Modeling Human Biology with Organoids

What’s the current gap

Due to the Covid-19 pandemic, the way the virus infects the human body and the potential long-term effects of this disease have become common knowledge. But how exactly do scientists study diseases? There are many models that researchers use to study infectious diseases. First, there is the most basic model – cell lines. Cell lines are a population of cells that are cheap and easy to culture since they survive indefinitely in vitro. However, a downside to this model is that it is not very complex in the sense that these cells don’t recapitulate epithelial functions such as cell differentiation and only grow to generate a 2D structure. Some of these problems are solved by using primary cell cultures, which come from specific tissues and can therefore mimic tissue function in a dish. Unfortunately, these cell cultures don’t have the expansion rate of cell lines and instead, depend on fresh tissue. Due to these limitations, researchers might want to use a more complex model such as a multicellular organism. Mice models are the most common animal models to study infectious diseases; however, 80% of treatments that promise to be a successful therapy in animal models do not show the same efficacy in human trials. In fact, coming back to Covid-19, the SARS-CoV-2 virus cannot bind to the mouse ACE-2 receptor and therefore wild type mice do not develop the disease as humans do. As a consequence, scientists have to genetically engineer mice to synthesize the hACE-2 receptors so they can be effective disease models. Amidst these many methods that researchers use to model infection, there is a promising model that can successfully recapitulate a human’s response to disease – organoids.  

What are organoids?

Engineering tiny brains and mini intestines sounds like an idea from a science fiction movie, but the truth is that researchers have been doing this for a while now. These “tiny” organs are called organoids, which are 3D tissue cultures made from stem cells. As you may remember from biology class, stem cells are cells that have the ability to divide an infinite amount of times and develop into specialized cells. The beauty of organoids is that these in vitro tissue cultures can effectively simulate the behavior of the organ in question.  

Application of Organoids In Research

There are many ways in which we can use organoids in research. We can use them to model diseases and how they impact and develop in the human body. For example, we can model how an infectious disease like COVID-19 can affect the brain by using cortical organoids, as well as analyze Alzheimer's Disease pathology in cerebral organoids. Because organoids divide indefinitely, they are also useful to perform drug screenings. For instance, we can generate cancer organoids from a patient’s tumor that will recapitulate the same phenotype and mutational development of the primary tumor. With these organoids, scientists can test a vast amount of drugs and see which ones the organoids are most sensitive to in order to create a more personalized therapy for a particular patient. Researchers in the human development field may also use organoids to better understand the formation of tissues and organs. For example, to better understand the Central Nervous System, scientists can culture organoids that model different parts of the brain such as the hippocampus, thalamus, cerebellum, etc. Finally, the use of organoids in regenerative medicine is arguably one of the most impressive applications. Research has been done on the generation of advanced intestinal organoids that can be transplanted to the native intestines. 

If you are interested in reading more about stem cell research, you can check out the research being conducted as part of the Columbia Stem Cell Initiative.