Researchers at University of Pennsylvania and Technical University of Dresden have identified a bone marrow protein that, when targeted, could improve stem cell transplants for both donors and recipients. They also found they may be able to modulate levels of the protein, called Del-1, to enhance immune cell production in patients with certain blood cancers.
“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 is easily manipulated, one can see that it could be a target in many potential applications,” said George Hajishengallis, the Thomas W. Evans Centennial Professor in the department of microbiology in Penn’s School of Dental Medicine and a senior author on the work.
Dr. Hajishengallis began studying Del-1 in the bone marrow as it applies to dental medicine. He and Triantafyllos Chavakis, co-senior author on the study and a professor at the Technical University of Dresden, identified Del-1 as a potential drug target for gum disease after finding that it prevents inflammatory cells from moving into the gums. When the scientists discovered that Del-1 was also expressed in bone marrow, they began to investigate further.
Drs. Hajishengallis and Chavakis found that Del-1 was expressed by at least three cell types in the bone marrow that support hematopoietic stem cells: endothelial cells, CAR cells and osteoblasts. They then conducted research on mice deficient in Del-1 which showed that the protein promotes proliferation and differentiation of hematopoietic stem cells. They also discovered through bone marrow transplant experiments that Del-1 is required to be present in recipient bone marrow in order for the transplanted stem cells to engraft in the recipient and produce myeloid cells.
“We saw roles for Del-1 in both steady state and emergency conditions,” Dr. Hajishengallis said.
The research could lead to therapeutic interventions thanks to the identification of the protein on hematopoietic stem cells with which Del-1 interacts, the ß3 integrin. The findings could impact bone marrow and stem cell transplants—for both the donors and the recipients—as well as people undergoing chemotherapy.
“It’s easy to think of practical applications for these findings,” said Dr. Hajishengallis. “Now we need to find out whether it works in practice, so our studies continue.”