Dept. of Clinical Application
Jun Takahashi (Professor)
Jun Takahashi M.D., Ph.D.
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We aim at the development of cell replacement therapy using iPS cells for intractable neurological diseases, mainly Parkinson's disease, for which clinical experience has been accumulated by the transplantation of fetal midbrain substantia nigra cells, and its effect and problems have been clarified. We have performed studies on the improvement of neuropathic symptoms by the induction of dopamine-producing neurons using ES cells and cell transplantation in model animals, and found that the motor function could be improved by the transplantation of cynomolgus monkey ES cells and induction of dopamine-producing nerves in a monkey Parkinson's disease model, and the transplantation of nervous system cells selected following differentiation induction inhibited tumor formation. There are many problems to be overcome to clinically apply cell transplantation using ES and iPS cells, and these are being resolved one by one: 1) the neural induction involving no animal-derived factors, 2) selection of cells to inhibit tumor formation, 3) inhibition of cell death and immunosuppression following transplantation, 4) and establishment of assessment systems to confirm the long-term effects and safety. Since we have already performed dopamine-producing nerve induction from human ES cells and its transplantation into a cynomolgus monkey model, behavioral analysis, and imaging analysis, firstly, we will optimize conditions for neural induction from human iPS cells, and confirm the safety in the primate model.
Induction of dopaminergic neurons from
Human iPS cell and transplantation to primate model
|Human iPS cell-derived dopaminergic neurons
Red : tyrosine hydroxylase positive
Green : positive cells of Tuj-1 which is general neural marker