A human brain microphysiological system derived from induced pluripotent stem cells to study neurological diseases and toxicity

Main Article Content

David Pamies
Paula Barreras
Katharina Block
Georgia Makri
Anupama Kumar
Daphne Wiersma
Lena Smirnova
Ce Zhang
Joseph Bressler
Kimberly M. Christian
Georgina Harris
Guo-li Ming
Cindy J. Berlinicke
Kelly Kyro
Hongjun Song
Carlos A. Pardo
Thomas Hartung
Helena T. Hogberg

Abstract

Human in vitro models of brain neurophysiology are needed to investigate molecular and cellular mechanisms associated with neurological disorders and neurotoxicity. We have developed a reproducible iPSC-derived human 3D brain microphysiological system (BMPS), comprised of differentiated mature neurons and glial cells (astrocytes and oligodendrocytes) that reproduce neuronal-glial interactions and connectivity. BMPS mature over eight weeks and show the critical elements of neuronal function: synaptogenesis and neuron-to-neuron (e.g., spontaneous electric field potentials) and neuronal-glial interactions (e.g., myelination), which mimic the microenvironment of the central nervous system, rarely seen in vitro before. The BMPS shows 40% overall myelination after 8 weeks of differentiation. Myelin was observed by immunohistochemistry and confirmed by confocal microscopy 3D reconstruction and electron microscopy. These findings are of particular relevance since myelin is crucial for proper neuronal function and development. The ability to assess oligodendroglial function and mechanisms associated with myelination in this BMPS model provide an excellent tool for future studies of neurological disorders such as multiple sclerosis and other demyelinating diseases. The BMPS provides a suitable and reliable model to investigate neuron-neuroglia function as well as pathogenic mechanisms in neurotoxicology.

Article Details

How to Cite
Pamies, D., Barreras, P., Block, K., Makri, G., Kumar, A., Wiersma, D., Smirnova, L., Zhang, C., Bressler, J., Christian, K., Harris, G., Ming, G.- li, Berlinicke, C., Kyro, K., Song, H., Pardo, C., Hartung, T. and Hogberg, H. (2017) “A human brain microphysiological system derived from induced pluripotent stem cells to study neurological diseases and toxicity”, ALTEX - Alternatives to animal experimentation, 34(3), pp. 362-376. doi: 10.14573/altex.1609122.
Section
Articles

Most read articles by the same author(s)