For breakthrough science draws inspiration from everywhere. Sticky plaque bacteria gave us the first antibiotic — penicillin. The connection of yeast with platinum electrode under tension has given us a powerful chemotherapeutic drug cisplatin. Dr. Andrew Pelling from the University of Ottawa draws its radical ideas of the classics of science fiction “Little shop of horrors.” In particular, he likes the main antagonist of the film: cannibal plant “Aubrey-2”.
This is something like a plant with the traits of a mammal, said Pelling at the Exponential Medicine conference in San Diego this week. “So we started to wonder: is it possible to grow it in the lab?”.
The ultimate goal of Pelling, of course, is not to revive the sci-Fi monster. Instead, he wants to see if ordinary plants to provide the necessary structure for replacement of human tissue.
The heyday of mechanobiology
The cultivation of the human ear from apples may seem a strange process, but the starting point of Pelling is that the fiber inside is strikingly similar to the microenvironment in which the laboratories are usually grown bioengineered human tissue.
To manufacture a replacement ear, for example, scientists usually cut out or print on a 3D printer hollow supporting structures of the expensive biocompatible materials. Then they seeded with human stem cells in this structure and carefully supply her with a cocktail of growth factors and nutrients, causing cells to grow. Eventually, after weeks and months of incubation, cells spread and differenciate in skin cells on the scaold. The result is a bioengineered ear.
The problem is that the entry threshold is very high: stem cells, growth factors, and materials for scaffolding — all expensive to buy and difficult to produce.
But do these components actually?
“We often think of biology through the prism of the genome or biochemistry,” says Pelling. But cells and tissues are the living components — they stretch, shrink and shift, generating mechanical forces that act on each other.
During a series of experiments Pelling and others have discovered that these mechanical forces are not simply a byproduct of biology; rather, they radically adjust the underlying molecular mechanisms of the cell.
Earlier studies have shown that each growth stage of the embryo — “a fundamental process in biology” — it is possible to regulate and control the mechanical information. In other words, physical force can induce a cell to divide and migrate through the tissue, because our genetic code guides the development of the whole organism.
In laboratory tensile and mechanical stimulation of cells, apparently, radically to change their behavior. In one of the analyses, the team of Pelling put cancer cells on a sheet of skin cells grown on the Petri dish bottom. Cancer cells are gathered together into small balls, forming a clear barrier between micropohone and skin cells.
But when a team of scientists put the entire cellular system to the device that it is slightly stretched — imitating breathing and movement of the body — the tumor cells are aggressive, penetrating the layer of skin cells.
“There is no gene or even biochemistry. This is a purely mechanical effect,” says Pelling. “Between these things there is a fundamental connection.”
What’s even cooler: to mechanical power transformed the behavior of the cells, active movement is not required. The shape of the microenvironment are sufficient to direct their actions.
For example, when Pelling put two types of cells in the physical structure with grooves, the cells salootdelenie within a few hours, and one type has grown in the grooves, and the other on the higher ledges. Just feeling the shape of this corrugated surface, they “learned” to separate and spatially to meet.
So: using only one form, you can stimulate the cells to form complex three-dimensional models.
And here we will help Apple.
Apple… or an ear?
Under the microscope the microenvironment of Apple is in the same scale length as an artificial surface for the fabrication of replacement tissues. This discovery led scientists to wonder: is it really possible to use this structure of the plant surface for growing human organs?
To test this, they took an Apple and washed it all plant cells, DNA and other biomolecules. It remains only a fibrous forest — they are still stuck in your teeth. When the team placed inside human and animal cells, the cells began to grow and spread.
Encouraged by the result, the scientists cut the Apple in the shape of a human ear and repeated the process above. Few weeks cells have spread and turned a piece of Apple into the fleshy human ear.
Of course, one form will not suffice. Replacement fabric also needs to fit inside the body.
The team then implanted the Apple of the forest right under the skin of the mouse. In just eight weeks the healthy cells of the mouse not only populated matrix, but the body rodent also produced new blood vessels that helped forests to live and thrive.
Have bioengineered tissue has three important properties: it is safe, it is biocompatible and it is made from renewable, ethical source.
“This thing becomes a living part of the body, as grown in the Apple, and it took us just go to the grocery store,” says Pelling.
The transition from theory to practice
Pelling particularly enthused with their results because of the simplicity: does not require stem cells or exotic growth factors. Elegant approach simply uses the physical structure of the plant.
Currently, the team is extending its work to the three main areas of tissue engineering: cartilage, soft tissue, bone tissue, spinal cord and nerves. The importance is to map the specific microstructure of the plants with cloth.
And why stop with the body that nature has given us? If forests are the only determinants of the engineered tissue or organ, why not create your own forms?
Pelling armed with this idea and created a design house that will make forests for the three different types of ears: normal human ears, pointed ears, like Spock, and wavy, which will be able in theory to suppress or enhance different frequencies.
In the end, we’ll all be there, right? Tell us in our chat in Telegram.