A study recently published in the renowned journal Science revealed a molecule able to accelerate tissue regeneration after bone marrow transplantation and other tissue injuries in mice. The study is entitled “Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration” and was led by researchers at the University of Texas Southwestern Medical Center, Case Western Reserve University and the University of Kentucky.
Tissue regeneration is an important feature in several clinical settings including diseases, injury, and certain treatments such as the recovery of the hematopoietic system after bone marrow transplantation, a common treatment for leukemia patients. Because of this, there is interest in developing agents able to accelerate the tissue regeneration process, especially if they can benefit several organ systems.
Researchers have now discovered a molecule that may accelerate tissue regeneration. The prostaglandin PGE2 is a signaling factor that is involved in the expansion of several types of tissue stem cells, contributing to tissue regeneration. In the study, researchers identified a prostaglandin-degrading enzyme known as 15-hydroxyprostaglandin dehydrogenase (15-PGDH), and investigated its potential role as a negative regulator of tissue regeneration.
The team used mice with depleted 15-PGDH in order to determine the role of this enzyme in controlling PGE2 levels and the tissue repair capacity in several organs. Researchers also developed a potent small-molecule inhibitor against 15-PGDH – SW033291.
Researchers found that 15-PGDH–deficient mice have a twofold increase in PGE2 levels in different tissues (including bone marrow, colon and liver) in comparison to wild-type mice, an increased capability to respond to cell damage in these particular tissues, and an enhanced hematopoietic capacity. Remarkably, by inhibiting 15–PGDH with SW033291, researchers found that it was possible to rescue the damaged hematopoietic system after bone marrow transplantation, prevent ulcerative colitis in the intestine, and accelerate liver regeneration after hepatic surgery in mice. These observations led the authors to establish that 15-PGDH negatively regulates tissue regeneration and repair.
In the particular case of bone marrow transplantation, an accelerated recovery of diverse blood cells (erythrocytes, neutrophils, platelets) was observed. According to the authors, this effect is most likely due to the fact that SW033291 molecule targets a 15-PGDH-regulated pathway of bone marrow regeneration in which bone marrow CD45– cells respond to increased PGE2 levels by enhancing the production of specific signaling molecules involved in hematopoietic stem cell homing and maintenance.
The research team concluded that 15-PGDH inhibition through SW033291 can lead to tissue regeneration in mice by interfering with a hematopoietic pathway in the bone marrow. The authors propose that 15-PGDH inhibition represents a strategy to accelerate tissue recovery after bone marrow transplantation and other tissue injuries.
“Patients undergoing bone marrow transplants and patients with colitis may benefit from this approach,” said the study’s co-senior author Dr. James K. Willson in a news release. “We propose that SW033291 will be useful in accelerating recovery of bone marrow cells following a bone marrow transplant and may also be a treatment for colitis.”
The study’s co-senior author Dr. Joseph Ready added that 15-PGDH inhibitors “increase prostaglandin levels in a variety of tissues. For this reason, they appear to help the healing process in at least the intestines, liver, and bone marrow. We are hopeful that inhibiting 15-PGDH represents a general strategy to promote tissue repair,”