A Comprehensive Update of Cerebral Organoids between Applications and Challenges

Table 1

Summary for current applications of cerebral organoids modeling and their cell/tissue types.

Organoid type	Cells or tissue	Disease modelled	Characteristics/phenotype	Reference
Oligocortical spheroids	Oligodendrocyte	Hypoxic injury	OLIG2, MBP/CNP	[16, 21, 22]
Cortical spheroid	Glutamatergic neurons	Rett’s syndrome	No embedding in the extracellular matrix. Generated repetitive action potentials at depolarization.; Contains nonreactive astrocytes.; vGLUT	[21, 23, 24]
	Neurons, neuronal progenitors	Tuberous sclerosis complex	mTORC1 hyperactivation, glia, and neuron hypertrophy.	[25]
Midbrain	Dopaminergic neurons	PD	TH, FOXA2	[4, 26, 27]
Hypothalamus or arcuate	Striatal neurons, GABAergic interneurons, hypothalamic neurons	Prader-Willi’s syndrome	OTP, POMC, Rax1	[26, 28, 29]
Retinal	Optic vesicle-like structures, multizone ocular progenitor cells	Retinitis pigmentosa, end-stage AMD	CRX, OTX2, the surface filled with collagen matrix; the apical edge has dense projections like crystalline	[30–32]
Ventral forebrain	GABAergic/glutamatergic neurons	ASD, epilepsy	Interneurons integrate into a synaptically connected microphysiological system, GAD67, GABA	[21, 33]
Forebrain	NPCs	ZIKV	ZIKV-induced cell apoptosis increased, neuronal cell-layer thickness decreased, and larger ventricular lumen in small size organoids.	[34, 35]
	vRGCs	Miller-Dieker’s syndrome	Reduced organoids size, typical genes of neurons and RGCs increased, atypical vRGCs cell division, cortical niche deformation with neuroepithelial loops decreasing, LHX2, EMX2, and FOXG1	[36, 37]
Dorsal forebrain	NPCs	Cytomegalovirus-induced microcephaly	Situated at the ventricular zone, induced-cystic and vacuolar degeneration, lamination necrosis of the malformed cortical, cellular proliferation dropped.	[38–40]
Forebrain assembloids	Cortical interneurons	Timothy syndrome	Integrate into cortical microcircuit and migrate in a saltatory manner. GSX2, CHAT, SP8	[19, 33, 41]
Organoid-grown microglia/dorsal forebrain	Microglia	Schizophrenia, amyotrophic lateral sclerosis	Contain astrocytes and neuronal architecture, TGFB1, CSF1, IL34, and IBA-1	[42, 43]
Neurosphere	Neurons	Herpes simplex virus (HSV)	Neurons have a vulnerability to destruction by HSV-1 lytic infection	[44]
Asteroids	Astrocyte	Amyotrophic lateral sclerosis	Transplanted into the nonimmunosuppressed mouse brain. GFAP	[8, 45, 46]