Anal sphincter repair with muscle progenitor cell transplantation: serial assessment with iron oxide-enhanced MRI.

ABSTRACT

OBJECTIVE: The purpose of this study was to assess homing of ultrasmall superparamagnetic iron oxide (USPIO)-labeled muscle progenitor cells in an experimental rabbit model of anal sphincter repair using MRI. MATERIALS AND METHODS: Twelve rabbits underwent external anal sphincterotomy and randomly received injection of either autologous muscle progenitor cells labeled with USPIO at a concentration of 4 mg/10(6) cells (experimental group) or saline (control group) at the site of sphincter damage. In vivo MRI, electromyography, and manometry were performed before, 1 hour after, and 1, 2, and 4 weeks after the injection. At the end time point, anal sphincter sections were obtained for histologic analysis. Semiquantitative analysis of fibrosis, desmin, iron, CD3, and CD68 was performed using two microscopic fields in two distinct regions of the sphincter according to either presence (zone I) or absence (zone II) of signal loss on the corresponding MR images. RESULTS: Labeling efficiency was 88.67% and did not influence cell viability. On follow-up images of the cell-transplanted rabbits, significant influence was reported at 1 hour, 1 and 2 weeks after transplantation. The maximum signal loss was detected at 1 hour (75.7%). Regenerating myofibers stained positively for desmin and mainly correlated to zone I on MR images. Clusters of iron-positive particles were detectable in the myofibers located mainly at the site of injection, which correlated well to zone I. Significant signal loss and Perls Prussian blue-positive area were not detected in the control group. Functional studies showed significant improvement in sphincter pressure and electrical activity in the experimental group after 4 weeks (p<0.001). CONCLUSION: Our results support the potential of iron oxide-enhanced MRI for serial monitoring of transplanted cells in an animal model of anal sphincter repair.