Restoration of Functional Anal Sphincter by Muscle Progenitor Cells Transplantation in a Rabbit Model of Fecal Incontinence

Abstract

Purpose Fecal incontinence is associated with reduced anal closure pressure and mechanical stress for maintaining tissue coaptation. Compared to other currently employed invasive surgical management techniques associated with morbidity and recurrence, regeneration of anal sphincter using cell therapy and tissue engineering hold great promise. We aimed to determine whether the injection of autologous muscle progenitor cells into the anal sphincter can improve sphincter muscle function in a rabbit model of fecal incontinence. Material and Methods The anal sphincter of male rabbits was damaged by surgical sphincterotomy. Myoblasts were isolated from quadriceps myofiber explants, cultured and labeled with PKH-26 red fluorescent linker, and injected into the injured sphincter (2 × 107 cells). In the control group, saline buffer was injected. At 7, 14, 28, 60 days after transplantation, following assessment of sphincter function (EMG and manometric study) animals were sacrificed for histological evaluation. Results Myoblast autografting accelerated sphincter myofiber repair and improvement in functional capacity of the damaged sphincter. Fluorescently labeled myoblasts were detected in all of the grafted sphincters; differentiated myofibers were detectable at the injection site as evidenced by the presence of αSMA. Manometry and EMG showed a significant improvement in the mean resting anal canal pressure and sphincteric EMG activity after myoblast transplantation respectively. Conclusions Transplanting muscle progenitor cells showed the potential for recapitulation of a myogenic program when injected into deficient anal sphincter. Myoblast-mediated cellular anal myoplasty warrants additional investigation as a new method to treatment of fecal incontinence.