title: Functional outcome after anal sphincter injury and treatment with mesenchymal stem cells.
abstract: 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 × 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 < .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 < .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 MSC-treated groups showed less scarring than the PBS-treated groups, with the i.v. infusion group showing the least scarring.
authors.affiliation: Department of Colorectal Surgery and Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio, USA; Summa Cardiovascular Institute and Northeast Ohio Medical University, Akron, Ohio, USA; Advanced Platform Technology Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
authors.forename: Levilester
authors.initials: L
authors.lastname: Salcedo
authors.affiliation: Department of Colorectal Surgery and Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio, USA; Summa Cardiovascular Institute and Northeast Ohio Medical University, Akron, Ohio, USA; Advanced Platform Technology Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Penn
authors.affiliation: Department of Colorectal Surgery and Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio, USA; Summa Cardiovascular Institute and Northeast Ohio Medical University, Akron, Ohio, USA; Advanced Platform Technology Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
authors.forename: Margot
authors.initials: M
authors.lastname: Damaser
authors.affiliation: Department of Colorectal Surgery and Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio, USA; Summa Cardiovascular Institute and Northeast Ohio Medical University, Akron, Ohio, USA; Advanced Platform Technology Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Balog
authors.affiliation: Department of Colorectal Surgery and Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio, USA; Summa Cardiovascular Institute and Northeast Ohio Medical University, Akron, Ohio, USA; Advanced Platform Technology Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA zutshim@ccf.org.
authors.forename: Massarat
authors.initials: M
authors.lastname: Zutshi
mesh_terms: D001003:Anal Canal / Q000293:injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D007262:Infusions, Intravenous; D015552:Injections, Intralesional; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012038:Regeneration; D013997:Time Factors; D014162:Transfection
chemical_list: D049452:Green Fluorescent Proteins
keywords: Anal pressures; Anal sphincter; Fecal incontinence; Mesenchymal stem cells; i.v. infusion