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Nat Biotechnol. 2018 Jun;36(5):432-441. doi: 10.1038/nbt.4127. Epub 2018 Apr 16.

An in vivo model of functional and vascularized human brain organoids.

Author information

1
Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California, USA.
2
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California, USA.
3
Department of Biology, San Diego State University, San Diego, California, USA.

Abstract

Differentiation of human pluripotent stem cells to small brain-like structures known as brain organoids offers an unprecedented opportunity to model human brain development and disease. To provide a vascularized and functional in vivo model of brain organoids, we established a method for transplanting human brain organoids into the adult mouse brain. Organoid grafts showed progressive neuronal differentiation and maturation, gliogenesis, integration of microglia, and growth of axons to multiple regions of the host brain. In vivo two-photon imaging demonstrated functional neuronal networks and blood vessels in the grafts. Finally, in vivo extracellular recording combined with optogenetics revealed intragraft neuronal activity and suggested graft-to-host functional synaptic connectivity. This combination of human neural organoids and an in vivo physiological environment in the animal brain may facilitate disease modeling under physiological conditions.

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PMID:
29658944
DOI:
10.1038/nbt.4127

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