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Elucidating New Mechanism for Blood Stem Cell Migration from the Bone Marrow

Scientists recently reported that a type of nerve cell plays an important role in the migration of blood stem cells from the bone marrow and into the circulation—potentially facilitating their collection for therapeutic uses. Blood stem cells--also called hematopoietic stem cells, or HSCs--have the potential either to self-renew into two identical daughter stem cells or to give rise (mature) into specialized cell types: red blood cells, white blood cells, or platelets. HSCs reside in specialized microenvironments in the bone marrow from which they can be mobilized via physiological stressors, such as significant blood loss, to enter the blood circulation and mature into all the body’s blood cells. However, the mechanisms by which HSCs migrate out of the bone marrow are largely unknown.

In new research using both female and male mice, scientists showed that the specialized microenvironments in the bone marrow also contain a high density of sensory nerves called nociceptive nerves. Found throughout the body, these nerves are normally important to pain perception and prevention of tissue damage, sending signals to the spinal cord and brain in response to a noxious (painful) stimulus. So what are nociceptive nerves doing in the bone marrow? It turns out that a molecule released by these specialized nerve cells, called CGRP, acts in concert with other signals in the bone marrow to drive a cascade of events ultimately instructing the HSCs to migrate and enter the blood circulation. In the mid-1990s, a report described how capsaicin, an ingredient in chili peppers, interacts with its cell surface receptor to “turn on” nociceptive nerves in the gastrointestinal tract to produce a burning sensation. With this knowledge in mind, the scientists asked whether capsaicin could affect HSC migration out of the bone marrow. Intriguingly, mice that consumed a capsaicin-containing spicy food diet were found to have significantly enhanced HSC migration into the bloodstream compared to mice fed a standard diet. Targeting the nociceptive nervous system could, therefore, represent a strategy to improve the yield of HSCs needed for stem cell-based therapeutic protocols.

Gao X, Zhang D, Xu C, Li H, Caron KM, and Frenette PS. Nociceptive nerves regulate haematopoietic stem cell mobilization. Nature 589: 591-596, 2021.

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