The National Heart, Lung and Blood Institute has awarded a total of $16.7 million to Irwin Bernstein, and Beverly Torok-Storb, both members of the Clinical Research Division at Fred Hutchinson Cancer Research Center. The Hutchinson Center grants represent part of a $170 million effort involving 18 teams of research scientists dedicated to developing stem- and progenitor-cell tools and therapies.

The seven-year awards create the NHLBI Progenitor Cell Biology Consortium, which assembles nine research hubs with multidisciplinary teams of principal investigators and an administrative coordinating center.

While a stem cell can renew itself indefinitely or differentiate, a progenitor cell can only divide a limited number of times and is often more constrained than a stem cell in the kinds of cells it can become. Given the potential of these cells for clinical applications, the consortium aims to identify and characterize progenitor cell lines, direct the differentiation of stem and progenitor cells to desired cell fates, and develop new clinical strategies to address the unique challenges presented by the transplantation of these cells.

Torok-Storb, along with Fred Hutchinson/University of Washington Cancer Consortium colleagues, will collaborate with Mortimer Poncz of Children's Hospital of Philadelphia to develop molecular- and cell-based therapies for a range of blood diseases, with an initial focus on the delayed recovery of blood-clotting platelets following stem-cell transplantation, a life-threatening complication called thrombocytopenia.

The partner institutions will focus on two complementary strategies to address delayed platelet production. With their $8.2 million grant, Torok-Storb's team will develop reagents that can be administered to patients to stimulate the differentiation and proliferation of precursor cells into platelets. The Philadelphia group will work to generate 'ex vivo', or outside the body, platelets and their precursors from embryonic stem cells for use as cell therapy.

Bernstein, along with Hutchinson Center/UW Cancer Consortium researchers and the University of Pennsylvania's Edward Morrisey, is using his $8.5 million award to determine how certain signalling pathways-ordered sequences of biochemical reactions inside cells-affect cardiac and blood-forming cell development and cardiac regeneration and repair. The team will also study whether these pathways can be harnessed for therapeutic applications. Drawing on Bernstein's success in expanding cord-blood stem cells, the researchers hope to refine methods for deriving therapeutically useful numbers of cells for transplantation and other treatments.

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