{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:00:21Z","timestamp":1791219621603,"version":"4.1.0"},"reference-count":55,"publisher":"American Diabetes Association","issue":"5","license":[{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"vor","delay-in-days":250,"URL":"http:\/\/www.diabetesjournals.org\/site\/license"}],"funder":[{"DOI":"10.13039\/100001078","name":"Diabetes Research Institute Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001078","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007028","name":"Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000901","name":"JDRF International","doi-asserted-by":"publisher","award":["17-2012-361"],"award-info":[{"award-number":["17-2012-361"]}],"id":[{"id":"10.13039\/100000901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,5,1]]},"abstract":"<jats:p>Transplantation of pancreatic islets is a therapeutic option to preserve or restore \u03b2-cell function. Our study was aimed at developing a clinically applicable protocol for extrahepatic transplantation of pancreatic islets. The potency of islets implanted onto the omentum, using an in situ\u2013generated adherent, resorbable plasma-thrombin biologic scaffold, was evaluated in diabetic rat and nonhuman primate (NHP) models. Intraomental islet engraftment in the biologic scaffold was confirmed by achievement of improved metabolic function and preservation of islet cytoarchitecture, with reconstitution of rich intrainsular vascular networks in both species. Long-term nonfasting normoglycemia and adequate glucose clearance (tolerance tests) were achieved in both intrahepatic and intraomental sites in rats. Intraomental graft recipients displayed lower levels of serum biomarkers of islet distress (e.g., acute serum insulin) and inflammation (e.g., leptin and \u03b12-macroglobulin). Importantly, low-purity (30:70% endocrine:exocrine) syngeneic rat islet preparations displayed function equivalent to that of pure (&amp;gt;95% endocrine) preparations after intraomental biologic scaffold implantation. Moreover, the biologic scaffold sustained allogeneic islet engraftment in immunosuppressed recipients. Collectively, our feasibility\/efficacy data, along with the simplicity of the procedure and the safety of the biologic scaffold components, represented sufficient preclinical testing to proceed to a pilot phase I\/II clinical trial.<\/jats:p>","DOI":"10.2337\/db15-1525","type":"journal-article","created":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T04:34:16Z","timestamp":1456461256000},"page":"1350-1361","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":131,"title":["Bioengineering the Endocrine Pancreas: Intraomental Islet Transplantation Within a Biologic Resorbable Scaffold"],"prefix":"10.2337","volume":"65","author":[{"given":"Dora M.","family":"Berman","sequence":"first","affiliation":[{"name":"Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL"},{"name":"The DeWitt Daughtry Family Department of Surgery, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Damaris","family":"Molano","sequence":"additional","affiliation":[{"name":"Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Fotino","sequence":"additional","affiliation":[{"name":"Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulisse","family":"Ulissi","sequence":"additional","affiliation":[{"name":"Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Gimeno","sequence":"additional","affiliation":[{"name":"Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando J.","family":"Mendez","sequence":"additional","affiliation":[{"name":"Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL"},{"name":"Department of Medicine, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman M.","family":"Kenyon","sequence":"additional","affiliation":[{"name":"Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL"},{"name":"The DeWitt Daughtry Family Department of Surgery, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma S.","family":"Kenyon","sequence":"additional","affiliation":[{"name":"Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL"},{"name":"The DeWitt Daughtry Family Department of Surgery, University of Miami, Miami, FL"},{"name":"Department of Microbiology and Immunology, University of Miami, Miami, FL"},{"name":"Department of Biomedical Engineering, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camillo","family":"Ricordi","sequence":"additional","affiliation":[{"name":"Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL"},{"name":"The DeWitt Daughtry Family Department of Surgery, University of Miami, Miami, FL"},{"name":"Department of Medicine, University of Miami, Miami, FL"},{"name":"Department of Microbiology and Immunology, University of Miami, Miami, FL"},{"name":"Department of Biomedical Engineering, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonello","family":"Pileggi","sequence":"additional","affiliation":[{"name":"Cell Transplant Center, Diabetes Research Institute, University of Miami, Miami, FL"},{"name":"The DeWitt Daughtry Family Department of Surgery, University of Miami, Miami, FL"},{"name":"Department of Microbiology and Immunology, University of Miami, Miami, FL"},{"name":"Department of Biomedical Engineering, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2016,2,25]]},"reference":[{"key":"2022031211292985700_B1"},{"key":"2022031211292985700_B2","first-page":"177","article-title":"Twenty