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Inhibitory Effect and Mechanism of Mesenchymal Stem Cells Cultured in 3D System on Hepatoma Cells HepG2

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Abstract

Mesenchymal stem cells (MSCs) exhibit the feature of homing to tumor site and being immunosuppressive, which have broad prospects in tumor therapy. However, MSCs are commonly cultured in a two-dimensional (2D) condition, which would gradually loss some in vivo important properties. In this study, we built a three-dimensional (3D) system with collagen/Matrigel scaffolds to culture MSCs. The results indicated that MSCs in 3D scaffolds showed higher proliferation ability than that of in 2D cells. In vitro, 3D-cultured MSC-conditioned media (CM) significantly inhibited the proliferation of hepatoma cells HepG2 than that of in 2D-cultured MSC-CM and control groups. In vivo, animal transplantation experiment showed that the treatment of 3D-cultured MSC-CM could further significantly delay the tumor initiation and decrease the tumor volume. The microarray, quantitative PCR, and ELISA assay found that MSCs cultured in the 3D system expressed and secreted more amounts of IL-24. RT-PCR and western blot results showed that IL-24 can activate JAK1-STAT3 pathway via IL22R1 and IL20R2, and further inhibit the proliferation of HepG2 cells. Taken together, these results demonstrated that MSCs cultured in the 3D system had an inhibitory effect on the proliferation of HepG2 cells, probably through secreting more IL-24, which activated JAK1-STAT3 signaling and finally inhibited the cell proliferation to delay tumor initiation. This study also provided a simpler and more reliable approach for MSCs to suppress tumor cells, and provided effective experimental data for clinical treatment of tumor and experimental basis.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81201762) and the National High Technology Research and Development Program (863 Program) of China (2014AA021605).

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Authors and Affiliations

  1. College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, People’s Republic of China

    Diandian Zhao, Lingling Hou, Mengwu Pan, Jilei Hua, Ziling Wang, Jinsheng He & Honggang Hu

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  1. Diandian Zhao
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  2. Lingling Hou
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  5. Ziling Wang
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Correspondence to Lingling Hou.

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The procedures involving animals and their care were conducted in accordance with theinstitutional guidelines for Laboratory Animal Care of Experimental Animal Cente r.

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Zhao, D., Hou, L., Pan, M. et al. Inhibitory Effect and Mechanism of Mesenchymal Stem Cells Cultured in 3D System on Hepatoma Cells HepG2. Appl Biochem Biotechnol 184, 212–227 (2018). https://doi.org/10.1007/s12010-017-2533-1

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