title: Determinates of muscle precursor cell therapy efficacy in a nonhuman primate model of intrinsic urinary sphincter deficiency.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA. kwilliam@wakehealth.edu.|Wake Forest Institute for Regenerative Medicine, Wake Forest University, 391 Technology Way, Winston-Salem, North Carolina, 27101, USA. kwilliam@wakehealth.edu.
authors.forename: James Koudy
authors.initials: JK
authors.lastname: Williams
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Dean
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Lankford
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Criswell
authors.affiliation: Department of Urology, Wake Forest University Baptist Medical Center, Winston-Salem, NC, 27157, USA.
authors.forename: Gopal
authors.initials: G
authors.lastname: Badlani
authors.affiliation: Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
mesh_terms: D000375:Aging; D000818:Animals; D001835:Body Weight; D064987:Cell- and Tissue-Based Therapy; D003094:Collagen / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D032446:Myoblasts / Q000166:cytology* / Q000637:transplantation*; D011312:Pressure; D011323:Primates; D012919:Social Behavior; D016896:Treatment Outcome; D014521:Urethra / Q000473:pathology* / Q000503:physiopathology
chemical_list: D003094:Collagen
keywords: Aging; Cell therapy; Dysmenorrhea; Nonhuman primate; Obesity; Urinary incontinence