A new approach to generating large quantities of two types of white blood cells that are critical for destroying invading bacteria, viruses and other pathogens in humans has been developed by researchers at the University of California, San Diego (UCSD) School of Medicine.
The ability to derive unlimited quantities of mouse macrophages and neutrophils in cell culture will enable scientists to more readily analyze the steps involved in normal blood cell differentiation, and to determine whether these steps are altered in blood cell diseases such as leukemia.
In the article published on line in Nature Methods last month, Mark P. Kamps, Ph.D., Professor and Director of the UCSD/Burnham Institute Graduate Program in Molecular Pathology, and colleagues describe an approach using Hoxb8, a protein that controls blood cell development. They produced a form of Hoxb8 whose activity can be turned on or off in order to control macrophage and neutrophil differentiation in standard cell culture.
When this form of Hoxb8 is introduced into bone marrow cells isolated from a mouse and its function is turned on, it induces expansion of stem cells that are precursors of macrophages and neutrophils. In cell culture, these stem cells proliferate under the influence of active Hoxb8 indefinitely; however, when Hoxb8 function is switched off, they differentiate into normal, functional, non-dividing neutrophils or macrophages. The system allows researchers to maintain a continuous supply of progenitors and then to produce large numbers of mature macrophages or neutrophils from those progenitors on demand.
"By discovering a method to derive unlimited quantities of mouse macrophages or neutrophils, researchers will have a renewable source of cells for functional studies at the cellular, biochemical and molecular levels," said Kamps. "Importantly, this new system allows researchers to produce macrophages or neutrophils easily and cheaply from any new strain of genetically modified mice, and replaces the expensive method of purifying mature macrophages and neutrophils from large numbers of adult mice."
Additional contributors to the paper include Gang G. Wang and Martina P. Pasillas, Department of Pathology & Molecular Pathology Graduate Program, UCSD School of Medicine; Katherine R. Calvo, UCSD Graduate Program and National Cancer Institute; David B. Sykes, UCSD Graduate Program and Harvard General Hospital, Department of Medicine; and Hans Hacker, St. Jude Children's Research Hospital, Department of Infectious Diseases.
Funding for this research was provided by a grant from the National Cancer institute of the National Institutes of Health.