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Donor’s lack of sleep may impact HSCT

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Sleep-deprived mice make poor donors for hematopoietic stem cell transplants (HSCTs), according to a study published in Nature Communications.

The research showed that a sleep deficit of just 4 hours can reduce—by more than 50%—the ability of HSCs to engraft and reconstitute the blood and bone marrow of an irradiated recipient mouse.

Researchers believe these findings may also apply to humans.

“Considering how little attention we typically pay to sleep in the hospital setting, this finding is troubling,” said study author Asya Rolls, PhD, of Technion–Israel Institute of Technology in Haifa.

“We go to all this trouble to find a matching donor, but this research suggests that, if the donor is not well-rested, it can impact the outcome of the transplantation. However, it’s heartening to think that this is not an insurmountable obstacle. A short period of recovery sleep before transplant can restore the donor’s cells’ ability to function normally.”

Dr Rolls and her colleagues studied mice that had been gently handled for 4 hours to prevent them from sleeping while control mice dozed. The team then collected HSCs from the sleep-deprived and well-rested mice and injected the cells into 12 irradiated mice.

The recipient mice also received an injection of their own HSCs collected prior to radiation so the researchers could quantify the relative abilities of the donated HSCs to engraft successfully.

The team then assessed the prevalence of myeloid cells derived from donated HSCs at 8 weeks and 16 weeks after transplant. At 16 weeks, donor myeloid chimerism was about 26% in HSCT recipients with well-rested donors and about 12% in recipients with sleep-deprived donors (P<0.0001).

Dr Rolls and her colleagues also compared the ability of fluorescently labeled HSCs from sleep-deprived mice and rested mice to home to the bone marrow. After 12 hours, 3.3% percent of HSCs from rested mice were found in the bone marrow, compared to 1.7% of HSCs from sleep-deprived mice (P<0.05).

Further investigation revealed that sleep deprivation downregulates the expression of miR-19b, a negative regulator of the suppressor of cytokine signaling (SOCS) genes, which inhibit HSC migration and homing.

Finally, Dr Rolls and her colleagues found the effects of sleep deprivation on HSCs could be reversed by letting mice catch up on sleep. Even 2 hours of recovery sleep restored the HSCs’ ability to function normally in transplantation tests.

“We still don’t know how sleep deprivation affects us all, not just bone marrow donors,” Dr Rolls said. “The fact that recovery sleep is so helpful only emphasizes how important it is to pay attention to sleep.”

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Lab mouse

Sleep-deprived mice make poor donors for hematopoietic stem cell transplants (HSCTs), according to a study published in Nature Communications.

The research showed that a sleep deficit of just 4 hours can reduce—by more than 50%—the ability of HSCs to engraft and reconstitute the blood and bone marrow of an irradiated recipient mouse.

Researchers believe these findings may also apply to humans.

“Considering how little attention we typically pay to sleep in the hospital setting, this finding is troubling,” said study author Asya Rolls, PhD, of Technion–Israel Institute of Technology in Haifa.

“We go to all this trouble to find a matching donor, but this research suggests that, if the donor is not well-rested, it can impact the outcome of the transplantation. However, it’s heartening to think that this is not an insurmountable obstacle. A short period of recovery sleep before transplant can restore the donor’s cells’ ability to function normally.”

Dr Rolls and her colleagues studied mice that had been gently handled for 4 hours to prevent them from sleeping while control mice dozed. The team then collected HSCs from the sleep-deprived and well-rested mice and injected the cells into 12 irradiated mice.

The recipient mice also received an injection of their own HSCs collected prior to radiation so the researchers could quantify the relative abilities of the donated HSCs to engraft successfully.

The team then assessed the prevalence of myeloid cells derived from donated HSCs at 8 weeks and 16 weeks after transplant. At 16 weeks, donor myeloid chimerism was about 26% in HSCT recipients with well-rested donors and about 12% in recipients with sleep-deprived donors (P<0.0001).

Dr Rolls and her colleagues also compared the ability of fluorescently labeled HSCs from sleep-deprived mice and rested mice to home to the bone marrow. After 12 hours, 3.3% percent of HSCs from rested mice were found in the bone marrow, compared to 1.7% of HSCs from sleep-deprived mice (P<0.05).

Further investigation revealed that sleep deprivation downregulates the expression of miR-19b, a negative regulator of the suppressor of cytokine signaling (SOCS) genes, which inhibit HSC migration and homing.

Finally, Dr Rolls and her colleagues found the effects of sleep deprivation on HSCs could be reversed by letting mice catch up on sleep. Even 2 hours of recovery sleep restored the HSCs’ ability to function normally in transplantation tests.

“We still don’t know how sleep deprivation affects us all, not just bone marrow donors,” Dr Rolls said. “The fact that recovery sleep is so helpful only emphasizes how important it is to pay attention to sleep.”

Lab mouse

Sleep-deprived mice make poor donors for hematopoietic stem cell transplants (HSCTs), according to a study published in Nature Communications.

The research showed that a sleep deficit of just 4 hours can reduce—by more than 50%—the ability of HSCs to engraft and reconstitute the blood and bone marrow of an irradiated recipient mouse.

Researchers believe these findings may also apply to humans.

“Considering how little attention we typically pay to sleep in the hospital setting, this finding is troubling,” said study author Asya Rolls, PhD, of Technion–Israel Institute of Technology in Haifa.

“We go to all this trouble to find a matching donor, but this research suggests that, if the donor is not well-rested, it can impact the outcome of the transplantation. However, it’s heartening to think that this is not an insurmountable obstacle. A short period of recovery sleep before transplant can restore the donor’s cells’ ability to function normally.”

Dr Rolls and her colleagues studied mice that had been gently handled for 4 hours to prevent them from sleeping while control mice dozed. The team then collected HSCs from the sleep-deprived and well-rested mice and injected the cells into 12 irradiated mice.

The recipient mice also received an injection of their own HSCs collected prior to radiation so the researchers could quantify the relative abilities of the donated HSCs to engraft successfully.

The team then assessed the prevalence of myeloid cells derived from donated HSCs at 8 weeks and 16 weeks after transplant. At 16 weeks, donor myeloid chimerism was about 26% in HSCT recipients with well-rested donors and about 12% in recipients with sleep-deprived donors (P<0.0001).

Dr Rolls and her colleagues also compared the ability of fluorescently labeled HSCs from sleep-deprived mice and rested mice to home to the bone marrow. After 12 hours, 3.3% percent of HSCs from rested mice were found in the bone marrow, compared to 1.7% of HSCs from sleep-deprived mice (P<0.05).

Further investigation revealed that sleep deprivation downregulates the expression of miR-19b, a negative regulator of the suppressor of cytokine signaling (SOCS) genes, which inhibit HSC migration and homing.

Finally, Dr Rolls and her colleagues found the effects of sleep deprivation on HSCs could be reversed by letting mice catch up on sleep. Even 2 hours of recovery sleep restored the HSCs’ ability to function normally in transplantation tests.

“We still don’t know how sleep deprivation affects us all, not just bone marrow donors,” Dr Rolls said. “The fact that recovery sleep is so helpful only emphasizes how important it is to pay attention to sleep.”

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