Many of today’s greatest disease challenges — including heart disease, diabetes, and Alzheimer’s and Parkinson’s diseases, to name just a few — develop over years, in complex organs. By the time a patient develops symptoms, the biological or environmental factors that triggered the disease may be long gone from the body. This means that we cannot only study how the disease affects patients. We need to understand how disease develops, in order to bring more effective treatments and cures to patients.
HSCI scientists have the increasing ability to create cells of any particular type, with or without gene editing. We can create the very cells affected by a certain disease, and watch how healthy and diseased cells grow, function, and die. This not only allows us to understand tissue development and disease mechanisms, but also enables us to test drugs and gene therapies that could be targeted therapeutic interventions.
Studying human disease in a dish
HSCI scientists use stem cells to study disease at multiple levels:
Some diseases or conditions primarily affect a particular cell type: the pancreatic beta cell in diabetes, the motor neuron in ALS, or the nociceptor neuron in pain conditions. In these cases, we can grow these specific cells in a dish and observe how they function compared to their healthy counterparts.
Multiple cell types
Two or more cell types can be involved in a disease, such as the neuromuscular junction in spinal muscular atrophy. We can grow both types of cells together to observe how they interact, how the cells signal to each other, and how the disease transmits.
By growing organoids — tiny, self-organized, three-dimensional tissue cultures that are derived from stem cells — we can study development and disease at a systems level. This is particularly useful in organs with complex structures, such as the kidney, or in organs that we cannot otherwise observe, such as the brain. To date, researchers have made organoids that resemble the brain, kidney, lung, intestine, stomach, and liver to study diseases ranging from cancer to neuropsychiatric conditions.
When diseases affect organs with mechanical properties, such as the heart or lung, we combine cell biology with bioengineering tools and technology in order to study them. For example, by growing heart muscle cells and putting them on a thin biomaterial film that can be electrically stimulated, we can study how the hearts of patients with Barth Syndrome function.
Leveraging gene editing
Researchers continue to make advances in gene editing tools and cellular programming. We leverage these techniques for a wide range of applications: to understand whether a disease with multiple genetic variants is really a single disease or multiple diseases, to edit “in” or “out” different gene corrections to find causal connections and therapeutic options, and to test if a drug could work for all patients or only those with a certain genetic background.