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Determinates of muscle precursor cell therapy efficacy in a nonhuman primate model of intrinsic urinary sphincter deficiency

BACKGROUND: Cell therapy for intrinsic urinary sphincter deficiency (ISD) in women has been moderately effective, and improvements are needed. To improve treatment efficacy, it is important to better understand determinates of cell efficacy in the different patient cohorts. We have reported that in...

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Autores principales: Williams, James Koudy, Dean, Ashley, Lankford, Shannon, Criswell, Tracy, Badlani, Gopal, Andersson, Karl-Erik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217333/
https://www.ncbi.nlm.nih.gov/pubmed/28057078
http://dx.doi.org/10.1186/s13287-016-0461-6
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author Williams, James Koudy
Dean, Ashley
Lankford, Shannon
Criswell, Tracy
Badlani, Gopal
Andersson, Karl-Erik
author_facet Williams, James Koudy
Dean, Ashley
Lankford, Shannon
Criswell, Tracy
Badlani, Gopal
Andersson, Karl-Erik
author_sort Williams, James Koudy
collection PubMed
description BACKGROUND: Cell therapy for intrinsic urinary sphincter deficiency (ISD) in women has been moderately effective, and improvements are needed. To improve treatment efficacy, it is important to better understand determinates of cell efficacy in the different patient cohorts. We have reported that in nonhuman primates the chronicity of ISD may affect cell efficacy, but additional factors (age, psychosocial stress, hormone status, body weight) can be associated with many disease/treatment outcomes in women – and these factors are the focus of this study. METHODS: Adult female cynomolgus monkeys were divided into groups: (1) younger (n = 10, 5–8 years of age) versus older (n = 10, 13–18 years of age); (2) age-matched/socially subordinate (n = 15) versus socially dominant (n = 15); and (3) age-matched lower body weight (n = 6) versus higher body weight (n = 6). Autologous skeletal muscle precursor cells (skMPCs, 5 million) were injected into the urinary sphincter 6 weeks after a surgically induced ISD procedure. Resting and pudendal nerve-stimulated maximal urethral pressures (MUP) were measured before, and 3 and 6 months post-skMPC treatment and urinary sphincter muscle/collagen content within the sphincter complex was measured by quantitative histology 6 months posttreatment. RESULTS: Efficacy of skMPCs on MUP and sphincter muscle/collagen ratios are affected by age (average 40% reduction in efficacy, p < 0.05 vs. younger NHPs), social stress (average 30% reduction in efficacy, p < 0.05 vs. socially dominant) and body weight/fasting glucose concentrations (average 35% reduction in efficacy, p < 0.05 vs. lower body weight). CONCLUSION: Multiple factors (age, stress-induced dysmenorrhea, and body weight) affect the efficacy of cell therapy to restore structure and function in the urinary sphincter complex in NHPs with ISD. Consideration of, and alternatives for, these patient cohorts should be considered.
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spelling pubmed-52173332017-01-09 Determinates of muscle precursor cell therapy efficacy in a nonhuman primate model of intrinsic urinary sphincter deficiency Williams, James Koudy Dean, Ashley Lankford, Shannon Criswell, Tracy Badlani, Gopal Andersson, Karl-Erik Stem Cell Res Ther Research BACKGROUND: Cell therapy for intrinsic urinary sphincter deficiency (ISD) in women has been moderately effective, and improvements are needed. To improve treatment efficacy, it is important to better understand determinates of cell efficacy in the different patient cohorts. We have reported that in nonhuman primates the chronicity of ISD may affect cell efficacy, but additional factors (age, psychosocial stress, hormone status, body weight) can be associated with many disease/treatment outcomes in women – and these factors are the focus of this study. METHODS: Adult female cynomolgus monkeys were divided into groups: (1) younger (n = 10, 5–8 years of age) versus older (n = 10, 13–18 years of age); (2) age-matched/socially subordinate (n = 15) versus socially dominant (n = 15); and (3) age-matched lower body weight (n = 6) versus higher body weight (n = 6). Autologous skeletal muscle precursor cells (skMPCs, 5 million) were injected into the urinary sphincter 6 weeks after a surgically induced ISD procedure. Resting and pudendal nerve-stimulated maximal urethral pressures (MUP) were measured before, and 3 and 6 months post-skMPC treatment and urinary sphincter muscle/collagen content within the sphincter complex was measured by quantitative histology 6 months posttreatment. RESULTS: Efficacy of skMPCs on MUP and sphincter muscle/collagen ratios are affected by age (average 40% reduction in efficacy, p < 0.05 vs. younger NHPs), social stress (average 30% reduction in efficacy, p < 0.05 vs. socially dominant) and body weight/fasting glucose concentrations (average 35% reduction in efficacy, p < 0.05 vs. lower body weight). CONCLUSION: Multiple factors (age, stress-induced dysmenorrhea, and body weight) affect the efficacy of cell therapy to restore structure and function in the urinary sphincter complex in NHPs with ISD. Consideration of, and alternatives for, these patient cohorts should be considered. BioMed Central 2017-01-06 /pmc/articles/PMC5217333/ /pubmed/28057078 http://dx.doi.org/10.1186/s13287-016-0461-6 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Williams, James Koudy
Dean, Ashley
Lankford, Shannon
Criswell, Tracy
Badlani, Gopal
Andersson, Karl-Erik
Determinates of muscle precursor cell therapy efficacy in a nonhuman primate model of intrinsic urinary sphincter deficiency
title Determinates of muscle precursor cell therapy efficacy in a nonhuman primate model of intrinsic urinary sphincter deficiency
title_full Determinates of muscle precursor cell therapy efficacy in a nonhuman primate model of intrinsic urinary sphincter deficiency
title_fullStr Determinates of muscle precursor cell therapy efficacy in a nonhuman primate model of intrinsic urinary sphincter deficiency
title_full_unstemmed Determinates of muscle precursor cell therapy efficacy in a nonhuman primate model of intrinsic urinary sphincter deficiency
title_short Determinates of muscle precursor cell therapy efficacy in a nonhuman primate model of intrinsic urinary sphincter deficiency
title_sort determinates of muscle precursor cell therapy efficacy in a nonhuman primate model of intrinsic urinary sphincter deficiency
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217333/
https://www.ncbi.nlm.nih.gov/pubmed/28057078
http://dx.doi.org/10.1186/s13287-016-0461-6
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