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Post-surgical adhesions are triggered by calcium-dependent membrane bridges between mesothelial surfaces.

Nature communications (2020-06-20)
Adrian Fischer, Tim Koopmans, Pushkar Ramesh, Simon Christ, Maximilian Strunz, Juliane Wannemacher, Michaela Aichler, Annette Feuchtinger, Axel Walch, Meshal Ansari, Fabian J Theis, Kenji Schorpp, Kamyar Hadian, Philipp-Alexander Neumann, Herbert B Schiller, Yuval Rinkevich
ABSTRACT

Surgical adhesions are bands of scar tissues that abnormally conjoin organ surfaces. Adhesions are a major cause of post-operative and dialysis-related complications, yet their patho-mechanism remains elusive, and prevention agents in clinical trials have thus far failed to achieve efficacy. Here, we uncover the adhesion initiation mechanism by coating beads with human mesothelial cells that normally line organ surfaces, and viewing them under adhesion stimuli. We document expansive membrane protrusions from mesothelia that tether beads with massive accompanying adherence forces. Membrane protrusions precede matrix deposition, and can transmit adhesion stimuli to healthy surfaces. We identify cytoskeletal effectors and calcium signaling as molecular triggers that initiate surgical adhesions. A single, localized dose targeting these early germinal events completely prevented adhesions in a preclinical mouse model, and in human assays. Our findings classifies the adhesion pathology as originating from mesothelial membrane bridges and offer a radically new therapeutic approach to treat adhesions.

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