Chinese Journal of Tissue Engineering Research ›› 2011, Vol. 15 ›› Issue (53): 9961-9964.doi: 10.3969/j.issn.1673-8225.2011.53.020

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Security for adenovirus-mediated p53 gene transfer to the donor heart

Wang Li-ping1, Song Fang-fang1, Li Xiang-lu1, Liu Yue2, Jia Zhi-bo3, Yin Xin-hua2   

  1. 1Department of Geriatrics, 3Department of Cardiac Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin  150086, Heilongjiang Province, China; 2Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin   150001, Heilongjiang Province, China
  • Received:2011-06-02 Revised:2011-09-18 Online:2011-12-31 Published:2011-12-31
  • Contact: Jia Zhi-bo, Associate chief physician, Department of Cardiac Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China doctor_jiazhibo@yahoo.com.cn
  • About author:Wang Li-ping☆, Doctor, Associate chief physician, Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China wlp0502@yahoo.com.cn
  • Supported by:

    Science and Technology Research Program of Education Department of Heilongjiang Province in 2010, No. 11551256*

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Abstract:

BACKGROUND: Wild-type p53 gene transfer to the donor heart can greatly inhibit graft coronary artery intima hyperplasia and lumen narrowness.
OBJECTIVE: To study the security of adenoviral-mediated wild-type p53 gene transfer to the donor heart after heart transplantation.
METHODS: Rat models of heterotopic (abdomen) heart transplantation were developed. Wistar rats served as donors and SD rats as recipients. After donor hearts were removed, 800 µL adenoviral vector encoding the wild-type p53 gene (Ad-p53 group), adenoviral vector encoding the β-galactosidase gene (LacZ) (Ad-LacZ group) or saline (control group) were infused into the donor heart respectively before transplantation. The donor heart was stored in the 4 ℃ saline for 30 minutes before heart transplantation. At 5 days after operation, P53 protein expressions in coronary artery of donor hearts were tested by western blot analysis. At 28 days after transplantation, the serum specimen was collected for the biochemical indicators, and the major organs of the recipients were tested by the histopathological analysis and the reverse transcription polymerase chain reaction of the adenoviral E1A sequences.
RESULTS AND CONCLUSION: The expression of P53 protein was found in donor hearts in Ad-p53 group at 5 days after operation, and no expression in Ad-LacZ group and control group. At 28 days after operation, rat serum biochemistry values in three groups was normal, the major organs of the recipients were not affected seriously, no virus spread to other organs in this experimental protocol. The results confirmed that the ex vivo adenoviral-mediated gene transfer to the donor heart via the coronary artery during the heart transplantation is safe.

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