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Targeting the protein Del-1 could potentially improve hematopoietic stem cell (HSC) transplants, according to researchers.
The team found that Del-1 promoted engraftment in murine transplant recipients, but the protein also promoted the retention of hematopoietic progenitors in the bone marrow of mice that received granulocyte colony-stimulating factor (G-CSF).
The researchers therefore believe that enhancing Del-1 in HSC transplant recipients might improve engraftment.
And inhibiting Del-1 could increase progenitor mobilization in transplant donors.
The researchers detailed these findings and theories 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 study author George Hajishengallis, DDS, PhD, of Penn Dental Medicine in Philadelphia, Pennsylvania.
For Dr Hajishengallis, the route to studying Del-1 in the bone marrow began in his field of dental medicine.
Dr Hajishengallis and Triantafyllos Chavakis, Dr med, of Technische Universität Dresden in Germany, identified Del-1 as a potential drug target for gum disease. (Del-1 prevents inflammatory cells from moving into the gums.)
Both of the researchers’ labs also discovered that Del-1 is expressed in bone marrow, so the groups began following up to examine the protein’s function there.
Their work revealed that Del-1 is a key regulator of the HSC niche.
Del-1 is expressed by cells that promote HSC maintenance under steady-state conditions. This includes arteriolar endothelial cells, CXCL12-abundant reticular cells, and cells of the osteoblastic lineage.
The researchers also found that Del-1 regulates long-term HSC proliferation and differentiation toward the myeloid lineage.
In mice that received HSC transplants, Del-1 promoted progenitor engraftment and the generation of both progenitors and mature myeloid cells. The researchers noted that this was dependent upon β3 integrin expression in hematopoietic cells.
The team also found that Del-1 promotes hematopoietic progenitors’ response to systemic inflammation (induced by lipopolysaccharide). And the protein promotes the retention of hematopoietic progenitors in the bone marrow after G-CSF administration.
Taken together, these findings suggest that manipulating Del-1 might enhance HSC transplants.
“It’s easy to think of practical applications,” Dr Hajishengallis said. “Now, we need to find out whether it works in practice, so our studies continue.” 
Targeting the protein Del-1 could potentially improve hematopoietic stem cell (HSC) transplants, according to researchers.
The team found that Del-1 promoted engraftment in murine transplant recipients, but the protein also promoted the retention of hematopoietic progenitors in the bone marrow of mice that received granulocyte colony-stimulating factor (G-CSF).
The researchers therefore believe that enhancing Del-1 in HSC transplant recipients might improve engraftment.
And inhibiting Del-1 could increase progenitor mobilization in transplant donors.
The researchers detailed these findings and theories 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 study author George Hajishengallis, DDS, PhD, of Penn Dental Medicine in Philadelphia, Pennsylvania.
For Dr Hajishengallis, the route to studying Del-1 in the bone marrow began in his field of dental medicine.
Dr Hajishengallis and Triantafyllos Chavakis, Dr med, of Technische Universität Dresden in Germany, identified Del-1 as a potential drug target for gum disease. (Del-1 prevents inflammatory cells from moving into the gums.)
Both of the researchers’ labs also discovered that Del-1 is expressed in bone marrow, so the groups began following up to examine the protein’s function there.
Their work revealed that Del-1 is a key regulator of the HSC niche.
Del-1 is expressed by cells that promote HSC maintenance under steady-state conditions. This includes arteriolar endothelial cells, CXCL12-abundant reticular cells, and cells of the osteoblastic lineage.
The researchers also found that Del-1 regulates long-term HSC proliferation and differentiation toward the myeloid lineage.
In mice that received HSC transplants, Del-1 promoted progenitor engraftment and the generation of both progenitors and mature myeloid cells. The researchers noted that this was dependent upon β3 integrin expression in hematopoietic cells.
The team also found that Del-1 promotes hematopoietic progenitors’ response to systemic inflammation (induced by lipopolysaccharide). And the protein promotes the retention of hematopoietic progenitors in the bone marrow after G-CSF administration.
Taken together, these findings suggest that manipulating Del-1 might enhance HSC transplants.
“It’s easy to think of practical applications,” Dr Hajishengallis said. “Now, we need to find out whether it works in practice, so our studies continue.”
Targeting the protein Del-1 could potentially improve hematopoietic stem cell (HSC) transplants, according to researchers.
The team found that Del-1 promoted engraftment in murine transplant recipients, but the protein also promoted the retention of hematopoietic progenitors in the bone marrow of mice that received granulocyte colony-stimulating factor (G-CSF).
The researchers therefore believe that enhancing Del-1 in HSC transplant recipients might improve engraftment.
And inhibiting Del-1 could increase progenitor mobilization in transplant donors.
The researchers detailed these findings and theories 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 study author George Hajishengallis, DDS, PhD, of Penn Dental Medicine in Philadelphia, Pennsylvania.
For Dr Hajishengallis, the route to studying Del-1 in the bone marrow began in his field of dental medicine.
Dr Hajishengallis and Triantafyllos Chavakis, Dr med, of Technische Universität Dresden in Germany, identified Del-1 as a potential drug target for gum disease. (Del-1 prevents inflammatory cells from moving into the gums.)
Both of the researchers’ labs also discovered that Del-1 is expressed in bone marrow, so the groups began following up to examine the protein’s function there.
Their work revealed that Del-1 is a key regulator of the HSC niche.
Del-1 is expressed by cells that promote HSC maintenance under steady-state conditions. This includes arteriolar endothelial cells, CXCL12-abundant reticular cells, and cells of the osteoblastic lineage.
The researchers also found that Del-1 regulates long-term HSC proliferation and differentiation toward the myeloid lineage.
In mice that received HSC transplants, Del-1 promoted progenitor engraftment and the generation of both progenitors and mature myeloid cells. The researchers noted that this was dependent upon β3 integrin expression in hematopoietic cells.
The team also found that Del-1 promotes hematopoietic progenitors’ response to systemic inflammation (induced by lipopolysaccharide). And the protein promotes the retention of hematopoietic progenitors in the bone marrow after G-CSF administration.
Taken together, these findings suggest that manipulating Del-1 might enhance HSC transplants.
“It’s easy to think of practical applications,” Dr Hajishengallis said. “Now, we need to find out whether it works in practice, so our studies continue.”