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Immunogenicity of allogeneic mesenchymal stem cells transplanted via different routes in diabetic rats

Cellular & Molecular Immunology volume 12, pages 444–455 (2015)Cite this article

Abstract

Due to their hypoimmunogenicity and unique immunosuppressive properties, mesenchymal stem cells (MSCs) are considered one of the most promising adult stem cell types for cell therapy. Although many studies have shown that MSCs exert therapeutic effects on several acute and subacute conditions, their long-term effects are not confirmed in chronic diseases. Immunogenicity is a major limitation for cell replacement therapy, and it is not well understood in vivo. We evaluated the immunogenicity of allogeneic MSCs in vivo by transplanting MSCs into normal and diabetic rats via the tail vein or pancreas and found that MSCs exhibited low immunogenicity in normal recipients and even exerted some immunosuppressive effects in diabetic rats during the initial phase. However, during the later stage in the pancreas group, MSCs expressed insulin and MHC II, eliciting a strong immune response in the pancreas. Simultaneously, the peripheral blood mononuclear cells in the recipients in the pancreas group were activated, and alloantibodies developed in vivo. Conversely, in the tail vein group, MSCs remained immunoprivileged and displayed immunosuppressive effects in vivo. These data indicate that different transplanting routes and microenvironments can lead to divergent immunogenicity of MSCs.

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Acknowledgements

We thank our colleagues Ya-Ying Zhou, Chun-Yan Deng and Li-Li Ren for their technical assistance. This work was supported by the National Natural Science Foundation of China (No. 81270857), the Natural Science Foundation of Guangdong (No. S2013010014832), and the Science and Technology Project of Shenzhen (JCYJ20120618153743791, GJHZ20120618153934353).

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Author notes

  1. Dr H Qi, The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Ji'nan University, 1017 Dongmen North Road, Shenzhen 518020, China. E-mail: qihui214@hotmail.com

  2. Dr FR Li, The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Ji'nan University, 1017 Dongmen North Road, Shenzhen 518020, China. E-mail: frli62@163.com

Authors and Affiliations

  1. Department of Rheumatology, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China

    Le-Hui Gu, Tian-Tian Zhang & Fu-Rong Li

  2. The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China

    Le-Hui Gu, Tian-Tian Zhang, Yang Li, Hong-Jie Yan, Hui Qi & Fu-Rong Li

  3. Shenzhen Institute of Gerontology, Shenzhen, China

    Yang Li & Fu-Rong Li

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Supplementary Information accompanies the paper on Cellular & Molecular Immunology's website. (http://www.nature.com/cmi).

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Gu, LH., Zhang, TT., Li, Y. et al. Immunogenicity of allogeneic mesenchymal stem cells transplanted via different routes in diabetic rats. Cell Mol Immunol 12, 444–455 (2015). https://doi.org/10.1038/cmi.2014.70

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