Characterization of the hematopoietic reconstitution enhancing activity of osteoblasts derived from human mesenchymal stromal cells

Patients undergoing cancer treatment or suffering from leukemia may require a stem cell transplantation to reconstitute their damaged marrow responsible for the daily production of the blood cells. Umbilical cord blood (UCB) transplantation provides the opportunity for patients without suitable donor to receive a lifesaving graft. Regrettably, this procedure is associated with a slower recovery of immune cells and platelets. Immune cells protect the patient against infections while platelets prevent hemorrhages. Adults can be safely transplanted with two independent cord blood units though it does not accelerate the recovery of either cell type. This procedure provides the opportunity to modify one of the cord blood units to accelerate the production of blood cells. Cord blood cells can be expanded in culture using growth factors but the expanded cells often lose their natural capacity to produce high levels of platelets and other cells. Conversely, stromal cells normally found in the bone marrow can provide complementary stimuli so that the expanded cells preserve their capacity to produce high level of blood cells. Our preliminary study showed that human osteoblasts derived in culture from mesenchymal stromal cells possess such activity. The hypothesis of this proposal is that osteoblasts secrete key biological mediators that will permit efficient expansion of cord blood cells and maintain the ability of the expanded cells to strongly contribute to blood cell production. In essence, we wish to discover how these cells create a bone marrow-like environment that generates optimized progenitors for transplantation. This research will foster new knowledge on the role of osteoblasts as important regulators of hematopoiesis, and may lead to new solutions to improve cord blood transplantation. Indeed, new approaches are urgently needed to address the needs of the increasing number of Canadian patients who will soon rely on UCB transplantation for their continuing health.

PINEAULT, Nicolas

Canadian Blood Services

Canadian Blood Services-CIHR Partnership Operating Grant Program

Ontario

$320,504