Neural stem cells derived from human midbrain organoids as a stable source for treating Parkinson’s disease
| Autor: | Minji Kang, Noviana Wulansari, Soo Hyun Kim, Sang Hun Lee, Hyun Seob Lee, Hyung Sun Kim, Jae Jin Song, Jangbeen Kyung, Wongyoung Lee, Seung Won Kim, Su Jeong Choi, Sang Myun Park, Han Na Suh, Ki Hean Kim, Hye Ji Woo, Se-Young Choi, Sung Hyun Kim, Kim Eunhee, Jungbin Lee, Jinhee Yang, Won Hyuk Jang, Mi Yoon Chang |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
General Neuroscience Biology Neural stem cell Cell biology Transplantation Cell therapy 03 medical and health sciences Astrocyte differentiation 030104 developmental biology 0302 clinical medicine nervous system Precursor cell Organoid Stem cell Induced pluripotent stem cell Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Progress in Neurobiology. 204:102086 |
| ISSN: | 0301-0082 |
| Popis: | Successful clinical translation of stem cell-based therapy largely relies on the scalable and reproducible preparation of donor cells with potent therapeutic capacities. In this study, midbrain organoids were yielded from human pluripotent stem cells (hPSCs) to prepare cells for Parkinson's disease (PD) therapy. Neural stem/precursor cells (NSCs) isolated from midbrain organoids (Og-NSCs) expanded stably and differentiated into midbrain-type dopamine(mDA) neurons, and an unprecedentedly high proportion expressed midbrain-specific factors, with relatively low cell line and batch-to-batch variations. Single cell transcriptome analysis followed by in vitro assays indicated that the majority of cells in the Og-NSC cultures are ventral midbrain (VM)-patterned with low levels of cellular senescence/aging and mitochondrial stress, compared to those derived from 2D-culture environments. Notably, in contrast to current methods yielding mDA neurons without astrocyte differentiation, mDA neurons that differentiated from Og-NSCs were interspersed with astrocytes as in the physiologic brain environment. Thus, the Og-NSC-derived mDA neurons exhibited improved synaptic maturity, functionality, resistance to toxic insults, and faithful expressions of the midbrain-specific factors, in vitro and in vivo long after transplantation. Consequently, Og-NSC transplantation yielded potent therapeutic outcomes that are reproducible in PD model animals. Collectively, our observations demonstrate that the organoid-based method may satisfy the demands needed in the clinical setting of PD cell therapy. |
| Databáze: | OpenAIRE |
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