Overexpression of CXCR4 increases migration and proliferation of human adipose tissue stromal cells.

Stromal-derived factor-1 (SDF-1)-mediated CXCR4 signaling plays important roles in migration, engraftment, and proliferation of stem cells. We report here that CXCR4 overexpression on human adipose tissue stromal cells (hADSCs) using a lentiviral gene transfer technique helped navigate these cells to the injured tissues in response to SDF-1 signaling. Transduced hADSCs, expressing high levels of CXCR4, displayed an increased capacity for cellular growth and protection against etoposide-induced cell death. CXCR4-overexpressed cells showed higher ERK activity than that of vector-transduced cells. U0126, an ERK inhibitor, and AMD3100, a CXCR4 antagonist, inhibited the proliferation of CXCR4 overexpression-induced proliferation and ERK phosphorylation. CXCR4-overexpressing cells showed increased level of beta-catenin and luciferase activity driven by the Tcf promoter. Our results suggest CXCR4 overexpression for improved hADSC motility, retention, and proliferation could be beneficial for in vivo navigation and expansion of stem cells.