[Embryonic stem cell therapy in experimental stroke: host-dependent malignant transformation].
BACKGROUND
Therapeutic application of embryonic stem cells in neurodegenerative disorders like stroke is widely investigated in preclinical animal models.


OBJECTIVE
The authors studied the therapeutic potential of murine embryonic stem cells in two rodent models of stroke.


METHODS
Undifferentiated and predifferentiated stem cells were implanted into the non-ischemic hemisphere of mice and rats following focal brain ischemia. The brains were analysed by immunohistochemistry and histology. The in vitro differentiation of the cells was checked by immunocytochemistry and Western-blot.


RESULTS
After xenotransplantation in rats undifferentiated cells migrated along the corpus callosum towards the ischemic injury. Later stem cells 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. These experiments demonstrated a hitherto unrecognized adverse outcome after xenotransplantation and homologous transplantation of embryonic stem cells.


CONCLUSIONS
This observation raises serious concerns about safety provisions when the therapeutic potential of human embryonic stem cells is tested in preclinical animal models. The clinical trials are based on the positive outcome of the xenologous experiments.
Erdo
Franciska
F
Experimentelle Neurologie, Max-Planck Institut für neurologische Forschung, Köln, Németország. franciska.erdo@idri.hu
Trapp
Thorsten
T
Bührle
Christian
C
Fleischmann
Bernd
B
Hossmann
Konstantin-A
KA
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000473:pathology* / Q000601:surgery*; D001932:Brain Neoplasms / Q000209:etiology; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000166:cytology; D007150:Immunohistochemistry; D051379:Mice; D051381:Rats; D033581:Stem Cell Transplantation; D020521:Stroke / Q000601:surgery*; D018243:Teratocarcinoma / Q000209:etiology; D013997:Time Factors; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous