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Endothelial progenitor cells overexpressing platelet derived growth factor-D facilitate deep vein thrombosis resolution

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Abstract

To assess the therapeutic efficacy of PDGF-D-overexpressing endothelial progenitor cells (EPCs) in deep vein thrombosis. Inferior vena cava thrombosis was induced in female Sprague Dawley (SD) rats. Animals were injected via the distal vena cava with EPCs overexpressing PDGF-D after transfection with a lentiviral vector containing the PDGF-D gene. The effect on thrombosis in animals who received EPCs was evaluated using MSB staining, immunohistochemistry, immunofluorescence, and venography; the steady-state mRNA and protein levels of PDGF-D and its receptor (PDGF-Rβ) were determined by RT-PCR and Western blotting, respectively; and the PDGF-D-induced mobilization of circulating EPCs was estimated by flow cytology. Compared with controls, injection of EPCs overexpressing PDGF-D was associated with increased thrombosis resolution; recanalization; PDGF-D and PDGF-Rβ expression; induction of monocyte homing; and mobilization of EPCs to the venous circulation. In a rat model, transplantation of PDGF-D-overexpressing EPCs facilitated the resolution of deep vein thrombosis.

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Acknowledgements

We would like to express our sincere appreciation to the reviewers for their helpful comments on this article.

Funding

This work was supported by the Grant from the National Natural Science Foundation of China (81400348) and the Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University.

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Authors and Affiliations

  1. Department of Vascular Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

    Haolong Zhang, Hailong Luo, Bo Tang, Yikuan Chen, Jian Fu & Jianming Sun

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  1. Haolong Zhang
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  2. Hailong Luo
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  3. Bo Tang
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  4. Yikuan Chen
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  5. Jian Fu
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Contributions

BT designed the experiments and wrote the manuscript. HZ performed most experiments and analyzed data. HL was involved in analyzing the data. YC helped in animal experiments. JS analyzed the histology and histopathology and interpreted data. Jian Fu designed and supervised all experiments and edited the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Bo Tang.

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Conflict of interest

We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled.

Ethical approval

The ethics committee of The Second Affiliated Hospital of Chongqing University (Chongqing, China) provided ethical approval for the experiments involved animals were implemented in accordance with the principles embodied in the National Institutes of Health Guide for the Care and Use of Laboratory. Efforts were made to avoid all unnecessary painful to the animals.

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Zhang, H., Luo, H., Tang, B. et al. Endothelial progenitor cells overexpressing platelet derived growth factor-D facilitate deep vein thrombosis resolution. J Thromb Thrombolysis 53, 750–760 (2022). https://doi.org/10.1007/s11239-021-02567-4

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