Since then studies by others have found that PTH stimulates osteoblasts to produce prostaglandin E2 (PGE2), and the current research team focused on the effects of PGE2 treatment on the number of a key type of hematopoietic stem cells compared to control-treated mice. PGE2 was found to preferentially expand fast-acting, shortlived stem cell populations (ST-HSCs and MPPs) in mice, but not Long Term-HSCs. Because the cell types increased in number act quickly to expand blood cell supply, but do not reproduce for very long, researchers were not surprised to see that the effect in live animals of PGE2 had disappeared by 16 weeks post stem cell transplant. This study represents the first time a single factor has been shown to expand a specific HSC subset.

Further experiments found that mice with PGE2 administered to their HSCs cells saw "superior" rebuilding of white blood cell supply versus control mice. Three weeks after transplantation, PGE2-treated mice saw an approximately 30 percent greater reconstitution of bone marrow white blood cell supply over control mice, as determined by flow cytometry, which fluorescently tags, then counts, cell types. Studies already underway in Calvi's lab seek to clarify the molecular mechanisms responsible for the regulation of ST-HSCs by PGE2, and whether existing drugs known to encourage the PGE2 signal can make a difference in blood marrow transplant recovery.

Regis J. O'Keefe, M.D., Ph.D., chair of the Medical Center's Department of Orthopaedics and Rehabilitation, and Craig Jordan, Ph.D., professor of Biomedical Genetics in the James P. Wilmot Cancer Center, collaborated with Calvi on the work. Key student contributors were Benjamin Frisch, Rebecca Porter, Benjamin Gigliotti, Adam Olm-Shipman and Jonathan Weber. The work was supported by the National Institute of Diabetes, Digestive and Kidney Diseases, the Wilmot Cancer Research Fellowship Program and the Pew Charitable Trusts.

"Also important for leukemia patients, this work places new importance on the discovery that PTH stimulates PGE2 production by turning up the action of COX 2, the enzyme targeted by a widely used anti-inflammatory pain medications like Celebrex," Calvi said. "Could painkillers used by patients recovering from stem cell transplants be hampering their ability to re-start blood cell production? Beyond leukemia, an emerging theory holds that cancer stem cells resemble normal stem cells and explain how cancer can be spread by a single cell. If this is true, then osteoblasts, PTH and PGE may regulate cancer growth, as they do HSC numbers, and might be manipulated to stop breast and prostate cancer cells from spreading to bone."