Using Stem Cells to Repair Tiny Hearts

A protein lining the inner layer of the heart. The protein is required for heart muscles to proliferate during development.

Ram Kumar Subramanyan, MD, PhD, brings a unique point of view to the laboratory, where his goal is to one day use stem cells to create replacement parts for children with heart defects.

“I have the dual perspective of understanding what it takes to make a sheet of cells in the lab—and knowing how I can use it in the operating room,” he says.

As a cardiothoracic surgeon, Subramanyan spends much of his time repairing the tiny hearts of babies born with congenital heart disease—whether it’s inserting a tube-shaped shunt to correct blood flow or sewing a patch over a hole in a baby’s heart. Today, the replacement parts used to correct heart defects are made from prosthetic materials, such as plastic or animal valves, which degrade and eventually need to be replaced.

As a basic science researcher, Subramanyan is focused on regenerative medicine, a field in which scientists grow human cells that could be implanted into a patient to repair damaged organs. Regenerative medicine research begins with understanding the fundamental factors of how a heart develops. Eventually, scientists may be able to use stem cells to create new parts that come from a patient’s own cells.

                                 Ram Kumar Subramanyan, MD, PhD

Creating replacement parts

Someday, Subramanyan says, a scientist may be able to take a blood sample from a newborn with a heart defect, isolate the stem cells, grow those cells in a tube and “teach” them to become the type of cells that, for example, line the inner layer of the heart. Finally, those engineered cells could be implanted and used to repair the child’s heart.

“What if, as surgeons, we can use a biologic material made of the baby’s own cells to repair a heart?” he asks. “Because it’s native tissue, it would have the potential to grow with the baby, so the baby would not need another operation. Also, since it would not be foreign material, the baby’s body would not reject it.”

While much of regenerative medicine is focused on creating whole organs such as kidneys and intestines, Subramanyan says this approach brings unique challenges for an organ as complex as the heart.

“Eventually, the goal will be to use stem cells to grow structures like a valve, but it doesn’t have to start there. I cannot make a new heart yet, but I may not need to,” he explains. “As a surgeon, all I require is a simple patch to repair a baby’s heart.”

The future of cardiac care

Harnessing the power of stem cells to create replacement parts is still years away, but today, Subramanyan is using stem cells to create a “sheet” of muscle cells that is about half the size of a standard 8 ½-by-11 sheet of paper. In theory, these sheets of cells could be rolled up to form a tube or used as a patch to repair a child’s heart.

Looking ahead to the next decade, he predicts that discoveries in the lab will have highly relevant clinical applications.

“CHLA will be the center that says, we’re not only going to provide you with a molecular basis for your disease, but we’re going to be able to create a patch made from your child’s own cells to fix the heart, and help us treat your child’s disease better,” he says. “We’ll be able to seamlessly integrate advances in regeneration and developmental biology into bedside care for babies with congenital heart disease.”

Image courtesy of the Subramanyan Lab, CHLA