Organoids are 3D cell culture models that more accurately reflect the structural and functional complexities of organs in vitro than traditional 2D cell culture methods. Generally derived from stem cells, organoids can be generated using a support matrix and a cocktail of specific growth factors. The creation of the first organoids in 2009 from intestinal stem cells opened up a world of new possibilities in biological research. Researchers now use these mini organs across a range of fields to understand biological functions, model disease, and test new therapies.
Pancreatic Organoids for Precision Medicine Development
Researchers stained pancreatic organoids to examine cellular structures with phalloidin (red) for actin, Hoechst (blue) for cell nuclei, and Krt19 (green) for pancreas stem cells.
Image of pancreatic organoids under a microscope with immunofluorescent staining.
While growing organoids from highly proliferative tissues, such as the stomach and liver, is relatively easy, generating them from the pancreas has been much more challenging. During her time as a postdoctoral researcher at the Hubrecht Institute, stem cell biologist Meritxell Huch managed to generate the first pancreatic organoids from mice. By further developing protocols for the visualization of the 3D tissue, Huch gained valuable insights into their architecture. Huch’s pancreatic organoids are now a promising avenue for disease modeling and generating precision medicines to treat pancreatic disorders.
Continue reading about how Huch generated the pancreatic organoids in this article.
Breast Cancer Organoids: Mammary Tissue That Secretes Milk
Researchers used mouse embryonic stem cells to generate mammary organoids including mammary lineage cells (green) and luminal epithelial cells (magenta).
Sounak Sahu
Researchers frequently use organoids derived from mammary glands and tumors to study breast cancer, but they have previously been unable to generate models for the development of mammary tissue. Using a specific combination of chemicals and growth factors, cancer geneticist Shyam Sharan and his team at the National Cancer Institute have now established 3D milk-secreting mammary organoids from mouse embryonic stem cells. After confirming that the organoids were specific to mammary lineages and inducing them to secrete milk, the team grafted them into mice, where they formed functioning mammary glands. These organoids could enable the study of cancer-causing mutations in mammary tissue, reducing the need to use animals.
Learn more about the use of mammary organoids in breast cancer research here.
Fetal Organoids Enable the Study of Congenital Diseases
Researchers generated various epithelial organoids, including lungs, using progenitor cells found in amniotic fluid.
Giuseppe Calà, Paolo De Coppi, Mattia Gerl
Models for the study of organ development and congenital disease progression in human embryos are much needed, but generating fetal organoids has been largely prevented by ethical and legal restrictions concerning the harvesting of human tissues. In a breakthrough study, stem cell biologists from University College London were able to create fetal organoids from cells found in amniotic and tracheal fluids. This method allows researchers to collect tissue in a minimally invasive way and generate fetal organoids to study congenital conditions while the fetus is still in utero, potentially using them to create personalized medicines and perform drug testing.
Read more about fetal organoids and their applications here.
CRISPR Organoids in Neurodevelopmental Research
Researchers are using CRISPR organoids to understand brain development and autism spectrum disorder (ASD), which is thought to emerge early in the development of the fetal brain. Neuroscientist and geneticist Jürgen Knoblich and his colleagues at Vienna’s Institute of Molecular Biotechnology used CRISPR to perturb a range of ASD-related genes in stem cells, then studied how the edited cells developed into brain organoids. The team revealed connections between well-established genetics and some lesser-understood developmental pathways, highlighting new directions for this field of research.
Delve into CRISPR organoids and their use in the study of ASD in this article.
Endometrial Organoids Enable Asherman Syndrome Studies
Rare gynecological conditions, such as Asherman syndrome, can now be accurately modeled with endometrial organoids. Clinical researcher, obstetrician, and gynecologist Carlos Simón Vallés and his team at the University of Valencia investigated the pathophysiology of the condition by comparing organoids derived from patient cells to those derived from healthy individuals. The resulting endometrial organoids demonstrated key differences between the groups, such as the number of specific cell types present and impaired interactions between cell types in the Asherman syndrome organoids. Further research using this model could provide avenues for the treatment and prevention of the disease.
Explore the use of endometrial organoids in gynecological research here.
Tumor Organoids Predict Drug Responses in High-Throughput Screens
Tumor organoids offer an alternative to the use of whole animals in the screening of new drug candidates. After overcoming obstacles in the use of automated liquid handlers for high-throughput drug screening of organoids on microwell plates, a multidisciplinary team at the University of California, Los Angeles developed a method to observe real-time responses of the organoids to drugs. While these organoids are derived from cancer cell lines and don’t accurately recapitulate the complexity of the tumor microenvironment, the team plans to test their approach using patient-derived organoids.
Discover more about drug screening using tumor organoids in this article.
Nicole Valenzuela, an evolutionary biologist at Iowa State University, has studied turtles for more than 30 years and is interested in the genes that regulate sex determination, anoxia, and freeze tolerance.
Christopher Gannon, Iowa State University
Turtle Liver Organoids Reveal Adaptations to Harsh Environments
Organoids can also be used to understand the adaptations of animals to harsh environmental conditions. Nicole Valenzuela, an evolutionary biologist at Iowa State University, created the first turtle organoids to study how painted turtles have adapted to survive freezing temperatures and lengthy periods without oxygen. Using stem cells taken from the liver of embryonic, hatchling, and adult painted turtles as well as two other species, the team created organoids for comparison between life stages and species. Although they have not yet tested how the organoids respond to extreme environmental conditions, this model can be used alongside CRISPR gene editing and other tools to examine the effects of different genes on turtle adaptations.
Read more about the first turtle organoids and their applications here.
Over the last 15 years, researchers have used organoids to generate valuable insights into the structure, function, and development of organs. By recapitulating much of the complexity of human organs and tumors in vitro, organoids provide crucial avenues for drug testing and disease modelling without the use of whole animals. Biologists continue to develop different types of organoids and complementary technologies for the imaging, genetic editing, and high-throughput screening of these models.
