Few concepts associated with tissue engineering have fired the public’s imagination like the idea of growing brand new hearts.
The need for such a breakthrough is clear: thousands succumb to heart disease each year because no transplant organ is available. But a huge amount of work lies ahead.
Lisa Freed is helping prepare the way for lab-grown hearts. The daughter of an MIT Lincoln Laboratory engineer, Freed says she’s “always been fascinated by the way natural systems work.” That passion helped her win a top prize at an MIT-based high school science fair. Later, while she was studying for both an M.D. and a Ph.D. degree and working in Robert Langer’s lab at MIT, it evolved into a determination to create new human tissues.
With collaborator Gordana Vunjak-Novakovic, Freed has since become a tissue-engineering pioneer. Eight years ago, using a so-called bioreactor vessel as a seedbed, she grew heart cells on a biodegradable scaffolding to form a “patch” that pulsated as if part of an actual organ. (“It was my most awesome laboratory moment ever,” she says.)
But Freed, a Harvard-MIT Division of Health Sciences and Technology principal research scientist, says such feats don’t mean engineered hearts are around the corner. Even creating patches for ailing hearts poses big challenges.
Why is engineering heart tissues so hard? The contrast with engineered cartilage tells the story.
Articular cartilage, the tough, slippery stuff that’s about a twelfth of an inch thick and fills the space between the bones in our joints, offers key advantages for tissue engineering.
“It doesn’t have blood vessels,” notes Freed, “it doesn’t need much oxygen, and it’s like skin in that it’s basically twodimensional.”
Those traits have made cartilage a favored focus for tissue engineers, including Freed and Vunjak-Novakovic. Using scaffolds and bioreactor vessels, in fact, the pair has created engineered cartilage that shares key qualities with the real tissue. (“I’m really eager to see it used in patients,” says Freed, who’s collaborating with various companies in pursuit of that goal.)
By contrast heart muscle, at about a third of an inch deep, poses major challenges to tissue engineers. Its cells demand a constant supply of oxygen. “Each heart cell is serviced by its own capillary,” notes Freed. “How to get blood supplies into engineered heart tissue is the $64 million question.” Moreover, mature heart cells, unlike their cartilage counterparts, can’t proliferate in a lab setting. And, heart cells should ideally be stretched as they grow — just as they would be in a real heart.
There have been key advances, though. Freed specializes in cell-biomaterial-bioreactor systems designed to regenerate functional tissues in the lab. “The idea is to trick cells into thinking they’re in a physiological environment,” she explains. Thanks to her efforts and those of others, heart cells are already being grown in the presence of some of the biochemical and physical signals that ready them for implantation.
Meanwhile, recent work suggests that stem cells — the turn-into-almost-anything entities being eyed for use in all kinds of engineered tissues — can be precursors for heartmuscle cells.
“We used to think obtaining cells would be a huge obstacle,” says Freed, “but if stem cells can be differentiated into cardiac cells, it may not be a problem.”
This doesn’t mean engineered heart patches will be ready for patient use soon. But, notes Freed, “there has been tremendous progress just in the past year.” And lab-grown hearts? On that question, Freed demurs. “All I’ll say,” she comments, “is that anything is possible.”