Researchers have identified an amino acid that's vital to the maintenance of hematopoietic stem cells. The finding hints at the potential for a safer pre-treatment regimen for bone marrow transplantation. Bone marrow transplants are used to treat a wide array of serious diseases including blood cancers, yet the procedure involves a high level of risk. Before new cells are introduced, cells in the bone marrow, which include hematopoietic stem cells (HSCs) and any resident cancer cells, are destroyed using radiation or chemotherapy; this can cause severe complications, including secondary malignancy, endocrinopathy, reproductive failure and even mortality. A more refined way to target these cells would make bone marrow transplants much safer. Therefore Yuki Taya et al. studied cultures of the cells that were each lacking a single amino acid, to determine which acids are essential to HSC maintenance. They found that HSC replication was severely impaired when the amino acid valine was missing; similar impairment and reduction was found in mice harboring human blood cells, suggesting that valine also plays a critical role for human HSPC maintenance. When mice were fed a diet lacking valine, they experienced a significant reduction in white blood cell (WBC) and red blood cell numbers. Critically, when mice were fed a valine-free diet for four weeks and were suddenly re-introduced to the nutrient, half experienced re-feeding syndrome, a form of shock associated with malnutrition, and did not survive; therefore gradual reintroduction of the amino acids is essential for mice. In a series of experiments evaluating this approach as a means to prime the body for a bone marrow transplant, the researchers found that using a valine-free diet with gradual reintroduction of the amino acid, rather than radiation, was successful, with majority of mice benefiting from long-term engraftment of healthy donor HSCs.
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Journal
Science