CNS organoids: an innovative tool for neurological disease modeling and drug neurotoxicity screening

Abstract

The paradigm of central nervous system (CNS) drug discovery has mostly relied on traditional approaches of rodent models or cell-based in vitro models. Owing to the issues of species differences between humans and rodents, it is difficult to correlate the robustness of data for neurodevelopmental studies. With advances in the stem-cell field, 3D CNS organoids have been developed and explored owing to their resemblance to the human brain architecture and functions. Further, CNS organoids provide a unique opportunity to mimic the human brain physiology and serve as a modeling tool to study the normal versus pathological brain or the elucidation of mechanisms of neurological disorders. Here, we discuss the recent application of a CNS organoid explored for neurodevelopment disease or a screening tool for CNS drug development.Teaser-3D cerebral organoids are a novel class of in vitro tool possessing a close resemblance to human brain architecture and function. They serve as a robust model to study early-stage neurodevelopment and CNS drug toxicity screening.

Drug screening model meets cancer organoid technology

“…Firstly, the drug screening of normal organoids and tumor organoids was extended to detect the drug toxicity and predict the prognosis of tumor patients [ 72 ]. For example, the organoids derived from the central nervous system were employed to detect the neurotoxicity of small molecular inhibitors [ 73 , 74 ]. After integrating the transcriptome data of organoid derived from Biliary Tract Carcinoma (BTC) and clinical data of BTC patients, Yoshimasa Saito et al discovered that SOX2, KLK6, and CPB2 were associated with BTC patients' prognosis [ 75 ].…”

Advancing Drug Discovery for Neurological Disorders Using iPSC-Derived Neural Organoids

“…Culturing cerebral organoids has enabled high-throughput screening to test genetic and chemical modifications on cellular phenotypes [ 2 ]. Quantification of these phenotypes has historically been a laborious process, involving painstaking manual work.…”

“…Organoids contain different cell types that self-organize through cell-sorting and spatially restricted lineage commitment, similarly to in vivo organs [ 1 ]. Different cell types have been used to generate organoids in vitro, including primary cultured cells from human tissues, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) [ 2 ]. iPSC cultures have provided invaluable information for modeling neurological and neuromuscular disorders [ 3 , 4 ].…”

Recent Advancements of Nanomedicine in Neurodegenerative Disorders Theranostics

“…Cerebral organoids have been widely used to model and study neurodegenerative diseases. [ 176 ] The 3D brain organoids with proper physico‐chemical signaling cues can help mimic patient specific tissue patterns. Induced pluripotent stem cells (iPSCs) based technologies can now be used to generate all types of neurons and model neurodegenerative diseases.…”