Mesenchymal stromal cells derived from umbilical cord blood migrate in response to complement C1q.

ABSTRACT

BACKGROUND AIMS: Mesenchymal stromal cells (MSC) have great potential for tissue regeneration and cellular therapy. They migrate preferentially to sites of inflammation and tissue injury, but the molecular signals that guide them to their target tissue remain to be elucidated. We have shown that complement component 1 subcomponent q (C1q) enhances the homing-related response of hematopoietic stem/progenitor cells. METHODS: In this study, we investigated whether C1q elicits directional signals that could influence the migration of MSC to injured tissues/organs. RESULTS: We found that C1q chemoattracted human umbilical cord blood-derived MSC in a dose-dependent manner and that the receptor for the global domains of Clq (gC1qR) is present on the surface of MSC. Specific gC1qR antibody blocked the chemotactic response of MSC to C1q, indicating that the C1q/gC1qR interaction may be responsible for the C1q-mediated migration of MSC. Further, we found that C1q enhanced/primed the migration of MSC across reconstituted basement membrane Matrigel towards a low gradient of the chemokine stromal cell-derived factor-1 (SDF-1), which is also present at sites of injury, partly as a result of an increase in surface expression of the SDF-1 receptor CXCR4. Moreover, C1q increased the secretion by MSC of matrix metalloproteinase (MMP)-2 and induced the phosphorylation of ERK1/2. CONCLUSIONS: These results indicate that C1q mediates the migration of MSC in two ways first, by acting as a chemoattractant, and second, by priming chemotactic responses to SDF-1. Our findings suggest new molecular mechanisms of MSC migration that may contribute to their clinical application in tissue repair.