Over the last decade, scientists have experimented with using stem cells to heal or replace the scarred tissue that mars the heart after a heart attack. While the cells do spur some level of repair in animals, human tests have resulted in modest or transient benefits at best. Now researchers have developed a new kind of biological sutures, made from polymer strands infused with stem cells, that might help surmount two major obstacles to using stem cells to heal the heart: getting the cells to the right spot and keeping them there long enough to trigger healing.
Scientists from the Worcester Polytechnic Institute, in Massachusetts, have shown that cells derived from human bone marrow, known as mesenchymal stem cells, can survive on the threads and maintain their ability to differentiate into different cell types after being sewn through a collagen matrix that mimics tissue. Preliminary tests in rats suggest that the technology helps the cells survive in the heart.
“This is an out-of-the-box approach,” says Charles Murry, a director of the Center for Cardiovascular Biology at the University of Washington, who was not involved in the study. “Putting cells on thread—once you hear it, it seems simple. But I’ve been in this field for 15 years, and I never thought of it.”
One major challenge has been to get an adequate number of cells to remain in the area of injury. For example, in human studies of injected mesenchymal stem cells, only one percent to about 10 percent of injected cells remained at the site after injection. “Presumably the cells will be much happier if they have something to adhere to than if you just put them in and left them to fend for themselves,” says Murry.
Glenn Gaudette and collaborators at Worcester Polytechnic created the sutures with hair-thin threads made of fibrin, a protein polymer that the body uses to initiate wound healing and a common ingredient in tissue engineering. The microthread technology was developed by George Pins, associate professor of bioengineering at the institute.
The strands are transferred to a tube filled with stem cells and growth solution; the tube slowly rotates, so the stem cells can adhere to the full circumference of the suture. Once populated by cells, the suture is attached to a surgical needle.
About 10,000 mesenchymal cells can inhabit a two-centimeter length of bundled threads. Scientists can vary the size of the bundle, and the speed at which the material breaks down, depending on the application.
“This new technique provides a wonderful tool for cell delivery for cardiac repair and for electrical problems as well, where you might want to create a new electrical path,” says Ira Cohen, director of the Institute for Molecular Cardiology at Stony Brook University in New York. Cohen has collaborated previously with Gaudette but was not involved in this project.
Gaudette’s team is now studying the sutures in rats, to determine how long the cells remain at the injury site, and whether they can help heal tissue. One question that remains to be answered is whether the technology can be scaled up to deliver the hundreds of millions of cells needed to repair the heart wall.
While both animal and human studies show that mesenchymal cells can boost heart function, it’s not clear how. The predominant idea is that the cells, rather than forming new tissue themselves, release growth factors and other molecules that spur the growth of new blood vessels. They may also signal resident cells to begin dividing in order to grow new tissue.
Tissue engineers are developing a number of different methods for delivering stem cells to a wounded heart, including growing patches of beating heart muscle. But Gaudette hopes that biological sutures will prove more versatile than patches, and ultimately less invasive. Because of the threadlike structure, the material has the potential to be delivered via a catheter that passes through a vein.
The research is also part of a larger trend to combine stem cells with tissue engineering and novel biomaterials to help cells grow more naturally and to improve their survival rate once implanted. “If you think of the heart as a damaged piece of material—a concept that I think is gaining traction—you’re not going to want to randomly introduce cells,” says Kenneth Chien, director of the Cardiovascular Research Center at Massachusetts General Hospital. “We want to force cells to go where we want and align the way we want.” He likens this approach to that of a skilled tailor who repairs a sweater using the same thread and stitching as the existing material.
While Gaudette’s study focused on mesenchymal stem cells, other researchers are pursuing the same approach with other cell types, such as cardiac myocytes, which make up the heart’s striated muscle. “Presumably you could make threads of vascular cells, cardiac muscle cells, or multiple cell types,” says Murry. “The greater limitation comes to how big a hole you can make in the heart to drag through a cable of cells.”