Summary of Research Project Results under JSPS FY2004
"Research for the Future Program"

1. Research Institution   Kyoto University
2. Research Area Life Sciences
3. Research Field Development, Differentiation, and Regeneration
4. Term of Project FY 2000 - FY 2004
5. Project Number 00L01503
6. Title of Project Tissue Regeneration and Construction by Control of Differentiation Programs

7. Project Leader

Name Institution, Department Title of Position
Norio, Nakatsuji Kyoto University Institute for Frontier Medical Sciences Professor

8. Core Members

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9. Summary of Research Results

  1. Establishment and characterization of cynomolgus monkey ES cell lines. Monkey ES cell lines are important for preclinical investigation. We have established several ES cell lines and distributed to other scientists in Japan after characterization of cell lines.
  2. Improvement of culture methods for primate ES cells. Primate ES cells are much more difficult to maintain compared to mouse ES cells. We have succeeded to maintain for long periods by improvement of the serum-free medium and subculture method. As the results, we can now maintain monkey and human ES cells stably as the undifferentiated stem cells more than one-year periods. Also, we can now maintain primate ES cells without feeder cells for a limited period.
  3. Development of gene transfection methods for primate ES cells. Primate ES cells are very sensitive to various stresses. We have developed reliable methods of electroporation and drug selection to produce ES cell lines with integrated transgenes.
  4. Analysis of maintenance mechanisms of undifferentiated status in primate ES cells, focused on LIF/STAT3 signaling. We have made clear that such signaling pathways are very different between primate and mouse ES cells.
  5. Preclinical investigation using monkey ES cell. We have carried out collaboration research with neurosurgeon group of Kyoto University Hospital. We have produced dopaminergic neurons from cynomolgus monkey ES cells and transplanted into brains of Parkinson disease model monkeys. They showed improvement of symptoms. This was recognized worldwide as the first success in treating Parkinson disease of monkeys using ES cells.

10. Key Words

( 1 ) ES cells ( 2 ) stem cells ( 3 ) regenerative medicine
( 4 ) cell differentiation ( 5 ) cell culture ( 6 ) embryonic stem cells
( 7 ) ( 8 ) ( 9 )
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