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Predictive Markers Guide Differentiation to Improve Graft Outcome in Clinical Translation of hESC-Based Therapy for Parkinson's Disease
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- Kirkeby, Agnete (author)
- Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Human neural utvecklingsbiologi,Developmental and Regenerative Neurobiology,Lund University Research Groups,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Human Neural Developmental Biology
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- Nolbrant, Sara (author)
- Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Developmental and Regenerative Neurobiology,Lund University Research Groups,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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- Tiklova, Katarina (author)
- Karolinska Institute
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- (creator_code:org_t)
- Elsevier BV, 2017
- 2017
- English 14 s.
- In: Cell Stem Cell. - : Elsevier BV. - 1934-5909 .- 1875-9777. ; 20:1, s. 135-148
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- 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
Publication and Content Type
- art (subject category)
- ref (subject category)
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- Kirkeby, Agnete
- Nolbrant, Sara
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- Heuer, Andreas
- Kee, Nigel
- Cardoso, Tiago
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- Ottosson, Daniel ...
- Lelos, Mariah J.
- Rifes, Pedro
- Dunnett, Stephen ...
- Grealish, Shane
- Perlmann, Thomas
- Parmar, Malin
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