Therapeutic Potential of Dental Pulp Stem Cells and Leukocyte- and Platelet-Rich Fibrin for Osteoarthritis

Osteoarthritis (OA) is a degenerative and inflammatory joint disorder with cartilage loss. Dental pulp stem cells (DPSCs) can undergo chondrogenic differentiation and secrete growth factors associated with tissue repair and immunomodulation. Leukocyte- and platelet-rich fibrin (L-PRF) emerges in regenerative medicine because of its growth factor content and fibrin matrix. This study evaluates the therapeutic application of DPSCs and L-PRF in OA via immunomodulation and cartilage regeneration. Chondrogenic differentiation of DPSCs, with or without L-PRF exudate (ex) and conditioned medium (CM), and of bone marrow-mesenchymal stem cells was compared. These cells showed differential chondrogenesis. L-PRF was unable to increase cartilage-associated components. Immature murine articular chondrocytes (iMACs) were cultured with L-PRF ex, L-PRF CM, or DPSC CM. L-PRF CM had pro-survival and proliferative effects on unstimulated and cytokine-stimulated iMACs. L-PRF CM stimulated the release of IL-6 and PGE2, and increased MMP-13, TIMP-1 and IL-6 mRNA levels in cytokine-stimulated iMACs. DPSC CM increased the survival and proliferation of unstimulated iMACs. In cytokine-stimulated iMACs, DPSC CM increased TIMP-1 gene expression, whereas it inhibited nitrite release in 3D culture. We showed promising effects of DPSCs in an in vitro OA model, as they undergo chondrogenesis in vitro, stimulate the survival of chondrocytes and have immunomodulatory effects. The study was performed within the framework of the cooperation between the University of Namur and Hasselt University. Melissa Lo Monaco is funded by "Bijzonder Onderzoeksfonds" and "Fonds Special de Recherche" (BOF16DOCNA02-FSR-confin UHasselt-UNamur). Pascal Gervois (12U7718N, 1502120N), Annelies Bronckaers and Ivo Lambrichts are funded by grants of the Fonds Wetenschappelijk Onderzoek Vlaanderen. Peter Clegg is funded by the MRC-Versus Arthritis Centre for Musculoskeletal Ageing, HBLB and the Horse Trust. Jean-Michel Vandeweerd is funded by FSR (Fonds de Soutien a la Recherche) UNamur. Lo Monaco, M (corresponding author), Hasselt Univ, Biomed Res Inst BIOMED, Cardio & Organ Syst COST, B-3590 Diepenbeek, Belgium; Univ Namur, Dept Vet Med, Integrated Vet Res Unit IVRU, Namur Res Inst Life Sci NARILIS, B-5000 Namur, Belgium. melissa.lomonaco@uhasselt.be; pascal.gervois@uhasselt.be; jej.beaumont@maastrichtuniversity.nl; P.D.Clegg@liverpool.ac.uk; annelies.bronckaers@uhasselt.be; jean-michel.vandeweerd@unamur.be; ivo.lambrichts@uhasselt.be