Journal Article

Vascularized human cortical organoids (vOrganoids) model cortical development in vivo

Guo, Lijie, Shi, Yingchao, Ge, Woo-Ping, Wu, Qian, Liu, Jianwei, Zhong, Suijuan, Wang, Mengdi, Chen, Ruiguo, Fang, Ai, Sun, Le, Li, Rui, Wang, Xiaoqun, Li, Peng

2020

Overview

Modeling the processes of neuronal progenitor proliferation and differentiation to produce mature cortical neuron subtypes is essential for the study of human brain development and the search for potential cell therapies. We demonstrated a novel paradigm for the generation of vascularized organoids (vOrganoids) consisting of typical human cortical cell types and a vascular structure for over 200 days as a vascularized and functional brain organoid model. The observation of spontaneous excitatory postsynaptic currents (sEPSCs), spontaneous inhibitory postsynaptic currents (sIPSCs), and bidirectional electrical transmission indicated the presence of chemical and electrical synapses in vOrganoids. More importantly, single-cell RNA-sequencing analysis illustrated that vOrganoids exhibited robust neurogenesis and that cells of vOrganoids differentially expressed genes (DEGs) related to blood vessel morphogenesis. The transplantation of vOrganoids into the mouse S1 cortex resulted in the construction of functional human-mouse blood vessels in the grafts that promoted cell survival in the grafts. This vOrganoid culture method could not only serve as a model to study human cortical development and explore brain disease pathology but also provide potential prospects for new cell therapies for nervous system disorders and injury.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Animals / Artificial organs / Biology and Life Sciences / Biophysics / Blood / Blood vessels / Brain / Brain diseases / Brain research / Cell culture / Cell Culture Techniques / Cell survival / Cortical columns / Electrical transmission / Embryonic Stem Cells / Engineering and Technology / Excitatory postsynaptic potentials / Gene sequencing / Human Umbilical Vein Endothelial Cells / Humans / Induced Pluripotent Stem Cells / Inhibitory postsynaptic potentials / Laboratories / Medicine and Health Sciences / Methods / Methods and Resources / Mice, Inbred NOD / Mice, SCID / Morphogenesis / Nervous system / Neurogenesis / Neurosciences / Organoids / Organoids - blood supply / Organoids - metabolism / Organoids - transplantation / Research and Analysis Methods / Ribonucleic acid / RNA / Sequence analysis / Stem cells / Supervision / Synapses / Telencephalon - embryology / Transplantation / Vascular grafts