Abstract

Purpose Prior to the application of myoblast transplantation technique for regeneration of anal sphincter to patients, noninvasive methods for tracking the temporal and spatial homings of these cells are essential. Magnetic resonance imaging (MRI) may emerge as an ideal imaging modality to monitor stem cell therapy with high spatial resolution. We investigated homing of transplanted superparamagnetic iron oxide (SPIO) nanoparticle-labeled muscle progenitor cells using MRI in an experimental rabbit model of fecal incontinence to determine the transplanted cell's engraftment efficiency and functional capability. Material and Methods The anal sphincters of sixteen male rabbits were damaged by sphincterotomy and were randomized to two groups. In group I myoblasts were isolated from quadriceps myofiber explants and labeled with SPIO nanoparticles, and injected into the injured sphincter. In group II, saline buffer was injected. Cell labeling efficiency was assessed using viability, proliferation, Prussian-blue staining, and MRI in-vitro. T2-weighted MR examinations were performed immediately before, 1 hour, 7, 14, 28, and 60 days after transplantation and findings were correlated with histomorphological, EMG, and manometric study. Results Labeling did not influence cellular parameters. Distribution and migration of SPIO-labeled cells was successfully documented with in-vivo MR imaging. Although, hypointense signals on T2-weighted images decreased significantly in the sphincter at the intervals, myoblasts could be tracked until 60 days after implantation. Histochemical analyses confirmed the presence of Prussian-blue-stain positive cells in the regenerating sphincter mainly at the injured site. The concurrent functional study revealed improvement in the mean resting anal canal pressure and sphincteric EMG activity. Conclusions Our study illustrates the potential of noninvasive MRI techniques for in-vivo monitoring of magnetically labeled myoblasts for anal sphincter myoplasty. The presence of the labeled cell corresponding with functional improvement confirmed their capability for recapitulation of a myogenic program in a deficient anal sphincter.

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