The ability to convert, or “reprogram,” cells into other types has raised hopes for regenerating damaged limbs and organs. But existing methods are risky or inefficient and have been tried only on laboratory animals. A new technology could overcome these limitations, however. Researchers have used it to restore injured mouse legs and claim the technique is safe enough to test in humans.
Cells are typically reprogrammed using mixtures of DNA, RNA and proteins. The most popular method uses viruses as a delivery vehicle—although they can infect unintended cells, provoke immune responses and even turn cells cancerous. One alternative, called bulk electroporation, exposes entire cells to an electric field that pokes holes in their membranes to let in genetic material and proteins. Yet this method can stress or kill them, and only a small proportion is converted to the desired cell type.
Tissue nanotransfection, described in a study published in October in Nature Nanotechnology, involves a chip containing an array of tiny channels that apply electric fields to individual cells. “You affect only a small area of the cell surface, compared with the conventional method, which upsets the entire cell,” says study co-author L. James Lee, a chemical and biomolecular engineer at the Ohio State University. “Essentially we create a tiny hole and inject DNA right into the cell, so we can control the dosage.”
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Chandan Sen, a physiologist at Ohio State, and his colleagues developed a genetic cocktail that rapidly converts skin cells into endothelial cells—the main component of blood vessels. They then used their technique on mice whose legs had been damaged by a severed artery that cut off blood supply. New blood vessels formed, blood flow increased, and after three weeks the legs had completely healed.
Additionally, the transformed cells appeared to secrete reprogramming materials in extracellular vesicles (EVs) that targeted deeper tissue. Injecting mice with EVs harvested from the skin of other treated mice was as effective as using the chip itself. The researchers also converted skin cells from mice into neuronlike cells and transplanted them into mouse brains damaged by stroke, improving the animals' mental function. “As a proof of principle, this [approach] is very nice,” says neurobiologist Benedikt Berninger of Johannes Gutenberg University Mainz in Germany, who was not involved in the study. “A big question would be: Can we get [EVs] to convert only specific cells?”
The team hopes to begin human trials within a year. “Considering what could be done,” Sen says, “this could be transformative.”
