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Focused Review ARTICLE

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

Ana Sofia Correia^*, Sergey V. Anisimov^*, Jia-Yi Li^* and Patrik Brundin^*

Neuronal Survival Unit, Department of Experimental Medical Science, Lund University, Wallenberg Neuroscience Center, Lund, Sweden

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.

Keywords:

human embryonic stem cells, fibroblast growth factor-20, dopaminergic neurons, differentiation, Parkinson’s disease, stem cell therapy, apoptosis, caspase-3

Citation:

Correia A, Anisimov S, Li J and Brundin P (2008). Growth factors and feeder cells promote differentiation of human embryonic stem cells into dopaminergic neurons: a novel role for fibroblast growth factor-20. Front. Neurosci. 2,1: 26-34 doi: 10.3389/neuro.01.011.2008

Received:

31 March 2008;

Paper pending published:

21 May 2008;

Accepted:

21 May 2008;

Published online:

15 July 2008.

Edited by:

Javier DeFelipe, Cajal Institute (CSIC), Spain

Reviewed by:

Jun Takahashi, Kyoto University, Japan
Brigitte Onteniente, Institut National de la Santé et de la Recherche Médicale, France

© 2008 Correia, Anisimov, Li and Brundin. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

*Correspondence:

Ana Sofia Correia, Lund University, Wallenberg Neuroscience Center, Sölvegatan 17, BMC A10, 221 84 Lund, Sweden. e-mail: Sofia.Correia@med.lu.se