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Growth factors and feeder cells promote differentiation of human embryonic stem cells into dopaminergic neurons: a novel role for fibroblast growth factor-20.

Correia, Sofia LU ; Anisimov, Sergey V; Li, Jia-Yi LU and Brundin, Patrik LU (2008) In Frontiers in Neuroscience 2(1). p.26-34
Abstract
Human embryonic stem cells (hESCs) are a potential source of dopaminergic neurons for treatment of patients with Parkinson's disease (PD). Dopaminergic neurons can be derived from hESCs and display a characteristic midbrain phenotype. Once transplanted, they can induce partial behavioral recovery in animal models of PD. However, the potential research field faces several challenges that need to be overcome before clinical application of hESCs in a transplantation therapy in PD can be considered. These include low survival of the hESC-derived, grafted dopaminergic neurons after transplantation; unclear functional integration of the grafted neurons in the host brain; and, the risk of teratoma/tumor formation from the transplanted cells. This... (More)
Human embryonic stem cells (hESCs) are a potential source of dopaminergic neurons for treatment of patients with Parkinson's disease (PD). Dopaminergic neurons can be derived from hESCs and display a characteristic midbrain phenotype. Once transplanted, they can induce partial behavioral recovery in animal models of PD. However, the potential research field faces several challenges that need to be overcome before clinical application of hESCs in a transplantation therapy in PD can be considered. These include low survival of the hESC-derived, grafted dopaminergic neurons after transplantation; unclear functional integration of the grafted neurons in the host brain; and, the risk of teratoma/tumor formation from the transplanted cells. This review is focused on our recent efforts to improve the survival of hESC-dervied dopaminergic neurons. In a recent study, we examined the effect of fibroblast growth factor (FGF)-20 in the differentiation of hESCs into dopaminergic neurons. We supplemented cultures of hESCs with FGF-20 during differentiation on PA6 mouse stromal cells for 3 weeks. When we added FGF-20 the yield of neurons expressing tyrosine hydroxylase increased. We demonstrated that at least part of the effect is contributed by enhanced cell differentiation towards the dopaminergic phenotype as well as reduced cell death. We compare our results with those obtained in other published protocols using different sets of growth factors. Taken together, our data indicate that FGF-20 has potent effects to generate large number of dopaminergic neurons derived from hESCs, which may be useful for hESC-based therapy in PD. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Frontiers in Neuroscience
volume
2
issue
1
pages
26 - 34
publisher
Frontiers
external identifiers
  • pmid:18982104
  • scopus:72649085005
ISSN
1662-4548
DOI
10.3389/neuro.01.011.2008
language
English
LU publication?
yes
id
62adee3e-d725-4928-9d27-5ecbf9a91b53 (old id 1271853)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18982104?dopt=Abstract
date added to LUP
2008-12-01 15:35:43
date last changed
2017-01-01 07:51:27
@article{62adee3e-d725-4928-9d27-5ecbf9a91b53,
  abstract     = {Human embryonic stem cells (hESCs) are a potential source of dopaminergic neurons for treatment of patients with Parkinson's disease (PD). Dopaminergic neurons can be derived from hESCs and display a characteristic midbrain phenotype. Once transplanted, they can induce partial behavioral recovery in animal models of PD. However, the potential research field faces several challenges that need to be overcome before clinical application of hESCs in a transplantation therapy in PD can be considered. These include low survival of the hESC-derived, grafted dopaminergic neurons after transplantation; unclear functional integration of the grafted neurons in the host brain; and, the risk of teratoma/tumor formation from the transplanted cells. This review is focused on our recent efforts to improve the survival of hESC-dervied dopaminergic neurons. In a recent study, we examined the effect of fibroblast growth factor (FGF)-20 in the differentiation of hESCs into dopaminergic neurons. We supplemented cultures of hESCs with FGF-20 during differentiation on PA6 mouse stromal cells for 3 weeks. When we added FGF-20 the yield of neurons expressing tyrosine hydroxylase increased. We demonstrated that at least part of the effect is contributed by enhanced cell differentiation towards the dopaminergic phenotype as well as reduced cell death. We compare our results with those obtained in other published protocols using different sets of growth factors. Taken together, our data indicate that FGF-20 has potent effects to generate large number of dopaminergic neurons derived from hESCs, which may be useful for hESC-based therapy in PD.},
  author       = {Correia, Sofia and Anisimov, Sergey V and Li, Jia-Yi and Brundin, Patrik},
  issn         = {1662-4548},
  language     = {eng},
  number       = {1},
  pages        = {26--34},
  publisher    = {Frontiers},
  series       = {Frontiers in Neuroscience},
  title        = {Growth factors and feeder cells promote differentiation of human embryonic stem cells into dopaminergic neurons: a novel role for fibroblast growth factor-20.},
  url          = {http://dx.doi.org/10.3389/neuro.01.011.2008},
  volume       = {2},
  year         = {2008},
}