Potential of Human Umbilical Cord Matrix and Rabbit Bone Marrow–Derived Mesenchymal Stem Cells in Repair of Surgically Incised Rabbit External Anal Sphincter

Abstract

Anal sphincter defects and fecal incontinence are complicated surgical problems. We investigated the ability of human umbilical cord matrix (hUCM) and rabbit bone marrow (rBM) stem cells to improve anal sphincter incontinence due to induced sphincter defects without surgical repair. We harvested hUCM cells from human Wharton's jelly and rBM stem cells from rabbit femurs and tibias. To induce sphincter defects, we made an incision in the external anal sphincter. Rabbits were randomly allocated to 5 groups to receive either no intervention (n = 3) or injections of 10 hUCM cells in medium (10 microL RPMI-1640), rBM cells in medium, medium only, or normal saline (n = 7 per group), 2 weeks after sphincterotomy. Transplanted cells were tracked in the injured sphincters by prelabeling with bromodeoxyuridine. Electromyography was performed before and 2 weeks after the external anal sphincterotomy, and 2 weeks after cell transplantation. We also evaluated the proliferation and differentiation of injected cells with histopathologic techniques. Electromyography showed significant improvement in sphincter function 2 weeks after local injection of rBM stem cells compared with pretreatment values and controls. Moderate, nonsignificant improvement was observed with hUCM cell injection. Cells with incorporated bromodeoxyuridine were detected at the site of injury after transplantation of hUCM and rBM. Histopathologic evaluation showed normal or muscle-dominant sphincter structure in all animals receiving rBM and fibrous-dominant sphincter structure in most animals receiving hUCM. Stem cell injection at the site of injury can enhance contractile function of the anal sphincter without surgical repair. Transplantation of stem cells, particularly bone marrow mesenchymal cells, may provide an effective tool for treating anal sphincter injuries in humans.