Mini-livers could shed new light on rare diseases

Scientists have developed ‘mini-organs’, called organoids, to help assist complex research into a rare liver condition. 

An organoid is an artificially grown and simplified version of an organ that is built on a miniature scale. They are three-dimensional cellular structures that are used by scientists to study disease and treatment in a laboratory. These structures can be crafted to replicate much of the complexity of an organ, or to imitate selected aspects of it, such as only producing certain types of cells.

The mini-liver organoids have been produced by a team of scientists at the Carlos III Health Institute (ISCiii) in Madrid, to support research into a rare condition called Alpha-1 antitrypsin (AAT) deficiency. This condition means that the body cannot produce sufficient amounts of AAT, a protein that protects the lungs and liver cells from damage. 

Beatriz Martínez-Delgado, one of the researchers from the Molecular Genetics Group at ISCiii, explains that: “The development of these organoids is based on the capacity of the immature stem cells to form structures that resemble an organ when cultivated in three-dimensional (3D) systems under appropriate culture conditions."

By using liver biopsies taken from patients affected by the rare AAT deficiency, and comparing them to healthy people, the researchers have been able to identify the specific gene mutation that causes the AAT deficiency. This identification is a vital part of improving research into this rare condition. 

There remains little available research focused on the development of liver disease as a result of an AAT deficiency. This is primarily because it’s extremely difficult to access AAT patients to carry out research with and it is particularly challenging to develop accurate and usable cellular models for research to be carried out. 

The production of the ‘mini-liver’ organoid is a very useful tool that could help to advance a more comprehensive understanding of liver disease linked to AAT deficiency, and is a process that could be extended to other rare disease research.

The developed organoids are: "An ideal system for studying the response to different stimuli, which will allow us to investigate in depth the mechanisms of disease initiation", explains Martínez-Delgado. 

Organoids open up the possibility to develop new hypotheses for understanding disease and offer scientists the potential to create new therapeutic strategies. They can be used for the most basic research, which seeks to gain information about the genetic and molecular mechanisms of disease. They can also be used to test new treatments, which will be particularly significant for the advancement of personalised and regenerative medicine. 

Martínez-Delgado concluded: "Organoid development is a very promising technology for the possible future application of gene therapy by means of genetic editing in diseases caused by faults in a single gene.”