On a recent Tuesday, biomedical engineering students gathered in Clark Hall to see the fruits of their labor. After spending the better part of two weeks coaxing human induced pluripotent stem cells, or iPSCs, to develop into cardiac muscle tissue by adding biological factors to the cells in a culture plate, students met to measure the force of contractions in the tissue when an electrical stimulus is applied.
"Oh my gosh, it's there!" one student exclaimed when seeing the twitching tissue, a miniaturized model of what happens when someone flexes their arm.
This work was part of a new course called Microphysiological Systems, created by Deok-Ho Kim, a professor of biomedical engineering. Kim says the curriculum for the class, the first of its kind at Johns Hopkins, focuses on applying biological and engineering fundamentals to design microphysiological systems, or MPS, such as organ and tissue chips, 3D-printed tissues, and organoids—artificially-grown masses of cells that resemble an organ.
MPS are used to study human disease, drug development, and precision medicine. Kim created the course because he believes that learning to work with MPS is essential for the next generation of biomedical engineers and scientists.
"MPS are now and will continue to be an integral part of advancing medical science and drug development, both for fundamental discoveries and testing clinical therapies," Kim says. "My course introduces MPS and provides hands-on experience in the design, construction, and implementation of MPS platforms."
The class features lessons on human stem cell technologies, organs-on-a-chip engineering, and education on MPS models for the heart, brain, lung, gut, kidney, tumors, and vascularization. The course also covers tissue chips for space biology, regulatory tools, and industrial applications.
The laboratory portion offers students hands-on experience in MPS design and application. Students learn biofabrication techniques such as microfluidics (manipulation of microscale fluid flow), microfabrication (making of miniaturized structures), and 3D bioprinting to create in vitro miniaturized, 3D complex human tissue models. In addition to the skeletal muscle work, students also learn about iPSC maintenance, turning iPSCs into heart tissue, and using MPS for cancer drug screening.
Kim has developed several MPS models and is a principal investigator on a National Institutes of Health-sponsored grant to study a muscular dystrophy tissue-on-a-chip model for future clinical trials. Kim also has twice sent human heart tissue-on-a-chip specimens to the International Space Station to study the effects of microgravity on heart cells' mitochondria (power supply) and their ability to contract. In 2015, he launched a company, Curi Bio, which develops human MPS platforms for drug discovery.
Kim says the MPS field has been emerging for the past 10 years and should gain even more traction following President Biden's signing of the FDA Modernization Act 2.0 in December. The legislation allows clinical trial investigators to use alternatives to animal testing, such as cell-based assays for drug and biological development. Instead of testing drugs directly on patients, Kim says, scientists could create iPSCs from a patient blood sample, then differentiate those cells into patient-specific heart, liver, brain, or other cells in the lab. "We can test new drugs using personalized patient chips instead of the actual patient."
Alessandra Osilia, a senior majoring in BME and French, says the class has been one of the best she has taken.
"I'm going into pharmaceuticals after graduation, and I was always interested in how people can ameliorate preclinical models," Osilia says. "Right now it's mainly animal testing, and the species' differences [between animals and humans] make it really hard to create accurate preclinical models. MPS platforms are a really cool way to make better models and conduct clinical trials on a chip."
Before enrolling in the class, Justin Zhou, a senior majoring in BME, had worked with blood-brain barrier MPS models in the laboratory of Peter Searson, the Joseph R. and Lynn C. Reynolds Professor of materials science and engineering. Zhou also has worked in Kim's laboratory modeling neuromuscular junctions on a chip.
"This was my first time working on stem cells and creating beating cardiomyocytes [heart muscle cells] from iPSCs, so that was really cool," Zhou says. "It was difficult with the maintenance of the stem cells having to come in every single day to switch the media, so that was kind of a hassle. But it was worth it to see the cells beating ... This is a very good course to be introduced to a very exciting and hot topic in science right now."