{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:05:20Z","timestamp":1791270320470,"version":"4.1.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2016,3,10]],"date-time":"2016-03-10T00:00:00Z","timestamp":1457568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2016,3,10]],"date-time":"2016-03-10T00:00:00Z","timestamp":1457568000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:p>\n                    Potent immunosuppressive drugs have significantly improved early patient survival after liver transplantation (LT). However, long\u2010term results remain unsatisfactory because of adverse events that are largely associated with lifelong immunosuppression. To solve this problem, different strategies have been undertaken to induce operational tolerance, for example, maintenance of normal graft function and histology without immunosuppressive therapy, but have achieved limited success. In this pilot study, we aimed to induce tolerance using a novel regulatory T\u2010cell\u2010based cell therapy in living donor LT. Adoptive transfer of an\n                    <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                    \u2010generated regulatory T\u2010cell\u2010enriched cell product was conducted in 10 consecutive adult patients early post\u2010LT. Cells were generated using a 2\u2010week coculture of recipient lymphocytes with irradiated donor cells in the presence of anti\u2010CD80\/86 monoclonal antibodies. Immunosuppressive agents were tapered from 6 months, reduced every 3 months, and completely discontinued by 18 months. After the culture, the generated cells displayed cell\u2010number\u2010dependent donor\u2010specific inhibition in the mixed lymphocyte reaction. Infusion of these cells caused no significant adverse events. Currently, all patients are well with normal graft function and histology. Seven patients have completed successful weaning and cessation of immunosuppressive agents. At present, they have been drug free for 16\u201033 months; 4 patients have been drug free for more than 24 months. The other 3 recipients with autoimmune liver diseases developed mild rejection during weaning and then resumed conventional low\u2010dose immunotherapy.\n                    <jats:italic toggle=\"yes\">Conclusions:<\/jats:italic>\n                    A cell therapy using an\n                    <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                    \u2010generated regulatory T\u2010cell\u2010enriched cell product is safe and effective for drug minimization and operational tolerance induction in living donor liver recipients with nonimmunological liver diseases. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2016;64:632\u2010643)\n                  <\/jats:p>","DOI":"10.1002\/hep.28459","type":"journal-article","created":{"date-parts":[[2016,1,16]],"date-time":"2016-01-16T13:15:00Z","timestamp":1452950100000},"page":"632-643","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":430,"title":["A pilot study of operational tolerance with a regulatory T\u2010cell\u2010based cell therapy in living donor liver transplantation"],"prefix":"10.1097","volume":"64","author":[{"given":"Satoru","family":"Todo","sequence":"first","affiliation":[{"name":"Department of Transplant Surgery,Hokkaido University Graduate School of Medicine,Sapporo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichiro","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Transplant Surgery,Hokkaido University Graduate School of 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Hospital,Sapporo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiya","family":"Kamiyama","sequence":"additional","affiliation":[{"name":"Department of Surgery I,Hokkaido University Graduate School of Medicine,Sapporo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiro","family":"Sato","sequence":"additional","affiliation":[{"name":"Division of Advanced Medical Research,Hokkaido University Hospital,Sapporo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Sugita","sequence":"additional","affiliation":[{"name":"Department of Hematology,Hokkaido University Hospital,Sapporo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Hatanaka","sequence":"additional","affiliation":[{"name":"Department of Pathology,Hokkaido University Graduate School of 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