Human Mesenchymal Stem Cells Constitutively Express Chemokines and Chemokine Receptors That Can Be Upregulated by Cytokines, IFN-β, and Copaxone

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Abstract
The factors associated with the migration of marrow-derived mesenchymal stem cells (MSCs) when transplanted into the diseased central nervous system (CNS) are unclear. Chemokines are key mediators of selective cell migration in neurodegenerative diseases and related inflammatory processes. We hypothesized that chemokines are likely to be the chief determinants of MSC migration. We, therefore, systematically assessed the expression and modulating factors for chemokines and chemokine receptors in human MSCs (HuMSCs). The present study demonstrates that unstimulated HuMSCs express a broad range of mRNAs encoding cytokines, chemokines, and their receptors. Using chemotaxis assays, we also assessed the functionality of the receptor expression in HuMSC and we show that CXCL12/stromal cell-derived factor-1α (SDF-1α), CX3CL1/fractalkine, and CXCL10/interferon-γ (IFN-γ)-inducible protein (IP-10) lead to significant HuMSC migration. Moreover, we provide evidence that tumor necrosis factor-α (TNF-α) and IFN-γ act as major regulators of the expression of chemokines and their receptors in HuMSCs. Correspondingly, we demonstrate for the first time that current multiple sclerosis (MS) therapies, namely, IFN-β and Copaxone, influence the expression of chemokines and their receptors in HuMSCs at both mRNA and protein levels. Administration of cytokines, including IFN-β and Copaxone, may be important in stem cell transplantation therapies and perhaps important in the efficacy of existing MS therapies.