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. 2019 Sep;13(9):1507-1517.
doi: 10.1002/term.2853. Epub 2019 Jul 25.

TGF-β1-activated Type 2 Dendritic Cells Promote Wound Healing and Induce Fibroblasts to Express Tenascin C Following Corneal Full-Thickness Hydrogel Transplantation

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TGF-β1-activated Type 2 Dendritic Cells Promote Wound Healing and Induce Fibroblasts to Express Tenascin C Following Corneal Full-Thickness Hydrogel Transplantation

Christine Mölzer et al. J Tissue Eng Regen Med. .

Abstract

We showed previously that 1-ethyl-3-(3-dimethylamino-propyl)-carbodiimide hydrochloride (EDC) cross-linked recombinant human collagen III hydrogels promoted stable regeneration of the human cornea (continued nerve and stromal cell repopulation) for over 4 years. However, as EDC cross linking kinetics were difficult to control, we additionally tested a sterically bulky carbodiimide. Here, we compared the effects of two carbodiimide cross linkers-bulky, aromatic N-cyclohexyl-N0-(2-morpholinoethyl)-carbodiimide (CMC), and nonbulky EDC-in a mouse corneal graft model. Murine corneas undergoing full-thickness implantation with these gels became opaque due to dense retro-corneal membranes (RCM). Corneal epithelial cytokeratin 12 and alpha smooth muscle actin indicative of functional tissue regeneration and wound contraction were observed in RCM surrounding both hydrogel types. However, quantitatively different levels of infiltrating CD11c+ dendritic cells (DC) were found, suggesting a hydrogel-specific innate immune response. More DC infiltrated the stroma surrounding EDC-N-hydroxysuccinimide (NHS) hydrogels concurrently with higher fibrosis-associated tenascin c expression. The opposite was true for CMC-NHS gels that had previously been shown to be more tolerising to DC. In vitro studies showed that DC cultured with transforming growth factor β1 (TGF-β1) induced fibroblasts to secrete more tenascin c than those cultured with lipopolysaccharide and this effect was blocked by TGF-β1 neutralisation. Furthermore, tenascin c staining was found in 40- to 50μm long membrane nanotubes formed in fibroblast/DC cocultures. We suggest that TGF-β1 alternatively activated (tolerising) DC regulate fibroblast-mediated tenascin c secretion, possibly via local production of TGF-β1 in early wound contraction, and that this is indirectly modulated by different hydrogel chemistries.

Keywords: biomaterial; corneal transplantation; tissue repair; transforming growth factor β1, membrane nanotubes, tectonic graft.

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References

REFERENCES

    1. Adnan, E., Matsumoto, T., Ishizaki, J., Onishi, S., Suemori, K., Yasukawa, M., & Hasegawa, H. (2016). Human tolerogenic dendritic cells generated with protein kinase C inhibitor are optimal for functional regulatory T cell induction-A comparative study. Clinical Immunology, 173(Supplement C, 96-108. https://doi.org/10.1016/j.clim.2016.09.007
    1. Ahn, J. I., Kuffova, L., Merrett, K., Mitra, D., Forrester, J. V., Li, F., & Griffith, M. (2013). Crosslinked collagen hydrogels as corneal implants: Effects of sterically bulky vs. non-bulky carbodiimides as crosslinkers. Acta Biomaterialia, 9(8), 7796-7805. https://doi.org/10.1016/j.actbio.2013.04.014
    1. Anderson, J. M., Rodriguez, A., & Chang, D. T. (2008). Foreign body reaction to biomaterials. Seminars in Immunology, 20(2), 86-100. https://doi.org/10.1016/j.smim.2007.11.004
    1. Babensee, J. E. (2008). Interaction of dendritic cells with biomaterials. Seminars in Immunology, 20(2), 101-108. https://doi.org/10.1016/j.smim.2007.10.013
    1. Badylak, S. F., & Gilbert, T. W. (2008). Immune response to biologic scaffold materials. Seminars in Immunology, 20(2), 109-116. https://doi.org/10.1016/j.smim.2007.11.003

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