International Journal of Stem Cells : eISSN 2005-5447

Table. 2.

Table. 2.

Disease model studies of developmental and degenerative disorders using brain organoids

Disease Cell Dedifferentiation/
gene editing/
disease induction
Organoid type Phenotype Reference
Microcephaly
(MCPH)
Patient-derived fibroblasts Dedifferentiation using lentiviral OSKM Whole-brain organoid Small organoid size
Immature neural differentiation
Lancaster et al., 2013 (31)
Patient-derived fibroblasts Dedifferentiation using retroviral OSKM Cerebral cortex organoid Incomplete neuroepithelial structure
Small organoid size
Reduced vRG and oRG cell count
Immature neurons
Li et al., 2017 (47)
Embryonic stem cells ZIKA virus infection Whole-brain organoid Increased apoptosis
Reduced stem cell self-renewal
Collapse of the neuroepithelium
Cugola et al., 2016 (50)
Pluripotent stem cells ZIKA virus infection Cerebral cortex organoid Small organoid size
Increased apoptosis
Qian et al., 2016 (51)
Autism spectrum disorder (ASD) Patient-derived fibroblasts Dedifferentiation using retroviral OSKM Forebrain organoid Increased FOXG1 expression
Increased GABAergic inhibitory neurons
Mariani et al., 2015 (52)
Patient-derived fibroblasts CHD9 knockout by gene editing Whole-brain organoid Abnormal DLX expression
Increased GABAergic inhibitory neurons
Wang et al., 2017 (53)
CNTNAP2- knockout mouse fibroblasts Dedifferentiation using retroviral OSKM Whole-brain organoid Increased GABAergic inhibitory neurons Hali et al., 2020 (54)
Rett’s syndrome
(RTT)
Patient-derived fibroblasts Dedifferentiation using retroviral OSKM Whole-brain organoid Abnormal miR-199 and miR0214 expression
Abnormal migration of neural progenitor cells
Mellios et al., 2018 (55)
Embryonic stem cells MECP2 gene knockout and insertion Cerebral cortex organoid, medial ganglionic eminence organoid Deformity and dysfunction of GABAergic inhibitory neurons Xiang et al., 2020 (56)
Patient-derived fibroblasts Dedifferentiation using retroviral OSKM Dorsal forebrain - ventral forebrain assembloid Abnormal tangential migration of interneurons Gomes et al., 2020 (57)
Timothy syndrome (TS) Patient-derived fibroblasts Dedifferentiation using retroviral OSKM Cerebral cortex - corpus striatum assembloid Abnormal tangential migration of interneurons Birey et al., 2017 (74)
Down syndrome
(DS)
Patient-derived fibroblasts Sendai virus-based OSKM Forebrain organoid Overproduction of OLIG2-positive progenitors
Overproduction of GABAergic inhibitory neurons
Xu et al., 2019 (58)
Patient-derived fibroblasts Sendai virus-based OSKM Whole-brain organoid Small organoid size
Abnormal DSCAM/PAK1 signaling
Decreased neurogenesis
Tang et al., 2021 (59)
Alzheimer’s disease (AD) Pluripotent stem cells PSEN2 mutation correction through gene editing Whole-brain organoid Small organoid size
High Aβ42/Aβ40 ratio
Abnormal Ca2 homeostasis
Excessive neuron activation
Yin and VanDongen, 2021 (62)
Patient-derived fibroblasts Dedifferentiation using an episomal vector Whole-brain organoid Increased apoptosis
Synaptic dysfunction
Increased amyloid beta
Increased phosphorylated tau
Zhao et al., 2020 (63)
Pluripotent stem cells PITRM1 gene knockout through gene editing Whole-brain organoid Synaptic dysfunction
Amyloid beta aggregation
Tau plaque formation
Pérez et al., 2021 (64)
Parkinson’s disease (PD) Patient-derived fibroblasts Dedifferentiation using a lentiviral OSKM Midbrain organoid Increased sensitivity to toxicity
Increased alpha synuclein
Increased thioflavin T-positive cells
Kim et al., 2019 (66)
Embryonic stem cells GBA1 knockout and SNCA overexpression through gene editing Midbrain organoid Accumulation of Lew bodies Jo et al., 2021 (67)

vRG: ventricular radial glia, oRG: outer radial glia.

International Journal of Stem Cells 2024;17:158-81 https://doi.org/10.15283/ijsc24056
© 2024 International Journal of Stem Cells