A Human 3D neural assembloid model for SARS-CoV-2 infection

Abstract

Clinical evidence suggests the central nervous system (CNS) is frequently impacted by SARS-CoV-2 infection, either directly or indirectly, although mechanisms remain unclear. Pericytes are perivascular cells within the brain that are proposed as SARS-CoV-2 infection points1. Here we show that pericyte-like cells (PLCs), when integrated into a cortical organoid, are capable of infection with authentic SARS-CoV-2. Prior to infection, PLCs elicited astrocytic maturation and production of basement membrane components, features attributed to pericyte functions in vivo. While traditional cortical organoids showed little evidence of infection, PLCs within cortical organoids served as viral replication hubs, with virus spreading to astrocytes and mediating inflammatory type I interferon transcriptional responses. Therefore, PLC-containing cortical organoids (PCCOs) represent a new assembloid model2 that supports SARS-CoV-2 entry and replication in neural tissue, and PCCOs serve as an experimental model for neural infection.

Engineering Human Brain Assembloids by Microfluidics

“…[6][7][8] To date, many assembloids including brain-colorectal assembloids, [9] cortico-striatal assembloids, [10] integrated forebrain assembloids, [11] cortical-motor assembloids, [12] and brain-pituitary gland assembloids [13] have been generated for etiology research, disease modeling, and drug development. [14] Despite the great progress, the wide applications of current assembloid models have been greatly limited due to tedious operations, high heterogeneity, and variable reproducibility. [1,[15][16][17] Additionally, the techniques to effectively assemble brain organoids have been poorly explored, [18] not to mention the controlled assembling of multiple organoids and investigation of complex cellular interactions in the brain.…”