Researchers have discovered a molecule that could help regenerate new tissue to repair and replace damaged ones. So far, it’s already helped rescue mice from colon, liver, and bone marrow damage, they report in Science this week.
"We have developed a drug that acts like a vitamin for tissue stem cells, stimulating their ability to repair tissues more quickly,” Sanford Markowitz of Case Western Reserve University (CWRU) says in a news release.
The drug relies on a molecule that the body naturally produces: Prostaglandin E2, or PGE2. PGE2 is a hormone-like fatty acid that supports the proliferation of many types of tissue stem cells. Previous work uncovered an enzyme called 15-PGDH that degrades and reduces the amount of PGE2 in the body. It’s found in all humans. It makes sense that blocking 15-PGDH should increase PGE2 in tissues, promoting quicker cell recovery. Experiments with genetically engineered mice lacking 15-PGDH confirmed this.
By combing through 230,000 different chemicals, Markowitz and a large team led by CWRU and University of Texas Southwestern Medical Center researchers were able to identify a chemical that inactivates 15-PGDH. It’s called SW033291, and after experiments in test tubes and with cells seemed to work, the team turned to mice.
A lethal dose of radiation was injected into the mice, and then they were given a partial bone marrow transplant. Without the chemical, the animals died. With SW033291, however, they recovered. These mice showed normal blood counts six days faster than mice who received a transplant without the drug. And their red blood cells, platelets, and infection-fighting neutrophils recovered faster. Furthermore, with the SW033291-induced increases of PGE2 in bone marrow, the body began producing other substances that bone marrow stem cells need to survive.
Additionally, SW033291 healed ulcers in mice with ulcerative colitis, and it also sped up the regrowth of new liver in mice with two-thirds of their livers removed. “The drug heals damage in multiple tissues, which suggests to us that it may have applications in treating many diseases,” Markowitz adds.
So far, all of these benefits seem to emerge without adverse side effects. The team is now working on developing SW033291 for human patients.