Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson's disease: effect of in vitro differentiation on graft survival and teratoma formation.
Human embryonic stem cells (hESCs) have been proposed as a source of dopamine (DA) neurons for transplantation in Parkinson's disease (PD). We have investigated the effect of in vitro predifferentiation on in vivo survival and differentiation of hESCs implanted into the 6-OHDA (6-hydroxydopamine)-lesion rat model of PD. The hESCs were cocultured with PA6 cells for 16, 20, or 23 days, leading to the in vitro differentiation into DA neurons. Grafted hESC-derived cells survived well and expressed neuronal markers. However, very few exhibited a DA neuron phenotype. Reversal of lesion-induced motor deficits was not observed. Rats grafted with hESCs predifferentiated in vitro for 16 days developed severe teratomas, whereas most rats grafted with hESCs predifferentiated for 20 and 23 days remained healthy until the end of the experiment. This indicates that prolonged in vitro differentiation of hESCs is essential for preventing formation of teratomas.
Institute of Anatomy and Cell Biology, Göteborg University, Gothenburg, Sweden.
Anke
A
Brederlau
Ana Sofia
AS
Correia
Sergey V
SV
Anisimov
Muna
M
Elmi
Gesine
G
Paul
Laurent
L
Roybon
Asuka
A
Morizane
Filip
F
Bergquist
Ilse
I
Riebe
Ulf
U
Nannmark
Manolo
M
Carta
Erik
E
Hanse
Jun
J
Takahashi
Yoshiki
Y
Sasai
Keiko
K
Funa
Patrick
P
Brundin
Peter S
PS
Eriksson
Jia-Yi
JY
Li
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009474:Neurons / Q000473:pathology; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000009:adverse effects; D013724:Teratoma / Q000209:etiology / Q000517:prevention & control; D014183:Transplantation, Heterologous