Beneficial effects of the transgenic expression of human sTNF-αR-Fc and HO-1 on pig-to-mouse islet xenograft survival

Ji Jing Yan, Hye Jeong Yeom, Jong Cheol Jeong, Jae Ghi Lee, Eun Won Lee, Bumrae Cho, Han Sin Lee, Su Jin Kim, Jong-Ik Hwang, Sung Joo Kim, Byeong Chun Lee, Curie Ahn, Jaeseok Yang

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Abstract

Both human soluble tumor necrosis factor-α receptor-Fc (sTNF-αR-Fc) and heme oxygenase-1 (HO-1) transgenic pigs have been generated previously for xenotransplantation. Here, we investigated whether overexpression of sTNF-αR-Fc or HO-1 in pig islets prolongs islet xenograft survival. Adult porcine islets were isolated from human sTNF-αR-Fc or HO-1 transgenic and wild type pigs, and were transplanted into diabetic nude mice. Effects of the expression of both genes on islet apoptosis, chemokine expression, cellular infiltration, antibody production, and islet xenograft survival were analyzed. Human sTNF-αR-Fc transgenic pigs successfully expressed sTNF-αR-Fc in the islets; human HO-1 transgenic pigs expressed significant levels of HO-1 in the islets. Pig-to-mouse islet xenograft survival was significantly prolonged in both the sTNF-αR-Fc and HO-1 groups compared with that in the wild type group. Both the sTNF-αR-Fc and HO-1 groups exhibited suppressed intragraft expression of monocyte chemoattractant protein-1 (MCP-1) and decreased perigraft infiltration of immune cells. However, there was no difference in the anti-pig antibody levels between the groups. Apoptosis of islet cells during the early engraftment was suppressed only in the HO-1 group. Porcine islets from both sTNF-αR-Fc and HO-1 transgenic pigs prolonged xenograft survival by suppressing islet cell apoptosis or secondary inflammatory responses following islet death, indicating that these transgenic pigs might have applications in successful islet xenotransplantation.

Original languageEnglish
Pages (from-to)25-32
Number of pages8
JournalTransplant Immunology
Volume34
DOIs
Publication statusPublished - 2016 Feb 1

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Keywords

  • Heme oxygenase-1
  • Islet transplantation
  • Soluble TNF-α receptor
  • Transgenic pig
  • Xenotransplantation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Transplantation

Cite this

Yan, J. J., Yeom, H. J., Jeong, J. C., Lee, J. G., Lee, E. W., Cho, B., Lee, H. S., Kim, S. J., Hwang, J-I., Kim, S. J., Lee, B. C., Ahn, C., & Yang, J. (2016). Beneficial effects of the transgenic expression of human sTNF-αR-Fc and HO-1 on pig-to-mouse islet xenograft survival. Transplant Immunology, 34, 25-32. https://doi.org/10.1016/j.trim.2016.01.002