User login
Researchers say they have identified a subpopulation of hematopoietic stem cells (HSCs) that immediately contributes to long-term, multilineage hematopoietic reconstitution after transplant.
These HSCs were discovered in macaques, but the cells are similar to a subset of HSCs found in humans.
The researchers found the 2 sets of cells behaved identically when tested in vitro.
The team believes their findings will increase the efficiency of future efforts for HSC transplants, gene therapies, and gene editing.
Hans-Peter Kiem, MD, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues reported these findings in Science Translational Medicine.
The researchers performed HSC transplants in pig-tailed macaques, following hundreds of thousands of cells immediately after transplant and over the course of 7.5 years.
Previous reports had suggested that successive waves of progenitor cells expand and contract to establish the new bone marrow after transplant.
However, Dr Kiem and his colleagues homed in on a distinct group of HSCs that took hold early after transplant and went on to produce all cell lineages that constitute a complete blood system.
“These findings came as a surprise,” Dr Kiem said. “We had thought that there were multiple types of blood stem cells that take on different roles in rebuilding a blood and immune system. This population does it all.”
The population is a subset of CD34+ cells expressing CD90 and lacking CD45RA markers.
“The gold standard target cell population for stem cell gene therapy are cells with the marker CD34,” said study author Stefan Radtke, PhD, of the Fred Hutchinson Cancer Research Center.
“But we used 2 additional markers to further distinguish the population from the other blood stem cells.”
The researchers noted that the CD34+ CD45RA- CD90+ HSCs started repopulating the hematopoietic system within 10 days of being infused in macaques undergoing transplant.
A year later, the researchers found strong molecular traces of the cells, suggesting they were responsible for the ongoing maintenance of the newly transplanted system.
The team also determined the minimum numbers of CD34+ CD45RA- CD90+ HSCs that were necessary for successful transplant (defined as sustained neutrophil and platelet recovery).
And the researchers found similar gene expression profiles between macaque and human CD34+ CD45RA- CD90+ HSCs.
The team therefore believes these findings could have implications for HSC transplants in humans.
The researchers are now working to move their findings into the clinic with the hopes of integrating them in ongoing clinical trials. The team is currently looking for commercial partners. 
Researchers say they have identified a subpopulation of hematopoietic stem cells (HSCs) that immediately contributes to long-term, multilineage hematopoietic reconstitution after transplant.
These HSCs were discovered in macaques, but the cells are similar to a subset of HSCs found in humans.
The researchers found the 2 sets of cells behaved identically when tested in vitro.
The team believes their findings will increase the efficiency of future efforts for HSC transplants, gene therapies, and gene editing.
Hans-Peter Kiem, MD, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues reported these findings in Science Translational Medicine.
The researchers performed HSC transplants in pig-tailed macaques, following hundreds of thousands of cells immediately after transplant and over the course of 7.5 years.
Previous reports had suggested that successive waves of progenitor cells expand and contract to establish the new bone marrow after transplant.
However, Dr Kiem and his colleagues homed in on a distinct group of HSCs that took hold early after transplant and went on to produce all cell lineages that constitute a complete blood system.
“These findings came as a surprise,” Dr Kiem said. “We had thought that there were multiple types of blood stem cells that take on different roles in rebuilding a blood and immune system. This population does it all.”
The population is a subset of CD34+ cells expressing CD90 and lacking CD45RA markers.
“The gold standard target cell population for stem cell gene therapy are cells with the marker CD34,” said study author Stefan Radtke, PhD, of the Fred Hutchinson Cancer Research Center.
“But we used 2 additional markers to further distinguish the population from the other blood stem cells.”
The researchers noted that the CD34+ CD45RA- CD90+ HSCs started repopulating the hematopoietic system within 10 days of being infused in macaques undergoing transplant.
A year later, the researchers found strong molecular traces of the cells, suggesting they were responsible for the ongoing maintenance of the newly transplanted system.
The team also determined the minimum numbers of CD34+ CD45RA- CD90+ HSCs that were necessary for successful transplant (defined as sustained neutrophil and platelet recovery).
And the researchers found similar gene expression profiles between macaque and human CD34+ CD45RA- CD90+ HSCs.
The team therefore believes these findings could have implications for HSC transplants in humans.
The researchers are now working to move their findings into the clinic with the hopes of integrating them in ongoing clinical trials. The team is currently looking for commercial partners.
Researchers say they have identified a subpopulation of hematopoietic stem cells (HSCs) that immediately contributes to long-term, multilineage hematopoietic reconstitution after transplant.
These HSCs were discovered in macaques, but the cells are similar to a subset of HSCs found in humans.
The researchers found the 2 sets of cells behaved identically when tested in vitro.
The team believes their findings will increase the efficiency of future efforts for HSC transplants, gene therapies, and gene editing.
Hans-Peter Kiem, MD, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues reported these findings in Science Translational Medicine.
The researchers performed HSC transplants in pig-tailed macaques, following hundreds of thousands of cells immediately after transplant and over the course of 7.5 years.
Previous reports had suggested that successive waves of progenitor cells expand and contract to establish the new bone marrow after transplant.
However, Dr Kiem and his colleagues homed in on a distinct group of HSCs that took hold early after transplant and went on to produce all cell lineages that constitute a complete blood system.
“These findings came as a surprise,” Dr Kiem said. “We had thought that there were multiple types of blood stem cells that take on different roles in rebuilding a blood and immune system. This population does it all.”
The population is a subset of CD34+ cells expressing CD90 and lacking CD45RA markers.
“The gold standard target cell population for stem cell gene therapy are cells with the marker CD34,” said study author Stefan Radtke, PhD, of the Fred Hutchinson Cancer Research Center.
“But we used 2 additional markers to further distinguish the population from the other blood stem cells.”
The researchers noted that the CD34+ CD45RA- CD90+ HSCs started repopulating the hematopoietic system within 10 days of being infused in macaques undergoing transplant.
A year later, the researchers found strong molecular traces of the cells, suggesting they were responsible for the ongoing maintenance of the newly transplanted system.
The team also determined the minimum numbers of CD34+ CD45RA- CD90+ HSCs that were necessary for successful transplant (defined as sustained neutrophil and platelet recovery).
And the researchers found similar gene expression profiles between macaque and human CD34+ CD45RA- CD90+ HSCs.
The team therefore believes these findings could have implications for HSC transplants in humans.
The researchers are now working to move their findings into the clinic with the hopes of integrating them in ongoing clinical trials. The team is currently looking for commercial partners.