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in the bone marrow
Preclinical research suggests chronic inflammation leads to an imbalanced blood system, which may have an impact on hematopoietic stem cell (HSC) transplant.
The study showed that chronic exposure to an inflammatory “emergency” signal, interleukin-1 (IL-1), has a negative effect on HSCs—restricting differentiation, impairing self-renewal capacity, and priming HSCs to fail massive replicative challenges such as transplantation.
However, these effects proved to be fully reversible.
Eric M. Pietras, PhD, of the University of Colorado Anschutz Medical Campus in Aurora, and his colleagues recounted these findings in Nature Cell Biology.
While HSCs are usually dormant in the bone marrow, Dr Pietras said he and his colleagues showed that, “these cells are also exquisitely sensitive to changes in their environment and react accordingly.”
The team showed that HSCs are sensitive to the amount of IL-1 they encounter. Chronic IL-1 exposure prompts accelerated cell division and pushes HSCs toward myeloid differentiation through activation of the NF-κB pathway and engagement of a PU.1-dependent myeloid gene program.
So HSCs that are overexposed to IL-1 lose their ability to differentiate into lymphoid and erythroid cells.
“[The HSCs are] receiving a signal telling them they need to keep building myeloid cells, and, as a result, they don’t make the other blood cells you need,” Dr Pietras explained.
“You can end up with too few red blood cells, reducing the body’s ability to deliver oxygen to cells. Or we see decreased production of new lymphoid cells, leaving the system potentially immunodeficient. These are all common features of chronically inflamed, and even aged, blood systems.”
Chronic IL-1 exposure also led to decreased self-renewal activity and regenerative potential in HSCs in response to transplantation in mice. Dr Pietras and his colleagues believe these findings may translate to HSC transplant in humans.
“Our results show that not only should we be looking for markers of blood system compatibility [in HSC donors], but we may also want to explore whether a potential donor’s [HSCs] have been exposed to inflammation and may not be as effective at rebuilding the patient’s blood system,” Dr Pietras said.
“Likewise, the presence of inflammation in the individual receiving the [HSC transplant] could also be an important factor in how well the stem cells regenerate a new blood system once they are transplanted.”
Fortunately, Dr Pietras and his colleagues found the damaging effects of chronic IL-1 exposure could be reversed upon IL-1 withdrawal.
To test the durability of IL-1’s effects, the researchers treated mice with IL-1 for 20 days and then stopped for several weeks to see if the HSCs recovered.
“Our data suggest that it is possible to turn back the clock and reverse the effects of chronic inflammation on [HSCs], perhaps using therapies already available in the clinic to block inflammatory signals such as IL-1,” Dr Pietras said.
“Of course, we don’t yet know, on a human scale, how long it takes a stem cell to ‘remember’ these insults. It may be that, after a longer period of exposure to IL-1, these changes become more fixed.” 
in the bone marrow
Preclinical research suggests chronic inflammation leads to an imbalanced blood system, which may have an impact on hematopoietic stem cell (HSC) transplant.
The study showed that chronic exposure to an inflammatory “emergency” signal, interleukin-1 (IL-1), has a negative effect on HSCs—restricting differentiation, impairing self-renewal capacity, and priming HSCs to fail massive replicative challenges such as transplantation.
However, these effects proved to be fully reversible.
Eric M. Pietras, PhD, of the University of Colorado Anschutz Medical Campus in Aurora, and his colleagues recounted these findings in Nature Cell Biology.
While HSCs are usually dormant in the bone marrow, Dr Pietras said he and his colleagues showed that, “these cells are also exquisitely sensitive to changes in their environment and react accordingly.”
The team showed that HSCs are sensitive to the amount of IL-1 they encounter. Chronic IL-1 exposure prompts accelerated cell division and pushes HSCs toward myeloid differentiation through activation of the NF-κB pathway and engagement of a PU.1-dependent myeloid gene program.
So HSCs that are overexposed to IL-1 lose their ability to differentiate into lymphoid and erythroid cells.
“[The HSCs are] receiving a signal telling them they need to keep building myeloid cells, and, as a result, they don’t make the other blood cells you need,” Dr Pietras explained.
