Based on what we know of the mechanisms by which stem cell therapies produce benefits, it shouldn't be surprising to find that there are signals that can be provided to tissues that enhance the pace of regeneration. We are still in the comparatively early days of the identification and understanding of those signals, but some efforts are further ahead than others:
"We have developed a drug that acts like a vitamin for tissue stem cells, stimulating their ability to repair tissues more quickly. The drug heals damage in multiple tissues, which suggests to us that it may have applications in treating many diseases." The institutions collaborating on this work next hope to develop the drug - now known as SW033291 - for use in human patients. Because of the areas of initial success, they first would focus on individuals who are receiving bone marrow transplants, individuals with ulcerative colitis, and individuals having liver surgery. The goal for each is the same: to increase dramatically the chances of a more rapid and successful recovery.
The key to the drug's potential involves a molecule the body produces that is known as prostaglandin E2, or PGE2. It is well established that PGE2 supports proliferation of many types of tissue stem cells. Researchers had demonstrated that a gene product found in all humans, 15-hydroxyprostaglandin dehydrogenase (15-PGDH), degrades and reduces the amount of PGE2 in the body. The researchers hypothesized that inhibiting 15-PGDH would increase PGE2 in tissues. In so doing, it would promote and speed tissue healing. When experiments on mice genetically engineered to lack 15-PGDH proved them correct, the pair began searching for a way to inactivate 15-PGDH on a short-term basis.
The preliminary work began in test tubes. Researchers developed a test where cells glowed when 15-PGDH levels changed and then combed through a library of 230,000 different chemicals. Ultimately they identified one chemical that they found inactivated 15-PGDH. A series of experiments showed that SW033291 could inactivate 15-PGDH in a test tube and inside a cell, and, most importantly, when injected into animal models. When investigators treated diseased mice, the SW033291 drug again accelerated tissue recovery. In a mouse model of ulcerative colitis SW033291 healed virtually all the ulcers in the animals' colons and prevented colitis symptoms. In mice where two-thirds of their livers had been removed surgically, SW033291 accelerated regrowth of new liver nearly twice as fast as normally happens without medication.
The investigators believe the pathway by which SW033291 speeds tissue regeneration is likely to work as well for treating diseases of many other tissues of the body. However, the next stages of the research will concentrate on diseases where SW033291 already shows promise to provide dramatic improvement.