NHLBI grantees at the Fred Hutchinson Cancer Center have published a “proof of principle” study demonstrating that the Notch ligand is able to expand the umbilical cord blood (UCB) stem cells and improve hematopoietic engraftment. Untreated UCB does not begin making new blood cells in a patient's bone marrow for about three weeks. The long period of poor bone marrow function can lead to serious infection and bleeding. UCB contains very low levels of progenitor cells compared to other sources of hematopoietic stem cells.
Colleen Delaney, M.D., Irwin Bernstein, M.D., and their team showed that manipulating the Notch signaling pathway, which helps control blood cell formation and cell fate, increased UCB progenitor cells 100-fold and shortened the average initial engraftment time to about one week in immunodeficient mice. The paper reports results from a Phase I safety trial in ten human patients, documenting the first instance of such rapid engraftment using ex vivo-expanded UCB progenitor cells. This work represents an early but important step toward making UCB stem cells more widely useful for patients. UCB can be obtained without risks to the donors, can be stored frozen for years, and have the potential to offer life-saving hematopoietic stem cell transplants to patients who have no other source of donor cells.