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RESEARCH BRIEFS
In Mice, Method Multiplies Stem Cells After Marrow TransplantFor cancer patients undergoing bone marrow transplants, hematopoietic stem cells are a precious commodity. Newly transplanted cells do not always thrive in sufficient numbers--an outcome that can have dire consequences for patients. A team of Massachusetts General Hospital researchers has found a way to increase the number of engrafted hematopoietic stem cells, and working in mice, to practically ensure the recipient's survival.
On the face of it, osteoblasts appear ideal neighbors--they lie close to stem cells and they release growth factors that can activate stem cells. Yet no one had explored the link between the two populations in vivo. Calvi, who is now at the University of Rochester School of Medicine, had developed a transgenic mouse that exhibited an excess of osteoblasts by virtue of a constitutively activated PTH/PTHrP receptor (PPR). Assaying the animals' bone marrow, the researchers found a significant increase in the number of hematopoietic stem cells. Scadden, HMS associate professor of medicine, and his colleagues knew from previous work that stem cells possess a receptor, Notch, that when stimulated causes the cells to proliferate. They also knew that osteoblasts produce a Notch-activating ligand, Jagged 1. Sure enough, both Notch signaling and Jagged 1 were elevated in the transgenic animals. Hoping to replicate the effects in normal animals, Scadden; Adams, research fellow in medicine; and their colleagues gave wild-type mice a PPR-stimulating hormone, PTH. The animals exhibited higher numbers of hematopoietic stem cells in their bone marrow. Encouraged by the results, the researchers gave PTH to mice after transplanting a limited number of hematopoietic stem cells, with stunning results. PTH has recently been approved for use in humans for osteoporosis and is very well tolerated. "We plan to be evaluating this approach in patients with cancers of the blood within the next year," said Scadden. "If we can improve the ability of patients to donate stem cells prior to transplant or reduce the number of cells needed for transplant, that would be a major benefit for patients." --Misia Landau
Brain May Build Memories in Three StagesScientists know that sleep is necessary for good memory retention, but new research indicates that three stages of waking and sleep time may determine how accurately motor-skill memories are recalled. The findings could help stroke and head injury patients more efficiently relearn how to walk, talk, and otherwise move.In the Oct. 9 Nature, Matthew Walker, an HMS instructor in psychiatry at Beth Israel Deaconess Medical Center, reports his investigation of motor skill memory, in which eight groups learned finger-tapping sequences similar to a piano exercise. Each group had a different schedule for being awake, sleeping, and recalling the sequences. Working in collaboration with Robert Stickgold, an HMS assistant professor of psychiatry at the Massachusetts Mental Health Center, Walker analyzed how accurately and quickly the groups performed the sequences and noted that three stages were necessary for the best memory recall. He compares these stages to the different processes a computer goes through establishing a file. The brain first initiates a memory as a computer creates a document file. To save the memory, the brain needs about six waking hours for processing. If the computer shuts down or the brain goes to sleep before the file is properly saved, it is lost. According to Walker, the second stage "is absolutely dependent on sleep in order to occur." During a good night's sleep, the brain edits the memory file and makes it more efficient. This editing process requires several hours of sleep. "If you don't get that full night's sleep, you may be shortchanging your brain of learning potential," said Walker. The final stage is the "recall phase," when a saved, edited memory becomes usable. "After the memory had been stabilized and enhanced, it once again became pliable so that it could be altered in the context of new ongoing experiences," Walker said. This stage allows the brain to tweak and perfect previously learned skills. Walker says the last stage may explain why some patients with posttraumatic stress disorder benefit from talking about their experiences. As the patients recall their traumas, the memories are slightly altered. "Over time, there may be the chance for these patients to redefine their memories and make them less traumatic." --Nicole Giese |
