Work in LMB has led the way towards the ambitious goal where stem cells can be used to replace tissue damaged by neurodegenerative diseases that cause the loss of neurons or glial cells. We have previously demonstrated that stem cells derived from the fetal brain can generate neurons that secrete the neurotransmitter dopamine but these cells can provide unlimited numbers of these neurons. In the last year we have continued to develop embryonic stem (ES) cells as a source of dopamine neurons. These are the type of neuron lacking in Parkinson's patients and these neurons have not previously been obtained in such large numbers. Parkinson's disease (PD) is a widespread neurological condition caused by the loss of neurons in the midbrain that synthesize the transmitter dopamine. Clinical experience suggests that cells derived from the fetal midbrain can modify the course of the disease. The limited supply of this tissue may be overcome by new stem cell technologies. Precursors from the fetal brain are not an adequate source of these neurons because their ability to generate dopamine neurons is not stable. In contrast, embryonic stem (ES) cells proliferate extensively and generate dopamine-synthesizing neurons that show electrophysiological and behavioral properties expected of neurons from the midbrain. These results were obtained with mouse ES cells but recent work from our group suggests that human ES cell differentiation to dopamine neuron fates.
| Joksimovic, Milan; Yun, Beth A; Kittappa, Raja et al. (2009) Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis. Nat Neurosci 12:125-31 |
| Rodriguez-Gomez, Jose A; Lu, Jian-Qiang; Velasco, Ivan et al. (2007) Persistent dopamine functions of neurons derived from embryonic stem cells in a rodent model of Parkinson disease. Stem Cells 25:918-28 |
| Kittappa, Raja; Chang, Wendy W; Awatramani, Rajeshwar B et al. (2007) The foxa2 gene controls the birth and spontaneous degeneration of dopamine neurons in old age. PLoS Biol 5:e325 |
| Shim, J H; Kim, S E; Woo, D H et al. (2007) Directed differentiation of human embryonic stem cells towards a pancreatic cell fate. Diabetologia 50:1228-38 |
| Leker, Ronen R; Soldner, Frank; Velasco, Ivan et al. (2007) Long-lasting regeneration after ischemia in the cerebral cortex. Stroke 38:153-61 |
| Chen, Hui-Ling; Pistollato, Francesca; Hoeppner, Daniel J et al. (2007) Oxygen tension regulates survival and fate of mouse central nervous system precursors at multiple levels. Stem Cells 25:2291-301 |
| International Stem Cell Initiative; Adewumi, Oluseun; Aflatoonian, Behrouz et al. (2007) Characterization of human embryonic stem cell lines by the International Stem Cell Initiative. Nat Biotechnol 25:803-16 |
| Androutsellis-Theotokis, Andreas; Leker, Ronen R; Soldner, Frank et al. (2006) Notch signalling regulates stem cell numbers in vitro and in vivo. Nature 442:823-6 |
| Murase, Sachiko; McKay, Ronald D (2006) A specific survival response in dopamine neurons at most risk in Parkinson's disease. J Neurosci 26:9750-60 |
| Mallon, Barbara S; Park, Kye-Yoon; Chen, Kevin G et al. (2006) Toward xeno-free culture of human embryonic stem cells. Int J Biochem Cell Biol 38:1063-75 |
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