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Embryonic Stem Cells |
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.
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Abstract |
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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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