Abstract

BackgroundMesenchymal stem cells derived from the chorionic villi of human placentae (pMSCs) produce a unique array of mediators that regulate the essential cellular functions of their target cells. These properties make pMSCs attractive candidates for cell-based therapy. Here, we examined the effects of culturing human natural killer (NK) cells with pMSCs on NK cell functions.MethodspMSCs were cultured with IL-2-activated and non-activated NK cells. NK cell proliferation and cytolytic activities were monitored. NK cell expression of receptors mediating their cytolytic activity against pMSCs, and the mechanisms underlying this effect on pMSCs, were also investigated.ResultsOur findings show that IL-2-activated NK cells, but not freshly isolated NK cells, efficiently lyse pMSCs and that this response might involve the activating NK cell receptor CD69. Interestingly, although pMSCs expressed HLA class I molecules, they were nevertheless lysed by NK cells, suggesting that HLA class I antigens do not play a significant role in protecting pMSCs from NK cell cytolytic activity. Co-culturing NK cells with pMSCs also inhibited NK cell expression of receptors, including CD69, NKpG2D, CD94, and NKp30, although these co-cultured NK cells were not inhibited in lysing cancer cells in vitro. Importantly, co-cultured NK cells significantly increased their production of molecules with anti-tumor effects.ConclusionsThese findings suggest that pMSCs might have potential applications in cancer therapy.

Highlights

  • Mesenchymal stem cells derived from the chorionic villi of human placentae produce a unique array of mediators that regulate the essential cellular functions of their target cells

  • The cytolytic activities of natural killer (NK) cells on target cells are mediated by several cell surface-activating receptors and inhibitory receptors [1,2,3,4,5,6,7,8,9,10,11], while other NK cell functions are mediated by a range of mediators including cytokines and their corresponding receptors, as well as their expression of Toll-like receptors (TLRs) [1, 12, 13]

  • We recently reported that the interaction between NK cells and mesenchymal stem/stromal cells (MSC) from the maternal side of human placenta known as decidua parietalis (DPMSCs) results in the lysis of DPMSCs [19]

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Summary

Introduction

Mesenchymal stem cells derived from the chorionic villi of human placentae (pMSCs) produce a unique array of mediators that regulate the essential cellular functions of their target cells. These properties make pMSCs attractive candidates for cell-based therapy. The interaction between human NK cells and mesenchymal stem/stromal cells (MSC) has been recently reported by us and others [15,16,17,18,19]. We recently reported that the interaction between NK cells and MSCs from the maternal side of human placenta known as decidua parietalis (DPMSCs) results in the lysis of DPMSCs [19]. NK cells can lyse human bone marrow-derived MSCs (BMMSCs) [15,16,17,18]

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