title: Developmental potential of the murine embryonic stem cells transplanted into the healthy rat brain--novel insights into tumorigenesis.
abstract: Although engraftment of undifferentiated pluripotent embryonic stem cells (ESCs) into the injured central nervous system (CNS) may lead to targeted cell replacement of lost/damaged cells, sustained proliferative activity combined with uncontrolled differentiation of implanted cells presents a risk of tumor formation. As tumorigenic potential is thought to be associated with pluripotency of embryonic stem cells, pre-differentiation may circumvent this problem. Recently, it has been demonstrated that tumorigenesis occurs despite pre-differentiation if the neural precursor cells are implanted into the brain of a homologous animal (e.g., mouse to mouse). However, xenotransplantation (e.g., mouse to rat) without pre-differentiation, lead to the development of healthy neuronal cells, in absence of tumor formation, suggesting that tumor-suppressive effects of host tissue on engrafted ESCs may play a role in transplant tumorigenesis. We critically investigated tumorigenesis and possible mechanisms of anticipated tumor-suppressive effect under conditions analogous to previously published studies. Xenotransplantation of D-3 murine ESCs into uninjured adult rat brains lacking any preliminary inflammatory potential was found to lead to tumor formation in 5 out of 8 of animals within 2 weeks postimplantation. Tumor-suppressive effects, reflected by Erdo et. al could possibly be ascribed to immunomodulatory activity of macrophages scavenging the tumorigenic fraction of the implanted cells. The importance of number of engrafted cells, implantation site and immunosuppressive effects are discussed as possible variables determining tumorigenic outcome after ESC transplantation.
authors: Clinic of Neurosurgery, University of Cologne, Germany.
authors: Marek
authors: M
authors: Molcanyi
authors: Peter
authors: P
authors: Riess
authors: Nadia Nabil
authors: NN
authors: Haj-Yasein
authors: Kristine
authors: K
authors: Bentz
authors: Mario
authors: M
authors: Loehr
authors: Johannes
authors: J
authors: Kuchta
authors: Jozef
authors: J
authors: Zivcak
authors: Werner
authors: W
authors: Stenzel
authors: Hrvoje
authors: H
authors: Miletic
authors: Jurgen
authors: J
authors: Hescheler
authors: Edmund
authors: E
authors: Neugebauer
authors: Jurgen Anton
authors: JA
authors: Hampl
authors: Ralf-Ingo
authors: RI
authors: Ernestus
authors: Ute
authors: U
authors: Schafer
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D001932:Brain Neoplasms / Q000209:etiology / Q000473:pathology*; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000637:transplantation*; D008297:Male; D051379:Mice; D010587:Phagocytosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous