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in the bone marrow
A 2-drug combination can be more effective than granulocyte colony-stimulating factor (G-CSF) for mobilizing hematopoietic stem cells (HSCs), according to preclinical research published in Nature Communications.
The combination consists of the dual α9β1/α4β1 antagonist BOP and the CXCR4 antagonist AMD3100, also known as plerixafor.
In experiments with mice, researchers found that treatment with BOP and AMD3100 directly impacts HSCs so they can be seen in the blood stream within an hour.
And when these HSCs are transplanted into recipient mice, they can replenish the entire hematopoietic system.
“Current treatment requires [a transplant donor] to have growth factor injections for several days leading up to the [harvesting] procedure,” said study author Susie Nilsson, PhD, of Monash University in Clayton, Victoria, Australia.
“Using the [2-drug combination] eliminates the need for this, meaning a procedure that once took days can be reduced to around an hour.”
Combination vs monotherapy
Dr Nilsson and her colleagues found that, when given alone, AMD3100 and BOP produced similar increases in white blood cell (WBC) counts and the proportion of progenitors (LSK cells) in the peripheral blood (PB) of mice.
However, BOP produced a significantly greater increase in the proportion of HSCs (LSKSLAM cells) in the PB. The researchers said this suggests that AMD3100 predominantly mobilizes progenitors, and BOP predominantly mobilizes HSCs.
The team also found that, in combination, BOP and AMD3100 mobilized WBCs, progenitors, and HSCs more effectively than either agent alone.
To determine if these drugs could mobilize HSCs and progenitors with long-term multi-lineage engraftment potential, the researchers performed limiting dilution transplant analysis using BOP, AMD3100, or both drugs.
The team observed superior survival in mice that received 30 ml of PB mobilized using the combination, when compared to either drug alone.
In addition, PB mobilized with the combination resulted in a greater repopulation frequency (1 HSC in 23 ml PB) than PB mobilized with BOP (1 HSC in 327 ml) or AMD3100 (1 HSC in 351 ml).
The researchers said this was a more than 10-fold improvement with the combination, as compared to monotherapy.
Comparisons with G-CSF
Treating mice with a single dose of BOP following 4 days of G-CSF treatment resulted in significant synergistic increases in HSCs (LSKSLAM cells) and progenitors (LSK cells), when compared to G-CSF alone.
BOP and AMD3100 in combination produced equivalent numbers of HSCs and progenitors as G-CSF alone.
And the combination of G-CSF and AMD3100 mobilized significantly more HSCs and progenitors than G-CSF alone.
But the greatest number of HSCs and progenitors were mobilized with the combination of G-CSF, AMD3100, and BOP. This combination produced a significant increase in cells when compared with G-CSF alone or the combination of AMD3100 and BOP.
The researchers also compared the hematopoietic potential of PB mobilized with multiple doses of G-CSF to PB mobilized with a single dose of BOP and AMD3100 in combination.
Although equivalent numbers of HSCs were mobilized, BOP and AMD3100 significantly enhanced short-term and long-term multi-lineage engraftment, when compared to G-CSF.
To determine whether the HSC mobilization observed in these experiments is equivalent in humans, the researchers tested the mobilizing agents in humanized NSG mice.
They found that a single dose of BOP or AMD3100 alone, or multiple doses of G-CSF for 4 days, did not significantly increase human WBCs or human CD34+ stem and progenitor cells.
However, a single dose of BOP and AMD3100 in combination produced a significant increase in both WBCs and stem and progenitor cells.
The researchers said the next step is a phase 1 trial assessing the combination of BOP with G-CSF before they can test the combination of BOP and AMD3100 in humans. 
in the bone marrow
A 2-drug combination can be more effective than granulocyte colony-stimulating factor (G-CSF) for mobilizing hematopoietic stem cells (HSCs), according to preclinical research published in Nature Communications.
The combination consists of the dual α9β1/α4β1 antagonist BOP and the CXCR4 antagonist AMD3100, also known as plerixafor.
In experiments with mice, researchers found that treatment with BOP and AMD3100 directly impacts HSCs so they can be seen in the blood stream within an hour.
And when these HSCs are transplanted into recipient mice, they can replenish the entire hematopoietic system.
“Current treatment requires [a transplant donor] to have growth factor injections for several days leading up to the [harvesting] procedure,” said study author Susie Nilsson, PhD, of Monash University in Clayton, Victoria, Australia.
“Using the [2-drug combination] eliminates the need for this, meaning a procedure that once took days can be reduced to around an hour.”
Combination vs monotherapy
Dr Nilsson and her colleagues found that, when given alone, AMD3100 and BOP produced similar increases in white blood cell (WBC) counts and the proportion of progenitors (LSK cells) in the peripheral blood (PB) of mice.
However, BOP produced a significantly greater increase in the proportion of HSCs (LSKSLAM cells) in the PB. The researchers said this suggests that AMD3100 predominantly mobilizes progenitors, and BOP predominantly mobilizes HSCs.
The team also found that, in combination, BOP and AMD3100 mobilized WBCs, progenitors, and HSCs more effectively than either agent alone.
To determine if these drugs could mobilize HSCs and progenitors with long-term multi-lineage engraftment potential, the researchers performed limiting dilution transplant analysis using BOP, AMD3100, or both drugs.
The team observed superior survival in mice that received 30 ml of PB mobilized using the combination, when compared to either drug alone.
