Assembloid

An assembloid is an in vitro model that combines two or more organoids, spheroids, or cultured cell types to recapitulate structural and functional properties of an organ.

Assembloids have been used to study cell migration, neural circuit assembly, neuro-immune interactions, metastasis, and other complex tissue processes.

[5] This was confirmed by multiple research groups applying similar approaches to model regionalized organoid interactions and study interneuron migration.

[11] Methods such as Cre recombination combined with G-deleted rabies tracing can be used to identify cells projecting within assembloids; additionally, optogenetic stimulation can demonstrate the assembly of functional neural circuits in vitro.

Initially, human induced pluripotent stem (hiPS) cells are aggregated to generate regionalized organoids through directed differentiation.

[11] B. Multi-lineage assembloids of the nervous system Some cell types of interest are challenging to differentiate within organoids but can be isolated from tissue explants or derived in monolayer culture.

For example, one current limitation of organoids and assembloids is their lack of functional vasculature, which hinders the supply of nutrients and trophic factors.

[27][28][29] Lastly, combining hiPS cell-derived intestinal organoids with neural crest cells can derive assembloids of the enteric nervous system.

First, assembloids, like organoids, lack vascularisation, which impairs nutrient diffusion to the surface and eventually leads to necrosis in the core, thus limiting their growth.

[34]Another critique of both assembloids and organoids is the lack of sensory input, which is important for the maturation and shaping of circuits during embryonic development.

[35] Assembloids and organoids do not currently have a blood brain barrier or immune cells, limiting the biological validity for drug screening or disease modeling.

Example image of an assembloid modeling human forebrain circuits (Pasca Lab, Stanford University)