Host-dependent tumorigenesis of embryonic stem cell transplantation in experimental stroke.
The therapeutical potential of transplantation of undifferentiated and predifferentiated murine embryonic stem cells for the regeneration of the injured brain was investigated in two rodent stroke models. Undifferentiated embryonic stem cells xenotransplanted into the rat brain at the hemisphere opposite to the ischemic injury migrated along the corpus callosum towards the damaged tissue and differentiated into neurons in the border zone of the lesion. In the homologous mouse brain, the same murine embryonic stem cells did not migrate, but produced highly malignant teratocarcinomas at the site of implantation, independent of whether they were predifferentiated in vitro to neural progenitor cells. The authors demonstrated a hitherto unrecognized inverse outcome after xenotransplantation and homologous transplantation of embryonic stem cells, which raises concerns about safety provisions when the therapeutical potential of human embryonic stem cells is tested in preclinical animal models.
Erdö
Franciska
F
Department of Experimental Neurology, Max-Planck Institute for Neurological Research, University of Cologne, Cologne, Germany.
Bührle
Christian
C
Blunk
James
J
Hoehn
Mathias
M
Xia
Ying
Y
Fleischmann
Bernd
B
Föcking
Melanie
M
Küstermann
Ekkehardt
E
Kolossov
Eugen
E
Hescheler
Jürgen
J
Hossmann
Konstantin-A
KA
Trapp
Thorsten
T
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000209:etiology* / Q000473:pathology; D002454:Cell Differentiation; D002465:Cell Movement; D004195:Disease Models, Animal; D006801:Humans; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation; D020521:Stroke / Q000473:pathology / Q000628:therapy; D018243:Teratocarcinoma / Q000209:etiology* / Q000473:pathology; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous