Local tissue response to a C-X-C motif chemokine ligand 12 therapy for fecal incontinence in a rabbit model.

Abstract

This study aimed to determine if local injection of C-X-C motif chemokine ligand 12 (CXCL12) reduces sphincter fibrosis, restores sphincter muscle content, vascularization, and innervation, and recruits progenitor cells in a rabbit model of anal sphincter injury and incontinence. Adult female rabbits were assigned to three groups: uninjured/no treatment (control), injured/treated (treated), and injured/no treatment (untreated) (= 4 each). Injured groups were anesthetized, and a section of external anal sphincter was removed at the 9 o'clock position. The treated sphincters were injected with 200 ng of human recombinant CXCL12 6 wk after injury, and necropsy was performed 6-wk post-treatment. The external anal sphincter was removed, fixed, embedded in paraffin, sectioned, and mounted to slides for histologic analysis of collagen and muscle content and fiber characteristics: innervation, vascularization, and progenitor cell content. Compared with controls, untreated had significantly decreased total skeletal muscle, indistinct muscle layers, and disorganized circumferential and inner longitudinal layers at the injury site. Untreated also had significantly increased collagen fiber density at the injury site compared with treated and controls. Cells staining positive for CD34 within the skeletal muscle layer were increased in treated and untreated compared with controls. Staining density for markers of nerves and vascular endothelium, cells staining positive for CD34 within the mucosa/submucosae, and cells staining positive for PAX7 were similar among all groups. Local injection of CXCL12 reduces postinjury fibrosis and results in statistically similar muscle content and organization between treated animals and controls. Further studies are needed for this promising new treatment for postparturient anal sphincter injury.Local injection of CXCL12 cytokine reduces postinjury fibrosis in a rabbit model of anal sphincter injury and fecal incontinence. The larger size of the rabbits aided in targeted injury and treatment. Further studies are needed to explore noninvasive treatment options for postparturient anal sphincter injury.