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A novel drug treatment that supercharges the production of cord blood stem cells is entering human testing at Dana-Farber. If successful, it could improve outcomes of such transplants while reducing the number of umbilical cords needed, says Corey Cutler, MD, MPH, a stem cell transplantation specialist at Dana-Farber who is heading the trial.
For cancer patients who need a life-saving transplant but lack a matched donor, the best alternative may be stem cells harvested from stored umbilical cord blood. But such transplants take longer to rebuild the patients' blood system and they sometimes fail. Moreover, adults may require stem cells from two umbilical cords, which are expensive and in limited supply.
Scientists in the laboratory of Leonard Zon, MD, director of the Stem Cell Program at Boston Children's Hospital, showed that adding a substance called prostaglandin E2 (PGE2) to cord blood stimulates blood stem cell production in both zebrafish and mouse models. If it works well in humans, it might be possible for enough blood stem cells from a single umbilical cord to rebuild the recipient's blood and immune systems.
"The hope is to shorten the engraftment time and increase the efficiency," says Cutler. "Other groups have tried cord blood expansion and haven't been very successful. We're excited to do this, and we've had an amazing collaboration with the Zon lab to take this research from fish tank to bedside."
The research with zebrafish and mice was carried out in Zon's laboratory by his former post-doctoral fellows, Trista North, PhD, now at Beth Israel Deaconess Medical Center, and Wolfram Goessling, MD, PhD, currently affiliated with Dana-Farber's Gastrointestinal Cancer Center and Brigham and Women's Hospital.
The phase I trial is being carried out at Dana-Farber and Massachusetts General Hospital in patients who have leukemia or lymphoma. The cord blood units, which come from the donated umbilical cord blood of newborn babies, will be processed at the Cell Manipulation Core Facility at Dana-Farber and infused into the patients at Brigham and Women's Hospital.
The trial will be carried out with groups of six patients at a time. The first six will receive one untreated cord blood unit followed by another unit of treated blood. The order will be reversed in the second six – treated blood first, then untreated – to determine if that makes a difference. The researchers can compare how quickly the cells engraft in the patient's bone marrow and bring up his or her blood-cell count.
If the method succeeds and is confirmed in larger trials, "it could improve the results of cord blood transplantation and increase the number of people who have access to it, and with better outcomes," says Cutler.
Cord blood from hospital-based banks is currently used in about 20 percent of transplants when the patient lacks a matched adult donor. The percentage is higher in ethnic minorities, who have lower odds of finding a compatible match in the available volunteer donor registries.
– Richard SaltusRichard_Saltus@dfci.harvard.edu
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