Xenogeneic Collagen-Membranes Affect Cytokine-Induced Immunomediator Expression in Human Gingiva-Derived MSCs

Objectives: One of the most used biomaterials for periodontal soft tissue regeneration are membranes consisting of non-cross-linked (Geistlich Mucograft®) or cross-linked (Geistlich Fibro-Gide®) porcine collagen. These soft tissue substitutes facilitate endogenous tissue regeneration, causing a sufficient increase in tissue volume/thickness.
Due to their immunomodulatory properties, tissue-resident mesenchymal stromal cells (MSCs) are essential for periodontal tissue regeneration. Their immunomodulatory activities are triggered by cytokines, such as interferon-(IFN)-γ, interleukin-(IL)-1β and tumor necrosis factor-(TNF)-α. These cytokines enhance the production of immunosuppressive immunomediators: indoleamine-2,3-dioxygenase-1 (IDO-1), tumor necrosis factor α-stimulated gene-6 (TSG-6), prostaglandin-E2 (PGE2) and programmed cell death ligand 1/2 (PD-L1/2). So far, no studies investigated the influence of the collagen-membranes on the expression of immunomediators in MSCs.
Methods: Gingiva-derived MSCs were seeded on Fibro-Gide® or Mucograft® in the absence or presence of IL-1β, TNF-α or IFN-γ. Unstimulated and cytokine-triggered cells, seeded on tissue culture plastic, served as control. After 24 hours incubation, IDO-1, TSG-6, PTGS-2, PD-L1 and PD-L2 gene expression levels were determined using qPCR.
Results: In the presence of IFN-γ, membranes significantly enhanced TSG-6 expression, whereas PTGS-2, PD-L1 and PD-L2 expression levels were significantly increased by Fibro-Gide®. TNF-α-induced IDO-1 and TSG-6 expression levels were significantly reduced by both membranes, whereas PD-L1 and PD-L2 expression levels were only diminished by Mucograft®. In contrast, PTGS-2 was significantly increased by Mucograft® in the presence of TNF-α. Both membranes caused a significant increase in IL-1β-trigged TSG-6 and PTGS-2 gene expression, whereas PD-L2 was significantly reduced and enhanced by Mucograft® and Fibro-Gide®, respectively. In the absence of cytokines, TSG-6 and PTGS-2 expression were significantly increased by Mucograft® and PD-L1/2 by Fibro-Gide®.
Conclusions: These data show that Mucograft® and Fibro-Gide® differently affect immunomediator expression in gingiva-derived MSCs. Further, this study indicates that xenogeneic collagen-membranes influence local inflammatory processes indirectly via gingiva-derived MSCs.