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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

Brederlau, Anke ; Correia, Ana Sofia ; Anisimov, Sergey LU ; Elmi, Muna ; Paul-Visse, Gesine LU ; Roybon, Laurent LU ; Morizane, Asuka ; Bergquist, Filip ; Riebe, Ilse and Nannmark, Ulf , et al. (2006) In Stem Cells 24(6). p.1433-1440
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
human embryonic stem cells, neural transplantation, disease, Parkinson's, dopaminergic neurons, differentiation, teratoma formation
in
Stem Cells
volume
24
issue
6
pages
1433 - 1440
publisher
AlphaMed Press
external identifiers
  • pmid:16556709
  • wos:000240639300006
  • scopus:33745542454
ISSN
1549-4918
DOI
10.1634/stemcells.2005-0393
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neuronal Survival (013212041), Neurobiology (013212024)
id
e85a12a0-df14-4ee1-99f3-092236aad9d6 (old id 392880)
date added to LUP
2016-04-01 16:18:05
date last changed
2020-12-08 03:33:22
@article{e85a12a0-df14-4ee1-99f3-092236aad9d6,
  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.},
  author       = {Brederlau, Anke and Correia, Ana Sofia and Anisimov, Sergey and Elmi, Muna and Paul-Visse, Gesine and Roybon, Laurent and Morizane, Asuka and Bergquist, Filip and Riebe, Ilse and Nannmark, Ulf and Carta, Manolo and Hansf, Erik and Takahashi, Jun and Sasai, Yoshiki and Funa, Keiko and Brundin, Patrik and Eriksson, Peter S. and Li, Jia-Yi},
  issn         = {1549-4918},
  language     = {eng},
  number       = {6},
  pages        = {1433--1440},
  publisher    = {AlphaMed Press},
  series       = {Stem Cells},
  title        = {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},
  url          = {http://dx.doi.org/10.1634/stemcells.2005-0393},
  doi          = {10.1634/stemcells.2005-0393},
  volume       = {24},
  year         = {2006},
}