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

PLoS Biol. 2020 May 13;18(5):e3000705. doi: 10.1371/journal.pbio.3000705. eCollection 2020 May.


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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques*
  • Embryonic Stem Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Induced Pluripotent Stem Cells
  • Mice, Inbred NOD
  • Mice, SCID
  • Neurogenesis*
  • Organoids / blood supply*
  • Organoids / metabolism
  • Organoids / transplantation
  • Telencephalon / embryology*

Grants and funding

This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16020601, XDB32010100) to XW, National Basic Research Program of China (2019YFA0110101 and 2017YFA0103303 to XW; 2017YFA0102601 to QW), the National Natural Science Foundation of China (31671072 to QW; 31771140 and 81891001 to XW), and the Grants of Beijing Brain Initiative of Beijing Municipal Science & Technology Commission (Z181100001518004) to XW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.