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Forced expression of indoleamine-2,3-dioxygenase in human umbilical cord-derived mesenchymal stem cells abolishes their anti-apoptotic effect on leukemia cell lines in vitro

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Abstract

The ability of mesenchymal stem cells (MSCs) to preserve cancer cells potentially constitutes the adverse effect of MSC-based cell therapy in the context of hematologic malignancy. In an effort to reverse this undesirable feature of MSCs, we manipulated human umbilical cord-derived MSCs (UC-MSCs) to express indoleamine-2,3-dioxygenase (IDO), an enzyme that induces immune suppression by inhibiting T cell proliferation and triggering apoptosis in immune cells. Cultures of human UC-MSCs were generated by plastic adherence method. Full-length cDNA of human IDO was cloned into adenovirus shuttle vector. Then, the recombinant virus harboring IDO gene was produced in 293 cells and used to infect UC-MSCs. Expression of IDO protein was detected within infected UC-MSCs, and accumulation of kynurenine was observed in the supernatant. Two human leukemia cell lines, Jurkat and HL-60, were cultured on the monolayer of native or infected UC-MSCs, respectively. It was observed that forced IDO expression abolished the anti-apoptotic effect of UC-MSCs on these leukemia cells and enhanced their proliferation inhibitory effect on activated human lymphocytes as well as leukemia cells. These results suggested that equipping MSCs with IDO could be one of the reasonable strategies to reverse their cancer-supportive effect unfavorable for clinical applications.

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Acknowledgments

We thank Dr. Xianhui He (Department of Immunobiology, Jinan University, Guangzhou, China) for offering human IDO gene and Dr. Wenfeng Zhang (School of Life Science and Biopharmacology, Guangdong Pharmaceutical University, Guangzhou, China) for providing the adenovirus plasmids. This study was supported by the National Natural Science Foundation of China (grant no. 31100664).

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Authors and Affiliations

  1. School of Life Science and Biopharmacology, Guangdong Provincial Key Laboratory of Biotechnology Candidate Drug Research, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, 510006, Guangdong, China

    Yin Yuan, Chang-li Tao, Xuan Chen, Hong-wei Shao & Shu-lin Huang

  2. Southern Medical University, Guangzhou, 510515, Guangdong, China

    Yin Yuan

  3. School of Life Science, South China Normal University, Guangzhou, 510631, Guangdong, China

    Xin Lu

Authors
  1. Yin Yuan
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  2. Xin Lu
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  3. Chang-li Tao
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  4. Xuan Chen
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  5. Hong-wei Shao
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  6. Shu-lin Huang
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Correspondence to Shu-lin Huang.

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Editor: T. Okamoto

Yin Yuan, Xin Lu, Chang-li Tao, and Xuan Chen contributed equally to this study.

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Yuan, Y., Lu, X., Tao, Cl. et al. Forced expression of indoleamine-2,3-dioxygenase in human umbilical cord-derived mesenchymal stem cells abolishes their anti-apoptotic effect on leukemia cell lines in vitro. In Vitro Cell.Dev.Biol.-Animal 49, 752–758 (2013). https://doi.org/10.1007/s11626-013-9667-4

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  • DOI: https://doi.org/10.1007/s11626-013-9667-4

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