Table 1 The advantages, limitations and applications in neurotoxicity testing of various neural organoids

Cerebral organoid

No patterning factors;

Shaking plates

Complete neurogenesis procedure;

Various brain in single model;

Genetic manipulation

Limited size;

Lack of cortical plate;

High variability;

Lack vasculature

Alcohol [50];

Tranylcypromine [51];

Vincristine [52];

SARS-CoV-2 virus [53];

Neocortex organoid

Extrinsic-patterning factors;

Floating culture

Recapitulating second-trimester neocorticogenesis;

Emergence of complex separation of cortical zones;

Not recapitulating the morphological separation of all neuronal layers (II/III–VI);

High variability;

Lack vasculature

Cocaine [54];

Cerebellar organoid

Extrinsic-patterning factors;

Floating

culturee/

Vertical wheel bioreactors

Recapitulating

cerebellar

primordium development

in first trimester;

High reproducibility;

Compliant with high-throughput screening (HTS);

Lack vasculature

_

Hippocampal /choroid plexus

Extrinsic-patterning factors;

Floating culture

Containing functional hippocampal granule- and pyramidal-like neurons;

High efficiency;

Not recapitulation of neural circuitry;

Lack vasculature

SARS-CoV-2 [55];

Forebrain organoid

Extrinsic-patterning factors;

SpinΩ

Better recapitulating developing human cortex;

High reproducibility;

Compliant with high-throughput screening (HTS);

Lack vasculature

Zika,BPA [38];

Alcohol [56];

Cd [57];

Midbrain organoid

Extrinsic-patterning factors;

SpinΩ/ Floating culture

Better recapitulating developing human cortex;

High reproducibility;

Compliant with high-throughput screening (HTS);

Lack vasculature

6-hydroxydopamine [58];

A library of 84 compounds [59];

Hypothalamus organoid

Extrinsic-patterning factors;

SpinΩ

Better recapitulating developing human cortex;

High reproducibility;

Compliant with high-throughput screening (HTS);

Lack vasculature

_

Spinal cord

Extrinsic-patterning factors; Floating culture

Partly recapitulating DV and AP patterning of neural tube

Not full patterning;

High variability; High tissue heterogeneity;

Lack vasculature

6 antiepileptic drugs [49];