Drug-Induced Regeneration in Adult Mice

What if you could take a pill to induce regeneration in your wounded body? Amphibians can lose a leg or tail and readily regenerate it spontaneously. Mammals, unfortunately, generally form scars over the injury site during the process of wound repair. However, a strain of mouse known as the MRL mouse strain is an exception because these mice have the ability to spontaneously regenerate and heal, and this animal is a model system for regeneration.

Ellen Heber Katz and her colleagues at the Wistar Institute in Philadelphia, Pennsylvania have examined the MRL mouse in some detail and have discovered that a protein called hypoxia-inducible factor 1α (HIF-1α) plays a central role in the regeneration ability of adult MRL mice. The HIF-1α protein is usually degraded when normal levels of oxygen are available. Degradation of HIF-1α is mediated by enzymes called PHDs, which stands for prolyl hydroxylases. The presence of oxygen provides the substrate for PHDs to modify HIF-1α so that the cell sees it as a protein that is marked for degradation. MRL mice seem to have a rather stable form of HIF-1α, which stimulates healing.

Heber Katz and her co-workers designed a drug that would inhibit PHDs and stabilize HIF-1α. Next they took their drug (1,4-dihydrophenonthrolin-4-one-3-carboxylic acid or 1,4-DPCA) and encased it in hydrogel that would slowly release it over a course of 4 to 10 days. Heber Katz and her fellow researchers then injected this drug-laced hydrogel beneath the skin of Swiss Webster mice, which do not show an ability to spontaneously regenerate. They discovered that their hydrogel increased stable expression of HIF-1α protein over a 5 day period. Then, when they subjected these mice to skin wounds by punching a hole in their ears, the Swiss-Webster mice showed regenerative wound healing. No stem cells were injected, but this drug-laced hydrogel increased the regenerative ability of these animals.

Thus, increased expression of the HIF-1α protein seems to provide a starting point for future studies on regeneration in mammals. This work in preliminary, but think of it – taking a pill or getting an injection of some hydrogel that increases your body’s healing ability many fold. Of course, this is far in the future, but the possibilities are remarkable.