title: Functional and histological evidence for the targeted therapy using biocompatible polycaprolactone beads and autologous myoblasts in a dog model of fecal incontinence.
abstract: BACKGROUND
  Injection of bulking agents into the anal canal is limited by several factors, including biological resorption, particle migration, and ongoing degradation of the injected bulking agent.
  
  
  OBJECTIVE
  We investigated whether an injection of polycaprolactone beads containing autologous myoblasts could improve sphincter function in a dog model of fecal incontinence.
  
  
  METHODS
  The control sham surgery group underwent skin incision around the anal sphincter (n = 5). Fecal incontinence was induced by resecting 25% of the posterior internal/external anal sphincter in another 10 dogs. After 1 month of sphincter injury, dogs were then treated with (n = 5) or without (n = 5) polycaprolactone beads containing PKH-26-labeled autologous myoblasts.
  
  
  METHODS
  This study was conducted at the department of surgery in collaboration with the department of advanced materials.
  
  
  METHODS
  Three months after injection treatment, the resting and contractile pressure differences of the anal sphincter were compared, and histopathological studies were performed.
  
  
  RESULTS
  The anal pressures in untreated dogs were significantly lower than those in the sham surgery group (p < 0.05). The resting and contractile pressure differences were higher in treated dogs than in untreated dogs (resting pressure difference: 0.7 ± 0.5 vs -0.6 ± 0.8 mmHg; coefficient of the difference in recovery rate, 0.38; 95% CI, 0.15-0.61, p = 0.001; contractile pressure difference: 1.1 ± 4.2 vs -3.9 ± 2.6 mmHg; coefficient, 1.63; 95% CI, 0.55-2.71, p = 0.003). Immunofluorescent staining confirmed that the myoblasts had differentiated and synthesized myosin heavy chain, as observed in vitro.
  
  
  CONCLUSIONS
  This study was limited by the lack of comparison of injecting beads containing autologous myoblasts with injecting myoblasts alone.
  
  
  CONCLUSIONS
  This study shows that an injection of polycaprolactone beads containing autologous myoblasts may improve anal sphincter function in an animal model of fecal incontinence.
authors: 1 Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea 2 Department of Pathology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea 3 Department of Advanced Materials, Hannam University, Daejeon, Republic of Korea 4 Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea 5 Department of Rehabilitation, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea 6 Division of Statistics, Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Republic of Korea 7 Preclinical Research Center, Biomedical Research Institute, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors: Heung-Kwon
authors: HK
authors: Oh
authors: Hye Seung
authors: HS
authors: Lee
authors: Jin Ho
authors: JH
authors: Lee
authors: Se Heang
authors: SH
authors: Oh
authors: Jae-Young
authors: JY
authors: Lim
authors: Soyeon
authors: S
authors: Ahn
authors: Ji-Yeon
authors: JY
authors: Hwang
authors: Sung-Bum
authors: SB
authors: Kang
mesh_terms: D001003:Anal Canal / Q000293:injuries*; D000818:Animals; D001672:Biocompatible Materials / Q000627:therapeutic use*; D002454:Cell Differentiation; D004195:Disease Models, Animal; D004285:Dogs; D005242:Fecal Incontinence / Q000628:therapy*; D005455:Fluorescent Antibody Technique; D008365:Manometry; D009119:Muscle Contraction; D032448:Myoblasts, Skeletal / Q000378:metabolism / Q000637:transplantation*; D018995:Myosin Heavy Chains / Q000378:metabolism; D011091:Polyesters / Q000627:therapeutic use*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D001672:Biocompatible Materials; D011091:Polyesters; C016240:polycaprolactone; D018995:Myosin Heavy Chains