title: The postischemic environment differentially impacts teratoma or tumor formation after transplantation of human embryonic stem cell-derived neural progenitors.
abstract: OBJECTIVE
  Risk of tumorigenesis is a major obstacle to human embryonic and induced pluripotent stem cell therapy. Likely linked to the stage of differentiation of the cells at the time of implantation, formation of teratoma/tumors can also be influenced by factors released by the host tissue. We have analyzed the relative effects of the stage of differentiation and the postischemic environment on the formation of adverse structures by transplanted human embryonic stem cell-derived neural progenitors.
  
  
  METHODS
  Four differentiation stages were identified on the basis of quantitative polymerase chain reaction expression of pluripotency, proliferation, and differentiation markers. Neural progenitors were transplanted at these 4 stages into rats with no, small, or large middle cerebral artery occlusion lesions. The fate of each transplant was compared with their pretransplantation status 1 to 4 months posttransplantation.
  
  
  RESULTS
  The influence of the postischemic environment was limited to graft survival and occurrence of nonneuroectodermal structures after transplantation of very immature neural progenitors. Both effects were lost with differentiation. We identified a particular stage of differentiation characterized in vitro by a rebound of proliferative activity that produced highly proliferative grafts susceptible to threaten surrounding host tissues.
  
  
  CONCLUSIONS
  The effects of the ischemic environment on the formation of teratoma by transplanted human embryonic stem cell-derived neural progenitors are limited to early differentiation stages that will likely not be used for stem cell therapy. In contrast, hyperproliferation observed at later stages of differentiation corresponds to an intrinsic activity that should be monitored to avoid tumorigenesis.
authors: INSERM UMR861, Université Evry-Val d'Essonne, Evry, France.
authors: Christine
authors: C
authors: Seminatore
authors: Jerome
authors: J
authors: Polentes
authors: Ditte
authors: D
authors: Ellman
authors: Nataliya
authors: N
authors: Kozubenko
authors: Valerie
authors: V
authors: Itier
authors: Samir
authors: S
authors: Tine
authors: Laurent
authors: L
authors: Tritschler
authors: Marion
authors: M
authors: Brenot
authors: Emmanuelle
authors: E
authors: Guidou
authors: Johanna
authors: J
authors: Blondeau
authors: Mickael
authors: M
authors: Lhuillier
authors: Aurore
authors: A
authors: Bugi
authors: Laetitia
authors: L
authors: Aubry
authors: Pavla
authors: P
authors: Jendelova
authors: Eva
authors: E
authors: Sykova
authors: Anselme L
authors: AL
authors: Perrier
authors: Bente
authors: B
authors: Finsen
authors: Brigitte
authors: B
authors: Onteniente
mesh_terms: D000367:Age Factors; D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology / Q000601:surgery*; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000637:transplantation*; D004777:Environment; D006801:Humans; D008297:Male; D009474:Neurons / Q000166:cytology / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000009:adverse effects; D013724:Teratoma / Q000209:etiology / Q000473:pathology*