From Mini-Guts to Mini-Brains: Organoids and Their Uses

I’ve written before about why I work with animals in my cancer research, and why mice can be very useful in biology research, but I want to talk today about advancements in alternatives to animal experiments. A common question in science is,

“Will we be able, one day, to create a suitable alternative that can replace animal experimentation?”

It’s a complicated question, because animals are widely used in research, to study a pretty large number of diseases. There are mice that develop Alzheimer’s Disease or Parkinson’s Disease. There are mice that develop breast tumors, or cervical cancer, or lung cancer. There are mice with the bleeding disorder hemophilia. These are useful not only to understand about different diseases, but to help to understand what kind of treatments might be useful to patients with these diseases (and to understand the treatments that would be too toxic to test on patients).

One really useful tool for studying cancer is cell culture. When a patient with cancer has a surgery to remove a tumor, researchers can take small pieces of the tumor and grow them in glass or plastic dishes in the science lab. These cells can then be used for a number of different experiments, including whether different cancer therapies are able to kill the cells.

Researchers can grow cancer cells on special plastic dishes. The cell culture medium (special broth with nutrients inside) is placed on top of the cells to keep them alive and growing well.

// So why aren’t cancer cells in cell culture enough?

Even though we have this really great tool, a tumor is much more complex than just the cancer cells. There are cells from your immune system (because your tumor often “tricks” your immune system in order to continue growing), there are often new blood vessels that form, and many other cells that make up the tumor. However, when researchers use cancer cells in cell culture, the results are only able to predict the reaction of one part of a tumor. Perhaps the immune system will respond in a way to counter-act the effect on the cancer cells, or to intensify it. Or sometimes just the simple fact that tumors are three dimensional, and cells in cell culture are grown in a two dimensional format, there can be differences in the way that the cells respond to a cancer therapy when they are no longer in 2D.

// Step 1: Growing cells in 3D

One way to start to think about using cancer cells to better represent a tumor would be to grow the cells in a 3D format, instead of 2D in a plastic dish. Normally, plastic dishes for cell culture have a coating on them to help cells to stick to the surface and give them a surface where they can grow. Instead, a different kind of coating will actually prevent cells from attaching to the bottom, so the cells will instead grow in 3D clumps instead. However, ultimately these are still clusters of just one type of cells, so when researchers want to make a model of something more complex like a tumor, this more simple 3D cell culture is still not quite enough.

// Step 2: Growing “organoids,” or “mini-organs”

An even more sophisticated way to grow cells in 3D is to use “organoids,” or “mini-organs,” (like the “mini-brain” below from Brown University) which bring us one step closer to animal-free alternatives for disease research. Mini-organs are composed of multiple different types of cells, instead of just one cell type. These different cells have different functions, and in many ways they are similar to different organs in our bodies. Because these mini-organs exist, and have some similarities to our organs, it could be possible to use them in research that might normally use animals.

In these mini-brains, researchers found that they are able to grow structures that look like blood vessels. This is important for studying things like brain injuries and strokes, but also for brain cancer research, and other neurological diseases like Alzheimer’s and  Parkinson’s Diseases.

Researchers can also grow organoids from a patient (for example with colon cancer), or with  in order to predict whether a therapy may be effective, in a type of treatment called personalized medicine. 

// Could mini-organs replace all animal research, or only some of it?

The landscape of organoid research has come a long way since the first reported organoid (a mini-brain) was reported nearly a decade ago. Organoids are more sophisticated, they can be grown from individual patients to understand a patient’s unique genetics and predict a response to therapy, and could one day be used to help repair damaged organs. But there are some key features that organoids are missing, particularly in the context of cancer research (at least for now): they don’t have an immune system, so it will be difficult to study the immune system’s interaction with a tumor therapy, for example. Since they are single structures not connected to other tissues, it is not possible to monitor metastasis of a cancer to other organs. These are hurdles that researchers and companies are investing a lot of time and energy to overcome, with the ultimate goal of working with the best systems that will allow researchers to develop new therapies, and to predict the best therapy for a patient’s needs.


// Want to learn more about organoids?

// Q&A with Hans Clevers, a researchers in the Netherlands working on organoids to study diseases.

// Read more about the Organoid Biobank that has been established for colon cancer patients.

// Listen to this Nature podcast, that talks about organoids in one section (starting around the 7:30 mark)