Stem cells are useful in part because they can be applied to lots of different medical problems. One such application is disease modeling, where stem cells are used to simulate or mimic real organs so that scientists and engineers can study how different diseases affect our bodies without actually making anyone sick. To do this, scientists create organoids, which act like mini 3D organs made up of self-organizing stem cells.

Once constructed, these little organs recreate in vivo (“in the body”) tissues in an in vitro (“in the lab”) environment. This means that the organoids act like the organs found inside the body even though they actually remain in a laboratory setting. For this reason, organoids are often called “organs in a dish,” as they’re usually stored on petri dishes.

Organoids have been extremely important to the stem cell field within the past decade; however, organoids have actually been around for a very long time. The phrase “organoid” was used for the first time in 1946 to describe a tumor which resembled an organ. It wasn’t until later on that the term “organoid” was used to describe structures which had similar or identical characteristics to real organs. The definition changed one final time, and it’s the one we use most often today: organoids are self-organizing 3D structures grown from stem cells which act like the tissues that make up the organs of many animals, including humans.

Scientists can use both pluripotent stem cells (including embryonic stem cells and induced pluripotent stem cells) and multipotent adult stem cells which have already committed to growing into a specific tissue type to make organoids. Depending on what type of organoid they want to make, certain types of stem cells make more sense. For example, different stem cells were used to make organoids that could be applied to modelling cancer, cystic fibrosis, and host-microbe interactions.

Cancer is a disease caused by abnormal division of cells in part of the body and can lead to the creation of tumors, which are the abnormal growth of tissue in the body’s organs. Although there are a number of different treatments for cancer, there is no cure which gets rid of cancer cells completely; scientists find it hard to predict how different sorts of cancer cells react to each type of treatment. In order to make better guesses about the effects of cancer, some scientists have made tumor organoids which model the tumors caused by cancer. Often called tumoroids (short for “tumor organoids”), these specific organoids are used to predict how cancer cells might respond to cancer treatments such as chemotherapy, surgery, and radiation therapy. Because cancer can take many different forms, different types of tissues have to be recreated using stem cells. To help speed this process along, scientists have developed “living biobanks,” or collections of organoids. Each organoid in the collection mimics a different type of cancer, such as lung, colon, or pancreas cancer. Even some rare types of cancer are represented by these organoids, making sure that the right type of cancer model is available for the scientists to study.

Another disease that organoids can be applied to is cystic fibrosis. This disorder, which leads to damage of epithelial cells which line the lungs and digestive system, is genetic, meaning that it can be passed down from parent to child. Because cystic fibrosis is potentially life-threatening, many scientists are working to find a cure; however, because every person with the disease has very different symptoms and experiences, the cures have to be personalized and patient-specific. Because of this, the organoids used to model cystic fibrosis must also be personalized and patient-specific in order for treatment options to be further explored. Currently, scientists are creating a living biobank of cystic fibrosis organoids so that, by using them in combination, they can start to see how different patients might respond to the same treatment. As they try out more treatments on these combined organoids, scientists hope to create medications which can be made specifically for each patient.

As good as organoids are at modeling different diseases, they aren’t perfect, and scientists are still hard at work trying to improve them every day! For example, because the organoids are kept outside of the body, they aren't surrounded by the same microenvironment, meaning that they don’t have other types of cells usually found in the body communicating with them. Also, some of the materials used to make and support the organoids, such as Matrigel (which looks like jelly and holds the organoids in place) and growth medium (the liquid that provides the organoids with all the nutrients and energy they need), don’t work as well once they’ve been removed from their petri dish homes. In order to fix this, scientists are trying to come up with other, stronger materials such as PEG hydrogels which will make the organoids more useful. While improvements can be made, organoids are an exciting application of disease modeling which are already helping scientists develop life-saving medicine and therapeutics that can help patients in the best way possible.

Applications: Disease Modeling