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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.

Journal article
Authors Anke Brederlau
Ana Sofia Correia
Sergey V Anisimov
Muna Elmi
Gesine Paul
Laurent Roybon
Asuka Morizane
Filip Bergquist
Ilse Riebe
Ulf Nannmark
Manolo Carta
Eric Hanse
Jun Takahashi
Yoshiki Sasai
Keiko Funa
Patrick Brundin
Peter S Eriksson
Jia-Yi Li
Published in Stem cells (Dayton, Ohio)
Volume 24
Issue 6
Pages 1433-40
ISSN 1066-5099
Publication year 2006
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Institute of Neuroscience and Physiology, Department of Physiology
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 1433-40
Language en
Links dx.doi.org/10.1634/stemcells.2005-0...
Keywords Animals, Cell Differentiation, Cell Proliferation, Cell Survival, Female, Humans, Neurons, pathology, Parkinsonian Disorders, pathology, physiopathology, therapy, Rats, Rats, Sprague-Dawley, Stem Cell Transplantation, adverse effects, Teratoma, etiology, prevention & control, Transplantation, Heterologous
Subject categories Cell and Molecular Biology

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.

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