Human iPSC-derived model to study myelin disruption
2021
Johns Hopkins Bloomberg School of Public Health, Baltimore, USA(1)
University of Lausanne, Lausanne, Switzerland(2)
University of Lausanne, Lausanne, Switzerland(2)
Myelin is critically important in the central nervous system, and its disruption is associated with a variety of neurological and neurodegenerative diseases. Recently, 3D cell cultures derived from human iPSC have become available that can partially reproduce the myelination process. Here, the researchers further refine a human iPSC-derived 3D brain organoid model ("BrainSpheres") that contains a high percentage of myelinated axons by using multiple measurement methods to study myelination disruption. Myelination was assessed by quantification of immunostaining/confocal microscopy of colocalized myelin-based protein (MBP) with neurofilament proteins as well as proteolipid protein 1 (PLP1). Levels of PLP1 were also determined by Western blot. To evaluate the relevance of the BrainSphere model for the study of myelination and demyelination processes, compounds capable of inducing developmental neurotoxicity by disrupting myelin are used. The results show that the positive reference compound (cuprizone) and two of the three potential myelin disruptors tested decreased myelination, while ibuprofen (negative control) had no effect. Thus, the presented method allows quantification of myelin disruption and provides reference substances for chemically induced myelin disruption.
Human iPSC-derived model to study myelin disruption
Helena T. Hogberg(1), David Pamies(2)
Added on: 10-06-2021
[1] https://www.mdpi.com/1422-0067/22/17/9473
