gms | German Medical Science

50. Jahrestagung der Deutschen Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen (DGPRÄC), 24. Jahrestagung der Vereinigung der Deutschen Ästhetisch-Plastischen Chirurgen (VDÄPC)

26.09. - 28.09.2019, Hamburg

Wnt11-Knockout as a Potential Target to Reduce Fibrosis Around Implants

Meeting Abstract

Suche in Medline nach

  • presenting/speaker Britta Kuehlmann - Stanford University, School of Medicine, California, Stanford; Universitätsklinikum Regensburg, Regensburg; Caritas Krankenhaus St. Josef, Regensburg
  • Clark Andrew Bonham - Stanford University, School of Medicine, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford
  • Geoffrey Gurtner - Stanford University, School of Medicine, California, USA, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford

Deutsche Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen. Vereinigung der Deutschen Ästhetisch-Plastischen Chirurgen. 50. Jahrestagung der Deutschen Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen (DGPRÄC), 24. Jahrestagung der Vereinigung der Deutschen Ästhetisch-Plastischen Chirurgen (VDÄPC). Hamburg, 26.-28.09.2019. Düsseldorf: German Medical Science GMS Publishing House; 2019. Doc020

doi: 10.3205/19dgpraec020, urn:nbn:de:0183-19dgpraec0201

Veröffentlicht: 24. September 2019

© 2019 Kuehlmann et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Purpose: Wnt signaling plays a central role in various forms of fibrotic diseases, including skin fibrosis. Activation of the Wnt pathway increases excessive collagen deposition. Foreign Body Responses around implant mediate remodeling of the extracellular matrix (ECM) resulting in a surrounding capsule of fibrotic tissue.

Methods: Fibrosis was induced by inserting implants in BL6-mice and Wnt11-knockout mice. H&E staining was done to qualitatively asses the morphology and density of the fibrotic tissues. Cells from the murine capsules were isolated and characterized by fluorescence-activated cell scanning (FACS), single cell quantitative polymerase chain reaction (qPCR) and single cell RNA sequencing to determine the their impact on fibrotic responses. Additionally, SEM, TEM and 3D confocal imaging were performed.

Results: FACS and immunohistochemistry stains revealed that collagen-depositing macrophages are responsible for the development of implant fibrosis. qPCR revealed that the majority of the cells in the fibrotic tissue expressed macrophage genes and were found to significantly increase Col1a1 and Wnt11. Therefore, we looked at an intervention to reduce these macrophages by using Wnt11-knockout mice and subsequent induction of fibrosis. Using transcriptional analysis we found distinct markers to differentiate three macrophage subgroups (Group 1= Cd36, Group 2= Cd209, Group 3= Ccr2). FACS revealed that Cd36 and Ccr2 were significantly reduced in the fibrotic tissue of Wnt11-knockout mice compared to Bl6-mice. Wnt11-knockout mice displayed significantly thinner capsules with loosely arranged fibers after 3 months, confirmed by H&E stains.

Conclusion: For the first time, we identify macrophage subgroups that are essential to capsule development through pro-fibrotic activity. Furthermore, we use a methodology to decrease capsular fibrosis in an animal model. These findings have promising therapeutic implications for the treatment of fibrosis around implants.