Once considered a waste product of birth, umbilical cord blood is now prized as a source of stem cells that can replace the diseased bone marrow of people with leukemia and other illnesses. Unfortunately, umbilical cords often don’t contain enough blood for a viable transplant of stem cells that, like marrow cells, can produce new blood cells of various types.
Scientists now report that cord-blood stem cells proliferate rapidly when the blood is cultured with a protein called Delta-1 and a combination of growth enhancers.
When transplanted into mice, these treated cells grafted well into the animals’ bone marrow, suggesting they had begun to rebuild the animals’ store of red and white blood cells. Some stem cells even found their way to the thymus to begin transformation into immune system workhorses called T cells, the researchers report in the Oct. 15 Journal of Clinical Investigation.
Study coauthor Irwin D. Bernstein of the Fred Hutchinson Cancer Research Center and the University of Washington in Seattle and his colleagues used Delta-1 because earlier tests had shown that it’s a signaling protein in the so-called notch pathway–a pattern of cell-to-cell interactions that influences cell proliferation.
Although other attempts to culture cord blood have doubled or tripled the quantities of its stem cells, Bernstein’s team found that Delta-1 cranked it up more than
14-fold. The most desirable stem cell, a virtual cellular blank slate called CD34+CD38–, proliferated rapidly in a lab dish without converting into a more advanced cell. For transplantation, such primitive cells are desirable because they’re less likely to attack or be rejected by their new host.
In some treatments for blood cancers such as leukemia, doctors first destroy a patient’s bone marrow with radiation, which diminishes the capacity to make white blood cells, important components of the immune system. The doctors then supply healthy marrow. To mimic this situation in animals, the researchers injected human cord-blood stem cells into mice lacking an immune system. Cells treated with Delta-1 promptly began repopulating the bone marrow in the animals. That done, the cells then differentiated into both red blood cells and white blood cells called B cells, which play an indispensable role in the immune system. Untreated stem cells grafted much more slowly.
Until now, scientists “haven’t been able to show an advantage to culturing” cord blood because, Bernstein says, cultured stem cells were often slow to graft in the marrow.
Pablo Rubinstein of the New York Blood Center says the findings could open a new avenue for expanding the cord-blood supply.
Lloyd T. Lam of the National Cancer Institute in Bethesda, Md., notes that Bernstein’s group bound Delta-1 to the base of lab dishes during cell culturing. This may explain why the researchers achieved better results than others who have tested Delta-1 in solution. Such immobilizing of the protein may better approximate cell-to-cell interactions, Lam says.
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