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

Author:

Brederlau Anke1,Correia Ana Sofia2,Anisimov Sergey V.2,Elmi Muna1,Paul Gesine2,Roybon Laurent2,Morizane Asuka3,Bergquist Filip4,Riebe Ilse4,Nannmark Ulf1,Carta Manolo2,Hanse Erik4,Takahashi Jun3,Sasai Yoshiki5,Funa Keiko1,Brundin Patrick2,Eriksson Peter S.6,Li Jia-Yi2

Affiliation:

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

Abstract

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 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.

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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