title: The dose-effect safety profile of skeletal muscle precursor cell therapy in a dog model of intrinsic urinary sphincter deficiency.
abstract: Locally injected skeletal muscle precursor cells (skMPCs) integrate into and restore the muscle layers, innervation, vasculature, and function of the sphincter complex in animal models of intrinsic urinary sphincter deficiency (ISD). The goal of the present study was to test the dose-effect safety profile of skMPC therapy in a dog model of ISD. Sphincter deficiency was created in 20 adult female dogs by surgically removing the skeletal muscle layer of the urinary sphincter complex. skMPCs isolated from the hind leg were expanded in culture and injected 4 weeks later into the sphincter complex at a dose of 25 million cells (n = 5), 50 million cells (n = 5), or 100 million cells (n = 5) per milliliter in a 2-ml volume. Five dogs received no sphincter injection. The measures of maximal sphincter pressure, complete blood count, and blood chemistry were performed monthly until their sacrifice at 9 months. At that point, full necropsy was performed to assess the safety of the skMPC injections. Injection of different doses of cells had no effects on the body weight, blood cell count, or kidney or liver function test results (p > .05 among the skMPC doses). Some incidental pathologic features were found in the lower urinary tract in all groups and were most likely associated with repeat catheterization. The maximal urinary sphincter pressure was higher in the 50 million cells per milliliter treatment group than in the other experimental groups (p < .05). The findings of the present study have confirmed that urinary sphincter injection of skMPCs results in no significant local or systemic pathologic features within the dose range that improves sphincter pressures.
authors: Wake Forest Institute for Regenerative Medicine and Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA; Biomedical Sciences Program, College of Health Sciences, Midwestern University, Glendale, Arizona, USA; Imam Reza General Hospital, Kermanshah University of Medical Science, Kermanshah, Iran kwilliam@wakehealth.edu.
authors: J Koudy
authors: JK
authors: Williams
authors: Wake Forest Institute for Regenerative Medicine and Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA; Biomedical Sciences Program, College of Health Sciences, Midwestern University, Glendale, Arizona, USA; Imam Reza General Hospital, Kermanshah University of Medical Science, Kermanshah, Iran.
authors: Delrae
authors: D
authors: Eckman
authors: Wake Forest Institute for Regenerative Medicine and Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA; Biomedical Sciences Program, College of Health Sciences, Midwestern University, Glendale, Arizona, USA; Imam Reza General Hospital, Kermanshah University of Medical Science, Kermanshah, Iran.
authors: Ashley
authors: A
authors: Dean
authors: Wake Forest Institute for Regenerative Medicine and Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA; Biomedical Sciences Program, College of Health Sciences, Midwestern University, Glendale, Arizona, USA; Imam Reza General Hospital, Kermanshah University of Medical Science, Kermanshah, Iran.
authors: Mahmoudreza
authors: M
authors: Moradi
authors: Wake Forest Institute for Regenerative Medicine and Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA; Biomedical Sciences Program, College of Health Sciences, Midwestern University, Glendale, Arizona, USA; Imam Reza General Hospital, Kermanshah University of Medical Science, Kermanshah, Iran.
authors: Julie
authors: J
authors: Allickson
authors: Wake Forest Institute for Regenerative Medicine and Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA; Biomedical Sciences Program, College of Health Sciences, Midwestern University, Glendale, Arizona, USA; Imam Reza General Hospital, Kermanshah University of Medical Science, Kermanshah, Iran.
authors: J Mark
authors: JM
authors: Cline
authors: Wake Forest Institute for Regenerative Medicine and Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA; Biomedical Sciences Program, College of Health Sciences, Midwestern University, Glendale, Arizona, USA; Imam Reza General Hospital, Kermanshah University of Medical Science, Kermanshah, Iran.
authors: James J
authors: JJ
authors: Yoo
authors: Wake Forest Institute for Regenerative Medicine and Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA; Biomedical Sciences Program, College of Health Sciences, Midwestern University, Glendale, Arizona, USA; Imam Reza General Hospital, Kermanshah University of Medical Science, Kermanshah, Iran.
authors: Anthony
authors: A
authors: Atala
mesh_terms: D064591:Allografts; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D032448:Myoblasts, Skeletal / Q000473:pathology / Q000637:transplantation*; D033581:Stem Cell Transplantation; D014521:Urethra / Q000473:pathology / Q000503:physiopathology*; D014550:Urinary Incontinence, Stress / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*
keywords: Maximal urethral pressure; Pathology; Skeletal muscle; Stem cells; Urinary incontinence
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