Science draws inspiration from everywhere for a breakthrough. A sticky plate with bacteria gave us the first antibiotic - penicillin. Combining yeast with a platinum electrode under voltage gave us a powerful chemotherapy drug - cisplatin. Dr. Andrew Pelling of the University of Ottawa draws his radical ideas from the science fiction classic The Little Horror Store. In particular, he likes the main antagonist of the film: the cannibalistic plant Aubrey 2.
It's something that looks like a plant with mammalian traits, Pelling said at the Exponential Medicine conference in San Diego this week. "So we started to wonder: can this be grown in a laboratory?"
Pelling's ultimate goal, of course, isn't to bring a sci-fi monster to life. Instead, he wants to understand if conventional plants can provide the necessary structure to replace human tissue.
Rise of mechanobiology
Growing a human ear from apples may seem like a strange process, but Pelling's starting point is that fibrous insides are strikingly similar to the microenvironments in which bioengineered human tissue is usually grown in laboratories.
To make an ear replacement, for example, scientists routinely cut or 3D-print hollow support structures from expensive biocompatible materials. They then inoculate human stem cells into this structure and painstakingly supply it with a cocktail of growth factors and nutrients, encouraging the cells to grow. Eventually, after weeks and months of incubation, the cells proliferate and differentiate into skin cells in the forests. The result is a bioengineered ear.
The problem is that the barrier to entry is very high: stem cells, growth factors and materials for forests are all expensive to buy and difficult to produce.
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But are these components really needed?
Through a series of experiments, Pelling and others have discovered that these mechanical forces are not just a by-product of biology; rather, they fundamentally regulate the underlying molecular mechanisms of the cell.
Previous studies have shown that each stage of embryo growth - “a fundamental process in biology” - can be regulated and controlled by mechanical information. In other words, physical forces can induce cells to divide and migrate through tissues, as our genetic code guides the development of the entire organism.
In the laboratory, stretching and mechanically stimulating cells appears to radically change their behavior. In one test, Pelling's team sprinkled cancer cells onto a sheet of skin cells grown at the bottom of a Petri dish. Cancer cells come together in small balls, forming a clear barrier between the microtumor and skin cells.
But when the team of scientists placed the entire cellular system in a device that stretched it slightly - mimicking respiration and body movement - the tumor cells became aggressive, invading the layer of skin cells.
What's even cooler: no active movement is required for mechanical forces to transform cell behavior. The form of the microenvironment is sufficient to guide their actions.
For example, when Pelling placed two types of cells in a physical structure with grooves, the cells self-detached within a few hours, and one type grew in the grooves and the other on higher projections. Simply by sensing the shape of this corrugated surface, they "learned" to separate and spatially fit.
So: using only one shape, cells can be stimulated to form complex three-dimensional models.
And here the apple will help us.
An apple … or an ear?
Under the microscope, the microenvironment of an apple is on the same length scale as artificial surfaces for making replacement tissues. This discovery made scientists wonder: is it really possible to use this plant surface structure to grow human organs?
To test this, they took an apple and washed all of its plant cells, DNA, and other biomolecules. There are only fibrous scaffolds left - they still get stuck in your teeth. When the team placed human and animal cells inside, the cells began to grow and spread.
Encouraged by the result, the scientists carved an apple in the shape of a human ear and repeated the process above. Within a few weeks, the cells proliferated and turned a piece of apple into a fleshy human ear.
Of course, one shape won't be enough. The replacement tissue must also take root inside the body.
The team then implanted apple forests right under the mouse's skin. In just eight weeks, healthy mouse cells not only colonized the matrix, but the rodent's body also produced new blood vessels that helped the forests live and thrive.
Bioengineered tissue has three important properties: it is safe, it is biocompatible, and it is produced from a renewable, ethical source.
Moving from theory to practice
Pelling is particularly impressed with her results because of its simplicity: it doesn't require stem cells or exotic growth factors to work. The elegant approach simply uses the physical structure of the plant.
The team is currently expanding their work to three main areas of tissue engineering: soft tissue cartilage, bone tissue, spinal cord and nerves. The importance is to match the specific microstructure of the plant with the tissue.
And why limit ourselves to the body that nature gave us? If scaffold shapes are the only determinant of tissue or organ engineering, why not create your own shapes?
Pelling armed himself with this idea and created a design company that would scaffold three different types of ears: regular human ears, pointy ears like Spock's, and wavy ears, which could, in theory, suppress or enhance various frequencies.
Ilya Khel
