Reproducible generation of human midbrain organoids for in vitro modeling of Parkinson's disease

Sarah Louise Nickels, Jennifer Modamio, Bárbara Mendes-Pinheiro, Anna Sophia Monzel, Fay Betsou, Jens Christian Schwamborn*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

32 Citations (Scopus)

Abstract

The study of human midbrain development and midbrain related diseases, like Parkinson's disease (PD), is limited by deficiencies in the currently available and validated laboratory models. Three dimensional midbrain organoids represent an innovative strategy to recapitulate some aspects of the complexity and physiology of the human midbrain. Nevertheless, also these novel organoid models exhibit some inherent weaknesses, including the presence of a necrotic core and batch-to-batch variability. Here we describe an optimized approach for the standardized generation of midbrain organoids that addresses these limitations, while maintaining key features of midbrain development like dopaminergic neuron and astrocyte differentiation. Moreover, we have established a novel time-efficient, fit for purpose analysis pipeline and provided proof of concept for its usage by investigating toxin induced PD.

Original languageEnglish
Article number101870
JournalStem Cell Research
Volume46
DOIs
Publication statusPublished - Jul 2020

Keywords

  • Brain organoid
  • Midbrain
  • Parkinson's disease
  • Standardization
  • in vitro disease modeling

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