Human pluripotent stem cell-derived brain organoids as in vitro models for studying neural disorders and cancer

Luo, Juan; Li, Peng

doi:10.1186/s13578-021-00617-1

Cell & Bioscience

Table 1 Types of hPSC-derived brain organoids

From: Human pluripotent stem cell-derived brain organoids as in vitro models for studying neural disorders and cancer

Organoid type	Brain region	Methodology	Culture conditions	Observed phenotypes	Main reference
EB-like aggregates	Cerebral cortex	Guided	Stationary floating culture, followed by re-plating of aggregates	The cortical tissues contained ventricular, early and late cortical-plate, and Cajal-Retzius cell zones along the apico-basal direction	[18]
Cerebral organoid	Whole brain	Unguided	Matrigel and spinning bioreactor	Apical-basal polarity, interkinetic nuclear migration, division modes of neural stem cells, and the pattern of neuronal migration were well maintained, and the enlarged OSVZ was exhibited	[11]
			Matrigel and spinning bioreactor	The molecular map of the diversity of cell types across organoids is provided by sc-RNA sequencing, and they showed organoids undergo substantial neuronal maturation	[12]
			Intracerebral grafting of brain organoids into mouse brain	The organoids showed progressive neuronal differentiation and maturation, gliogenesis, and established the graft-to-host functional synaptic connectivity	[27]
Region-specific brain organoid	Cerebellum	Guided	Stationary floating culture	The induced cells self-organized into neural-tube-like structures with dorso-ventral and apico-basal polarities, and eventually formed layered structures that recapitulate cerebellar ontogenesis	[30]
	Forebrain		Matrigel and miniaturized multi-well spinning bioreactor	Forebrain organoids exhibited multi-layer progenitor zone organization and generated diverse neuronal subtypes of all six cortical layers	[21, 22]
	Midbrain		Matrigel and miniaturized multi-well spinning bioreactor	Midbrain organoids showed organized neuroepithelium-like structures expressing NESTIN and floor-plate precursor marker FOXA2 at early stage, TH⁺ DA neurons, NURR1⁺ and PITX3⁺ cells appeared at late stage	[21, 22]
	Hypothalamus		Matrigel and miniaturized multi-well spinning bioreactor	Hypothalamus organoids expressed NKX2.1, SOX2, NESTIN and FOXA2 at early stage, and then the peptidergic neuronal markers and homeobox protein OTP appeared at late stage	[21, 22]
	Hippocampus		Floating culture permeable film-based culture plates, mechanical cutting	The organoids produced Zbtb20⁺/Prox1⁺ granule neurons and Zbtb20⁺/KA1⁺ pyramidal neurons, and both of which were electrically functional with network formation	[31]
	Choroid plexus		Floating culture in 40% oxygen	The organoids produced Lmx1a⁺, Otx2⁺ and TTR⁺ neurons, which are neuronal markers for choroid plexus	[31, 32]
	MGE organoid		Orbital shaker	The organoids specifically enriched the NKX2-1⁺ and DLX2⁺ neurons like in MGE	[33]
	Thalamus		Orbital shaker	The organoids specifically enriched the OTX2⁺, GBX2⁺ and DBX1⁺ neurons like in thalamus	[34]
	Hindbrain/spinal cord		Stationary floating culture	The neurons in hindbrain/spinal cord have established synaptical connection with neurons in cortical organoids	[40]
Fused organoids: “assembloids”	Dorsal and ventral forebrain	Guided	Stationary floating culture	The assembloids have recapitulated the interactions between glutamatergic neurons and GABAergic interneurons resembling the dorsal and ventral forebrains in human brain	[37]
	Dorsal and ventral forebrain		Orbital shaker	The assembloids have recapitulated the interactions between glutamatergic neurons and GABAergic interneurons resembling the dorsal and ventral forebrains in human brain	[38]
	Thalamus and forebrain		Orbital shaker	The axons from both cortex and thalamus reach the other side within 6 days in assembloids	[34]
	Cortical-mouse spinal cord		Air–liquid interface cerebral organoid method	Synapses could be detected between ALI-CO projecting axons and spinal cord neurons; axon tracts could guide mouse muscle contraction when innervated	[39]
	Cortico-striatal assembloids		Stationary floating culture	The cortical neurons send axonal projections into striatal organoids and form synaptic connections in assembloids	[35]
	Cortico-motor assembloids		Stationary floating culture	The corticofugal neurons could project and connect with spinal spheroids, while spinal-derived motor neurons further connect with muscle to control its contraction	[40]

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ISSN: 2045-3701

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