PMID- 26777482 OWN - NLM STAT- MEDLINE DCOM- 20161111 LR - 20170103 IS - 1878-5492 (Electronic) IS - 0966-3274 (Linking) VI - 34 DP - 2016 Feb TI - Beneficial effects of the transgenic expression of human sTNF-alphaR-Fc and HO-1 on pig-to-mouse islet xenograft survival. PG - 25-32 LID - S0966-3274(16)30002-8 [pii] LID - 10.1016/j.trim.2016.01.002 [doi] AB - Both human soluble tumor necrosis factor-alpha receptor-Fc (sTNF-alphaR-Fc) and heme oxygenase-1 (HO-1) transgenic pigs have been generated previously for xenotransplantation. Here, we investigated whether overexpression of sTNF-alphaR-Fc or HO-1 in pig islets prolongs islet xenograft survival. Adult porcine islets were isolated from human sTNF-alphaR-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-alphaR-Fc transgenic pigs successfully expressed sTNF-alphaR-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-alphaR-Fc and HO-1 groups compared with that in the wild type group. Both the sTNF-alphaR-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-alphaR-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. CI - Copyright (c) 2016 Elsevier B.V. All rights reserved. FAU - Yan, Ji-Jing AU - Yan JJ AD - Transplantation Research Institute, Seoul National University College of Medicine, Republic of Korea. FAU - Yeom, Hye-Jeong AU - Yeom HJ AD - Transplantation Research Institute, Seoul National University College of Medicine, Republic of Korea. FAU - Jeong, Jong Cheol AU - Jeong JC AD - Transplantation Research Institute, Seoul National University College of Medicine, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Republic of Korea. FAU - Lee, Jae-Ghi AU - Lee JG AD - Transplantation Research Institute, Seoul National University College of Medicine, Republic of Korea. FAU - Lee, Eun Won AU - Lee EW AD - Transplantation Research Institute, Seoul National University College of Medicine, Republic of Korea. FAU - Cho, Bumrae AU - Cho B AD - Institute of Green Bio Science and Technology, Seoul National University, Republic of Korea. FAU - Lee, Han Sin AU - Lee HS AD - Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Republic of Korea. FAU - Kim, Su Jin AU - Kim SJ AD - Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Seoul National University, Republic of Korea. FAU - Hwang, Jong-Ik AU - Hwang JI AD - Graduate School of Medicine, Korea University, Republic of Korea. FAU - Kim, Sung Joo AU - Kim SJ AD - Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Republic of Korea. FAU - Lee, Byeong-Chun AU - Lee BC AD - Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Seoul National University, Republic of Korea. FAU - Ahn, Curie AU - Ahn C AD - Transplantation Research Institute, Seoul National University College of Medicine, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Republic of Korea; Institute of Green Bio Science and Technology, Seoul National University, Republic of Korea; Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea. FAU - Yang, Jaeseok AU - Yang J AD - Transplantation Research Institute, Seoul National University College of Medicine, Republic of Korea; Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: jcyjs@dreamwiz.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160109 PL - Netherlands TA - Transpl Immunol JT - Transplant immunology JID - 9309923 RN - 0 (Antibodies, Heterophile) RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Receptors, Fc) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.14.14.18 (HMOX1 protein, human) RN - EC 1.14.14.18 (Heme Oxygenase-1) SB - IM MH - Animals MH - Animals, Genetically Modified MH - Antibodies, Heterophile/blood MH - Cell Movement/genetics MH - Cells, Cultured MH - Chemokine CCL2/genetics/metabolism MH - Graft Survival/genetics MH - Heme Oxygenase-1/genetics/*metabolism MH - Humans MH - *Islets of Langerhans Transplantation MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Receptors, Fc/genetics MH - Receptors, Tumor Necrosis Factor/genetics MH - Recombinant Fusion Proteins/genetics/*metabolism MH - Swine MH - Transgenes/genetics MH - Transplantation, Heterologous MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - Heme oxygenase-1 OT - Islet transplantation OT - Soluble TNF-alpha receptor OT - Transgenic pig OT - Xenotransplantation EDAT- 2016/01/19 06:00 MHDA- 2016/11/12 06:00 CRDT- 2016/01/19 06:00 PHST- 2015/10/11 00:00 [received] PHST- 2015/12/24 00:00 [revised] PHST- 2016/01/06 00:00 [accepted] PHST- 2016/01/19 06:00 [entrez] PHST- 2016/01/19 06:00 [pubmed] PHST- 2016/11/12 06:00 [medline] AID - S0966-3274(16)30002-8 [pii] AID - 10.1016/j.trim.2016.01.002 [doi] PST - ppublish SO - Transpl Immunol. 2016 Feb;34:25-32. doi: 10.1016/j.trim.2016.01.002. Epub 2016 Jan 9.