Characterization of the T-cell response to polypropylene mesh in women with complications

Abstract

Background Polypropylene mesh is used widely for surgical treatment of pelvic organ prolapse and stress urinary incontinence. Although these surgeries demonstrate favorable functional and anatomic outcomes, their use has been limited by complications, the 2 most common being exposure and pain. Growing evidence suggests that T lymphocytes play a critical role in the regulation of the host response to biomaterials. Objective The purpose of this study was to define and characterize the T-cell response and to correlate the response to collagen deposition in fibrotic capsules in mesh tissue complexes that are removed for the complications of pain vs exposure. Study design Patients who were scheduled to undergo a surgical excision of mesh for pain or exposure at Magee-Women's Hospital were offered enrollment. Forty-two mesh-vagina tissue complexes were removed for the primary complaint of exposure (n=24) vs pain (n=18). Twenty-one patients agreed to have an additional vaginal biopsy away from the site of mesh that served as control tissue. T cells were examined via immunofluorescent labeling for cell surface markers CD4+ (T h), CD8+ (cytotoxic) and foxp3 (T-regulatory cell). Frozen sections were stained with hematoxylin-eosin for gross morphologic condition and picrosirius red for collagen fiber analysis. Interrupted sodium-dodecyl sulfate gel electrophoresis was used to quantify the content of collagens type I and III, and the collagen III/I ratio. Transforming growth factor-β and connective tissue growth factor, which are implicated in the development of fibrosis, were measured via enzyme-linked immunosorbent assays. Data were analyzed with the Student's t tests, mixed effects linear regression, and Spearman's correlation coefficients. Results Demographic data were not different between groups, except for body mass index, which was 31.7 kg/m 2 for the exposure group and 28.2 kg/m 2 for pain (P=.04). Tissue complexes demonstrated a marked, but highly localized, foreign body response. We consistently observed a teardrop-shaped fibroma that encapsulated mesh fibers in both pain and exposure groups, with the T cells localized within the tip of this configuration away from the mesh-tissue interface. All 3 T-cell populations were significantly increased relative to control: CD4+ T helper (P<.001), foxp3+ T regulatory (P<.001), and CD8+ cytotoxic T cell (P=.034) in the exposure group. In the pain group, only T-helper (P<.001) and T-regulatory cells (P<.001) were increased, with cytotoxic T cells (P=.520) not different from control. Picrosirius red staining showed a greater area of green (thin) fibers in the exposure group (P=.025) and red (thick) fibers in the pain group (P<.001). The ratio of area green/(yellow + orange + red) that represented thin vs thick fibers was significantly greater in the exposure group (P=.005). Analysis of collagen showed that collagen type I was increased by 35% in samples with mesh complications (exposure and pain) when compared with control samples (P=.043). Strong correlations between the profibrosis cytokine transforming growth factor-β and collagen type I and III were found in patients with pain (r≥0.833; P=.01) but not exposure (P>.7). Conclusion T cells appear to play a critical role in the long-term host response to mesh and may be a central pathway that leads to complications. The complexity of this response warrants further investigation and has the potential to broaden our understanding of mesh biology and clinical outcomes.