MP03-02 ASSESSMENT OF MATRIX METALLOPROTEINASE-9 AND TISSUE INHIBITOR OF METALLOPROTEINASE-1 VIA M2 MACROPHAGE-SEEDED COLLAGEN MESH FOR TREATMENT OF STRESS URINARY INCONTENCE

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP03-02 ASSESSMENT OF MATRIX METALLOPROTEINASE-9 AND TISSUE INHIBITOR OF METALLOPROTEINASE-1 VIA M2 MACROPHAGE-SEEDED COLLAGEN MESH FOR TREATMENT OF STRESS URINARY INCONTENCE Ilaha Isali, Phillip McClellan, Thomas R. Wong, James M. Anderson, Ozan Akkus, and Adonis Hijaz Ilaha IsaliIlaha Isali More articles by this author , Phillip McClellanPhillip McClellan More articles by this author , Thomas R. WongThomas R. Wong More articles by this author , James M. AndersonJames M. Anderson More articles by this author , Ozan AkkusOzan Akkus More articles by this author , and Adonis HijazAdonis Hijaz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003214.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Over the past decade, there have been several innovations with respect to macrophage-based therapies and biomaterials. Patients suffering from stress urinary incontinence (SUI) exhibit a significant increase in matrix metalloproteinase-9 (MMP-9) and a significant decrease in tissue inhibitor of metalloproteinase-1 (TIMP-1) expression. These findings are consistent with elevated rates of collagen breakdown and may play a critical role in the onset and development of SUI. Our recent study demonstrated improved biomechanical and histological outcomes following incorporation of M2 macrophages into a collagen mesh developed for tissue repair and offers future strategies focused on connective tissue regeneration. This study aims to assess the regulation of MMP-9 and TIMP-1 by M2 macrophages in terms of regenerating connective tissue in a rat model. METHODS: Macrophages were harvested from rat bone marrow, and macrophage subtypes were identified by flow cytometry. Electrochemically aligned collagen threads were filament wound to produce small collagen meshes and seeded with macrophages and cultured for up to 3 days. Macrophage subtype-seeded meshes were implanted subcutaneously in rats and harvested at 3 weeks and 3 months, respectively. Explanted meshes were analyzed using histology and immunohistochemistry. Specimens stained separately for MMP-9 and TIMP-1, and quantified to determine overall presence of MMP-9 and TIMP-1 in the harvested tissues. RESULTS: Immunohistochemical staining demonstrated a reduction of MMP-9 with addition of M2 macrophages, whereas the M1-seeded group continued to exhibit elevated MMP-9 after 3 months. TIMP-1 presence was elevated with the addition of M2 macrophages, whereas the M1-seeded group showed low TIMP-1 after 3 months (Figure 1). CONCLUSIONS: Delivery of M2 macrophages via collagen mesh can reduce MMP-9 while increasing TIMP-1, which may limit collagen breakdown associated with the development of SUI. This study shows the potential for improved restoration of extracellular matrix following the incorporation of M2 macrophages into a genipin-crosslinked collagen mesh for tissue repair and remodeling. Source of Funding: NIH grant: R21HD095439 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e21 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ilaha Isali More articles by this author Phillip McClellan More articles by this author Thomas R. Wong More articles by this author James M. Anderson More articles by this author Ozan Akkus More articles by this author Adonis Hijaz More articles by this author Expand All Advertisement PDF downloadLoading ...