Scientists highlight progress and uses of organoids in gastroenterology and hepatology

One of the most interesting advances in stem cell research has been the development of organoidal systems, three-dimensional structures similar to organs that mimic their corresponding organ in vivo. In this important review in Digestive and hepatic disease, published by Elsevier, scientists point to some of the new and well established and exciting uses of organoids or "organs in a dish" in gastroenterology and hepatology and look to the future in this exciting field.

Recent advances in stem cell biology have allowed the long-term culture of intestinal or hepatic organotypic tissues derived from resident or pluripotent tissue stem cells. These 3D structures, called organoids, represent a substantial advance in terms of structural and functional complexity compared to traditional in vitro cell culture models, often non-physiological and transformed. Organoids can summarize the in vivo architecture, functionality and genetic signature of the corresponding tissue. Therefore, there is growing interest in using such cells in culture as a source of tissue engineering, regenerative medicine and personalized medicine.

Organoid technology can be used to reveal new knowledge in basic biology such as stem cell biology, organogenesis, cell differentiation, cell-cell interaction and physiological functions, but is also important for the future of regenerative medicine. They can also be used to study the pathophysiology of various human diseases such as cancer, infections (host-microbe interaction), inflammation, and inherited diseases such as cystic fibrosis. "

Principal author Prof. Dr. Markus F. Neurath, MD, Department of Medicine, University Hospital, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Germany

As organoids provide a new tool for modeling epithelial cell biology, epithelial turnover, barrier dynamics, immunoepithelial communication, and host-microbe interaction, organoids have been chosen as the method of choice. 39, year 2017, not only for medical approaches, but also for basic treatments. science.

The authors highlight some of the most significant advances made over the past decade in the areas of gastroenterology and hepatology, likely to improve outcomes for patients:

• Hepatobiliary organelles were introduced for the first time in 2007 to demonstrate the ability of bipotent hepatoblasts to enter a biliary line. They were based on spontaneous differentiation and gave organelles with limited function and maturity, which was proof of principle for the current generation of hepatobiliary organoids.
• Intestinal organoids were first described in 2009 and can be used to study the pathophysiology of various human diseases, including gastrointestinal inflammations such as inflammatory bowel disease (IBD) and celiac disease. , as Helicobacter and Salmonella, malignant tumor and genetic diseases. Organoids derived from patients provide drug screening and personalized approaches to treat intestinal diseases.
• Studies using epithelial organoids have provided a better understanding of the underlying pathophysiology of Crohn's disease, a disease that is still poorly understood. In 2011, scientists demonstrated that caspase-8-deficient intestinal organoids exhibited increased sensitivity to a type of proinflammatory cell death (necroptosis) as well as a change in the immune system. 39, homeostasis of Paneth cells. The researchers compared the results obtained in caspase-8 deficient organoid cultures with data from primary human tissues and found significant overlap. These data indicate that organelles are useful for understanding the physiology of Paneth cells in particular, which is important because Paneth cell dysfunction is a hallmark of ileal inflammation in Crohn's disease.
• The ability to develop organoids from healthy murine and human intestinal tissues has paved the way for organoids derived from the tumor material of the patient. These tumor organoids are phenotypically and genetically similar to the tumor epithelium from which they are derived and therefore represent a promising tool for potentially enabling the patient-specific anti-cancer drug test.
• In vitro production of authentic hepatocytes could provide a unique platform for disease modeling and high throughput screening of drugs for liver diseases. Recent research has led to the successful spread of primary hepatocytes from whole fetal or adult liver in humans and mice. The resulting hepatocyte organelles express markers and function at levels comparable to those of the primary tissue, providing a promising platform for translational applications such as drug screening. Hepatobiliary organelles have been used to model several monogenic liver diseases, including cystic fibrosis, polycystic liver disease, Alagille syndrome, Wilson's disease, and alpha1-antitrypsin deficiency. These organoids derived from the patient summarize the phenotype of the disease in vitro and can be used as drug screening platforms for the development of new treatments for personalized medicine.
• The treatment of liver disorders is limited by the shortage of healthy tissue suitable for transplantation. In the future, organelles represent a source of functionally and easily extensible mature cells that could solve this problem. Experiments on animal models provided the first proof of principle as to the feasibility and effectiveness of transplantation of hepatobiliary organoids.

"Although gastrointestinal and hepatobiliary organelles have only been developed in the past decade, they have already proved to be a valuable tool for drug testing, disease modeling and medicine. regenerative ", concluded Professor Neurath and his co-authors. "Challenges remain, but recent advances in bioengineering, organ-on-a-chip technology, single-cell badysis and the development of synthetic matrices hold great promise for addressing current limitations and advancing the field even further. both in terms of mechanistic studies and clinical tests. "

Source:

Elsevier

Journal reference:

Neurath, M.F. et al. (2019) What gastroenterologists and hepatologists should know about organoids in 2019. Digestive and hepatic disease. doi.org/10.1016/j.dld.2019.02.020.