Wolfram Goessling, MD, PhD, of the Department of Medicine at BWH, and colleagues in the laboratory of Leonard Zon at Children’s Hospital Boston, have demonstrated that molecules that interact to shape embryonic development also contribute to tissue regeneration in adults. Using a combination of genetic and chemical approaches in fish embryos, they showed that the lipid compound prostaglandin E2 (PGE2) modulates Wnt signaling to stimulate blood stem cell proliferation by stabilizing beta-catenin, a downstream component of the Wnt pathway. PGE2 and Wnt activity also cooperated to promote blood stem cell regeneration in adult zebrafish following irradiation-induced marrow injury. Furthermore, they interact in other processes of tissue repair, such as during liver regeneration. These findings appear in the March 20 issue of Cell.

In earlier work, Trista North , PhD, of Beth Israel Deaconess Medical Center, and Dr. Goessling isolated PGE2 from a chemical screen for small molecules that stimulate blood stem cell production in zebrafish embryos. PGE2 was found to have a powerful regulatory effect on blood stem cells both during development and in the adult. Dr. Goessling and Dr. North also examined whether these findings extended to mammalian biology, and confirmed this by obtaining similar findings in the study of mice. 

PGE2 has now been FDA-approved for use in clinical cord blood transplantation trials to treat leukemia, after demonstrating potential to accelerate blood stem cell regeneration. The research team also plans to investigate whether PGE2 can be used clinically in other regenerative settings.