An in vivo model of functional and vascularized human brain organoids

Abed Alfatah Mansour, J. Tiago Gonçalves, Cooper W. Bloyd, Hao Li, Sarah Fernandes, Daphne Quang, Stephen Johnston, Sarah L. Parylak, Xin Jin, Fred H. Gage

Research output: Contribution to journalArticle

206 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)432-441
Number of pages10
JournalNature biotechnology
Volume36
Issue number5
DOIs
StatePublished - Jun 1 2018

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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    Mansour, A. A., Gonçalves, J. T., Bloyd, C. W., Li, H., Fernandes, S., Quang, D., Johnston, S., Parylak, S. L., Jin, X., & Gage, F. H. (2018). An in vivo model of functional and vascularized human brain organoids. Nature biotechnology, 36(5), 432-441. https://doi.org/10.1038/nbt.4127