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Sonoporation of the Minicircle-VEGF165 for Wound Healing of Diabetic Mice

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Abstract

Purpose

The purpose of this study is to examine the efficiency of sonoporation with minicircle DNA for the skin wound healing in diabetic mice.

Methods

Minicircle DNA containing the human VEGF165 was constructed and tested in vitro. Diabetes was induced in 2-week old male C57BL/6J mice via streptozotocin (STZ) injection. 6 mm circular skin wounds were made on the mice back. After the subcutaneous injection of the minicircle DNA at the edge of the wound, the mice were exposed to the ultrasound irradiation for the sonoporation. Wound areas were analyzed until the day 12. Blood perfusion and angiogenesis were evaluated using a laser Doppler imaging and CD31 immunostaining, respectively. Re-epithelialization was assessed by histochemical analysis using hematoxylin and eosin staining.

Results

Accelerated wound closure was observed in the mice receiving sonoporation of minicircle-VEGF165, which corresponds to the markedly increased skin blood perfusion and CD31 expression. Histological analysis revealed that the minicircle treated wound tissues showed fully restored normal architectures as compared with the non-treated diabetic controls with the markedly edematous and chaotic morphologies.

Conclusions

Ultrasound mediated gene therapy with the minicircle-VEGF165 is effective for the healing of the skin wound of the diabetic mice.

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Acknowledgements

The part of this work was accepted as an abstract at the 42nd Annual Meeting of the European Association for the Study of Diabetes in Denmark Copenhagen-Malmoe, September 2006. The present study was financially supported by the Inje University Research Grant 2005. We thank Dr. Mark A Kay (Stanford University) for generously providing plasmid p2øC31.

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Authors and Affiliations

  1. Molecular Therapy Laboratory, Paik Memorial Institute for Clinical Research, Inje University, Busan, South Korea

    C. S. Yoon & H. S. Jung

  2. Molecular Therapy Laboratory, Paik Memorial Institute for Clinical Research, Paik Diabetes Center, Department of Internal Medicine, Pusan Paik Hospital, College of Medicine, Inje University, 633-165 Gaegum-Dong, Pusanjin-Gu, 614-735, Busan, South Korea

    M. J. Kwon, S. H. Lee & J. H. Park

  3. Department of Pathology, Pusan Paik Hospital, College of Medicine, Inje University, Busan, South Korea

    C. W. Kim

  4. Department of Internal Medicine, Maryknoll Medical Center, Busan, South Korea

    M. K. Kim

  5. Department of Bioengineering, Hanyang University, Seoul, South Korea

    M. Lee

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  1. C. S. Yoon
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Correspondence to J. H. Park.

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Yoon, C.S., Jung, H.S., Kwon, M.J. et al. Sonoporation of the Minicircle-VEGF165 for Wound Healing of Diabetic Mice. Pharm Res 26, 794–801 (2009). https://doi.org/10.1007/s11095-008-9778-x

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  • DOI: https://doi.org/10.1007/s11095-008-9778-x

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