Organoid

Organoid, cluster of cells cultivated within a three-dimensional matrix under laboratory conditions that replicates the structure and function of a specific organ in the human body. Organoids are engineered to facilitate interactions between cells and multiple cell types, as well as between cells and their surrounding environment. These structures differ from conventional cell cultures in that the latter are two-dimensional, generally feature only a single cell type, and are produced on a flat, rigid surface, such as glass. Despite often being referred to as “mini organs,” organoids do not possess the entire structural or functional complexity of the organs they mimic.

Generation and function

Organoids are generated using stem cells, which have the capacity to differentiate into specialized cell types. These cells can be applied to a three-dimensional scaffold consisting of a gel-like material that resembles an extracellular matrix, encouraging cells to coalesce into an organlike structure. In other cases the cells may be cultivated in a bioreactor, in which they are suspended and kept in motion; constant spinning encourages the cells to self-organize into multilayered, three-dimensional structures. Organoids can also be generated by bioprinting, in which bio-inks that are composed of cells, elements of the extracellular matrix (e.g., collagen, fibrin, gelatin), and networks of water-absorbing polymer chains known as hydrogels are deposited in layers. This process allows for precise positioning of cells and the generation of custom three-dimensional structures and also overcomes challenges with random cellular self-organization.

Organoids are encouraged to resemble specific organs in the body by directing stem cells into developmental pathways they would typically follow in a human embryo. In this way, organoids that are engineered to represent the brain, for example, can be modeled after distinct regions, with different types of neurons capable of signaling across regions. Likewise, intestinal organoids are steered into developing native types of intestinal cells, including epithelial cells and cells in specialized structures such as crypts. Thus, organoids often reproduce activities specific to the organs they represent; such activities can include the absorption of nutrients, the secretion of substances, or the transmission of electrical signals.

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Applications

Organoids have a tremendous range of applications in biomedicine, particularly because in many instances they can more effectively capture human-specific cell behavior and cell-cell and cell-environment interactions compared to conventional animal and two-dimensional cell cultures. Organoids further support efforts to move away from animal testing for the preclinical investigation of novel treatments.

Some examples of specific applications of organoids in medical research include the investigation of genetic disorders, where they can be used to explore the effects of gene mutation on cell function in the context of entire organs, and infectious disease, where they provide insight into the effects of disease on organ function and host-pathogen interactions. Organoids also are used to assess the effectiveness and toxicity of experimental drugs in organlike conditions that closely resemble real-world effects in human tissues. Patient-derived tumor organoids, which are generated from a patient’s tumor tissue and therefore match the genetic and structural features of that individual’s cancer, can potentially inform decisions regarding the use of personalized cancer treatments.