Human IPSC-derived model to study myelin disruption

Megan Chesnut, Hélène Paschoud, Cendrine Repond, Lena Smirnova, Thomas Hartung, Marie Gabrielle Zurich, Helena T. Hogberg, David Pamies

Research output: Contribution to journalArticlepeer-review


Myelin is of vital importance to the central nervous system and its disruption is related to a large number of both neurodevelopmental and neurodegenerative diseases. The differences ob-served between human and rodent oligodendrocytes make animals inadequate for modeling these diseases. Although developing human in vitro models for oligodendrocytes and myelinated axons has been a great challenge, 3D cell cultures derived from iPSC are now available and able to partially reproduce the myelination process. We have previously developed a human iPSC-derived 3D brain organoid model (also called BrainSpheres) that contains a high percentage of myelinated axons and is highly reproducible. Here, we have further refined this technology by applying multiple readouts to study myelination disruption. Myelin was assessed by quantifying immunostaining/confocal mi-croscopy of co-localized myelin basic protein (MBP) with neurofilament proteins as well as prote-olipid protein 1 (PLP1). Levels of PLP1 were also assessed by Western blot. We identified compounds capable of inducing developmental neurotoxicity by disrupting myelin in a systematic review to evaluate the relevance of our BrainSphere model for the study of the myelination/demye-lination processes. Results demonstrated that the positive reference compound (cuprizone) and two of the three potential myelin disruptors tested (Bisphenol A, Tris(1,3-dichloro-2-propyl) phosphate, but not methyl mercury) decreased myelination, while ibuprofen (negative control) had no effect. Here, we define a methodology that allows quantification of myelin disruption and provides reference compounds for chemical-induced myelin disruption.

Original languageEnglish (US)
Article number9473
JournalInternational journal of molecular sciences
Issue number17
StatePublished - Sep 1 2021


  • Developmental diseases
  • Developmental neurotoxicity
  • Myelin
  • Neurotoxicity
  • Oligodendrocytes
  • Organoid
  • Organotypic

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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