The TAFA2 neurokine stimulates Skeletal Stem Cells to migrate to bone fracture sites

Skeletal (mesenchymal or stromal) Stem Cells (MSCs) are cells present in the bone marrow that have the ability to differentiate into mature bone cells. The use of MSCs is considered as an attractive approach for regenerative medicine purposes, including bone tissue regeneration. In the context of cell therapy applications, several studies have reported limited migration of infused MSCs to site of tissue injury, highlighting the importance of understanding the regulatory mechanisms of MSCs migration. In a recently published work in Stem Cells, Abbas Jafari, member of the ECTS Academy, and his colleagues screened several molecules with the capacity to increase the migration of MSCs. Among these molecules, they identified the TAFA2 neurokine, already reported as regulator of immune and nervous cells migration, as the most interesting molecule potentially involved in bone regeneration process. They proved, in vitro, that TAFA2 protein does not affect the ability of MSCs to differentiate into bone cells, but it stimulates their proliferation and, by a chemical sensing (chemotactic) effect, enhances their migration.

They also found that TAFA2 induces formation of specific cellular structures required for cellular movement (the lamellipodia) via the activation of the Rac1-p38 intracellular signaling. In vitro studies were further consistently confirmed in an in vivo femoral fracture model, where, in presence of high amount of TAFA2, MSCs were strongly recruited at sites where the bone regeneration is needed. More importantly, during the inflammation phase of fracture healing, they found that the pro-inflammatory cytokine interleukin 1b represents an important upstream effector of the TAFA2 protein. In patients with hip fractures, the level of the TAFA2 protein was found to correlate with the different phases of inflammation after fracture and the following bone regeneration process. All these findings strongly suggest TAFA2 protein as a promising factor for future fracture healing therapies.

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