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Andreas Heuer

Andreas Heuer

Research team manager

Andreas Heuer

Predictive Markers Guide Differentiation to Improve Graft Outcome in Clinical Translation of hESC-Based Therapy for Parkinson's Disease

Author

  • Agnete Kirkeby
  • Sara Nolbrant
  • Katarina Tiklova
  • Andreas Heuer
  • Nigel Kee
  • Tiago Cardoso
  • Daniella Rylander Ottosson
  • Mariah J. Lelos
  • Pedro Rifes
  • Stephen B Dunnett
  • Shane Grealish
  • Thomas Perlmann
  • Malin Parmar
Show all

Summary, in English

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.

Department/s

  • Human Neural Developmental Biology
  • Stem Cell Center
  • Developmental and Regenerative Neurobiology
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
  • MultiPark: Multidisciplinary research focused on Parkinson´s disease

Publishing year

2017-01-05

Language

English

Pages

135-148

Publication/Series

Cell Stem Cell

Volume

20

Issue

1

Document type

Journal article

Publisher

Cell Press

Topic

  • Neurosciences
  • Neurology

Keywords

  • diencephalon
  • dopaminergic neurons
  • FGF8
  • GMP
  • good manufacturing practice
  • hESCs
  • human embryonic stem cells
  • MHB
  • midbrain-hindbrain boundary
  • Parkinson's disease
  • STN
  • subthalamic nucleus
  • transplantation
  • ventral midbrain
  • VM

Status

Published

Research group

  • Human Neural Developmental Biology
  • Developmental and Regenerative Neurobiology

ISBN/ISSN/Other

  • ISSN: 1934-5909