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

2017; Nature Portfolio; Volume: 35; Issue: 7 Linguagem: Inglês

10.1038/nbt.3906

1546-1696

Madeline A. Lancaster, Nina S. Corsini, Simone Wolfinger, E. Hilary Gustafson, Alexander William Phillips, Thomas R. Burkard, Tomoki Otani, Frederick J. Livesey, Juergen A. Knoblich,

Neurogenesis and neuroplasticity mechanisms

Engineering human brain organoids with floating scaffolds enhances the maturity and reproducibility of cortical tissue structure. Three-dimensional cell culture models have either relied on the self-organizing properties of mammalian cells1,2,3,4,5,6 or used bioengineered constructs to arrange cells in an organ-like configuration7,8. 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.