A team of researchers at Ohio State University has built a nanochip that successfully reprogrammed skin cells into muscle and nerve cells, which could help to regenerate worn-out heart muscles, damaged nerves, deteriorated retina, or severely burnt skin.
Unlike lizards, which can regrow tails, or axolotls, an amphibian that can rebuild limbs and organ parts, humans can renew only a few types of cells, such as hair, nails and skin. Regenerating worn-out heart muscles, damaged nerves, deteriorated retina, or severely burnt skin is beyond our body’s natural abilities.
A team of researchers at Ohio State University has built a nanochip that successfully reprogrammed skin cells into muscle and nerve cells to reverse some of those limitations. The researchers believe they can expand their technique to generate other tissue types as well.
The chip’s technology grows out of the concept of electroporation, says L. James Lee, professor of chemical and biomolecular engineering at the Ohio State’s College of Engineering.
Electroporation is a microbiology technique in which an electrical field is applied to a cell in order to increase the permeability of its wall. When stimulated by short electrical pulses, the cell wall, which acts as a strong protective membrane, temporarily opens to allow drugs, chemical compounds, or even DNA molecules to slip inside.
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Researchers have explored electroporation for injecting various therapeutic agents into the cell that could not otherwise pass through the membrane. The Ohio State team, however, took this concept in a different direction.
The team’s engineers and medics worked together to create a chip that can inject DNA molecules into skin cells. These DNA snippets, which can be custom-synthesized to the required specs, carry biological instructions to reprogram the skin cells into vascular or nerve cells.
The chip injects these reprogramming instructions into 4,000 cells via 4,000 electric nanochannels that deliver a quick electric shock to propel the DNA molecules through the membrane. When placed on a skin of a living organism such as a mouse it only takes seconds to work.
The nanoscale design was important, Lee says. If the voltage is applied to a large area of the cell membrane, it could severely damage or even kill the cells. That’s why the team devised a chip with nanochannels for voltage delivery.
“A typical cell is a ball of about 10 microns, and our channel is 0.1 micron,” Lee says. “That’s why we don’t damage the cell—we don’t touch 99 percent of its surface.”
Lee likens the concept to a flu shot. “The nurse puts a needle into the skin,” he says. “It’s not going to hurt the person, but it will deliver the medicine into the body.”
When the team first built the chip, they thought it would only be able to inject the genetic reprogramming instructions into the top layer of cells. The layers of cells below the top one would not prove reachable.
“I thought the DNA couldn’t penetrate many cells; only one cell on the surface,” Lee says.
But that’s not what happened. When the team experimented with the chip on a live mouse, they were surprised to see that the DNA not only began to reprogram the layer of top, but also the deeper layers. The researchers believe the injection of reprogramming instructions triggered a biological messaging cascade from one cell layer to others.
“Cells get stimulated and they release biomolecules, which propagate to other cells,” he says. “We were very surprised to see that.”
It’s possible to use the chip on other tissues, not just skin, Lee says. The only problem is that it would require surgery to place it on internal organs. To regenerate a worn-out heart muscle, for example, a surgeon would have to make an incision to reach the heart.
Lee also thinks it may prove possible to use the chip to regenerate retinal cells, too.
The team experimented on mice and pigs, and was able to reprogram skin cells into vascular cells in injured legs that lacked blood flow. “We produced a blood vessel under the skin,” Lee says.
Lee and his researchers also managed to reprogram skin cells into nerve cells in lab settings. It then injected those new nerve cells into brain-injured mice to help them recover from stroke.
The experiments yielded better results in living animals than they did in laboratory settings, a rare occurrence of an experiment that worked better in-vivo than in in-vitro. Lee attributes this to the cell-to-cell communication process, something that needs greater study.
The method has drawn lots of interest from doctors and patients alike, Lee says. He and his team are hoping to do human trials soon, but currently they’re focusing on deciphering the biological underpinnings of the cell communication phenomenon.
“Right now, my team is working to understand why it happens,” he says.
Lina Zeldovich is an independent technology writer.
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