In addition, PB mobilized with the combination resulted in a greater repopulation frequency (1 HSC in 23 ml PB) than PB mobilized with BOP (1 HSC in 327 ml) or AMD3100 (1 HSC in 351 ml).
The researchers said this was a more than 10-fold improvement with the combination, as compared to monotherapy.
Comparisons with G-CSF
Treating mice with a single dose of BOP following 4 days of G-CSF treatment resulted in significant synergistic increases in HSCs (LSKSLAM cells) and progenitors (LSK cells), when compared to G-CSF alone.
BOP and AMD3100 in combination produced equivalent numbers of HSCs and progenitors as G-CSF alone.
And the combination of G-CSF and AMD3100 mobilized significantly more HSCs and progenitors than G-CSF alone.
But the greatest number of HSCs and progenitors were mobilized with the combination of G-CSF, AMD3100, and BOP. This combination produced a significant increase in cells when compared with G-CSF alone or the combination of AMD3100 and BOP.
The researchers also compared the hematopoietic potential of PB mobilized with multiple doses of G-CSF to PB mobilized with a single dose of BOP and AMD3100 in combination.
Although equivalent numbers of HSCs were mobilized, BOP and AMD3100 significantly enhanced short-term and long-term multi-lineage engraftment, when compared to G-CSF.
To determine whether the HSC mobilization observed in these experiments is equivalent in humans, the researchers tested the mobilizing agents in humanized NSG mice.
They found that a single dose of BOP or AMD3100 alone, or multiple doses of G-CSF for 4 days, did not significantly increase human WBCs or human CD34+ stem and progenitor cells.
However, a single dose of BOP and AMD3100 in combination produced a significant increase in both WBCs and stem and progenitor cells.
The researchers said the next step is a phase 1 trial assessing the combination of BOP with G-CSF before they can test the combination of BOP and AMD3100 in humans.
in the bone marrow
A 2-drug combination can be more effective than granulocyte colony-stimulating factor (G-CSF) for mobilizing hematopoietic stem cells (HSCs), according to preclinical research published in Nature Communications.
The combination consists of the dual α9β1/α4β1 antagonist BOP and the CXCR4 antagonist AMD3100, also known as plerixafor.
In experiments with mice, researchers found that treatment with BOP and AMD3100 directly impacts HSCs so they can be seen in the blood stream within an hour.
And when these HSCs are transplanted into recipient mice, they can replenish the entire hematopoietic system.
“Current treatment requires [a transplant donor] to have growth factor injections for several days leading up to the [harvesting] procedure,” said study author Susie Nilsson, PhD, of Monash University in Clayton, Victoria, Australia.
“Using the [2-drug combination] eliminates the need for this, meaning a procedure that once took days can be reduced to around an hour.”
Combination vs monotherapy
Dr Nilsson and her colleagues found that, when given alone, AMD3100 and BOP produced similar increases in white blood cell (WBC) counts and the proportion of progenitors (LSK cells) in the peripheral blood (PB) of mice.
However, BOP produced a significantly greater increase in the proportion of HSCs (LSKSLAM cells) in the PB. The researchers said this suggests that AMD3100 predominantly mobilizes progenitors, and BOP predominantly mobilizes HSCs.
The team also found that, in combination, BOP and AMD3100 mobilized WBCs, progenitors, and HSCs more effectively than either agent alone.
To determine if these drugs could mobilize HSCs and progenitors with long-term multi-lineage engraftment potential, the researchers performed limiting dilution transplant analysis using BOP, AMD3100, or both drugs.
The team observed superior survival in mice that received 30 ml of PB mobilized using the combination, when compared to either drug alone.
In addition, PB mobilized with the combination resulted in a greater repopulation frequency (1 HSC in 23 ml PB) than PB mobilized with BOP (1 HSC in 327 ml) or AMD3100 (1 HSC in 351 ml).
The researchers said this was a more than 10-fold improvement with the combination, as compared to monotherapy.
Comparisons with G-CSF
Treating mice with a single dose of BOP following 4 days of G-CSF treatment resulted in significant synergistic increases in HSCs (LSKSLAM cells) and progenitors (LSK cells), when compared to G-CSF alone.
BOP and AMD3100 in combination produced equivalent numbers of HSCs and progenitors as G-CSF alone.
And the combination of G-CSF and AMD3100 mobilized significantly more HSCs and progenitors than G-CSF alone.
But the greatest number of HSCs and progenitors were mobilized with the combination of G-CSF, AMD3100, and BOP. This combination produced a significant increase in cells when compared with G-CSF alone or the combination of AMD3100 and BOP.
The researchers also compared the hematopoietic potential of PB mobilized with multiple doses of G-CSF to PB mobilized with a single dose of BOP and AMD3100 in combination.
Although equivalent numbers of HSCs were mobilized, BOP and AMD3100 significantly enhanced short-term and long-term multi-lineage engraftment, when compared to G-CSF.
To determine whether the HSC mobilization observed in these experiments is equivalent in humans, the researchers tested the mobilizing agents in humanized NSG mice.
They found that a single dose of BOP or AMD3100 alone, or multiple doses of G-CSF for 4 days, did not significantly increase human WBCs or human CD34+ stem and progenitor cells.
However, a single dose of BOP and AMD3100 in combination produced a significant increase in both WBCs and stem and progenitor cells.
The researchers said the next step is a phase 1 trial assessing the combination of BOP with G-CSF before they can test the combination of BOP and AMD3100 in humans.