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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Karolinska Institute
  • Cardiff University
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurovetenskaper
  • Neurologi

Nyckelord

Originalspråkengelska
Sidor (från-till)135-148
Antal sidor14
TidskriftCell Stem Cell
Volym20
Utgåva nummer1
StatusPublished - 2017 jan 5
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

Sara Nolbrant, 2020, Lund: Lund University, Faculty of Medicine. 102 s.

Forskningsoutput: AvhandlingDoktorsavhandling (monografi)

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