Stem cell-derived astrocytes: are they physiologically credible?

Eric Hill*, David Nagel, Rheinallt Parri, Michael Coleman

*Corresponding author for this work

Research output: Contribution to journalBook/Film/Article reviewpeer-review

Abstract

Astrocytes are now increasingly acknowledged as having fundamental and sophisticated roles in brain function and dysfunction. Unravelling the complex mechanisms that underlie human brain astrocyte-neuron interactions is therefore an essential step on the way to understanding how the brain operates. Insights into astrocyte function to date, have almost exclusively been derived from studies conducted using murine or rodent models. Whilst these have led to significant discoveries, preliminary work with human astrocytes has revealed a hitherto unknown range of astrocyte types with potentially greater functional complexity and increased neuronal interaction with respect to animal astrocytes. It is becoming apparent, therefore, that many important functions of astrocytes will only be discovered by direct physiological interrogation of human astrocytes. Recent advancements in the field of stem cell biology have provided a source of human based models. These will provide a platform to facilitate our understanding of normal astrocyte functions as well as their role in CNS pathology. A number of recent studies have demonstrated that stem cell derived astrocytes exhibit a range of properties, suggesting that they may be functionally equivalent to their in vivo counterparts. Further validation against in vivo models will ultimately confirm the future utility of these stem-cell based approaches in fulfilling the need for human- based cellular models for basic and clinical research. In this review we discuss the roles of astrocytes in the brain and highlight the extent to which human stem cell derived astrocytes have demonstrated functional activities that are equivalent to that observed in vivo.
Original languageEnglish
Pages (from-to)6595-6606
Number of pages12
JournalJournal of Physiology
Volume594
Issue number22
Early online date4 Dec 2015
DOIs
Publication statusPublished - 15 Nov 2016

Bibliographical note

This is the peer reviewed version of the following article: Hill, E., Nagel, D., Parri, R., & Coleman, M. (2016). Stem cell-derived astrocytes: are they physiologically credible? Journal of Physiology, 594(22), 6595-6606, which has been published in final form at http://dx.doi.org/10.1113/JP270658. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

Funding: Alzheimer’s research UK (ART-PPG2009B-3 and ART-PG2007B-6) and BBSRC (BB/H008527/1).

Keywords

  • stem cells
  • astrocytes
  • neurons
  • metabolism
  • gliotransmission

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