If an overhyped vegetable existed before marketers coined the term superfood — and long before Oprah Winfrey chatted up acai berries with Dr. Oz — look no further than spinach. (Here’s to Popeye, eating the stuff by the can to inflate his biceps.) Spinach alone, of course, won’t pump anyone up. But it does have a few physical properties of the type that excite biomedical engineers. Spinach grows a network of veins, for instance, that thread through its leaves in a way similar to blood vessels through a human heart.
These leafy veins allowed researchers at Massachusetts’s Worcester Polytechnic Institute to give a new meaning to heart-healthy spinach. The tissue engineers, as they reported recently in the journal Biomaterials, stripped green spinach leaves of their cells. The spinach turned translucent. The scientists seeded the gaps that the plant cells left behind with human heart tissue. Heart cells, in clusters, beat for up to three weeks in this unusual environment.
The inspiration for the human-plant fusion came over lunch — and, yes, the leafy greens were involved — when WPI bioengineers Glenn Gaudette and Joshua Gershlak began to brainstorm new ways to tackle a deadly medical problem: the lack of donor organs. Of the more than 100,000 people on the donor list, nearly two dozen people die each day while waiting for an organ transplant.
To meet the demand, scientists have tried to create artificial organs through innovations such as 3-D-printing tissue. So far, however, no one has been able to print a perfect heart.
“One of the big problems in engineering heart muscle is getting blood flow to all of the cells,” Gaudette, a professor of biomedical engineering at WPI, told The Washington Post. “Heart muscle is pretty thick.” Current technology cannot construct tissue dense enough to replace a damaged heart while also allowing for the tiny blood vessels needed to deliver life-giving oxygen.
Rather than creating minuscule blood vessels, the scientists decided to borrow from what nature already evolved. First, they removed the cells from spinach leaves purchased at a local market. “We use detergent — soaps — which strips away the cellular material of tissues,” said Gershlak, a WPI graduate student in Gaudette’s lab. “This leaves behind the protein matrix and structure.” The soap punctured plant cell membranes and washed the deflated cells away; the overall effect was not unlike turning over a garden before planting new crops.
Left behind was cellulose, a plant material known to be compatible with mammal tissue, as well as the intact leaf veins. The scientists seeded the now-vacated cellulose matrix with cardiac muscle cells. After five days, the muscle cells began to beat.
It was not quite as if researchers grew an entire slab of quivering muscle from spinach. And, though the scientists watched red liquid course through the spinach veins, this was dye, not blood. But to witness individual human cells contracting on a spinach leaf, via microscope, was exciting enough for Gaudette to whip out his cellphone and began recording in grainy video.
“It was definitely a double take,” Gershlak said, of discovering the beating muscle cells. “All of a sudden you see cells moving.”
This was not the only instance in which researchers cultivated human tissue on a plant scaffold. Recently, a team of Ottawa scientists stripped an apple of its plant cells, carved a fruit slice to look like a human ear and filled its extracellular matrix with cervical tissue.
But Gershlak, Gaudette and their colleagues were the first, they said, to use the technique in an attempt to repurpose plant veins. They poured tiny spheres through the spinach leaves. Beads 10 microns in diameter, a size on par with red blood cells, successfully flowed through the vein network.
Though these early experiments served as proof-of-concept work, Gaudette said the study could be the foundation for stitching the veins of spinach leaves to human blood vessels. “Long term, we’re definitely envisioning implanting a graft in damaged heart tissue,” he said.
But the researchers first need to make sure that plant scaffolds like these would not be rejected, once inside a host. They also plan to make their heart-spinach hybrids stronger. “If we stack decellularized leaves, can we create a large thickness,” Gaudette wondered, “more along the thickness of a human heart wall?”
One advantage of working with plants was the cornucopia of options at the scientists’ disposal. In the new report, the biomedical engineers successfully stripped plant cells from parsley, peanut hairy roots and a species of wormwood in addition to spinach. The biomedical engineers imagined that a piece of broccoli or cauliflower, once stripped of its cells, could be a foundation for growing lung tissue. And researchers in Wisconsin, collaborating with the WPI lab, recently strolled through their campus arboretum, plucking exotic leaves to test.
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