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Transplantation of IL-10-transfected endothelial progenitor cells improves retinal vascular repair via suppressing inflammation in diabetic rats

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Abstract

Purpose

We aimed to evaluate the effect of IL-10 gene transfection on endothelial progenitor cells (EPCs) under inflammatory conditions, and explore the therapeutic potential of IL-10-transfected EPC transplantation on nonproliferative diabetic retinopathy (NPDR).

Methods

Lentivirus vectors encoding IL-10 were constructed and introduced into EPCs isolated from rat bone marrow. After exposure to recombinant rat TNF-α, abilities of nontransfected EPCs (non-EPCs) and EPCs transfected with normal control lentivirus (EPCs-GFP) or IL-10 expressing lentivirus (EPCs-IL-10-GFP) were assessed, including migration, adhesion, and tube formation. IL-10 production by EPCs-IL-10-GFP was determined by ELISA. Following 12 weeks after establishment of diabetes, diabetic rats were randomly injected with non-EPCs, EPCs-GFP, or EPCs-IL-10-GFP via tail vein. Expression of inflammatory factors and factors associated with nuclear factor-kappa B (NF-kB) signal pathway, retinal histological analysis, and retinal vascular permeability were assessed 2 weeks after transplantation.

Results

The detrimental effects of TNF-ɑ on the abilities of EPCs were significantly attenuated in EPCs-IL-10-GFP compared with non-EPCs and EPCs-GFP. The concentration of IL-10 in the EPCs-IL-10-GFP group was significantly higher than the non-EPCs and EPCs-GFP groups. Additionally, transplantation of EPCs-IL-10-GFP significantly inhibited inflammatory factors expression and activation of NF-kB signal pathway, improved retinal histological changes, and attenuated retinal vascular permeability.

Conclusion

In conclusion, transplantation of IL-10-transfected EPCs significantly improved EPCs-mediated retinal vascular repair and subsequently suppressed NPDR progression. This was associated with inflammation suppression, at least partly via inhibiting the NF-kB signal pathway. Transplantation of IL-10-transfected EPCs may be a new strategy for treatment of NPDR.

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Acknowledgments

This study was supported by Natural Science Foundation of Tianjin (Grant Numbers 12JCYBJC33900 and 14JCYBJC28000) and National Natural Science Foundation of China (Grant numbers 81371038 and 91442124).

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Author notes

    Authors and Affiliations

    1. Department of Ophthalmology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Tianjin, 300052, China

      Ying Wang, Lingling Fan, Xiangda Meng, Feng Jiang, Qingzhong Chen, Zhuhong Zhang & Hua Yan

    2. Shenyang Aier Eye Hospital, NO.11, Shiyi Wei Road, Shenyang, 110003, China

      Ying Wang

    3. Department of Ophthalmology, The First Hospital Affiliated of Anhui Medical University, Hefei, Anhui, 230022, China

      Lingling Fan

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    1. Ying Wang
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    Correspondence to Hua Yan.

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    Funding

    This study was supported by Natural Science Foundation of Tianjin (Grant Numbers 12JCYBJC33900 and 14JCYBJC28000) and National Natural Science Foundation of China (Grant numbers 81371038 and 91442124). The sponsor had no role in the design or conduct of this research.

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    All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.

    Ethical approval

    The Association for Research in Vision and Ophthalmology statement for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of Animal Care and Use Committee of Tianjin Medical University.

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    Ying Wang and Lingling Fan contributed equally to this work.

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    Wang, Y., Fan, L., Meng, X. et al. Transplantation of IL-10-transfected endothelial progenitor cells improves retinal vascular repair via suppressing inflammation in diabetic rats. Graefes Arch Clin Exp Ophthalmol 254, 1957–1965 (2016). https://doi.org/10.1007/s00417-016-3427-6

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