Predictive Markers Guide Differentiation to Improve Graft Outcome in Clinical Translation of hESC-Based Therapy for Parkinson’s Disease
Kirkeby A., Nolbrant S., Tiklova K., Heuer A., Kee N., Cardoso T., Rylander Ottosson D., Lelos M.J., Rifes P., Dunnett S.B., Grealish S., Perlmann T., Parmar M.
Cell Stem Cell, 2016
Here, the authors developed a good manufacturing practice (GMP) differentiation protocol for the highly efficient and reproducible production of transplantable dopamine progenitors from hESCs on laminin-111. They identified predictive markers expressed in dopamine neuron progenitors that correlate with graft outcome in an animal model of Parkinson’s disease. Timed FGF8b resulted in a high yield of caudal VM cells and good graft outcomes correlate with markers of caudal VM and MHB. Commonly used markers did not accurately predict in vivo subtype-specific maturation. Instead, we identified a specific set of markers associated with the caudal midbrain that correlate with high dopaminergic yield after transplantation in vivo. Using these markers, a GMP-adapted dopamine differentiation protocol was developed.
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