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A medication used to treat joint and skin conditions might also improve allogeneic hematopoietic stem cell transplant (HSCT), according to research published in Science Translational Medicine.
Researchers discovered that, once transplanted, some differentiated cells produce tumor necrosis factor-alpha (TNFα), which impairs cell division and survival of hematopoietic stem and progenitor cells (HSPCs).
This led the researchers to explore whether a drug that blocks TNFα would allow HSPCs to thrive in a new host.
The team administered etanercept, an antibody that binds to and disables TNFα, to mice receiving umbilical cord blood (UCB) transplants.
Mice that received the drug had better bone marrow reconstitution than control mice.
“If this strategy boosts the survival rate of blood stem cells in humans, then we can get away with using smaller grafts,” said study author Peter Zandstra, PhD, of the University of British Columbia in Vancouver, British Columbia, Canada.
“That would vastly increase the pool of usable umbilical cord blood donations, making stem cell transplants more feasible, not only for blood cancers, which we are already doing, but also for auto-immune diseases, like Crohn’s disease, even HIV.”
Dr Zandstra and his colleagues began this research by performing UCB transplants in immunodeficient mice.
The team was surprised to find that mice receiving the highest numbers of UCB cells had the worst outcomes in terms of bone marrow reconstitution. The researchers also found elevated levels of cytokines in the animals’ sera.
The team speculated that mature immune cells within UCB might be producing inflammatory cytokines, thus preventing HSPCs from successfully repopulating the bone marrow.
One molecule in particular, TNFα, inhibited HSPC survival and division.
Treating recipient mice with the TNFα blocker etanercept enhanced short-term HSPC engraftment and accelerated hematopoietic recovery after UCB transplants.
According to the researchers, these results implicate TNFα as a central player in setting off the cytokine storm that can impair donor HSPC survival.
The team also believes their results provide a strong basis for conducting a clinical trial to see whether etanercept or another TNFα blocker would improve outcomes for people receiving HSCTs.
“Failure of the graft after stem cell transplantation is always a potentially life-threatening complication,” said Kirk Schultz, MD, a professor at the University of British Columbia who was not involved in this study.
“This is especially the case when we must use mismatched stem cells derived from umbilical cord blood. This advance may offer a significant advance in making these transplants more successful.” 
A medication used to treat joint and skin conditions might also improve allogeneic hematopoietic stem cell transplant (HSCT), according to research published in Science Translational Medicine.
Researchers discovered that, once transplanted, some differentiated cells produce tumor necrosis factor-alpha (TNFα), which impairs cell division and survival of hematopoietic stem and progenitor cells (HSPCs).
This led the researchers to explore whether a drug that blocks TNFα would allow HSPCs to thrive in a new host.
The team administered etanercept, an antibody that binds to and disables TNFα, to mice receiving umbilical cord blood (UCB) transplants.
Mice that received the drug had better bone marrow reconstitution than control mice.
“If this strategy boosts the survival rate of blood stem cells in humans, then we can get away with using smaller grafts,” said study author Peter Zandstra, PhD, of the University of British Columbia in Vancouver, British Columbia, Canada.
“That would vastly increase the pool of usable umbilical cord blood donations, making stem cell transplants more feasible, not only for blood cancers, which we are already doing, but also for auto-immune diseases, like Crohn’s disease, even HIV.”
Dr Zandstra and his colleagues began this research by performing UCB transplants in immunodeficient mice.
The team was surprised to find that mice receiving the highest numbers of UCB cells had the worst outcomes in terms of bone marrow reconstitution. The researchers also found elevated levels of cytokines in the animals’ sera.
The team speculated that mature immune cells within UCB might be producing inflammatory cytokines, thus preventing HSPCs from successfully repopulating the bone marrow.
One molecule in particular, TNFα, inhibited HSPC survival and division.
Treating recipient mice with the TNFα blocker etanercept enhanced short-term HSPC engraftment and accelerated hematopoietic recovery after UCB transplants.
According to the researchers, these results implicate TNFα as a central player in setting off the cytokine storm that can impair donor HSPC survival.
The team also believes their results provide a strong basis for conducting a clinical trial to see whether etanercept or another TNFα blocker would improve outcomes for people receiving HSCTs.
“Failure of the graft after stem cell transplantation is always a potentially life-threatening complication,” said Kirk Schultz, MD, a professor at the University of British Columbia who was not involved in this study.
“This is especially the case when we must use mismatched stem cells derived from umbilical cord blood. This advance may offer a significant advance in making these transplants more successful.”
A medication used to treat joint and skin conditions might also improve allogeneic hematopoietic stem cell transplant (HSCT), according to research published in Science Translational Medicine.
Researchers discovered that, once transplanted, some differentiated cells produce tumor necrosis factor-alpha (TNFα), which impairs cell division and survival of hematopoietic stem and progenitor cells (HSPCs).
This led the researchers to explore whether a drug that blocks TNFα would allow HSPCs to thrive in a new host.
The team administered etanercept, an antibody that binds to and disables TNFα, to mice receiving umbilical cord blood (UCB) transplants.
Mice that received the drug had better bone marrow reconstitution than control mice.
“If this strategy boosts the survival rate of blood stem cells in humans, then we can get away with using smaller grafts,” said study author Peter Zandstra, PhD, of the University of British Columbia in Vancouver, British Columbia, Canada.
“That would vastly increase the pool of usable umbilical cord blood donations, making stem cell transplants more feasible, not only for blood cancers, which we are already doing, but also for auto-immune diseases, like Crohn’s disease, even HIV.”
Dr Zandstra and his colleagues began this research by performing UCB transplants in immunodeficient mice.
The team was surprised to find that mice receiving the highest numbers of UCB cells had the worst outcomes in terms of bone marrow reconstitution. The researchers also found elevated levels of cytokines in the animals’ sera.
The team speculated that mature immune cells within UCB might be producing inflammatory cytokines, thus preventing HSPCs from successfully repopulating the bone marrow.
One molecule in particular, TNFα, inhibited HSPC survival and division.
Treating recipient mice with the TNFα blocker etanercept enhanced short-term HSPC engraftment and accelerated hematopoietic recovery after UCB transplants.
According to the researchers, these results implicate TNFα as a central player in setting off the cytokine storm that can impair donor HSPC survival.
The team also believes their results provide a strong basis for conducting a clinical trial to see whether etanercept or another TNFα blocker would improve outcomes for people receiving HSCTs.
“Failure of the graft after stem cell transplantation is always a potentially life-threatening complication,” said Kirk Schultz, MD, a professor at the University of British Columbia who was not involved in this study.
“This is especially the case when we must use mismatched stem cells derived from umbilical cord blood. This advance may offer a significant advance in making these transplants more successful.”