○Luganoids are 3D cell culture models that more accurately reflect the structural and functional complexity of organs in vitro than traditional 2D cell culture methods. Organoids, generally derived from stem cells, can be generated using a supporting matrix and a cocktail of specific growth factors. The creation of the first organoids from intestinal stem cells in 2009 opened a world of new possibilities for biological research. Researchers are now using these small organs in a variety of fields to understand biological function, model disease, and test new treatments.
Pancreatic organoids for precision medicine development
The researchers stained pancreatic organoids to examine cell structure using phalloidin (red) for actin, Hoechst (blue) for cell nuclei, and Krt19 (green) for pancreatic stem cells.
image of Pancreatic organoids under the microscope using immunofluorescence staining.
Although it is relatively easy to grow organoids from highly proliferative tissues such as the stomach and liver, generating them from the pancreas has been much more difficult. While working as a postdoctoral fellow at the Hübrecht Institute, stem cell biologist Meritcell Fufu They succeeded in generating the first pancreatic organoids from mice. By further developing protocols for 3D tissue visualization, Huch gained valuable insight into their structure. Huch’s pancreatic organoids are now a promising tool for disease modeling and generation of precision medicines to treat pancreatic diseases.
Continue reading to learn more about how Huch generated pancreatic organoids.
Breast cancer organoid: mammary gland tissue that secretes milk
Researchers used mouse embryonic stem cells to generate mammary gland organoids containing mammary lineage cells (green) and luminal epithelial cells (magenta).
Sounak Sahu
Researchers frequently use mammary gland and tumor-derived organoids to study breast cancer, but until now they have been unable to generate developmental models of mammary tissue. Cancer geneticists use specific combinations of chemicals and growth factors Shyam Sharan and his team at the National Cancer Institute have now established 3D mammary gland organoids that secrete milk from mouse embryonic stem cells. After confirming that the organoids were mammary lineage-specific and inducing them to secrete milk, the researchers transplanted them into mice and formed functioning mammary glands. These organoids allow the study of cancer-causing mutations in mammary tissue, potentially reducing the need to use animals.
Learn more about the use of mammary organoids in breast cancer research.
Fetal organoids enable research into congenital diseases
The researchers used progenitor cells found in amniotic fluid to generate a variety of epithelial organoids, including lungs.
Giuseppe Cara, Paolo De Coppi, Mattia Guerre
Models to study organ development and congenital disease progression in human embryos are highly needed, but the generation of fetal organoids is largely hampered by ethical and legal restrictions on human tissue collection. In a groundbreaking study, stem cell biologists at University College London have successfully created fetal organoids from cells found in amniotic fluid and tracheal fluid. This method allows researchers to collect tissue in a minimally invasive manner and generate fetal organoids to study congenital diseases while the fetus is still in the womb, and to create personalized medicines and drugs. It may be used to conduct tests.
Learn 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 appear early in fetal brain development. neuroscientist and geneticist Jurgen Knoblich The researchers at the Vienna Institute for Molecular Biotechnology used CRISPR to disrupt various ASD-related genes in stem cells and study how the edited cells develop into brain organoids. The researchers uncovered a link between well-established genetics and a poorly understood developmental pathway, highlighting a new direction for this research field.
This article details CRISPR organoids and their use in ASD research.
Endometrial organoids enable research into Asherman syndrome
Rare gynecological diseases such as Asherman syndrome can now also be accurately modeled using endometrial organoids. Clinical researcher, obstetrician and gynecologist carlos simon barres His team at the University of Valencia studied the pathophysiology of the condition by comparing organoids derived from patients’ cells with those from healthy individuals. The resulting endometrial organoids showed important differences between the groups, including the number of specific cell types present and impaired interactions between cell types in Asherman syndrome organoids. Further research using this model may provide a path to treatment and prevention of the disease.
Find out about the use of endometrial organoids in gynecological research here.
Tumor organoids predict drug response in high-throughput screening
Tumor organoids offer an alternative to the use of whole animals in screening new drug candidates. After overcoming obstacles in using automated liquid handlers for high-throughput drug screening of organoids on microwell plates, an interdisciplinary team at the University of California, Los Angeles has developed a method to observe the real-time response of organoids to drugs. Although these organoids are derived from cancer cell lines and do not accurately reproduce the complexity of the tumor microenvironment, the research team plans to test the approach using patient-derived organoids.
Read this article to learn more about drug screening using tumor organoids.
Nicole Valenzuela, an evolutionary biologist at Iowa State University, has been studying turtles for more than 30 years and is interested in the genes that control sex determination, anoxia, and cold tolerance.
Christopher Gannon, Iowa State University
Turtle liver organoids reveal adaptation to harsh environments
Organoids can also be used to understand animal adaptations to harsh environmental conditions. nicole valenzuelaAn evolutionary biologist at Iowa State University, he created the first turtle organoids to study how painted turtles adapted to survive subzero temperatures and long periods without oxygen. did. The researchers used stem cells from the livers of embryos, hatchlings, adult loggerheads and two other species to create organoids to compare life stages and species. How the organoids respond to extreme environmental conditions remains to be tested, but this model can be used in conjunction with CRISPR gene editing and other tools to examine the influence of different genes on turtle adaptation. .
Learn more about the first turtle organoids and their applications here.
Over the past 15 years, researchers have used organoids to generate valuable insights into organ structure, function, and development. Organoids recapitulate much of the complexity of human organs and tumors in vitro, providing an important tool for drug testing and disease modeling without the use of whole animals. Biologists continue to develop different types of organoids and complementary technologies for imaging, gene editing, and high-throughput screening of these models.
