title: Safety assessment of myogenic stem cell transplantation and resulting tumor formation.
abstract: OBJECTIVE
  To assess for stem cell migration to liver and lung after transplantation in injured rat anal sphincters. To evaluate histological findings of unanticipated ectopic foci of growth.
  
  
  METHODS
  This is a prospective study involving 33 female virginal Sprague-Dawley rats. Anal sphincters were transected and repaired under sterile technique. Animals received injections of 5.0 × 10 myogenic stem cells (24 rats) or sham control (9 rats) and were killed on day 30. Liver and lung samples were obtained. Upon encountering abnormal foci of growth, further staining protocols were employed. Enzyme-linked immunosorbent assay studies evaluated stem cell media for in vitro growth factor secretion.
  
  
  RESULTS
  No evidence of cell migration to liver or lung was found at the time of euthanasia in any study animal. Ectopic foci of growth were noted in 2 transplant rats. Further histological evaluations of these growths were consistent with benign tumors: no nuclear abnormalities and no evidence of proliferation at day 30. Enzyme-linked immunosorbent assay studies demonstrated positive secretion of vascular endothelial growth factor and insulin growth factor into the media of cultured rat myogenic stem cells.
  
  
  CONCLUSIONS
  Whereas distant migration was not encountered in the liver or lung, 2 transplanted rats developed abnormal foci of growth, that is, tumors, from the external anal sphincter-raising further safety questions. Additional evaluation of these foci seemed benign. Possible explanations include cell trapping, stem cell overgrowth, and/or paracrine factors. The lack of cell migration supports that future investigation of safety parameters could focus locally.
authors.affiliation: From the *Division of Urogynecology, Department of Obstetrics and Gynecology, University of California, Irvine Medical Center, Orange, CA; and †Department of Anatomy and Neurobiology Reeve-Irvine Research Center, University of California-Irvine, Irvine, CA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Jacobs
authors.forename: Felicia L
authors.initials: FL
authors.lastname: Lane
authors.forename: Quynh-Anh
authors.initials: QA
authors.lastname: Pham
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nistor
authors.forename: Rockelle
authors.initials: R
authors.lastname: Robles
authors.forename: Camille
authors.initials: C
authors.lastname: Chua
authors.forename: Bryan
authors.initials: B
authors.lastname: Boubion
authors.forename: Kathryn
authors.initials: K
authors.lastname: Osann
authors.forename: Hans
authors.initials: H
authors.lastname: Keirstead
mesh_terms: D001003:Anal Canal / Q000473:pathology; D000818:Animals; D001005:Anus Neoplasms / Q000453:epidemiology; D002465:Cell Movement; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005242:Fecal Incontinence / Q000601:surgery*; D005260:Female; D006801:Humans; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000009:adverse effects