TABLE 1.
3D-culture models implemented in the study of ALS.
| Objective | 3D-system | Cell types identified/added to the system | ALS model | Central findings | References |
|---|---|---|---|---|---|
| NMJ modeling and drug testing (Rapamycin/Bosutinib) | Microfluidic device (ALS-on-a-chip) | iPSC-ALS-MNs | sALS (TDP-43) | - iPSC-ALS motor units generated fewer contractions and NMJ formation | Osaki et al. (2018) |
| iPSC-ALS-ACs | - iPSC-ALS-MN degradation | ||||
| iPSC-SMCs | Non-ALS | - Apoptosis of iPSC-SMCs | |||
| iPSC-ECs | - Drug combination improved iPSC-ALS-MN survival and muscle contraction | ||||
| NMJ modeling | Sensorimotor organoid | iPSC-ALS-MNs | - fALS (C9orf72 and FUS) | - Reduced contraction | Pereira et al. (2021) |
| iPSC-ALS-SNs | - Abnormal NMJs | ||||
| iPSC-ALS-ACs | |||||
| iPSC-ALS-Microglia | |||||
| iPSC-ALS-SMCs | - sALS | ||||
| iPSC-ALS-ECs | |||||
| Model development | Polystyrene scaffold 3D-culture plates (Alvetex, Reprocell) | iPSC-ALS-Cortex neurons | fALS (C9orf72) | - Spontaneous cell cycle protein expression | Porterfield et al. (2020) |
| iPSC-ALS-ACs | - Senescence-associated gene expression and protein secretion | ||||
| Drug testing (Rapamycin) | Microfluidic device (Drug gradient control) | mESC-ALS-MNs | Transgenic mouse (TDP-43-A315T) | - MN’s survival increased in a dosage-dependent manner | Chennampally et al. (2021) |
| Model development and drug testing (GSK 2606414) | Cerebral cortical organoid slice | iPSC-ALS-ULNs | ALS (C9orf72) | - Astroglia and neurons present transcriptional and proteostasis disturbance-P26 and DPR poly (GA)—GKS2606414 treatment reduces cell damage | Szebényi et al. (2021) |
| iPSC-ALS-DLNs | |||||
| iPSC-ALS-IN | |||||
| iPSC-ALS-OL/OPC | |||||
| iPSC-ALS-iRG/oRG | |||||
| iPSC-ALS-ACs | |||||
| Unidentified cells and other immature/progenitors |
Abbreviations: NMJs, neuromuscular junctions; SNs, sensory neurons; ACs, astrocytes; SMCs, skeletal muscle cells; ECs, endothelial cells; mESC, mouse embryonic stem cell; ULN, upper layer cortical neuron; DLN, deep layer neuron; IN, interneurons; OL/OPC, oligodendrocyte/progenitor cells; iRG, inner radial glia; oRG, outer radial glia; CP, choroid plexus; DPR poly (GA), dipeptide repeat protein (DPR) poly (GA).