Table 2.

iPSC usage in cell therapy and drug screening for several neuropathologies.

Trial Type	Disease	Target	Result	Reference
Cell Therapy	AD	Rat	The transplanted rats rescued Alzheimer’s cognition.	[278]
Cell Therapy	AD	Mouse	Grafted mice showed improved memory, synaptic plasticity, and reduced AD brain pathology, including a reduction in amyloid and tangle deposits.	[279]
Drug Screening	AD	hiPSC	β-secretase inhibitor IV (BSI) and γ-secretase inhibitor XXI/compound E (GSI) showed similar effects as screening in other models.	[280]
Drug Screening	AD	hiPSC	Docosahexaenoic acid (DHA) treatment alleviated the stress responses in the AD neural cells.	[270]
Drug Screening	AD	hiPSC	The anthelminthic avermectins increase the relative production of short forms of Aβ and reduce the relative production of longer Aβ fragments in human cortical neurons.	[281]
Cell Therapy	HD	Mice	iPSCs survived and differentiated into region-specific neurons in both mice groups without tumor formation.	[282]
Cell Therapy	HD	Mice	Grafted mice showed a significant increase in lifespan. In iPSC groups, animals showed significant improvement in motor functions and grip strength.	[283]
Cell Therapy	HD	Rat	Grafted rats showed significant behavioral improvements for up to 12 weeks. iPSCs enhanced endogenous neurogenesis and reconstituted the damaged neuronal connections.	[166]
Cell Therapy	HD	Mice	Improved neuronal dysfunction by SUPT4H1-edited iPSC grafts.	[284]
Cell Therapy	MLD	Mice	Transplantation of ARSA-overexpressing precursors into ARSA-deficient mice significantly reduced sulfatide storage up to 300 µm from grafted cells.	[285]
Cell Therapy	MLD	Mice	Grafts of iPSCs into neonatal and adult immunodeficient MLD mice stably restored arylsulfatase A (ARSA) activity in the whole CNS and a significant decrease in sulfatide storage when ARSA-overexpressing cells were used.	[165]
Cell Therapy	PD	Rat	iPSC graft differentiated into mature mDA neurons that survive over long term and restored motor function.	[286]
Cell Therapy	PD	Mice	hiPSCs differentiated into mDA neurons and long-term motor functional recovery was achieved after transplantation.	[287]
Cell Therapy	PD	Rat	Grafted iPSCs could survive in Parkinsonian rat brains for at least 150 days, and many of them differentiated into tyrosine hydroxylase (TH)-positive cells.	[288]
Cell Therapy	PD	Rat	Intranigral engraftment to the ventral midbrain demonstrated that mDA progenitors cryopreserved on day 17, and cells had a greater capacity than immature mDA neuron cells to innervate over long distances to forebrain structures.	[289]
Cell Therapy	PD	Rat	hiPSC-derived dopaminergic progenitor cells integrate better into the striatum of neonates than older rats.	[290]
Cell Therapy	PD	Mice	More than 90% of the engrafted cells differentiated into the lineage of mDA neurons, and approximately 15% developed into mature mDA neurons without tumor formation.	[291]
Cell Therapy	PD	Rat	There was a neural remodel of basal ganglia circuitry and no tumorigenicity.	[292]
Cell Therapy	PD	Mice	iPSCs matured into mDA neurons, reverse motor function, and established bidirectional connections with natural brain target regions without tumor formation.	[217]
Cell Therapy	SCI	Rat	Transplanted cells displayed robust integration properties, including synapse formation and myelination by host.	[293]
Cell Therapy	SCI	Mice	Due to DREADD expression, it was shown a significant decrease in locomotor dysfunction in SCI-grafted mice, which was exclusively observed following the neurons’ maturation.	[294]
Cell Therapy	SCI	Mice	The combination of iPSC graft and rehabilitative training therapy significantly improved motor functions.	[295]
Cell Therapy	SCI	Rat	Neuro-pluripotent cells derived from iPSC were able to survive and differentiate into both neurons and astrocytes, which improved forelimb locomotor function.	[296]
Cell Therapy	Stroke	Mice	Combination of electroacupuncture and iPSC-derived extracellular vesicle treatment ameliorated neurological impairments and reduced the infarct volume and neuronal apoptosis in MCAO mice.	[297]
Cell Therapy	Stroke	Pig	Tanshinone IIA nanoparticles increased iPSC engraftment, enhanced cellular and tissue recovery, and improved neurological function in a translational pig stroke model.	[298]
Cell Therapy	Stroke	Rat	Increased glucose metabolism and neurofunctional in iPSC-transplanted rats.	[299]
Cell Therapy	Stroke	Rat	Graft of iPSCs inhibited microglial activation and expression of proinflammatory cytokines and suppressed oxidative stress and neuronal death in the cerebral cortex at the ischemic border zone.	[300]
Cell Therapy	Stroke	Mice	Graft survived well and primarily differentiated into GABAergic interneurons and significantly restored the sensorimotor deficits of stroke mice for a long time.	[301]
Cell Therapy	Stroke	Rat	Generated oligodendrocytes survived and formed myelin-ensheathing human axons in the host tissue after grafting onto adult human cortical organotypic cultures.	[302]
Cell Therapy	TLE	Mice	A much-reduced frequency of spontaneous recurrent seizures in grafted animals.	[262]

Legend: AD—Alzheimer’s disease; HD—Huntington’s disease; MLD—metachromatic leukodystrophy; PD—Parkinson’s disease; SCI—spinal cord injury; TLE—temporal lobe epilepsy; mDA—midbrain dopaminergic. SCI and PD papers presented are only from 2023 and 2022 due to the large number of publications.