{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T05:53:26Z","timestamp":1761630806787,"version":"3.41.2"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,14]],"date-time":"2017-11-14T00:00:00Z","timestamp":1510617600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["NRF\u20102017R1A6A3A 11028885"],"award-info":[{"award-number":["NRF\u20102017R1A6A3A 11028885"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2018,1]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Porcine islet xenotransplantation is considered an attractive alternative treatment for type 1 diabetes mellitus. However, it is largely limited because of initial rejection due to Instant Blood\u2010Mediated Inflammatory Reaction (IBMIR<\/jats:styled-content>), oxidative stress, and inflammatory responses. Recently, soluble tumor necrosis factor\u2010\u0251 receptor type I (sTNF<\/jats:styled-content>\u2010\u03b1R) and heme oxygenase (HO<\/jats:styled-content>)\u20101 genes (HO<\/jats:styled-content>\u20101\/sTNF<\/jats:styled-content>\u2010\u03b1R) have been shown to improve the viability and functionality of porcine islets after transplantation.<\/jats:p><\/jats:sec>Methods<\/jats:title>In this study, genetically modified mesenchymal stem cells (MSC<\/jats:styled-content>s) expressing the HO<\/jats:styled-content>\u20101\/sTNF<\/jats:styled-content>\u2010\u03b1R genes (HO<\/jats:styled-content>\u20101\/sTNF<\/jats:styled-content>\u2010\u03b1R\u2010MSC<\/jats:styled-content>) were developed using an adenoviral system, and porcine islet viability and function were confirmed by in vitro tests such as GSIS<\/jats:styled-content>, AO<\/jats:styled-content>\/PI<\/jats:styled-content>, and the ADP<\/jats:styled-content>\/ATP<\/jats:styled-content> ratio after coculturing with HO<\/jats:styled-content>\u20101\/sTNF<\/jats:styled-content>\u2010\u03b1R\u2010MSC<\/jats:styled-content>s. Subsequently, isolated porcine islets were transplanted underneath the kidney capsule of diabetic humanized mice without MSC<\/jats:styled-content>s, with MSC<\/jats:styled-content>s or with HO<\/jats:styled-content>\u20101\/sTNF<\/jats:styled-content>\u2010\u03b1R\u2010MSCs.<\/jats:p><\/jats:sec>Results<\/jats:title>According to the results, the HO<\/jats:styled-content>\u20101\/sTNF<\/jats:styled-content>\u2010\u03b1R\u2010MSC<\/jats:styled-content>\u2010treated group exhibited improved survival of porcine islets and could reverse hyperglycemia more than porcine islets not treated with MSC<\/jats:styled-content>s or islets cotransplanted with MSC<\/jats:styled-content>s. Moreover, the HO<\/jats:styled-content>\u20101\/sTNF<\/jats:styled-content>\u2010\u03b1R\u2010MSC<\/jats:styled-content> group maintained its morphological characteristics and the insulin secretion pattern of transplanted porcine islets similar to endogenous islets in immunocompetent humanized mice.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Our results suggest that HO<\/jats:styled-content>\u20101\/sTNF<\/jats:styled-content>\u2010\u03b1R\u2010MSC<\/jats:styled-content>s are efficient tools for porcine islet xenotransplantation, and this study may provide basic information for\u00a0pre\u2010clinical animal models and future clinical trials of porcine islet xenotransplantation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/xen.12342","type":"journal-article","created":{"date-parts":[[2017,11,14]],"date-time":"2017-11-14T12:07:59Z","timestamp":1510661279000},"source":"Crossref","is-referenced-by-count":15,"title":["Enhanced effect of human mesenchymal stem cells expressing human TNF<\/scp>\u2010\u03b1R\u2010Fc and HO<\/scp>\u20101 gene on porcine islet xenotransplantation in humanized mice"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6362-9429","authenticated-orcid":false,"given":"Han\u2010Sin","family":"Lee","sequence":"first","affiliation":[{"name":"Transplantation Research Center Samsung Biomedical Research Institute Seoul Korea"},{"name":"Samsung Medical Center Stem Cell & Regenerative Medicine Institute Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanghyun","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Surgery Dankook University College of Medicine Dankook University Hospital Cheonam Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Du Yeon","family":"Shin","sequence":"additional","affiliation":[{"name":"Transplantation Research Center Samsung Biomedical Research Institute Seoul Korea"},{"name":"Samsung Medical Center Stem Cell & 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