Regenerative medicine is closely related to individualized medicine, said Dr. Robert Simari, who chairs the Cardiovascular Cell Therapy Research Network for the National Heart, Lung, and Blood Institute.
At Mayo, Simari codirects Mayo’s cardiac valve and vascular regeneration efforts and oversees a project that he hopes will lead to the fabrication of custom heart valves and other parts for defective hearts.
The project started two years ago, when a patient from the Middle East asked if stem cell technology could be used to create a valve, Simari said. He assigned Dr. Daniel Spoon, 33, to spearhead research on whether valves could be fabricated on what resembles a fancy inkjet printer, with a goal of having a working valve implanted in sheep by August 2014. Spoon said the work is on track.
The project illustrates the confluence of computer science, genomics and medicine.
Printing a heart valve essentially involves two parts: creating an anatomically correct scaffold and coating it with bioengineered stem cells — possibly from a patient’s skin or heart muscle.
The scaffold can be made by removing the cells from a pig’s heart valve, a process known as decellularization, which leaves a framework of collagen and elastin. Or an exact replica of the patient’s own valve can be made using advanced imaging technology and then manufacturing a duplicate from biocompatible products.
Last month, Mayo installed a three-dimensional “bio-plotter,” made by a German company, that is capable of printing both the scaffold and the cells in a sterile solution. Spoon said it’s one of just three bioprinters in the United States capable of doing both.
Researchers have found that while it’s easy to remove cells from a heart valve, it can be difficult to “recellularize” it. Blood flow and pressure in the heart kill the cells, Spoon said.
Spoon and his colleagues developed a way to inject the cells into the scaffold. But the key to keeping them alive may be a state-of-the-art “bioreactor” that Mayo developed in conjunction with a company in Massachusetts. Mayo hired Brandon Tefft, a 30-year-old biomedical engineer, to help design a bioreactor that would mimic conditions in the heart at rest. The bioreactor’s unique design will let researchers gradually increase the pressures on the valves, Spoon said, “and it’s our hypothesis that will enable us then to take them from static conditions to large animals.”
Simari called the study a “shakedown cruise” for a procedure that could be used to create custom valves, especially for children who need valves that can grow as their bodies grow. He said that could happen in five to 10 years, though it may take longer for adults, because they already have good alternatives that last 10 to 15 years.
In the meantime, Simari said he expects the research to spin off related technologies, such as printing heart patches and blood vessels. The printing of tendons, ligaments and cartilage could come even sooner, he said.
Dr. Dennis Wigle, 46, is a thoracic surgeon who oversees a massive library of genomic data, cells, tissue, blood and other specimens in what Mayo calls its Regenerative Medicine Biotrust.
While replacing diseased organs via transplantation remains the only option in many cases now, Wigle said, nearly everyone believes that the future lies in regenerative and individualized medicine, and the Biotrust is a critical component.
“We can decellularize a lung to use as a matrix and recellularize it. No one has actually done it in a human yet, but we’ve seen in mice and rats what’s coming down the line,” Wigle said. “We’re at the science-fiction stage, but we’re getting to where it’s almost … an engineering problem.”
The new directions for medicine are so complex, Wigle said, that they require cross-collaboration of physicians, research scientists, engineers, mathematicians, data analysts, and so on.
He added: “One person sitting at a desk with a big notepad in front of them can’t do this anymore.”