“You can end up with too few red blood cells, reducing the body’s ability to deliver oxygen to cells. Or we see decreased production of new lymphoid cells, leaving the system potentially immunodeficient. These are all common features of chronically inflamed, and even aged, blood systems.”
Chronic IL-1 exposure also led to decreased self-renewal activity and regenerative potential in HSCs in response to transplantation in mice. Dr Pietras and his colleagues believe these findings may translate to HSC transplant in humans.
“Our results show that not only should we be looking for markers of blood system compatibility [in HSC donors], but we may also want to explore whether a potential donor’s [HSCs] have been exposed to inflammation and may not be as effective at rebuilding the patient’s blood system,” Dr Pietras said.
“Likewise, the presence of inflammation in the individual receiving the [HSC transplant] could also be an important factor in how well the stem cells regenerate a new blood system once they are transplanted.”
Fortunately, Dr Pietras and his colleagues found the damaging effects of chronic IL-1 exposure could be reversed upon IL-1 withdrawal.
To test the durability of IL-1’s effects, the researchers treated mice with IL-1 for 20 days and then stopped for several weeks to see if the HSCs recovered.
“Our data suggest that it is possible to turn back the clock and reverse the effects of chronic inflammation on [HSCs], perhaps using therapies already available in the clinic to block inflammatory signals such as IL-1,” Dr Pietras said.
“Of course, we don’t yet know, on a human scale, how long it takes a stem cell to ‘remember’ these insults. It may be that, after a longer period of exposure to IL-1, these changes become more fixed.”
in the bone marrow
Preclinical research suggests chronic inflammation leads to an imbalanced blood system, which may have an impact on hematopoietic stem cell (HSC) transplant.
The study showed that chronic exposure to an inflammatory “emergency” signal, interleukin-1 (IL-1), has a negative effect on HSCs—restricting differentiation, impairing self-renewal capacity, and priming HSCs to fail massive replicative challenges such as transplantation.
However, these effects proved to be fully reversible.
Eric M. Pietras, PhD, of the University of Colorado Anschutz Medical Campus in Aurora, and his colleagues recounted these findings in Nature Cell Biology.
While HSCs are usually dormant in the bone marrow, Dr Pietras said he and his colleagues showed that, “these cells are also exquisitely sensitive to changes in their environment and react accordingly.”
The team showed that HSCs are sensitive to the amount of IL-1 they encounter. Chronic IL-1 exposure prompts accelerated cell division and pushes HSCs toward myeloid differentiation through activation of the NF-κB pathway and engagement of a PU.1-dependent myeloid gene program.
So HSCs that are overexposed to IL-1 lose their ability to differentiate into lymphoid and erythroid cells.
“[The HSCs are] receiving a signal telling them they need to keep building myeloid cells, and, as a result, they don’t make the other blood cells you need,” Dr Pietras explained.
“You can end up with too few red blood cells, reducing the body’s ability to deliver oxygen to cells. Or we see decreased production of new lymphoid cells, leaving the system potentially immunodeficient. These are all common features of chronically inflamed, and even aged, blood systems.”
Chronic IL-1 exposure also led to decreased self-renewal activity and regenerative potential in HSCs in response to transplantation in mice. Dr Pietras and his colleagues believe these findings may translate to HSC transplant in humans.
“Our results show that not only should we be looking for markers of blood system compatibility [in HSC donors], but we may also want to explore whether a potential donor’s [HSCs] have been exposed to inflammation and may not be as effective at rebuilding the patient’s blood system,” Dr Pietras said.
“Likewise, the presence of inflammation in the individual receiving the [HSC transplant] could also be an important factor in how well the stem cells regenerate a new blood system once they are transplanted.”
Fortunately, Dr Pietras and his colleagues found the damaging effects of chronic IL-1 exposure could be reversed upon IL-1 withdrawal.
To test the durability of IL-1’s effects, the researchers treated mice with IL-1 for 20 days and then stopped for several weeks to see if the HSCs recovered.
“Our data suggest that it is possible to turn back the clock and reverse the effects of chronic inflammation on [HSCs], perhaps using therapies already available in the clinic to block inflammatory signals such as IL-1,” Dr Pietras said.
“Of course, we don’t yet know, on a human scale, how long it takes a stem cell to ‘remember’ these insults. It may be that, after a longer period of exposure to IL-1, these changes become more fixed.”