Table 1 Approaches in the establishment of 3D brain organoids

Xenotransplantation

Forebrain

Axonal projections, synaptogenesis mapping

Long-term culturing

Lack of vascular bed

Mansour et al., 2018 [6], Cakir, B. et al., 2019 [7], Wang, Z et al., 2020 [8]

Air–liquid interface-cerebral organoids (ALI-COs)

Whole brain organoid

Axonal tracts

Proper neural tract formation, long-term culturing

Devoid of vascularity

Giandomenico et al., 2019 [9]

Miniaturized spinning bioreactors

Forebrain, midbrain and hypothalamus

Defined oSVZ, and human oRGC-like NPCs, hypothalamic neurons

Patterning into different brain-like subregions, smaller volume of medium required, high reproducibility

Expensive for mass production and lacks vascularization

Qian, X et al., 2018 [10], Romero-Morales et al., 2019 [11]

Assembloids

Dorsal and ventral forebrain

Dorsal-ventral axis

Robust directional GABAergic interneuron migration, rough organization into cortical layers

Lack of output and input systems

Bagley et al., 2017 [3], Xiang, Y et al., 2019 [12]

Bioengineered scaffolds

Forebrain

Polarized cortical plate and radial units

Enhance tissue identity and architecture, and establish organoid models for teratogenic compounds Generation of patients’ specific disease-relevant cell types

Poor spatial orientation

Lancaster et al., 2016 [13], Sood et al., 2019 [14], Zafeiriou, et al., 2020 [15]