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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)362-376
Number of pages15
JournalAltex
Volume34
Issue number3
DOIs
StatePublished - 2017

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Induced Pluripotent Stem Cells
Brain
Neuroglia
Neurons
Myelin Sheath
Nervous System Diseases
In Vitro Techniques
Neurophysiology
Oligodendroglia
Demyelinating Diseases
Confocal Microscopy
Astrocytes
Multiple Sclerosis
Electron Microscopy
Central Nervous System
Immunohistochemistry

Keywords

  • 3D culture
  • Brain
  • CNS
  • Microphysiological system
  • Myelination

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology
  • Medical Laboratory Technology

Cite this

A human brain microphysiological system derived from induced pluripotent stem cells to study neurological diseases and toxicity. / Pamies, David; Barreras, Paula; Block, Katharina; Makri, Georgia; Kumar, Anupama; Wiersma, Daphne; Smirnova, Lena; Zhang, Ce; Bressler, Joseph; Christian, Kimberly M.; Harris, Georgina; Ming, Guo Li; Berlinicke, Cindy J.; Kyro, Kelly; Song, Hongjun; Pardo, Carlos A.; Hartung, Thomas; Hogberg, Helena T.

In: Altex, Vol. 34, No. 3, 2017, p. 362-376.

Research output: Contribution to journalArticle

Pamies, David; Barreras, Paula; Block, Katharina; Makri, Georgia; Kumar, Anupama; Wiersma, Daphne; Smirnova, Lena; Zhang, Ce; Bressler, Joseph; Christian, Kimberly M.; Harris, Georgina; Ming, Guo Li; Berlinicke, Cindy J.; Kyro, Kelly; Song, Hongjun; Pardo, Carlos A.; Hartung, Thomas; Hogberg, Helena T. / A human brain microphysiological system derived from induced pluripotent stem cells to study neurological diseases and toxicity.

In: Altex, Vol. 34, No. 3, 2017, p. 362-376.

Research output: Contribution to journalArticle

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