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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 Institute of Anatomy and Cell Biology, Göteborg University, Gothenburg, Sweden;
^b Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden;
^c Department of Neurosurgery, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan;
^d Institute of Physiology and Pharmacology, Department of Pharmacology, Göteborg University, Gothenburg, Sweden;
^e RIKEN Center for Developmental Biology, Chuo, Kobe, Japan;
^f The Arvid Carlsson Institute for Neuroscience, Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Göteborg University, Gothenburg, Sweden

Key Words. Differentiation • Teratoma formation • Dopaminergic neurons • Parkinson’s disease • Neural transplantation • Human embryonic stem cells

Correspondence: Jia-Yi Li, M.D., Ph.D., Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, BMC A10, 221 84 Lund, Sweden. Telephone: +46-46-222 05 25; Fax: +46-46-222 05 31; e-mail: jia-yi.li{at}med.lu.se or Prof. Peter S. Eriksson, M.D., Ph.D., Institute of Clinical Neuroscience, Göteborg University, Sahlgrenska University Hospital, 413145, Göteborg, Sweden. Telephone: +46-31-7733433; Fax: +46-773401; e-mail: peter.eriksson{at}neuro.gu.se

Received August 16, 2005; accepted for publication March 14, 2006.

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.

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