What exactly are organoids?

An organoid is a group of cells derived from stem cells that are a tiny, self-organized 3D culture with the support of an extracellular matrix in a dish. Compared to 2D culture, organoids have a high order of self-assembly, which often better represents cell interactions and responses in the body. Most organoids can also be propagated, frozen, and thawed, so that they can be shared and distributed to other scientists.

How do we define an organoid? In relation to the particular organ or tissue of origin, here are three main characterizations:

1. 3D microtissue containing at least two cell types
2. Display structure and organization
3. Resemble some level of functionality

How do 3D organoid cultures help biologists?

Cell culture is a powerful tool for studying basic cell biology, understanding disease mechanisms, and assisting with drug discoveries and biotechnological applications. 3D organoid cultures are a more advanced experimental system compared to traditional 2D cultures, providing even more benefits for research. Human organoids, for example, can be used in a variety of fields such as organogenesis, regenerative-to-personalized medicine, and cancer research. Currently, organoids are being generated from a wide range of organs, including brain, liver, kidney, intestine, lung, eye, and ovary.

In addition to humans, organoids from other species, such as mice, zebrafish, snakes, chickens, and pigs, have also been developed to facilitate studying developmental processes and diseases. Furthermore, they have important applications, including cross-species comparisons, environmental toxicology, and comparative medicine.

What is the benefit of having this technology at the Stowers Institute?

Cell cultures have been extensively utilized by many labs at the Stowers Institute. As an emerging in vitro model, organoids are more physiologically relevant to the original organs and can better represent interactions between cells and tissue-specific cellular functions. For example, tumor organoids can be generated to study tumor growth, drug resistance, and metastasis. Cerebral organoids have been developed to study brain development (learning, memory) and neurodegenerative diseases. Intestinal organoids are widely used to study digestion, nutrient absorption, and gastrointestinal diseases.

What are some of the most exciting discoveries achieved with this technology?

Assembloids are a cutting-edge technology that combines organoids, tissue engineering, and microfabrication (microfluidics, 3D printing) to create functional models of complex organs in a laboratory setting. Assembloids aim to address some of the limitations from traditional organoids. For example, with limited cell types, organoids cannot recapitulate the complex structure and function of actual organs, whereas assembloids are better approximations.

Recently, an exciting discovery involving brain assembloids illustrated that these represented the combination of multiple brain regions to capture cell–to-cell interactions and study the assembly of neural circuits. In addition, the interaction between neuronal and non-neuronal cell interactions can be modeled by adding non-neuronal cells to brain region-specific organoids (multilineage assembloids) to understand the role of microglia and astrocytes during neural development.