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Predictive markers guide differentiation to improve graft outcome in clinical translation of hESC-based therapy for Parkinson's Disease

Kirkeby, Agnete, Nolbrant, Sara, Tiklova, Katarina, Heuer, Andreas, Kee, Nigel, Cardoso, Tiago, Ottosson, Daniella Rylander, Lelos, Mariah Jillian, Rifes, Pedro, Dunnett, Stephen Bruce, Grealish, Shane, Perlmann, Thomas and Parmar, Malin 2017. Predictive markers guide differentiation to improve graft outcome in clinical translation of hESC-based therapy for Parkinson's Disease. Cell Stem Cell 20 (1) , pp. 135-148. 10.1016/j.stem.2016.09.004

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Abstract

Stem cell treatments for neurodegenerative diseases are expected to reach clinical trials soon. Most of the approaches currently under development involve transplantation of immature progenitors that subsequently undergo phenotypic and functional maturation in vivo, and predicting the long-term graft outcome already at the progenitor stage remains a challenge. Here, we took an unbiased approach to identify predictive markers expressed in dopamine neuron progenitors that correlate with graft outcome in an animal model of Parkinson’s disease through gene expression analysis of >30 batches of grafted human embryonic stem cell (hESC)-derived progenitors. We found that many of the 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, we developed a good manufacturing practice (GMP) differentiation protocol for highly efficient and reproducible production of transplantable dopamine progenitors from hESCs.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Additional Information: This is an open access article under the CC BY-NC-ND license
Publisher: Elsevier
ISSN: 1934-5909
Date of First Compliant Deposit: 18 April 2018
Date of Acceptance: 15 September 2016
Last Modified: 15 Jul 2019 11:53
URI: http://orca.cf.ac.uk/id/eprint/99434

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