Organoids have been generated for a number of organs from both mouse and human stem cells. To date, human pluripotent stem cells have been coaxed to generate intestinal, kidney, brain, and retinal organoids, as well as liver organoid-like tissues called liver buds.
Derivation methods are specific to each of these systems, with a focus on recapitulation of endogenous developmental processes. Specifically, the methods so far developed use growth factors or nutrient combinations to drive the acquisition of organ precursor tissue identity.
Then, a permissive three-dimensional culture environment is applied, often involving the use of extracellular matrix gels such as Matrigel. This allows the tissue to self-organize through cell sorting out and stem cell lineage commitment in a spatially defined manner to recapitulate organization of different organ cell types.
These complex structures provide a unique opportunity to model human organ development in a system remarkably similar to development in vivo. Although the full extent of similarity in many cases still remains to be determined, organoids are already being applied to human-specific biological questions. Indeed, brain and retinal organoids have both been shown to exhibit properties that recapitulate human organ development and that cannot be observed in animal models. Naturally, limitations exist, such as the lack of blood supply, but future endeavors will advance the technology and, it is hoped, fully overcome these technical hurdles.
Furthermore, organoids that model disease can be used as an alternative system for drug testing that may not only better recapitulate effects in human patients but could also cut down on animal studies. Liver organoids, in particular, represent a system with high expectations, particularly for drug testing, because of the unique metabolic profile of the human liver. Finally, tissues derived in vitro could be generated from patient cells to provide alternative organ replacement strategies. Unlike current organ transplant treatments, such autologous tissues would not suffer from issues of immunocompetency and rejection.