UCSF and the Cell Technologies business of GE Healthcare Life Sciences have begun a unique collaboration aimed at overcoming the lack of blood-forming stem cells available to patients suffering from life-threatening diseases such as lymphoma, myeloma, leukemia or sickle cell anemia.
The goal of the $841,000, three-year project is to make better use of a rich source of routinely discarded stem cells: umbilical cord blood gathered at the birth of a baby.
Every year, more than 14,000 patients in the U.S. are diagnosed with diseases that have the potential to be treated with a transplant of blood-forming stem cells. These patients need a way to replace their diseased blood cells with healthy ones that can grow and flourish.
For many patients, the best option would be a transplant of stem cells from the bone marrow or blood of a closely matched sibling or family member. But, for at least 70 percent of these patients, no matching family donor is available. Finding unrelated donors whose tissue types match isn't easy.
As a result, many patients die or become too ill for a transplant. At UCSF, specialists perform about 190 transplants in adults each year and the number is rising, according to Andrew Leavitt, MD, medical director of the UCSF Adult Blood and Marrow Transplant Laboratory. "We are acutely aware of the fact that we have patients who can't get optimal therapy because we can't find a matching donor who can provide a transplant," Leavitt said. "For these patients, it's a matter of life and death."
Another potential source is cord blood, the blood that remains in the umbilical cord and placenta after the birth of a baby. It is a rich source of hematopoietic (blood-forming) stem cells. After a birth, the umbilical cord and placenta are usually discarded. Many countries are now establishing cord blood banks and associated facilities to allow parents to donate their baby's cord blood to bring potentially lifesaving treatment to others.
The UCSF/GE Healthcare collaboration will focus on cord blood, which has some key advantages for transplants: It's loaded with the stem and progenitor cells that make all the other cells in the blood system - including white cells, red cells and platelets. It can be collected easily without causing pain or risk to the donor. And cord blood doesn't need to match the tissue type of the patient receiving it as closely as bone marrow does.
In recent years, a growing number of patients have received cord-blood transplants. They work wonderfully for many sick children, Leavitt said, but for most adult patients, cord blood simply doesn't provide a large enough number of stem cells.
Now, using a Discovery Grant awarded by the University of California's Office of the President, along with matching funds from GE Healthcare, a group of scientists led by Leavitt has begun a three-year project. They'll be hunting for chemical compounds that can be added to the stem cells and progenitor cells in cord blood to increase their population. If the process works, the number of cells transplanted should be large enough to replace the patient's diseased blood system with a healthy one.
During the first year of the project, UCSF scientists led by Michelle Arkin, PhD, associate director of the Small Molecule Discovery Center, will use ultra-fast, robotic technology like that used in pharmaceutical companies to screen about 120,000 chemicals searching for those that may trigger the expansion of the stem and progenitor cells.
A high-tech automated microscope provided by GE, the IN Cell 2000, will help Arkin and her team to identify a tiny number of compounds - probably no more than one-tenth of 1 percent - that look like potential candidates.
"One hundred-twenty thousand compounds is a huge number," said Stephen Minger, PhD, global head of research & development for Cell Technologies at GE Healthcare. "Slowly but surely we'll narrow the list.'' GE Healthcare is funding the project as part of the broader vision of its cell technologies business, which is to develop technologies that will support the emerging era of regenerative medicine.
During the project's second year, the scientists hope to test the best candidates to learn how they act when they're mixed with blood cells in lab conditions and in animals. Later, they'll use GE's Cell FactoryTM to produce large quantities of cells for further testing. By the end of the project, the team hopes to have promising compounds moving toward clinical trials.
"If this succeeds it will be incredibly important," Minger said. "The clinical potential of being able to expand hematopoietic stem cells in cord blood is huge. If this works, we'll have discovered something that the world desperately needs."