Stem Cells
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First published online March 23, 2006
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2005-0393v1
24/6/1433    most recent
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Submitted on August 16, 2005
Accepted on March 14, 2006

Embryonic Stem Cells

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

A. Brederlau 1, A. S. Correia 2, S. V. Anisimov 2, M. Elmi 1, L. Roybon 2, G. Paul 2, A. Morizane 3, F. Bergquist 4, I. Riebe 4, U. Nannmark 1, M. Carta 2, E. Hanse 4, J. Takahashi 3, Y. Sasai 5, K. Funa 1, P. Brundin 2, P. S. Eriksson 6, J.-Y. Li 2*

1 Institute of Anatomy and Cell Biology, Göteborg University, Gothenburg, Sweden
2 Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden
3 Department of Neurosurgery, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan
4 Institute of Physiology and Pharmacology, Department of Pharmacology, Göteborg University, Gothenburg, Sweden
5 RIKEN Center for Developmental Biology, Chuo, Kobe, Japan
6 The Arvid Carlsson Institute for Neuroscience, Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Göteborg University, Gothenburg, Sweden

* To whom correspondence should be addressed. E-mail: jia-yi.li{at}med.lu.se.


  Abstract

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 pre-differentiation on in vivo survival and differentiation of hESCs implanted into the 6- hydroxydopamine (OHDA)-lesion rat model of PD. The hESCs were co-cultured 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 pre-differentiated in vitro for 16 days developed severe teratomas, while most rats grafted with hESCs pre-differentiated for 20 and 23 days remained healthy until the end of the experiment. This indicates that prolonged in vitro differentiation of hESCs is essential to prevent formation of teratomas.




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