Minnesota builds expertise in coaxing the body to heal itself

An obsolete surgical balloon might not sound like a tool of cutting-edge health care, but doctors at Mayo Clinic are repurposing it as they expand the field of regenerative medicine beyond organ transplants and stem cells to new therapies that can coax the body to repair itself.

Mayo physicians are testing the balloon on unborn babies who have a defect that causes their lower organs to bunch up and choke lung growth. By threading the balloon into the womb and inflating it to block the baby's throat, doctors can reverse chest pressure, pushing the organs back down and giving the lungs space to heal and grow on their own.

The technique illustrates how the state's expertise has grown in five years under the Regenerative Medicine Minnesota program. The state-funded initiative has issued 162 grants worth $21.7 million to advance the knowledge and use of stem-cell therapies, but also to explore ways to help the body heal itself without transplanting these powerful but sometimes problematic cells.

"We all thought regenerative medicine equaled stem cells," said Dr. Andre Terzic, director of Mayo's Center for Regenerative Medicine, "but if you go through the applications, especially those that have been breakthrough applications, you realize that … there are new technologies that are going beyond stem cells."

Terzic and Dr. Jakub Tolar, current dean of the University of Minnesota's Medical School and former director of the U's Stem Cell Institute, co-lead the state program, with the goal of turning Minnesota into the "Silicon Valley of regenerative medicine." It receives $4 million per year from the state's general fund that is divided into two-year grants for research and medical education.

Terzic said the range of grants shows the acceleration in regenerative medicine, a field that in many ways got its start in Minnesota, where the first islet transplant was performed at the U in 1974 to create new insulin supplies in patients with diabetes. Once focused on elderly patients and cancer, or chronic diseases such as diabetes, regenerative medicine is expanding as doctors learn how multiple organs have healing powers that can be activated, he said.

Many studies still focus on stem cells — the body's so-called master cells that can grow other cells and tissues — with some testing them as therapies and others just aiming to understand how they can be activated in patients to accelerate healing, Tolar said.

Robert Tranquillo, a biomedical engineer at the U, for example, received grant funding to seed artificial blood vessels with stem cells so they can become suitable replacements for clogged arteries. Funding also supported 4-D printing by mechanical engineer Michael McAlpine, also at the U, to create cellular scaffolds that can harness and direct transplanted stem cells so they can regenerate damaged heart tissue.

A common goal of all the grants, including some awards to local biotech companies, is to hasten the transfer of research discoveries into clinical applications, Tolar said. "The science is not enough. What really matters is what you get from the science, which is understanding."

Mayo received $500,000 to test the balloon placement, a procedure formally known as fetoscopic endoluminal tracheal occlusion, on 10 fetuses, and to join a half-dozen other U.S. institutions that are studying the treatment for an often-fatal birth complication.

Alyse Ahern-Mittelsted was still grieving the loss of a daughter in utero when she discovered in the 20th week of her latest pregnancy last year that her fetus' heart was out of place. His lungs had reached only 22% of expected growth due to a hole in his diaphragm that allowed lower abdominal organs to press up against them. For her, joining the study was an easy choice.

"We had lost our daughter and then we found this out," said the Cresco, Iowa, woman. "To me, it wasn't really a question. I wanted to do everything and anything that we could."

At the 27th week, Mayo's Dr. Rodrigo Ruano lined up the baby so he could thread a balloon through the mother's abdomen and straight into his throat.

This surgical balloon was invented to stop bleeding in the brain, but other techniques now work better for that. It is not approved for the fetal procedure by the U.S. Food and Drug Administration, but Ruano said he is trying to prove its worth. Ruano had performed the procedure in Brazil before coming to Mayo.

During pregnancy, babies receive oxygen from their mothers' umbilical cords. Their throats are filled with fluid, and the inflated balloons create a pressure change that pushes the fluid downward, creating space for the lungs.

"It's the only mechanism we have so far to help promote lung growth" in babies with this condition, he said.

By the time the balloon was deflated and removed from Ahern-Mittelsted's baby, at 34 weeks' gestation, his lower organs had already receded to their expected locations and his lungs were growing. The baby, born last Nov. 20 and named Zane, still needed surgery to close the hole in his diaphragm, but he was breathing on his own.

"I figured he'd be born and he'd turn blue because he couldn't breathe," his mother said, "but when he came out his eyes were open and he made a little tiny peep."