Andrews, W;
(2019)
Large-Scale Generation and Characterization of Homogeneous Populations of Migratory Cortical Interneurons from Human Pluripotent Stem Cells.
Molecular Therapy. Methods & Clinical Development
, 13
pp. 414-430.
10.1016/j.omtm.2019.04.002.
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Abstract
During development, cortical interneurons (cINs) are generated from the ventral telencephalon, robustly migrate to the dorsal telencephalon, make local synaptic connections, and critically regulate brain circuitry by inhibiting other neurons. Thus, their abnormality is associated with various brain disorders. Human pluripotent stem cell (hPSC)-derived cINs can provide unlimited sources with which to study the pathogenesis mechanism of these disorders as well as provide a platform to develop novel therapeutics. By employing spinner culture, we could obtain a >10-fold higher yield of cIN progenitors compared to conventional culture without affecting their phenotype. Generated cIN spheres can be maintained feeder-free up to 10 months and are optimized for passaging and cryopreservation. In addition, we identified a combination of chemicals that synchronously matures generated progenitors into SOX6+KI67− migratory cINs and extensively characterized their maturation in terms of metabolism, migration, arborization, and electrophysiology. When transplanted into mouse brains, chemically matured migratory cINs generated grafts that efficiently disperse and integrate into the host circuitry without uncontrolled growth, making them an optimal cell population for cell therapy. Efficient large-scale generation of homogeneous migratory cINs without the need of feeder cells will play a critical role in the full realization of hPSC-derived cINs for development of novel therapeutics.
| Type: | Article |
|---|---|
| Title: | Large-Scale Generation and Characterization of Homogeneous Populations of Migratory Cortical Interneurons from Human Pluripotent Stem Cells |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.omtm.2019.04.002 |
| Publisher version: | https://doi.org/10.1016/j.omtm.2019.04.002 |
| Language: | English |
| Additional information: | © 2019 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | cortical interneurons, GABA, human pluripotent stem cells, differentiation, transplantation, maturation, migration |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10075865 |
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