Functional outcome after anal sphincter injury and treatment with mesenchymal stem cells.

Functional outcome after anal sphincter injury and treatment with mesenchymal stem cells.

Salcedo Levilester; Penn Marc; Damaser Margot; Balog Brian; Zutshi Massarat

Stem cells translational medicine

2014

2014-06

This research demonstrates the regenerative effects of mesenchymal stem cells (MSCs) on the injured anal sphincter by comparing anal sphincter pressures following intramuscular and serial intravascular MSC infusion in a rat model of anal sphincter injury. Fifty rats were divided into injury (n = 35) and no injury (NI; n = 15) groups. Each group was further divided into i.m., serial i.v., or no-treatment (n = 5) groups and followed for 5 weeks. The injury consisted of an excision of 25% of the anal sphincter complex. Twenty-four hours after injury, 5 x 10(5) green fluorescent protein-labeled MSCs in 0.2 ml of phosphate-buffered saline (PBS) or PBS alone (sham) were injected into the anal sphincter for i.m. treatment; i.v. and sham i.v. treatments were delivered daily for 6 consecutive days via the tail vein. Anal pressures were recorded before injury and 10 days and 5 weeks after treatment. Ten days after i.m. MSC treatment, resting and peak pressures were significantly increased compared with those in sham i.m. treatment (p \textless .001). When compared with the NI group, the injury groups had anal pressures that were not significantly different 5 weeks after i.m./i.v. treatment. Both resting and peak pressures were also significantly increased after i.m./i.v. MSC treatment compared with treatment with PBS (p \textless .001), suggesting recovery. Statistical analysis was done using paired t test with Bonferroni correction. Marked decrease in fibrosis and scar tissue was seen in both MSC-treated groups. Both i.m. and i.v. MSC treatment after injury caused an increase in anal pressures sustained at 5 weeks, although fewer cells were injected i.m. The

Female; Time Factors; Animals; Rats; Mesenchymal stem cells; Transfection; Recovery of Function; Fibrosis; *Mesenchymal Stem Cell Transplantation; *Regeneration; Anal Canal/injuries/metabolism/pathology/physiopathology/*surgery; Anal pressures; Anal sphincter; Fecal incontinence; Green Fluorescent Proteins/biosynthesis/genetics; i.v. infusion; Mesenchymal Stem Cells/metabolism; Pressure; Injections; Intralesional; Sprague-Dawley; Cells; Cultured; Animal; Disease Models; Infusions; Intravenous

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760–767

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