Fig. 2. Process for the establishment of human PSC-derived and AdSC-derived organoids.

Pluripotent stem cell (PSC)-derived organoids are established following directed differentiation of PSCs, which requires a first step that involves germ-layer specification (endoderm, mesoderm or ectoderm), followed by induction and maturation, by culturing with specific growth and signalling factors to obtain the specific cell types that form the desired organ. Some PSC-derived organoids may contain cells from multiple germ layers to closely mimic the in vivo counterpart. Adult stem cell (AdSC)-derived organoid cultures require isolation of the tissue-specific stem cell population, which can then be embedded into an extracellular matrix (ECM) with defined, tissue-specific combinations of growth factors to allow propagation. AdSC-derived organoids, as shown here, are of epithelial origin and lack a mesenchymal or immune component unless it is added separately. Signalling components that are important for guided differentiation and niche function are shown; activated signalling pathways are shown in green, and inhibited ones in red. BMP, bone morphogenetic protein; EGF, epidermal growth factor; FGF, fibroblast growth factors; HGF, hepatocyte growth factor; IGF, insulin-like growth factor; ROCK, RHO-associated protein kinase; TGF, transforming growth factor; VEGF, vascular endothelial growth factor.