Table 1.
Organoid models generated for studying several neuropathological diseases.
| Organoid Type | Disease | Cell Type | Result | Reference |
|---|---|---|---|---|
| Cerebral Organoid | AD | iPSC | Modeling sporadic Alzheimer’s disease in human brain organoids under serum exposure | [204] |
| Cerebral Organoid | AD | hiPSC | Mechanisms of hyperexcitability in Alzheimer’s disease hiPSC-derived neurons and cerebral organoids vs. isogenic controls | [205] |
| Cerebral Organoid | AD | iPSC | Modeling amyloid beta and tau pathology in human cerebral organoids | [206] |
| Disease Stem Cell | AD | iPSC | Familial Alzheimer’s disease mutations in PSEN1 lead to premature human stem cell neurogenesis | [207] |
| Disease Stem Cell | AD | iPSC and hiPSC | iPSC-derived human microglia-like cells to study neurological diseases | [208] |
| Cerebral Organoid | AD | iPSC | APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer’s disease patients’ iPSC-derived cerebral organoids | [209] |
| Cerebral Organoid | AD | iPSC | A logical network-based drug-screening platform for Alzheimer’s disease representing pathological features of human brain organoids | [210] |
| Cerebral Organoid | AD | iPSC | Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer’s disease-like pathology in human cerebral organoids | [211] |
| Cerebral Organoid | AD | iPSC | Tau pathology epigenetically remodels the neuron-glial cross-talk in Alzheimer’s disease | [212] |
| Disease Stem Cell | AD | iPSC | APOE4 causes widespread molecular and cellular alterations associated with Alzheimer’s disease phenotypes in human iPSC-derived brain cell types | [95] |
| Disease Stem Cell | AD | iPSC | Type I interferon signaling drives microglial dysfunction and senescence in human iPSC models of Down syndrome and Alzheimer’s disease | [213] |
| Cerebral Organoid | AD | iPSC | Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models | [214] |
| Cerebral Organoid | PD | hiPSC | Modeling G2019S-LRRK2 sporadic Parkinson’s disease in 3D midbrain organoids | [215] |
| Cerebral Organoid | PD | hiPSC | Lewy body-like pathology and loss of dopaminergic neurons in midbrain organoids derived from familial Parkinson’s disease patient | [216] |
| Midbrain Organoid | PD | hiPSC | Human iPSC-derived midbrain organoids functionally integrate into striatum circuits and restore motor function in a mouse model of Parkinson’s disease | [217] |
| Neurospheres | PD | hiPSC and iPSC | Patient-derived three-dimensional cortical neurospheres to model Parkinson’s disease | [218] |
| Midbrain Organoid | PD | hiPSC and iPSC | Neurodevelopmental defects and neurodegenerative phenotypes in human brain organoids carrying Parkinson’s disease linked DNAJC6 mutations | [219] |
| Midbrain Organoid | PD | iPSC | Microglia integration into human midbrain organoids leads to increased neuronal maturation and functionality | [220] |
| Cerebral Organoid | PD | iPSC | Use of 3D organoids as a model to study idiopathic form of Parkinson’s disease | [221] |
| Cerebral Organoid | PD | iPSC | The Parkinson’s disease-associated mutation LRRK2-G2019S alters dopaminergic differentiation dynamics via NR2F1 | [222] |
| Cerebral Organoid | Rett syndrome | hiPSC | Identification of neural oscillations and epileptiform changes in human brain organoids | [223] |
| Cerebral Organoid | TLE | iPSC | Modeling genetic epileptic encephalopathies using brain organoids | [224] |
| Cerebral Organoid | TSC | hiPSC | Amplification of human interneuron progenitors promotes brain tumors and neurological defects | [225] |
| Motor neurons study | ALS | iPSC | Aberrant axon branching via Fos-B dysregulation in FUS-ALS motor neurons | [226] |
| Sensorimotor organoids | ALS | iPSC | Human sensorimotor organoids derived from healthy and amyotrophic lateral sclerosis stem cells form neuromuscular junctions | [99] |
| Cerebral Organoid | ALS | iPSC | Spinal cord extracts of amyotrophic lateral sclerosis spread TDP-43 pathology in cerebral organoids | [227] |
| Motor neurons and brain organoids | ALS and FTD | iPSC | CRISPR/Cas9-mediated excision of ALS/FTD-causing hexanucleotide repeat expansion in C9ORF72 rescues major disease mechanisms in vivo and in vitro | [228] |
| Cerebral organoid slice model | ALS and FTD | iPSC | Human ALS/FTD brain organoid slice cultures display distinct early astrocyte and targetable neuronal pathology | [134] |
| Brain organoids | ALS and FTD | iPSC | Granulin loss of function in human mature brain organoids implicates astrocytes in TDP-43 pathology | [229] |
| Motor neurons | ALS | hiPSC | Exploring motor neuron diseases using iPSC platforms | [230] |
