Researchers Take Steps To Growing Replacement Blood Vessels

Researchers here are investigating ways to re-grow tiny blood vessels to keep damaged heart tissue alive after a heart attack, by a process called therapeutic angiogenesis.

"Our bodies already contain cells that trigger the growth of new blood vessels. We want to use those same cells to create seeds for blood vessels in the laboratory and transplant them into the body," said Nicanor Moldovan, research scientist and assistant professor in Ohio State's Biomedical Engineering Center, and Heart and Lung Institute.

He relayed the researchers' initial results in a presentation September 25 in Columbus at the BioMEMS and Biomedical Nanotechnology World 2000 conference, co-sponsored by Ohio State.

Moldovan admits that his plan of growing capillaries in tissue culture and implanting them in the body is very complex,and relies on ideas about blood vessel formation that are just beginning to emerge.

"We've had to deal with a lot of speculation or supposition, but our approach appears to be a very promising one," he said. "Of course, this is just our dream, but we are working on it."

In these earliest results, Moldovan and his colleagues have demonstrated that these "seed" cells, called endothelial cells, will grow in grooves carved in the surface of a soft transparent gel in the laboratory.

The researchers' ultimate plan is to grow endothelial cells inside or on the surface of silicon molds resembling capillaries. If the cells could assume the shape of capillaries under those conditions, they could one day be transplanted -- either alone or with some kind of carrier -- into the heart to start the replacement of blood vessels that died during a heart attack.

Showing that the cells can grow two-dimensionally following the shape of grooves in the gel is a necessary first step, Moldovan said.

To demonstrate that the cells were indeed following the shape of the grooves, Moldovan and his colleagues first had to develop a method to let them accurately view the shape of the tiny grooves, which measure only a few micrometers across -- less than the width of a human hair. Normal viewing instruments would have torn the delicate surface of the gel, he said.

They developed a method Moldovan characterizes as fast and inexpensive. After they scrape the tiny grooves into the gel, they spray the gel with even tinier fluorescent beads, which spill along the surface and fill the grooves. A quick look through the microscope reveals the location of the grooves.

The researchers then literally wash the beads from the gel, leaving its delicate surface intact.

Moldovan envisions that one day capillaries could be carried into the heart tissue by micromachines called "angiochips." Once inside the heart, the implants could begin to undo the damage of a heart attack.

This relates to his other work in the Biomedical Engineering Center at Ohio State, Moldovan said. There the aim is to the stimulate capillary growth by angiogenic drugs released from implantable silicon capsules.

"We probably couldn't bring tissue back in its original form, but we could try to re-vascularize, to make a heart beat again. Or, at least, keep the heart tissue from dying by creating new capillaries that would provide blood and oxygen as soon as possible," he said.

When it comes time to create three-dimensional molds to shape the capillaries, the researchers will turn from gel to silicon, Moldovan said. Methods already exist to create complex 3D shapes in the metal, he said, and his previous research demonstrated that endothelial cells could grow on silicon.

"Once we have proof that we can grow cells in specific three-dimensional shapes on or inside silicon, then we hope to come back to the tissue," he said.