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

Aghaee-afshar, Mahmoud M.D.1; Rezazadehkermani, Mohammad M.D.2; Asadi, Alireza M.D.3; Malekpour-afshar, Reza M.D.4; Shahesmaeili, Armita M.D.6; Nematollahi-mahani, Seyed Noureddin Ph.D.

doi: 10.1007/DCR.0b013e3181b55112
Original Contribution

PURPOSE: 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.

METHODS: 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 104 hUCM cells in medium (10 μL 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.

RESULTS: 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.

CONCLUSIONS: 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.

1 Department of Surgery, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran

2 Kerman Medical Students Research Center, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

3 Kerman Neuroscience Research Center, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

4 Department of Pathology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

5 Department of Anatomy, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

6 Kerman Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran

7 Afzal Research Institute (NGO), Kerman, Iran

Supported by Grant No. 85-32 from the Vice-Chancellor for Research, Kerman University of Medical Sciences, Kerman, Iran.

Presented at the RCSEd/CSHK Conjoint Scientific Congress, Hong Kong, October 10 to 13, 2006, and the 5th Asian Pacific International Congress of Anatomy, Tehran, Iran, May 16 to 19, 2008.

Address of correspondence: Seyed Noureddin Nematollahi-mahani, Ph.D., Department of Anatomy, Afzalipour School of Medicine, 22 Bahman Blvd., Kerman, Iran. E-mail: nnematollahi@kmu.ac.ir

© The ASCRS 2009