Abstract

BackgroundThe soluble factors secreted by mesenchymal stem cells are thought to either support or inhibit tumor growth. Herein, we investigated whether the human lung-derived mesenchymal stem cell-conditioned medium (hlMSC-CM) exerts antitumor activity in malignant pleural mesothelioma cell lines H28, H2052 and Meso4.MethodshlMSC-CM was collected from the human lung-derived mesenchymal stem cells. Inhibition of tumor cell growth was based on the reduction of cell viability and inhibition of cell proliferation using the XTT and BrdU assays, respectively. Elimination of tumor spheroids was assessed by the anchorage-independent sphere formation assay. The cytokine profile of hlMSC-CM was determined by a chemiluminescence-based cytokine array.ResultsOur data showed that hlMSC-CM contains a broad range of soluble factors which include: cytokines, chemokines, hormones, growth and angiogenic factors, matrix metalloproteinases, metalloproteinase inhibitors and cell–cell mediator proteins. The 48- and 72-hour hlMSC-CM treatments of H28, H2052 and Meso4 cell lines elicited significant decreases in cell viability and inhibited cell proliferation. The 72-hour hlMSC-CM incubation of H28 cells completely eliminated the drug-resistant sphere-forming cells, which is more potent than twice the half maximal inhibitory concentration of cisplatin.ConclusionsOur findings indicate that the cell-free hlMSC-CM confers in vitro antitumor activities via soluble factors in the tested mesothelioma cells and, hence, may serve as a therapeutic tool to augment the current treatment strategies in malignant pleural mesothelioma.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0282-7) contains supplementary material, which is available to authorized users.

Highlights

  • In contrast to the early paradigm of cell replacement and differentiation of mesenchymal stem cells (MSCs) as a therapeutic mechanism, reports are accumulating that cell secretions are responsible for their beneficial effects [1]

  • We initially investigated whether our Human lung mesenchymal stem cell (hlMSC)-Conditioned medium (CM) contains soluble factors

  • We collected the CM of the hlMSCs grown for 24 hours in the absence of fetal bovine serum (FBS) and analyzed it using the cytokine array. hlMSC-CM contained a broad range of soluble factors which included: cytokines, chemokines, hormones, growth factors, neurotrophic factors, endocrine and angiogenic factors, matrix metalloproteinases (MMPs), metalloproteinase inhibitors (TIMPs) and cell– cell mediator proteins (Fig. 1)

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Summary

Introduction

In contrast to the early paradigm of cell replacement and differentiation of mesenchymal stem cells (MSCs) as a therapeutic mechanism, reports are accumulating that cell secretions are responsible for their beneficial effects [1]. Cell lysates or supernatants of Wharton’s jelly-derived MSCs have manifested a capacity to inhibit cell growth of breast cancer, ovarian tumor and osteosarcoma cell lines, indicating tumor inhibitory properties [6]. HMSCs have been demonstrated to suppress proliferation and induce apoptosis of SKMES-1 and A549 lung adenocarcinoma cells via some soluble factors [7], no current knowledge of hMSC-CM actions on malignant pleural mesothelioma (MPM) is known. The soluble factors secreted by mesenchymal stem cells are thought to either support or inhibit tumor growth. We investigated whether the human lung-derived mesenchymal stem cell-conditioned medium (hlMSC-CM) exerts antitumor activity in malignant pleural mesothelioma cell lines H28, H2052 and Meso

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