In a paper to appear the week of Dec. 13 in the online edition of the Proceedings of the National Academy of Sciences, they report creating a small swatch of heart tissue that displays many of the hallmarks of mature cardiac tissue, including regular contractions.
"We have been trying to engineer a patch of tissue that has the same properties as native heart tissue, or myocardium, that could be attached over injured myocardium," said Gordana Vunjak-Novakovic, a principal research scientist in the Harvard-MIT Division of Health Sciences and Technology (HST) and leader of the work.
"Think of it as a patch for a broken heart," she said.
The MIT approach involves seeding cardiac cells, in this case from a rat, onto a 3D polymer scaffold that slowly biodegrades as the cells develop into a full tissue. The cell/scaffold constructs, which are a little smaller than a dime and about the same thickness, are bathed in a medium that supplies nutrients and gases.
In a patent-pending technique, the researchers then apply electrical signals designed to mimic those in a native heart. They do so by essentially connecting the constructs to a pacemaker. "Initially we had no idea if this would work. As it turns out, electrical stimulation was crucial for rapid assembly of functional tissue," said Milica Radisic, MIT PhD 2004, who will be joining the faculty of the University of Toronto next year.
After only eight days of cultivation, single cells grew into a tissue "with a remarkable level of structural and functional organization," Vunjak-Novakovic said.
"The real advance here is we mimicked what the body does itself and got it to work," said Robert Langer, the Germeshausen Professor of Chemical and Biomedical Engineering and another member of the team.
Other authors of the PNAS article are Hyoungshin Park, an HST research engineer and co-first author with Radisic; Helen Shing and Frederick Schoen of Harvard Medical School; Thomas Consi, now on the faculty at the University of Wisconsin, Milwaukee; and Lisa Freed, an HST principal research scientist.
Among other things, the researchers believe that the electrical stimulation helps condition the cells so that they'll contract in a synchronized form. "We don't want them beating at different rates," Park said. The conditioning coaxes the cells into an ultrastructure "that allows electrical signals to pass quickly from cell to cell, and lets them communicate with each other."
Work continues. For example, the researchers would like to create constructs of clinically relevant thickness, Vunjak-Novakovic said. That depends on providing enough oxygen to cells throughout the tissue. To that end, they have developed a system involving cell culture on channeled scaffolds perfused with a synthetic blood that can carry large loads of oxygen to the cells. Currently the researchers are working to merge the electrical stimulation technique with the new system for oxygenating the constructs.
"But the greatest challenge," said Vunjak-Novakovic, "is to reproduce this with human cells, and test how all this works in the body."
This work was funded by NASA, the NIH, and a Poitras fellowship.
Journal
Proceedings of the National Academy of Sciences