Hastening immune-system renewal

Hutchinson Center researchers have found a way to hasten immune-system recovery following blood stem-cell transplantation in a mouse model by growing the stem cells on a particular protein. This method accelerates the growth of a single immune cell to more than 1 billion, a 100-fold average increase.

Dr. Mari Dallas, a scientist in the Clinical Research Division, conducted the study with colleagues Drs. Barbara Varnum-Finney, Paul Martin and Irwin Bernstein. They reported their results in the April 15 issue of the journal Blood. "We're trying to manipulate the fate of stem cells by altering what we culture them with to try to push them to become early T-cells," Dallas said. T-cells belong to a group of white blood cells known as lymphocytes and play a major role in the immune system.

Dallas' work is similar to Dr. Colleen Delaney's cord-blood stem-cell expansion research. Both use techniques pioneered in the Bernstein Lab to influence stem-cell growth and differentiation into specialized cell types. They grow the cells on a protein called Delta, which activates a receptor — Notch — that can prevent stem cells from differentiating. Delaney works with cord-blood cells, responsible for the critical bone-marrow engraftment phase right after transplantation, while Dallas studies T-cells, which re-establish a patient's immune system over the course of a year.

Dallas found that culturing the cells hastened T-cell recovery by about two weeks in the mouse model. "In the future, it's possible that we might be able to infuse these cultured cells into patients for faster T-cell recovery," she said.

"So many people are worried about engraftment in the first couple of weeks after transplant, but we really need to think also about how to improve immune recovery," said Dallas, who is also a pediatric oncologist. "I really believe this is a potential avenue to do that, and it has great promise in humans."

Dallas aims to translate the findings into clinical practice by launching a clinical trial within two to three years. She will also continue to study immature T-cells to better understand the cell behavior.

A career-development award from the National Cancer Institute funded the research.