Wear Your Heart on Your Leaf

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We’ve heard of the organ-on-a-chip, and now there’s a tree-on-a-chip, but this is a new one— the heart-on-a-spinach-leaf.

Not a whole heart, that is— just clusters of cells— and the spinach leaf in question was a transparent shadow of its former green self.

A joint team of researchers stripped the plant cells from spinach leaves in order to grow human heart tissue on the leaves’ remaining skeleton. They hope that the technology could one day help doctors replace damaged heart muscle in heart attack victims. As the resulting paper’s title, “Crossing Kingdoms,” suggests, the work bridges the very different worlds of the plant and animal kingdoms by growing humans cells on an exposed leaf scaffold. The study will appear in the upcoming May issue of the journal Biomaterials, and represents the efforts of researchers from Worcester Polytechnic Institute, the University of Wisconsin-Madison and Arkansas State University-Jonesboro.

The spinach scaffold consists of cellulose, a key component of the cell walls that provide structural support for plants and some microorganisms. Cellulose is biocompatible, which means that it can be used in humans without triggering an immune response. But any biology student can tell you that animal cells lack a cell wall — so why would researchers seek to use this plant structure to grow human tissue?

It turns out that for all our fancy tissue engineering and 3D printing technology, we still can’t create blood vessels as well as Mother Nature does. The real hurdle for creating artificial tissues is recreating the tiniest blood vessels, the capillaries. They are so small and numerous that we haven’t been able to replicate their intricate, branching structure in lab-grown tissue. This means that oxygen and vital nutrients in the blood have trouble reaching deep into artificial tissue, hindering the development of man-made organs. Leaves, although different from a heart in innumerable ways, do have well-developed microvasculature similar to human tissue.

Of all plants, why spinach? According to the researchers, it has a “high vascular density” and it’s readily available. These two factors make it ideal to test heart tissue, which also has a lot of blood vessels. Other leaves might work better for other kinds of tissue, and wood might be analogous to bone due to the strength and shape of its internal structures.

Personally, I associate spinach with E coli outbreaks and my occasional attempts to eat more salad, but the spinach leaves the researchers used don’t much resemble what goes in my omelette. First, the researchers flushed the spinach leaves with detergent to remove plant cells, exposing a cellulose scaffold that retained the structure of the leaf, but none of its characteristic green color. When they fed a red dye through the naked leaf’s stem to check its structural integrity, it worked its way toward the outer edges of the now-transparent leaf and stained the vasculature red. By that point, it looked like something I’d firmly keep away from any fork.

Once they established that the transparent leaf structure could “hold water,” so to speak, they wanted to make sure that tiny red blood cells could pass through it— after all, that’s what makes this technology relevant to tissue growth and development. They used tiny microbeads the size of a red blood cell to establish that the leaf’s plumbing could function similarly to the smallest human blood vessels.

Then they seeded the scaffold with human heart cells, which grew into little clusters and began contracting on day five. Eventually, they hope to grow layers of heart tissue that doctors could use to help people who have had heart attacks, adding a whole new dimension to the “heart healthy” attributes of leafy greens.

But surgeons won’t be recreating autumn leaf piles in human chest cavities anytime soon. The researchers aren’t sure if the detergent they used to remove the plant cells could affect the ability of the human tissues to survive, or if the body would reject an entire leaf structure (it’s not exactly a normal shape for an organ). Additionally, human vasculature has separate systems for blood flowing into tissue and blood flowing back to the heart. Plants only have one system, so recreating the human structure might require multiple leaves.

Though there’s a lot of work to be done before the technology tested in this study assumes any valid medical applicability, it’s still really cool to think about growing beating human heart cells on a spinach leaf.

 

WPI has also published a short video on the research, which can be found here:

 

 

If you’re in the Boston area and want to learn more about this, Joshua Gershlak, the paper’s first author and a graduate student at WPI, will be speaking at the National Academy of Inventor’s first Student Innovation Showcase. The showcase is scheduled for April 7 at the Marriott Long Wharf.

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