Biotechnology

Neuroscience

In vivo

Biology

Gene

Induced pluripotent stem cell

Embryonic stem cell

Neural stem cell

Immunology

Human brain

Inflammation

Stem cell

Microglia

Organoid

Cell biology

Gliogenesis

Optogenetics

Biochemistry

Nature Biotechnology

Human cerebral organoids undergo vascularization and maturation in the mouse brain. 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.

An in vivo model of functional and vascularized human brain organoids