Safety assessment of myogenic stem cell transplantation and resulting tumor formation

Stephanie Jacobs, Felicia L. Lane, Quynh Anh Pham, Gabriel Nistor, Rockelle Robles, Camille Chua, Bryan Boubion, Kathryn Osann, Hans Keirstead

Research output: Contribution to journalArticle

Abstract

Objectives: 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 × 106 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. Enzymelinked 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 sphincterVraising 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.

Original languageEnglish (US)
Pages (from-to)362-368
Number of pages7
JournalFemale Pelvic Medicine and Reconstructive Surgery
Volume19
Issue number6
DOIs
Publication statusPublished - Jan 1 2013
Externally publishedYes

    Fingerprint

Keywords

  • Anal incontinence
  • Myoblast
  • Stem cell transplantation

ASJC Scopus subject areas

  • Surgery
  • Obstetrics and Gynecology
  • Urology

Cite this