PHILADELPHIA, Oct. 31, 2017 – Bone marrow contains hematopoietic stem cells, the precursors to every blood cell type. These cells spring into action following bone marrow transplants, bone marrow injury and during systemic infection, creating new blood cells, including immune cells, in a process known as hematopoiesis.
A study by Penn Dental Medicine and Technical University of Dresden has identified an important regulator of this process, a protein called Del-1. Targeting it, the researchers noted, could potentially improve stem cell transplants for both donors and recipients. There may also be ways to modulate levels of Del-1 in patients with certain blood cancers to enhance immune cell production. The findings are reported in The Journal of Clinical Investigation.
“Because the hematopoietic stem cell niche is so important for the creation of bone marrow and blood cells and because Del-1 is a soluble protein and easily manipulated, one can see that it could be a target in many potential applications,” said senior author George Hajishengallis, Thomas W. Evans Centennial Professor of Microbiology at Penn Dental Medicine.
For Hajishengallis, the route to studying Del-1 in bone marrow began in his field of dental medicine. Working with co-senior author Triantafyllos Chavakis, he had identified Del-1 as a potential drug target for gum disease after finding that it prevents inflammatory cells from moving into the gums.
Both of their labs had discovered that Del-1 was also expressed in bone marrow and began following up to see its function there. Their work revealed that Del-1 was expressed by at least three cell types in the bone marrow and promoted proliferation and differentiation of hematopoietic stem cells, sending more of these progenitor cells down a path toward becoming myeloid cells, such as macrophages and neutrophils.
Hajishengallis and Chavakis see potential applications in bone marrow and stem cell transplants. In donors, blocking the interaction between Del-1 and hematopoietic stem cells could be helpful for increasing donor cell numbers for transplantation. On the other hand, transplant recipients may need enhanced Del-1 interaction to ensure the transplanted cells engraft and begin making new blood cells more rapidly.
“It’s easy to think of practical applications,” said Hajishengallis. “Now we need to find out whether it works in practice, so our studies continue.”
The study was supported by the Deutsche Forschungsgemeinschaft, European Commission, European Research Council and National Institutes of Health (grants AI068730, DE024153, DE024716, DE0152 54 and DE026152).
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SOURCE Penn Dental Medicine