated and post-traumatic IVD contains significant amounts of IgG antibodies, a sign of lymphocyte infiltration. Further we investigated whether MSCs in vitro, which were characterized for their multilineage differentiation potential and may have immunomodulatory effects on IVD fragments. IVD fragments were co-cultured in contact with peripheral blood lymphocytes (PBLs) and MSCs, and as functional controls we used contact co-cultures of PBLs stimulated with pokeweed mitogen (2.5 lg/mL) and MSCs. The time course of lymphocyte proliferation (Alamar Blue), IgG (ELISA) and gene expression (RT-PCR) of anti-inflammatory cytokines (TGF-b1, IL-10) by MSCs and proinflammatory molecules (IL-1a, IL-1b and TNF-a) by the IVD fragments were analyzed. Depending on the response to the presence of MSCs, the IVD fragments (n = 13) were divided in two groups: responders (n = 9), where inflammation was inhibited by MSCs and non-responders (n = 4), where MSCs did not decrease inflammation. At 1 week in co-culture, MSCs reduced significantly the IgG production in the IVD responders group to 69% and PBLs proliferation to 57% of the control. MSCs expression of the anti-inflammatory TGF-b1 increased with time, while IL-10 was expressed only at day 1. IVD gene expression of TNF-a decreased constantly, whereas IL-1a and IL-1b expression increased. In conclusion, these data suggest that MSCs may modulate disc-specific inflammatory and pain status and aid regeneration of the host tissue.
If an undertaking infringes European or national competition law, the infringers must reckon with a large range of possible sanctions, of both a public law and a private law nature. Regarding the latter, we take note in this paper of anti-trust actions for damages by private claimants, which have become ever more significant in the anti-trust debate. Against a background of divergent developments in the European Member States, the European legislator has adopted Directive 2014/104/ EU (Directive 2014/104/EU of the European Parliament and of the Council of 26 November 2014 on certain rules governing actions for damages under national law for infringements of the competition law provisions of the Member States and of the European Union Text with EEA relevance, OJ 2014 L 349, 1 ff (DADA)), with the aim of facilitating the full compensation of damage suffered by those affected by violations of European or national competition law, and to coordinate public and private enforcement measures. The Member States must implement this Directive into their national systems. This paper gives an overview of the Directive, analyses its most important provisions, and then discusses the international issues raised in cases concerning cross-border anti-competitive activities.
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