Drowsy mice make poor stem cell donors, according to a new study published in Nature Communications (2015; doi:10.1038/ncomms9516).
A sleep deficit of just 4 hours affects the ability of blood and immune-system stem cells to migrate to the proper spots in the bone marrow of recipient mice and churn out the cell types necessary to reconstitute a damaged immune system by as much as 50%, the researchers found.
Although the research was done in laboratory mice, the findings have possible implications for human stem cell transplants. Tens of thousands of these procedures, often referred to as bone marrow transplants but more properly called hematopoietic stem cell transplants, are performed each year to rescue patients with immune system disorders or cancers.
“Considering how little attention we typically pay to sleep in the hospital setting, this finding is troubling,” said Asya Rolls, PhD, a former postdoctoral scholar at Stanford University School of Medicine in California. “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.”
Rolls studied laboratory mice that had been gently handled for 4 hours to prevent them from sleeping while their comrades dozed. She and her colleagues then collected stem cells from the bone marrow of drowsy and of well-rested mice and injected them into 12 mice that had received what would normally be a lethal dose of radiation. (The recipient mice also received an injection of their own bone marrow cells collected prior to radiation to make it possible to quantify the relative abilities of the donated stem cells to engraft successfully.)
The researchers then assessed the prevalence of myeloid cells (immune cells derived from the donated stem cells in the blood of the recipient mice) at 8 and 16 weeks after transplantation. They found that, although stem cells obtained from well-rested donors made up approximately 26% of the myeloid cells in the animal over time, stem cells from sleepy donors made up only approximately 12% of the recipients’ myeloid cells.
Rolls and her colleagues compared the ability of fluorescently labeled stem cells from sleepy and from rested mice to migrate properly from the recipients’ blood into the bone marrow. After 12 hours, 3.3% of stem cells from spritely mice were found in the bone marrow vs. only 1.7% of stem cells from sleepy mice.
Further testing in the laboratory dish showed that hematopoietic stem cells from the sleep-deprived mice responded less strongly than their peers to naturally occurring chemical signals that trigger cellular migration. They also expressed lower levels of an RNA message that controls the expression of a family of proteins called SOC, known to inhibit the migration of hematopoietic stem cells.
Although the effect of sleep deprivation was stark in this study, Rolls and her colleagues found that allowing the drowsy mice catch up on their sleep could reverse the effects of sleep deprivation. Even just 2 hours of recovery sleep restored the ability of the animals’ stem cells to function normally in the transplantation tests.