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.
Brederlau
Anke
A
Institute of Anatomy and Cell Biology, Göteborg University, Gothenburg, Sweden.
Correia
Ana Sofia
AS
Anisimov
Sergey V
SV
Elmi
Muna
M
Paul
Gesine
G
Roybon
Laurent
L
Morizane
Asuka
A
Bergquist
Filip
F
Riebe
Ilse
I
Nannmark
Ulf
U
Carta
Manolo
M
Hanse
Erik
E
Takahashi
Jun
J
Sasai
Yoshiki
Y
Funa
Keiko
K
Brundin
Patrick
P
Eriksson
Peter S
PS
Li
Jia-Yi
JY
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