User login
New research suggests a 2-drug combination might improve hematopoietic stem cell transplant (HSCT) for donors and recipients.
Researchers found that a single dose of the drugs provides HSC mobilization that rivals 5-day treatment with granulocyte colony-stimulating factor (G-CSF).
And the combination mobilizes HSCs that have higher engraftment efficiency than HSCs mobilized by G-CSF.
Jonathan Hoggatt, PhD, of Massachusetts General Hospital in Boston, and his colleagues reported these findings in Cell.
“Our new method of harvesting stem cells requires only a single injection and mobilizes the cells needed in 15 minutes,” Dr Hoggatt said. “So in the time it takes to boil an egg, we are able to acquire the number of stem cells produced by the current standard 5-day protocol. This means less pain, time off work, and lifestyle disruption for the donor, more convenience for the clinical staff, and more predictability for the harvesting procedure.”
Dr Hoggatt and his colleagues have investigated ways to enhance HSC donation for several years. In a previous study, the researchers found that a CXCR2 agonist called GRO-beta induced rapid movement of HSCs from the marrow into the blood in animal models.
Initial experiments in the current study revealed that GRO-beta injections were safe and well tolerated in human volunteers but had only a modest effect in mobilizing HSCs. Therefore, the team tried combining GRO-beta with the CXCR4 antagonist AMD3100 (plerixafor).
The researchers found that simultaneous administration of both drugs rapidly (within 15 minutes) produced a quantity of HSCs equal to that provided by the 5-day G-CSF protocol.
When transplanted in mice, the HSCs mobilized by AMD3100 and GRO-beta prompted faster reconstitution of bone marrow and recovery of immune cell populations than HSCs mobilized by G-CSF.
The HSCs mobilized by AMD3100 and GRO-beta showed patterns of gene expression similar to those of fetal HSCs.
“These highly engraftable hematopoietic stem cells produced by our new strategy are essentially the A+ students of bone marrow stem cells,” Dr Hoggatt said. “Finding that they express genes similar to those of fetal liver HSCs . . . suggests that they will be very good at moving into an empty bone marrow space and rapidly dividing to fill the marrow and produce blood. Now, we need to test the combination in a clinical trial to confirm its safety and effectiveness in humans.” 
New research suggests a 2-drug combination might improve hematopoietic stem cell transplant (HSCT) for donors and recipients.
Researchers found that a single dose of the drugs provides HSC mobilization that rivals 5-day treatment with granulocyte colony-stimulating factor (G-CSF).
And the combination mobilizes HSCs that have higher engraftment efficiency than HSCs mobilized by G-CSF.
Jonathan Hoggatt, PhD, of Massachusetts General Hospital in Boston, and his colleagues reported these findings in Cell.
“Our new method of harvesting stem cells requires only a single injection and mobilizes the cells needed in 15 minutes,” Dr Hoggatt said. “So in the time it takes to boil an egg, we are able to acquire the number of stem cells produced by the current standard 5-day protocol. This means less pain, time off work, and lifestyle disruption for the donor, more convenience for the clinical staff, and more predictability for the harvesting procedure.”
Dr Hoggatt and his colleagues have investigated ways to enhance HSC donation for several years. In a previous study, the researchers found that a CXCR2 agonist called GRO-beta induced rapid movement of HSCs from the marrow into the blood in animal models.
Initial experiments in the current study revealed that GRO-beta injections were safe and well tolerated in human volunteers but had only a modest effect in mobilizing HSCs. Therefore, the team tried combining GRO-beta with the CXCR4 antagonist AMD3100 (plerixafor).
The researchers found that simultaneous administration of both drugs rapidly (within 15 minutes) produced a quantity of HSCs equal to that provided by the 5-day G-CSF protocol.
When transplanted in mice, the HSCs mobilized by AMD3100 and GRO-beta prompted faster reconstitution of bone marrow and recovery of immune cell populations than HSCs mobilized by G-CSF.
The HSCs mobilized by AMD3100 and GRO-beta showed patterns of gene expression similar to those of fetal HSCs.
“These highly engraftable hematopoietic stem cells produced by our new strategy are essentially the A+ students of bone marrow stem cells,” Dr Hoggatt said. “Finding that they express genes similar to those of fetal liver HSCs . . . suggests that they will be very good at moving into an empty bone marrow space and rapidly dividing to fill the marrow and produce blood. Now, we need to test the combination in a clinical trial to confirm its safety and effectiveness in humans.”
New research suggests a 2-drug combination might improve hematopoietic stem cell transplant (HSCT) for donors and recipients.
Researchers found that a single dose of the drugs provides HSC mobilization that rivals 5-day treatment with granulocyte colony-stimulating factor (G-CSF).
And the combination mobilizes HSCs that have higher engraftment efficiency than HSCs mobilized by G-CSF.
Jonathan Hoggatt, PhD, of Massachusetts General Hospital in Boston, and his colleagues reported these findings in Cell.
“Our new method of harvesting stem cells requires only a single injection and mobilizes the cells needed in 15 minutes,” Dr Hoggatt said. “So in the time it takes to boil an egg, we are able to acquire the number of stem cells produced by the current standard 5-day protocol. This means less pain, time off work, and lifestyle disruption for the donor, more convenience for the clinical staff, and more predictability for the harvesting procedure.”
Dr Hoggatt and his colleagues have investigated ways to enhance HSC donation for several years. In a previous study, the researchers found that a CXCR2 agonist called GRO-beta induced rapid movement of HSCs from the marrow into the blood in animal models.
Initial experiments in the current study revealed that GRO-beta injections were safe and well tolerated in human volunteers but had only a modest effect in mobilizing HSCs. Therefore, the team tried combining GRO-beta with the CXCR4 antagonist AMD3100 (plerixafor).
The researchers found that simultaneous administration of both drugs rapidly (within 15 minutes) produced a quantity of HSCs equal to that provided by the 5-day G-CSF protocol.
When transplanted in mice, the HSCs mobilized by AMD3100 and GRO-beta prompted faster reconstitution of bone marrow and recovery of immune cell populations than HSCs mobilized by G-CSF.
The HSCs mobilized by AMD3100 and GRO-beta showed patterns of gene expression similar to those of fetal HSCs.
“These highly engraftable hematopoietic stem cells produced by our new strategy are essentially the A+ students of bone marrow stem cells,” Dr Hoggatt said. “Finding that they express genes similar to those of fetal liver HSCs . . . suggests that they will be very good at moving into an empty bone marrow space and rapidly dividing to fill the marrow and produce blood. Now, we need to test the combination in a clinical trial to confirm its safety and effectiveness in humans.”