Cytokines and Chemokines Involved in the Inflammatory Process Have Potent Chemoattractive Properties on MSC.

Background : Recent studies have demonstrated the transmigration capacity of mesenchymal stem cells (MSC) over the endothelial cell barrier into various tissues including brain, bone marrow and many others. Nevertheless, little is know about the agents that promote and control their migration.

Methods : The MSC (5.10⁵ cells) migration potential was evaluated using matrigel invasion chamber assay in the presence/absence of SDF-1 (100ng/mL), PDGFbb (100ng/mL), IGF (500ng/mL), IL-6 (100ng/mL) and 10% of conditioned medium in the bottom chamber. The chemotactic properties of these cytokines/chemokines were compared to the spontaneous migration of MSC in DMEM medium without FCS. After 24 hours, cells that migrated through the membrane were counted. The presence of specific receptors was analysed using Raybio Assay, Western Blot and semi-quantitative RT-PCR.

Results : We observed that PDGFbb has the highest chemoattractive property on the MSC and correlates with the strongest expression of PDGF-bb receptor. We also noted that the migratory response to IL-6, IGF and SDF-1 is correlated with the expression of their respective receptors. However, a weak migration was observed in response to SDF-1 due to the low extracellular expression of CXCR4. Nevertheless, a high intracellular expression of CXCR4 was demonstrated with western blots and FACS analysis. In addition, using Raybio assay, we demonstrated the expression of various receptors and metalloproteinases involved in the migration of MSC including ALCAM, L-selectin, ICAM-1, MMP2 and MMP9.

Conclusions : Our observations suggest that chemokines or cytokines involved in the regulation of immunity or the inflammatory process promotes the migration of MSC into bone marrow or damaged tissues.