New Method Heals Mice by Transforming Their Skin into Blood Vessels
Scientists may bypass problems with stem cell therapies by directly transforming body cells.
Stem cells sometimes seem like a will-o'-the-wisp, offering incredible promise but leading to dead ends or missteps in the effort to harness patients’ own regenerative potential for healing and medicine. Cells that are pluripotent—meaning they can convert themselves into any other type of body cell—don’t always follow instructions, and there may be many unintended consequences, including cancer. Furthermore, stem cell and gene therapies often use viruses to ferry these conversion instructions into target cells, but this can trigger inflammation and other immune system resistance. The viruses may even go rogue, attacking nontarget cells throughout the body and inserting their own DNA rather than the instructions they were meant to carry.
Now, a multidisciplinary team led by Chandan Sen at Ohio State University in Columbus has demonstrated a method that may bypass those problems. The team has successfully used regular body cells—not pluripotent stem cells—in a living mouse, not a test tube, to restore tissue damage and severed blood vessels. The process, dubbed “tissue nano-transfection,” or TNT, is "transformative," said Sen. The study was published in the 7 August issue of Nature Nanotechnology.
The team identified a series of signaling molecules that nudged mouse skin cells to turn into blood vessel cells. To insert the signaling molecules, the team exposed the skin on a live mouse's leg to an electric field using nanoscale electrodes for one-tenth of a second, just enough time for a small opening in the cells’ walls to accept the signaling molecules without taking in other substances. From there the cells followed the instructions and became the cell types needed to rescue the injured leg.
After about a week, the test mouse’s leg tissue and its severed artery had repaired themselves as the transformed skin cells did their work. They even extended blood vessels down into the mouse’s calf muscle, reversing the blood-starved state that occurs when tissue loses circulation and starts to die.
One beauty of this method, said Sen, is that it is low risk; “If you fail, your skin is still your skin." Moreover, the process doesn’t require numerous burdensome laboratory steps to transform stem cells—it can be done topically, right at the body’s surface. “Now we are not talking about a stem cell,” Sen added. “We are talking about tissue conversion.”
Pouyan Boukany, a biochemical engineer at Delft University of Technology in the Netherlands, who was not involved in the study, calls the work “carefully and thoroughly” done. The method, he said, has potential with other biomolecules for “a wide variety of applications for both fundamental and therapeutic applications.”
In addition to converting skin cells into blood vessels, the team has also converted them into functional neurons. The immediate application of the current study would be to prevent amputation in diabetics and others with chronic blood vessel abnormalities that prevent wounds from healing, Sen said. The team wants to start testing it in humans as soon as possible.