UW-Madison’s legacy in stem cell research continues – molding cell behavior through material, ex-vitro modeling made in-vitro
Just over 26 years ago, developmental biologist James Thomson of UW-Madison isolated human embryonic stem cells for the first time, ushering in a new age of medical research, controversy, and possibilities. Less than a year after his breakthrough, local cell banking, testing, and distribution company WiCell was founded. To this day, it continues to provide stem cells to global research, Madison-based companies, and UW-Madison research labs at the Stem Cell and Regenerative Medicine Center.
Among these research groups is the Bioinspired Materials Lab, led by William Murphy, UW-Madison professor of Biomedical Engineering, Orthopedics and Rehabilitation, and director of Forward Bio Institute. Created in 2004, the lab aims to control the behavior of these cells through their material environments.
“We’re really trying to use materials as instructions to control and instruct stem cells to form new tissues,” explains Murphy.
The intricate process of directing stem cell differentiation is crucial to research and its application. Margot Amitrano, a PhD student at the Bioinspired Materials Lab, describes this dilemma: “The main challenge that I had was narrowing down the variables of interest… the cells will respond to basically everything,
“[There are] a million potential variables – so where do you start looking? What do you start manipulating to see how the cells are going to respond?”
Margot Amitrano, PhD student
What do you start manipulating to see how the cells are going to respond?”
To navigate these variables, Amitrano uses material screening. “We generate classes of materials [whose] properties can be systematically varied,” Murphy explains. “We can change mechanical properties, what the cells are adhering to, [and] what soluble molecules the cells are exposed to… and then we can use computational methods [such as AI and machine learning] to narrow down the experimental space.”
Amitrano uses this process to grow and stabilize cardiomyocytes, the muscle cells that control heart beats. “A very important advantage of using stem cells to differentiate cardiomyocytes [is that] you can create a big population relatively quickly.” Generating a large population of cells is necessary for stem cell therapies, given the need for billions of cells per clinical treatment.
However, clinical uses aren’t the only revolutionary application of stem cells. Contrary to early expectations, their primary impact has been in tissue modeling. “Developing ex-vivo [outside of the body] tissues that can be used as models of human cells [has been] useful for disease modeling, drug discovery, and understanding tissue development,” Murphy says.
While part of his lab utilizes materials as instructions for cell differentiation, his team also uses the stem cells as in-vitro models to understand therapy delivery processes. One of their current projects mimics brain-like environments to understand and treat neuroinflammation, a symptom of central nervous system diseases like Alzheimer’s, Parkinsons, and multiple sclerosis.
Although stem cells have become less controversial since the development of induced pluripotent stem cells in 2006 – stem cells that can be created from adult tissue – the confusion surrounding them remains. “[It’s] a science communication issue,” admits Murphy. “People will look at our work and say, ‘you’re growing how many brains?’ We are mimicking some key conditions of the brain to study brain disease… but none of these models can reach the consciousness that we typically associate with the human brain.”
Amitrano, close to defending her thesis, works to mitigate this miscommunication. “Something that’s interesting with [biomedical engineering] is that we do a lot of scientific communication exercises … people don’t necessarily understand [stem cells]. It hasn’t been clearly communicated to the public what their purpose and potential applications are.”
Built on the foundation laid here for stem cells 26 years ago, the Murphy lab forms just one part of Madison’s thriving research sector. “Madison is in some ways the birthplace of human stem cell research,” Murphy concludes. As the field continues to develop and differentiate, Madison will remain central to the innovation of stem-cells.