Getting more mileage out of cord blood

Blood from human umbilical cords is a rich source of hematopoeitic stem cells, the progenitors that can reconstitute all of the different cell types in our blood, including oxygen-carrying red blood cells and white blood cells that are our major defense against infections. Cord blood contains a higher percentage of stem cells than adult bone marrow (another source of blood stem cells), and has several additional advantages: cord blood stem cells divide faster than stem cells from bone marrow and have longer telomeres. In addition, cord blood contains fewer immune cells, and those present have not yet undergone the extensive education process that allows them to distinguish between self and non-self. This is important in the context of transplantation, where host cells can attack donor cells and vice versa (a process known as graft-versus-host disease that is responsible for many deaths after bone marrow transplantation).

One obstacle to using cord blood more routinely as a source of stem cells in transplantation patients is the amount of blood required. Clinical trials have established that higher numbers of blood cells per kilogram of body weight of the recipient are associated with improved transplantation outcome. However, the amount of blood cells collected from cords is often not sufficient for an adult recipient. Scientists have therefore attempted to culture and expand cord blood-derived cells before transplanting them into patients. As they report in the October 21 issue of the Journal of Clinical Investigation, Irwin Bernstein and colleagues (Fred Hutchinson Cancer Center, Seattle, and University of Washington, Seattle), have been successful in doing so. Exposing human cord blood to a particular molecule called Delta-1 under defined culture conditions resulted in an over 100-fold increase in the number of the most immature stem cells. Other progenitors that maintained the potential to differentiate into multiple different blood cell types were also expanded.

When the scientists harvested the cells after the expansion and transplanted them into immuno-deficient mice (who in many ways resemble leukemia patients who have undergone radiation treatment prior to a bone-marrow transplant), they found that the cultured cells were more potent in reconstituting the recipients blood and immune cell systems that non-cultured cells or those cultured in the absence of Delta-1.

These results demonstrate that it is possible to increase the number of stem cells derived from cord blood in culture, and suggests that such strategies could be employed to increase the utility of cord blood as a source for human transplantation.

CONTACT:
Irwin D. Bernstein
Dept. Of Pediatric Oncology
Fred Hutchinson Cancer Research Center
1100 Fairview Ave. N
Seattle, WA 98109
PHONE: 206-667-4886
FAX: 206-667-6084
E-mail: ibernste@fhcrc.org