The primary focus of the Delaney Lab is the development and clinical translation of methodologies for the ex vivo expansion of hematopoietic stem and progenitor cells. In particular, we have focused on methods for the ex vivo expansion of cord blood stem and progenitor cells with the goal of improving outcomes for patients undergoing cord blood transplantation.
Cord blood is now accepted as a source of blood stem cells for patients in need of a bone marrow transplant who have no other suitable donor. This is of particular importance in patients who are of mixed ethnicity or minority background as these patients are very unlikely to find a suitable unrelated donor for bone marrow transplantation, but can almost always find a cord blood donor. However, delayed hematopoietic recovery, resulting from inadequate stem cell numbers in cord blood grafts, is a known disadvantage when cord blood is used as the source of donor stem cells for transplantation and results in increased risk of early mortality. One approach to overcome the limiting number of stem/progenitor cells in a cord blood graft is ex vivo expansion of the progenitor cells prior to infusion.
In collaboration with the Bernstein Lab where a role for Notch signaling in hematopoiesis was originally suggested, we have developed and successfully translated novel methods for clinically feasible ex vivo expansion of cord blood stem/progenitor cells using an engineered Notch ligand which result in marked increase in the absolute number of stem/progenitor cells. Preclinical data demonstrates not only the ability to expand cord blood progenitor cells ex vivo that retain repopulating ability, but also indicates that the expanded cells may lead to more rapid engraftment as compared to the non-expanded cells and therefore have the potential to overcome delayed engraftment, the major disadvantage after undergoing cord blood transplantation.
This work was translated into a novel pilot study investigating the use of ex vivo expanded cord blood progenitors to augment conventional cord blood transplantation. The results of this clinical trial were published by Nature Medicine (Delaney C et al, Nature Medicine, 2010 Feb;16(2):232-6). We have since extended this work to investigate the potential of cryopreserved, non-HLA matched "off the shelf" ex vivo expanded cord blood progenitors in the setting of cord blood transplant and dose-intensive chemotherapy.
In addition to this primary focus of research, Dr. Delaney established and is the Director of the FHCRC Program in Cord Blood Transplantation. We are investigating the kinetics of engraftmen, graft-versus-graft effects and the kinetics of immune reconstitution in transplant recipients on 5 actively accruing cord blood transplant protocols.
