Purinergic Signaling Modulates Human Bone Marrow-Derived Mesenchymal Stem Cells Function.

Abstract 1441

Poster Board I-464

Nucleotides triphosphates are extracellular messengers binding to specific plasma membrane receptors (P2Rs) modulating a wide variety of biological responses in several cell types. In this study, we show that bone marrow-derived human mesenchymal stem cells (hMSCs) express several functional P2R subtypes at the molecular and protein level. hMSCs are very resistant to the cytotoxic effects of high concentrations of extracellular ATP, as demonstrated by the lack of morphological and mitochondrial changes or release of intracellular markers of cell death. Gene expression profiling revealed that hMSCs stimulated with ATP underwent a down-regulation of genes involved in cell proliferation, whereas those involved in cell migration were strongly up-regulated. Functional studies confirmed the inhibitory activity of ATP on proliferation of hMSCs and clonogenic stromal progenitors. Furthermore, ATP potentiated the chemotactic response of hMSCs to the chemokine CXCL12, and increased their spontaneous migration. In vivo, xenotransplant experiments demonstrated that the homing capacity of hMSCs to murine bone marrow was significantly increased by pre-treatment with ATP. Moreover ATP increased the production of the pro-inflammatory cytokines IL-2, IFN-gamma, and IL-12p70, while decreasing the anti-inflammatory cytokine IL-10. Thus, our data show that purinergic signaling modulates hMSCs functions and highlight a role for extracellular nucleotides in hMSCs biology.