Table 2 Summary of studies using hiPSC technology
Disease | Type of Culture | Main Findings | Study |
|---|---|---|---|
AD | 2D | Increased abnormal p-tau production Gene expression patterns related to AD | Hossini et al. (2015) [134] |
AD | 2D | Accumulation of Aβ oligomers in hiPSC-derived neurons and astrocytes | Kondo et al. (2013) [131] |
AD | 2D and 3D | hiPSCs neuro-spheroid model obtained from patient’s blood successfully differentiated into neuronal culture 3D neurons showed less reduction of Aβ compared to 2D neurons in same concentrations of BACE1 or γ-secretase inhibitors | Lee et al. (2016) [77] |
AD | 3D | Aβ aggregation Hyperphosphorylated tau protein Endosome abnormalities Reduction of amyloid and tau pathology using β- and γ-secretase inhibitors | Raja et al. (2016) [110] |
AD | 2D | Higher Aβ42/Aβ40 ratio in PSEN-mutated cells | Sproul et al. (2014) [133] |
AD | 2D | Higher Aβ42/ Aβ40 ratio in diseased hiPSCs Neurons responded to y-secretase inhibitors | Yagi et al. (2011) [132] |
AD | 2D and 3D | 3D model was able to recapitulate AD pathology whilst 2D was not | Zhang et al. (2014) [71] |
ALS | 2D | Higher levels of soluble TDP-43 Increased cell death | Bilican et al. (2012) [159] |
ALS | 2D | Recapitulated TDP-43 proteinopathy | Burkhardt et al. (2013) [164] |
ALS | 2D | Neurofilament aggregation and neurite degeneration | Chen et al. (2014) [163] |
ALS | 2D | C9orf72 mutations liked to dysregulation of calcium signalling and altered proteostasis Increased susceptibility to cell death | Dafinca et al. (2016) [166] |
ALS | 2D | Dysregulation of neuronal synaptic activity | Devlin et al.(2015) [167] |
ALS | Â | Successful generation of hiPSC-derived motor neurons | Dimos et al.(2008) [28] |
ALS | 2D | Degeneration of astrocytes during disease progression Astrocytes unable to support neurons | Hall et al. (2017) [169] |
ALS | 2D | Aberrant gene expression in fALS motor neuron progenitor cells Stress vulnerability in fALS motor neurons | Ichiyanagi et al. (2016) [161] |
ALS | 2D | Suggests astrocyte role in neuron death by impairing autophagy mechanisms | Madill et al. (2017) [170] |
ALS | 2D | Recapitulated C9ORF72 repeat toxicity | Sareen et al. (2013) [165] |
ALS | 2D | Generation of motor neurons from hiPSCs Neurons were electrically excitable Increased neuron cell death in response to SOD1-mutated glia | Toli et al. (2015) [162] |
ALS | 2D | Dysregulation of neuronal synaptic activity | Wainger et al. (2014) [168] |
ALS | 2D | Recapitulated TDP-43 proteinopathy | Zhang et al. (2013) [160] |
HD | 2D | Reverted HD phenotypes in hiPSCs using homologous recombination to replace mutated sequence with normal one | An et al. (2012) [145] |
HD | 2D | Generated several iPSC lines from homozygous and heterozygous HD patients Significant increase in lysosomal activity in HD-iPSCs | Camnasio et al. (2012) [27] |
HD | 2D | Proteomic analysis showing that HD-iPSCs are highly susceptible to oxidative stress | Chae et al. (2012) [150] |
HD | 2D | Recapitulated disease phenotype using hiPSCs | Consortium (2012) [146] |
HD | 2D | hiPSCs generated mostly GABAergic neurons (that are more susceptible to degeneration) Behavioural recovery after transplantation of hiPSCs-derived neural precursors into rats | Jeon et al. (2012) [149] |
HD | 2D | iPSC-derived astrocytes showed increased cytoplasmic vacuolation | Juopperi et al. (2012) [147] |
PD | 2D | Generation of ventral midbrain dopaminergic neurons from hiPSCs | Cooper et al. (2010) [140] |
PD | 2D | Generation of dopaminergic neurons from hiPSCs Successful transplantation into rodent brain | Hargus et al. (2010) [142] |
PD | 3D | Generation of mid-brain specific organoids containing organized groups of dopaminergic neurons | Monzel et al. (2017) [109] |
PD | 3D | Generation of dopaminergic neurons from hiPSCs Cells showed spontaneous electrophysiological activity | Moreno et al. (2015) [78] |
PD | 2D | Generation of dopaminergic neurons from footprint-free hiPSCs | Soldner et al. (2009) [40] |
PD | 3D | Generation of neural organoids from patient-derived iPSCs with familial PD mutation in LRRK2 gene | Son et al. (2017) [108] |