While volunteering at the University of New Mexico Children’s Hospital in Albuquerque, Quinton Smith quickly realized that he could never be a doctor.
Smith, then a college student, was too sad to see sick children all the time. But, he thought, “maybe I can help them with the science.”
Smith had chosen his specialty, chemical engineering, because he saw it as “a cooler way to get a preparation.” Though he ultimately landed in the lab instead of the bedside, he has remained passionate about finding ways to cure what ails people.
Today, his lab at the University of California, Irvine, uses tools often used in the manufacture of small electronic devices to create miniature lab-grown organs that mimic their real-life counterparts. “Most of the time when we study cells, we study them in a petri dish,” says Smith. “But that’s not its native form.” Pushing cells to assemble into these three-dimensional structures, called organoids, may give researchers a new way to study diseases and test possible treatments.
By combining Silicon Valley technology and stem cell biology, scientists are now “creating tissues that look, react and function like human tissue,” says Smith. “And that hasn’t been done before.”
The power of stem cells
Smith’s work began in two dimensions. During her undergraduate studies, she spent two summers in the lab of biomedical engineer Sharon Gerecht, then at Johns Hopkins University. Her project aimed to develop a device that could control oxygen and fluid flow inside tiny chambers on silicon wafers, aiming to mimic the environment in which a blood vessel forms. It was there that Smith came to respect human-induced pluripotent stem cells.
These stem cells are formed from cells in the body that are reprogrammed to an early embryonic stage that can give rise to any type of cell. “It just amazed me that you can take these cells and turn them into anything,” Smith says.
Smith eventually returned to Gerecht’s lab for his PhD, exploring how physical and chemical signals it can push these stem cells to become blood vessels. Using a technique called micropatterning, where the researchers stamp proteins onto glass slides to help cells stick, he prompted the cells to organize themselves into the beginnings of artificial blood vessels. Depending on the pattern, the cells formed Stars, circles or triangles in 2Dshowing how cells come together to form such tubular structures.
While doing a postdoc at MIT, he transitioned to 3-D, with a focus on liver organoids.
Like branching blood vessels, a network of bile ducts transports bile acid throughout the liver. This liquid helps the body digest and absorb fat. But artificial liver tissue doesn’t always recreate the branching ducts like they do in the body. Cells grown in the lab “need a little bit of help,” Smith says.
To get around the problems, Smith and his team pour a stiff gel around tiny acupuncture needles to create channels. After the gel solidifies, the researchers seed stem cells inside and spray the cells with chemical signals to coax them into forming conduits. “We can create bile ducts on demand using an engineering approach,” she says.
This approach to making liver organoids is possible because Smith speaks the language of biology and the language of engineering, says biomedical engineer Sangeeta Bhatia, a Howard Hughes Medical Institute Investigator at MIT and Smith’s postdoctoral mentor. She can draw on her knowledge of cell biology and take advantage of engineering techniques to study how specific cell types are organized to work together in the body.
For example, Smith’s lab now uses 3D printing to ensure that lab-grown liver tissues, including blood vessels and bile ducts, are organized the right way. Such engineering techniques could help researchers study and pinpoint the root causes of some liver diseases, such as fatty liver disease, Smith says. Comparison of organoids grown from cells of healthy people with those grown from cells of patients with liver disease, including Hispanics, who are disproportionately affected, may point to a mechanism.
Looking beyond the liver
But Smith is not limited to the liver. He and his students are branching out to explore other tissues and diseases as well.
One such activity is preeclampsia, a disease that affects pregnant women and disproportionately affects African-American women. Women with preeclampsia develop dangerously high blood pressure because the placenta is inflamed and constricts the mother’s blood vessels. Smith plans to examine lab-grown placentas to determine how environmental factors, such as physical forces and chemical signals from the organ, impact maternal blood vessels.
“We are very excited about this work,” Smith says. Recently, scientists have tricked stem cells into entering an earlier stage of development that can form placentas. These lab-grown placentas even produce human chorionic gonadotropin, the hormone responsible for positive pregnancy tests.
Yet another victory for the power of stem cells.
Quinton Smith is one of this year’s SN 10: Scientists to Watch, our list of 10 early and mid-career scientists who are making extraordinary contributions to their field. We will be releasing the full list throughout 2023.
Do you want to nominate someone for SN 10? Send their name, affiliation and a few sentences about them and their work to sn10@sciencenews.org.
