How different progenitor cells are called from the bone marrow

by Alicia Chung¹

VEGF prompts cells to get out and help

Part of the body's inherent healing response is to mobilize progenitor cells from the bone marrow to the site of injury. Rather than trying to collect and purify sufficient numbers of progenitor cells from bone marrow and blood donors, many clinicians hope to find better ways to summon the right types of cells from their natural reservoir in the bone marrow. In a recent study published in Cell Stem Cell, Sara Rankin and colleagues at Imperial College London demonstrate how naturally occurring growth factors can call different types of progenitor cells into duty¹.

 When the body heals, the progenitor cells that emerge from the bone marrow depend on the type of injury. Haematopoietic progenitor (HP) cells move into new sites in the bone marrow and begin generating all blood types; endothelial progenitor (EP) cells are recruited to sites of ischemia to help new blood vessels form; and mesenchymal stem (MS) cells help heal injuries by differentiating into adipocytes, chondrocytes and osteocytes, among other cell types.

Progenitor cells are kept in the bone marrow when high concentrations of SDF-1 bind to the cells' CXCR4 receptors, through a process called the CXCR4/SDF-1 retention axis. Granulocyte–colony stimulating factor (G-CSF) can effectively disrupt this retention mechanism for HP cells, but it is relatively ineffective for both EP cells and stromal progenitor (SP) cells, which are responsible for regenerating connective tissue cells. This new study demonstrates that another protein, vascular endothelial growth factor (VEGF), stimulates these two progenitor subtypes to migrate into circulation. It does this synergistically with a CXCR4 inhibitor, mozobil, which was recently approved by the FDA to be used alongside G-CSF to collect HP cells. However, unlike G-CSF, VEGF does not alter the CXCR4/SDF-1 retention axis, suggesting that another mechanism must keep EP and SP cells in the bone marrow. Nonetheless, says Rankin, "this suggests that novel therapies could be developed to selectively boost circulating levels of the stem cells involved in tissue regeneration."

Furthermore, Rankin's study reveals that whereas VEGF keeps HP cells in the bone marrow, it stimulates EP cells to migrate; additional evidence suggests that VEGF activates distinct receptors on these cell types.

Although Rankin's study offers a mechanism to explain why haematopoietic and endothelial progenitors can be summoned specifically from the bone marrow, that mechanism does not apply to the stromal progenitor cells, says Paul Frenette, who studies the mobilization of bone marrow stem cells at Mount Sinai School of Medicine in New York.

Moreover, he says, getting progenitor cells to move out of the bone marrow is not necessarily the same as using them to heal injury. "It is not clear whether the endothelial progenitors mobilized with this protocol have functional activities, and while the stromal progenitor mobilization is intriguing, the functional significance is unknown." Rankin agrees that there is more work ahead. To assess the therapeutic value of these results, she says, researchers will need to test whether mobilized EP cells and SP cells actually improve tissue repair and regeneration in animal models of disease and injury.

Author affiliations

1. Alicia Chung is a freelance writer based in San Francisco.

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