A Special Issue of Science featuring four Reviews illuminates ways in which organoid technology is opening up frontiers of research in biomedicine, allowing for the testing of cancer drugs on cells from individual patients, for example. As the technology expands, researchers are working to solve unmet needs, including related to production, control, and analysis of organoids and their microenvironments.
In one Review, Hans Clevers and David Tuveson talk about a decade of efforts to use organoids to study cancer. "This allows for the first time," Clevers says in a related video, "the researcher to take small samples of tumors from many, many patients, grow them in the lab, build them into ... a living biobank." The biobank can be used for research, in lieu of using animals. Using cancer organoids developed in this way permits testing samples of individual drugs on individual cancer patients, or engineering of cancer mutations into the organoid to understand their individual contributions to disease. In the video, Clevers discusses how immune cells are recently considered particularly important to cancer drug development. "Organoids now for the first time offer the possibility to take cancer cells [and] immune cells from the patient, bring them together in a tumor organoid and study how to how to encourage the immune cells to go and kill the cancer cells," Clevers says.
In another Review in the issue, Sunghee Estelle Park, Andrei Georgescu, and Dongeun Huh colleagues discuss how integrating organoids with organ-on-a-chip technology will make it more likely that organoids can be harnessed for biomedical applications - including to test scenarios that aren't testable in humans. Though organoids allow for more accurately modeling the human body than organ-on-a-chip technology, organoids can develop in a highly variable way, making them challenging to control. "We can use [organ-on-chip devices] to control the cells in their microenvironment very precisely," says Huh in a related video. "What's compelling is to combine the physiological realism of organoids with the [control] and reproducibility of organ-on-a-chip technology to develop a more advanced system that would give us the best of both worlds," Huh says. In the video, he describes recently launching some of his institution's organ-on-a-chip technology on the International Space Station to study how and why astronauts become more prone to infection during spaceflight.
A third Review in the issue, by Takanori Takebe and James M. Wells, highlights a current challenge in organoid design - engineering cellular complexity into organoids in a controlled manner. The next generation of organoids will require an engineering-based narrative design to control patterning, assembly, morphogenesis, growth, and function, the authors say. A fourth Review, by Marti Shahbazi, Eric D. Siggia, Magdalena Zernicka-Goetz, discusses how creating stem cell-derived organoid-like embryo structures could overcome challenges in studying embryonic development.