Production of highly uniform midbrain organoids from human pluripotent stem cells

Abstract

Brain organoids have been considered as an advanced platform for in vitro disease modeling and drug screening, but numerous roadblocks exist, such as lack of large-scale production technology and lengthy protocols with multiple manipulation steps, impeding the industrial translation of brain organoid technology. Here, we describe the high-speed and large-scale production of midbrain organoids using a high-throughput screening-compatible platform within 30 days. Micro midbrain organoids (μMOs) exhibit a highly uniform morphology and gene expression pattern with minimal variability. Notably, μMOs show dramatically accelerated maturation, resulting in the generation of functional μMOs within only 30 days of differentiation. Furthermore, individual μMOs display highly consistent responsiveness to neurotoxin, suggesting their usefulness as an in vitro high-throughput drug toxicity screening platform. Collectively, our data indicate that μMO technology could represent an advanced and robust platform for in vitro disease modeling and drug screening for human neuronal diseases.