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Mesenchymal stem cells can improve anal pressures after anal sphincter injury
Authors:Levilester Salcedo  Maritza Mayorga  Margot Damaser  Brian Balog  Robert Butler  Marc Penn  Massarat Zutshi
Affiliation:1. Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH, USA;2. Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, OH, USA;3. Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH, USA;4. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA;5. Advanced Platform Technology Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA;6. Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA
Abstract:Objective.Fecal incontinence reduces the quality of life of many women but has no long-term cure. Research on mesenchymal stem cell (MSC)-based therapies has shown promising results. The primary aim of this study was to evaluate functional recovery after treatment with MSCs in two animal models of anal sphincter injury.Methods.Seventy virgin female rats received a sphincterotomy (SP) to model episiotomy, a pudendal nerve crush (PNC) to model the nerve injuries of childbirth, a sham SP, or a sham PNC. Anal sphincter pressures and electromyography (EMG) were recorded after injury but before treatment and 10 days after injury. Twenty-four hours after injury, each animal received either 0.2 ml saline or 2 million MSCs labelled with green fluorescing protein (GFP) suspended in 0.2 ml saline, either intravenously (IV) into the tail vein or intramuscularly (IM) into the anal sphincter.Results.MSCs delivered IV after SP resulted in a significant increase in resting anal sphincter pressure and peak pressure, as well as anal sphincter EMG amplitude and frequency 10 days after injury. MSCs delivered IM after SP resulted in a significant increase in resting anal sphincter pressure and anal sphincter EMG frequency but not amplitude. There was no improvement in anal sphincter pressure or EMG with in animals receiving MSCs after PNC. GFP-labelled cells were not found near the external anal sphincter in MSC-treated animals after SP.Conclusion.MSC treatment resulted in significant improvement in anal pressures after SP but not after PNC, suggesting that MSCs could be utilized to facilitate recovery after anal sphincter injury.
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