Generation of homogeneous midbrain organoids with in vivo<i>-</i>like cellular composition facilitates neurotoxin-based Parkinson's disease modeling
Tae Hwan Kwak, Ji Hyun Kang, Sai Hali, Jonghun Kim, Kee-Pyo Kim, Chanhyeok Park, Ju‐Hyun Lee, Ha Kyun Ryu, Ji Eun Na, Junghyun Jo, H. Shawn Je, Huck‐Hui Ng, Jeongwoo Kwon, Nam‐Hyung Kim, Kwon Ho Hong, Woong Sun, Chi Hye Chung, Im Joo Rhyu, Dong Wook Han
Abstract
Recent studies have demonstrated the generation of midbrain-like organoids (MOs) from human pluripotent stem cells. However, the low efficiency of MO generation and the relatively immature and heterogeneous structures of the MOs hinder the translation of these organoids from the bench to the clinic. Here we describe the robust generation of MOs with homogeneous distribution of midbrain dopaminergic (mDA) neurons. Our MOs contain not only mDA neurons but also other neuronal subtypes as well as functional glial cells, including astrocytes and oligodendrocytes. Furthermore, our MOs exhibit mDA neuron-specific cell death upon treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, indicating that MOs could be a proper human model system for studying the in vivo pathology of Parkinson's disease (PD). Our optimized conditions for producing homogeneous and mature MOs might provide an advanced patient-specific platform for in vitro disease modeling as well as for drug screening for PD.