| Cerebral organoids | FTD | iPSC | ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids | [133] |
| Molecular study | FTD | iPSC | Pathological progression induced by the frontotemporal dementia-associated R406W tau mutation in patient-derived iPSCs | [231] |
| iPSC-derived astrocytes | MS | iPSC | iPSC-derived reactive astrocytes from patients with multiple sclerosis protect cocultured neurons in inflammatory conditions | [232] |
| Model study | MS | iPSC | Selective PDE4 subtype inhibition provides new opportunities to intervene in neuroinflammatory versus myelin-damaging hallmarks of multiple sclerosis | [233] |
| RRMS and PPMS iPSC cellular models | MS | iPSC | Generation of RRMS- and PPMS-specific iPSCs as a platform for modeling multiple sclerosis | [234] |
| Cerebral organoids | MS | iPSC | Cerebral organoids in primary progressive multiple sclerosis reveal stem cell and oligodendrocyte differentiation defect | [165] |
| Model study | MS | iPSC | Generation and characterization of four multiple sclerosis iPSC lines from a single family | [235] |
| Cerebral organoids | ASD | iPSC | Single-cell brain organoid screening identifies developmental defects in autism | [236] |
| Forebrain organoids/Molecular study | ASD | iPSC | Cortical overgrowth in a preclinical forebrain organoid model of CNTNAP2-associated autism spectrum disorder | [237] |
| Organoids/Molecular study | ASD | iPSC | FOXG1-dependent dysregulation of GABA/glutamate neuron differentiation in autism spectrum disorders | [113] |
| Brain organoids | ASD | iPSC | Superoxide dismutase isozymes in cerebral organoids from autism spectrum disorder patients | [238] |
| Organoids/Molecular study | ASD | iPSC | CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in cerebral organoids derived from iPSC cells | [239] |
| Cell Therapy | TBI | Rat | Combining enriched environment and induced pluripotent stem cell therapy results in improved cognitive and motor function following traumatic brain injury | [240] |
| Cell Therapy | TBI | Mice | Controlled cortical impact model of mouse brain injury with therapeutic transplantation of human induced pluripotent stem cell-derived neural cells | [241] |
| Cerebral Organoid | TBI | hiPSC | Modeling traumatic brain injury in human cerebral organoids | [198] |
| Cell Therapy | CD | Mice | Cell-based therapy for Canavan disease using human iPSC-derived NPCs and OPCs | [122] |
| Cerebral Organoid | Stroke | hiPSC | Gene expression profiles of human cerebral organoids identify PPAR pathway and PKM2 as key markers for oxygen glucose deprivation and reoxygenation | [242] |
| iPSC derived telencephalon organoids | ADHD | iPSC | Telencephalon organoids derived from an individual with ADHD show altered neurodevelopment of early cortical layer structure | [105] |
| Model study | ASD and ADHD | iPSC | Modeling human cerebellar development in vitro in 2D structure | [243] |
| Molecular study | ADHD | iPSC | Generation of a human induced pluripotent stem cell (iPSC) line from a 51-year-old female with attention-deficit/hyperactivity disorder (ADHD) carrying a duplication of SLC2A3 | [244] |
| Model study | ADHD | iPSC | Generation of four iPSC lines from peripheral blood mononuclear cells (PBMCs) of an attention-deficit/hyperactivity disorder (ADHD) individual and a healthy sibling in a Caucasian family in Australia | [245] |
| Model study | ADHD | iPSCs and NSCs | Growth rates of human induced pluripotent stem cells and neural stem cells from attention-deficit/hyperactivity disorder patients: a preliminary study | [246] |
| Molecular study | HD | iPSC | An alternative splicing modulator decreases mutant HTT and improves the molecular fingerprint in Huntington’s disease patient neurons | [247] |
| Molecular study | HD | iPSC-derived neurons (Mice) | CryoET reveals organelle phenotypes in Huntington’s disease patient iPSC-derived and mouse primary neurons | [248] |
| Model study | HD | iPSC-derived neural cells | Bioenergetic deficits in Huntington’s disease iPSC-derived neural cells and rescue with glycolytic metabolites | [249] |
| Model study | HD | iPSC-derived neural cells | Extracellular vesicles improve GABAergic transmission in Huntington’s disease iPSC-derived neurons | [250] |
Legend: AD—Alzheimer’s disease; ADHD—attention-deficit/hyperactivity disorder; ALS—amyotrophic lateral sclerosis; ASD—autism spectrum disorder; CD—Canavan disease; HD—Huntington’s disease; FTD—frontotemporal dementia; MS—multiple sclerosis; PD—Parkinson’s disease; TLE—temporal lobe epilepsy; TSC—tuberous sclerosis complex.