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Guided self-organization and cortical plate formation in human brain organoids.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Lancaster, Madeline A 
Corsini, Nina S 
Wolfinger, Simone 
Gustafson, E Hilary 
Phillips, Alex W 

Abstract

Three-dimensional cell culture models have either relied on the self-organizing properties of mammalian cells or used bioengineered constructs to arrange cells in an organ-like configuration. While self-organizing organoids excel at recapitulating early developmental events, bioengineered constructs reproducibly generate desired tissue architectures. Here, we combine these two approaches to reproducibly generate human forebrain tissue while maintaining its self-organizing capacity. We use poly(lactide-co-glycolide) copolymer (PLGA) fiber microfilaments as a floating scaffold to generate elongated embryoid bodies. Microfilament-engineered cerebral organoids (enCORs) display enhanced neuroectoderm formation and improved cortical development. Furthermore, reconstitution of the basement membrane leads to characteristic cortical tissue architecture, including formation of a polarized cortical plate and radial units. Thus, enCORs model the distinctive radial organization of the cerebral cortex and allow for the study of neuronal migration. Our data demonstrate that combining 3D cell culture with bioengineering can increase reproducibility and improve tissue architecture.

Description

Keywords

Batch Cell Culture Techniques, Cells, Cultured, Guided Tissue Regeneration, Humans, Neural Stem Cells, Neurogenesis, Organ Culture Techniques, Organoids, Prosencephalon, Tissue Engineering

Journal Title

Nature Biotechnology

Conference Name

Journal ISSN

1087-0156
1546-1696

Volume Title

35

Publisher

Nature Research

Rights

All rights reserved
Sponsorship
Wellcome Trust (101052/Z/13/Z)
Medical Research Council (MR/L023784/2)
Medical Research Council (MR/L023784/1)