Neural stem/precursor cells derived from human midbrain organoids stably yield midbrain-type dopamine neurons for Parkinson's disease therapy
- Title
- Neural stem/precursor cells derived from human midbrain organoids stably yield midbrain-type dopamine neurons for Parkinson's disease therapy
- Author
- 우혜지
- Alternative Author(s)
- 우혜지
- Advisor(s)
- 이상훈
- Issue Date
- 2022. 2
- Publisher
- 한양대학교
- Degree
- Doctor
- Abstract
- 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.
- URI
- http://hanyang.dcollection.net/common/orgView/200000589658https://repository.hanyang.ac.kr/handle/20.500.11754/167702
- Appears in Collections:
- GRADUATE SCHOOL OF BIOMEDICAL SCIENCE AND ENGINEERING[S](의생명공학전문대학원) > BIOMEDICAL SCIENCE(의생명과학과) > Theses (Ph.D.)
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