How to Fix a Broken Heart

Syracuse Biomaterials Institute

Through stem cell research in his Syracuse Biomaterials Institute lab, Professor Zhen Ma and his team are growing human hearts so they can find better ways to fix them when they break.

Composition with heart muscle cells overlaid on top of a portrait of Zhen Ma
Photo by Douglas Lloyd Photography

Sarah Moore ’19 pauses to think of a way to describe the work she’s been doing since January in biomedical engineering professor Zhen Ma’s lab at the Syracuse Biomaterials Institute (SBI). “It’s sort of like taking care of a fish,” says Moore, a biomedical engineering major. Except the “fish” is actually dozens of real heart cells that have been engineered from human stem cells and are now growing in petri dishes in the SBI labs in Bowne Hall. Throughout the spring semester, Moore would stop in the lab daily just to check on the cells she was responsible for. “You need to feed them and change out the solution that they sit in,” she says. 

The goal is to get the cells to grow consistently, so she and the other lab members can study the growth patterns and figure out the formula for what keeps the cells—known as cardiomyocytes—alive. “They’re finicky,” she says. “One day we’ll have beautiful beating heart cells—and the next day they’ll be dead.” 

Once Moore and the other lab members are able to keep the heart cells growing long enough, the plan is to use them to study how various heart diseases develop and to test how a patient’s heart cells will react to a specific drug before that patient actually receives it.

Sarah Moore looking into a microscope in a bioengineering lab
Bioengineering major Sarah Moore ’19 checks on the growth of heart muscle cells, known as cardiomyocytes, in Professor Zhen Ma’s lab. Photo by Steve Sartori.

The science is there in terms of turning stem cells into heart cells, says Ma, the Samuel and Carol Nappi Research Scholar in the Department of Biomedical and Chemical Engineering in the College of Engineering and Computer Science. The challenge—and the question Ma’s team is trying to answer—is the engineering one: How do you make the heart cells that have been engineered from stem cells grow in the same way and with the same structures as real heart cells? 

“Basically we want to use stem cells to build a mini-heart in a lab in a cell culture dish,” Ma says. It’s a matter of using microtechnologies to build the microsystems that force the cells to grow into three-dimensional structures that resemble a real heart. A cell is typically 10 microns in length, with a micron equal to one one-millionth of a meter, Ma explains. 

It’s these engineering questions that led Ma to Syracuse in the first place.

How to Study Broken Hearts

Ma’s lab—the System Tissue Engineering and Morphogenesis (STEM) lab—is currently pursuing two major projects. One focuses on growing developing heart cells that will allow researchers to better study what causes congenital heart disease (any problem with the structure of the heart) in developing fetuses. These diseases represent the most common birth defect, affecting nearly 40,000 infants born in the United States each year, according to the Centers for Disease Control and Prevention. The engineering challenge is combining biochemical and physical cues to mimic the way real heart cells grow, so stem cell-derived heart cells grow the same way in the culture dish, Ma says. Once the team can get the model to grow, they’ll be able to study why certain genetic mutations cause specific malformations of the heart.

Colorful close-up images of human induced pluripotent stem cells
Human induced pluripotent stem cells are human blood or skin cells that have been reprogrammed back to the embryonic stem cell-like state. This allows them to duplicate and generate any type of tissue or organ. Images by Professor Zhen Ma.

Once this model is developed, another potential application is for pharmaceutical companies to be able to test whether certain life-saving drugs that an expectant mother might need to take actually pose a risk to a developing fetus—such as chemotherapy drugs for a mom-to-be with cancer, Ma explains. “The science is important because it offers us a way to study how the heart forms, outside of the body, so we can better understand the biological process.” 

The lab’s other major project is the development of personalized drugs for patients with genetic defects that cause heart problems. The team wants to figure out how to generate heart cells from stem cells from a patient’s blood sample, transforming them into heart muscle tissue that can then be used to test drugs tailored to that patient’s genetic defect. The lab-grown heart muscle tissue will have the same genetic defect as the patient, Ma says. “So we can minimize the risk of a drug that we give a patient if we can test the drug on the patient’s live heart tissue in the lab first.”

Ma’s team is currently working with induced pluripotent stem cells from humans that have been engineered to feature the genetic mutations that cause long QT syndrome—a condition where the heart’s electrical activity doesn’t function properly and can cause dangerous, uncontrollable problems with the rate and rhythm of a person’s heartbeat. The condition affects approximately one in 7,000 people in the United States and can be fatal. The team is also investigating human induced pluripotent stem cells that have been genetically edited to have the genetic mutations that cause hypertrophic cardiomyopathy—a common condition that can affect people at any age and can cause high blood pressure, irregular heart beats, and sometimes sudden cardiac arrest. The next step, Ma says, is looking at even more genetic mutations and how they lead to other heart diseases.

Collaboration Makes It Possible

One of SBI’s unique features that makes Ma’s work possible is the collaborative atmosphere. Ma has been working with biomedical and chemical engineering professor Pranav Soman to build some of the materials Ma’s team needs for its research. Soman’s work focuses specifically on biomedical 3D printing of materials that range in size from an inch to even smaller than the microscale required for Ma’s work.

Nature makes “fantastically complex” things—and current manufacturing technologies are way behind that, Soman says. “My philosophy is that if we can remove the limitation of what we can make, we can have a direct impact on the entire field of biomedical engineering.”

Plansky Hoang and Zhen Ma working in the lab
As Professor Zhen Ma looks on, chemical engineering doctoral student Plansky Hoang G’20 works with stem cell-derived heart cells engineered in Ma’s lab. Photo by Evan C. Jenkins.

For Ma’s team, Soman’s task was to create a mold that could be used to grow a ring of heart tissue. To do this, Soman drew the design using 3D modeling software and input those instructions into a 3D printer, which produced the mold. It’s cylindrical in shape with a post in the center that the stem cell-derived heart cells can form a ring around (the whole thing is just a few millimeters tall and wide). 

Ma’s team uses the molds to create the heart models to study long QT syndrome, hypertrophic cardiomyopathy, and other heart diseases caused by genetic mutations—and test what drugs work. “The collaboration with Dr. Soman gives us the diversity and flexibility to generate different cardiac tissue structures for different disease modeling purposes,” Ma says.

If a researcher had to figure out how to make this type of mold on their own, it might take six months to a year, Soman says. But that’s the benefit of the collaborative environment at SBI, where you have someone with expertise in 3D printing working alongside other researchers. “It’s a fantastic environment for research,” says Soman, whose team is also contributing to other projects with applications for kidneys and bones.

Both Ma and Soman hope the collaboration continues. They also hope it will open up new grant opportunities to get funding from external sources. Ma’s work is currently supported by the Nappi Research Scholar funding. “The best way to go forward is to join hands and join forces,” Soman says.

And that collaborative force is already moving Ma and his team closer to their research goals. “The technology is here,” Ma says, “and it’s allowing us to study the heart outside of the human body and better understand the biological process of how it forms.”

Sarah DiGiulio

This story was first published on December 14, 2017 and last updated on . It also appeared as “Model Hearts” in the Summer 2017 issue of Syracuse University Magazine.

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