September 15, 2020

When fighting cancer, patients need every advantage possible, and new research results have shown a potential breakthrough that could help protect the health of those undergoing chemotherapy.

Scientists at the Wisconsin National Primate Research Center (WiNPRC) at the University of Wisconsin–Madison (UW) have developed a more efficient way to grow white blood cells, which serve as front-line defenders against bacterial infections but are often depleted during cancer treatment. Chemotherapy can leave cancer patients with a very low number of a specific type of white blood cell called neutrophils. This can result in febrile neutropenia, a dangerous condition marked by fever and heightened risk of infection.

This condition is usually treated with a transfusion of the white blood cells from a donor. But collecting enough neutrophils for transfusion is difficult, according to Igor Slukvin, MD, PhD, professor of pathology and laboratory medicine at the UW School of Medicine and Public Health, and the transfusions don’t always show the intended benefit in controlled trials.

“The complicated logistics of granulocyte collection, the need for pre-treating donors with G-CSF (a treatment that stimulates bone marrow to produce granulocytes) or steroids, difficulties in collecting a sufficient number of good quality granulocytes and the limited storage time of around 24 hours all hamper the utility of granulocyte transfusion for correcting neutropenia and may contribute to the inconclusive results observed in clinical trials,” he said.

Now, Sluvkin and a team of researchers have developed a method to generate neutrophils for weeks on end using stem cells. This solution replaces the standard, expensive, relatively inefficient and time-intensive process for neutrophil production.

Using modified messenger RNA, the technique sparks the production of a specific protein that guides the stem cells through a developmental process to become a sheet of hemogenic endothelium (found in blood vessels), which then begins producing neutrophils. These white blood cells can eventually be collected and administered to patients without some of the risk caused by other blood products often carried along in transfusions.

This technique produces neutrophils in as soon as 14 days, compared to as much as a month in previous studies, and can generate up to 17 million neutrophils from one million human induced pluripotent stem cells.

Notably, the scientists learned the neutrophils generated using this method are functionally similar to peripheral blood neutrophils and can phagocytize (surround and swallow) and kill bacteria.

These neutrophils also create opportunities to study other diseases, since white blood cells produced from stem cells carrying genetic disorders that weaken or otherwise affect the neutrophils will still retain those problems. The new production method could give researchers a ready source of malfunctioning cells and enable observation in the earliest stages of development.

The NPRCs are conducting stem cell studies at our locations across the nation. See more ways we’re applying this research to help solve a variety of health issues.