years of clinical islet transplantation at the Diabetes Research Institute--University of Miami","author":"Pileggi","year":"2004","journal-title":"Clin Transpl"},{"key":"2022031211292985700_B3","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1172\/JCI112720","article-title":"Natural history of intrahepatic canine islet cell autografts","volume":"78","author":"Alejandro","year":"1986","journal-title":"J Clin Invest"},{"key":"2022031211292985700_B4","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1517\/03009734000000059","article-title":"Isolated human islets trigger an instant blood mediated inflammatory reaction: implications for intraportal islet transplantation as a treatment for patients with type 1 diabetes","volume":"105","author":"Bennet","year":"2000","journal-title":"Ups J Med Sci"},{"key":"2022031211292985700_B5","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1016\/S0140-6736(02)12020-4","article-title":"Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation","volume":"360","author":"Moberg","year":"2002","journal-title":"Lancet"},{"key":"2022031211292985700_B6","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.2337\/diabetes.54.6.1755","article-title":"Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation","volume":"54","author":"Johansson","year":"2005","journal-title":"Diabetes"},{"key":"2022031211292985700_B7","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1097\/01.tp.0000275401.80187.1e","article-title":"Interference with tissue factor prolongs intrahepatic islet allograft survival in a nonhuman primate marginal mass model","volume":"84","author":"Berman","year":"2007","journal-title":"Transplantation"},{"key":"2022031211292985700_B8","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.2337\/diabetes.52.7.1591","article-title":"Magnetic resonance-defined periportal steatosis following intraportal islet transplantation: a functional footprint of islet graft survival","volume":"52","author":"Markmann","year":"2003","journal-title":"Diabetes"},{"key":"2022031211292985700_B9","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.2337\/diabetes.53.5.1311","article-title":"Prevalence of hepatic steatosis after islet transplantation and its relation to graft function","volume":"53","author":"Bhargava","year":"2004","journal-title":"Diabetes"},{"key":"2022031211292985700_B10","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.transproceed.2004.04.047","article-title":"Disseminated periportal fatty degeneration after allogeneic intraportal islet transplantation in a patient with type 1 diabetes mellitus: a case report","volume":"36","author":"Eckhard","year":"2004","journal-title":"Transplant Proc"},{"key":"2022031211292985700_B11","doi-asserted-by":"crossref","first-page":"727","DOI":"10.3727\/000000005783982567","article-title":"Minimal focal steatosis of liver after islet transplantation in humans: a long-term study","volume":"14","author":"Maffi","year":"2005","journal-title":"Cell Transplant"},{"key":"2022031211292985700_B12","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.3727\/096368913X668663","article-title":"Liver fat accumulation after islet transplantation and graft survival","volume":"23","author":"Leit\u00e3o","year":"2014","journal-title":"Cell Transplant"},{"key":"2022031211292985700_B13","doi-asserted-by":"crossref","first-page":"16","DOI":"10.4161\/isl.24058","article-title":"Long-term follow-up of hepatic ultrasound findings in subjects with magnetic resonance imaging defined hepatic steatosis following clinical islet transplantation: a case-control study","volume":"5","author":"Jackson","year":"2013","journal-title":"Islets"},{"key":"2022031211292985700_B14","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.phrs.2015.02.010","article-title":"Re-engineering islet cell transplantation","volume":"98","author":"Fotino","year":"2015","journal-title":"Pharmacol Res"},{"key":"2022031211292985700_B15","doi-asserted-by":"crossref","first-page":"3333","DOI":"10.2337\/db13-1039","article-title":"A new home for pancreatic islet transplants: the bone marrow","volume":"62","author":"Pileggi","year":"2013","journal-title":"Diabetes"},{"key":"2022031211292985700_B16","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1097\/00000658-200111000-00016","article-title":"Superiority of portal venous drainage over systemic venous drainage in pancreas transplantation: a retrospective study","volume":"234","author":"Philosophe","year":"2001","journal-title":"Ann Surg"},{"key":"2022031211292985700_B17","first-page":"169","article-title":"The omentum","volume":"6","author":"Platell","year":"2000","journal-title":"World J Gastroenterol"},{"key":"2022031211292985700_B18","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00276-005-0329-4","article-title":"Omental anatomy of non-human primates","volume":"27","author":"Chaffanjon","year":"2005","journal-title":"Surg Radiol Anat"},{"key":"2022031211292985700_B19","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1159\/000147051","article-title":"Microcirculation of the rat omentum studied by means of corrosion casts","volume":"140","author":"Ackermann","year":"1991","journal-title":"Acta Anat (Basel)"},{"key":"2022031211292985700_B20","first-page":"3236","article-title":"Liver-omental pouch and intrahepatic islet transplants produce portal insulin delivery and prevent hyperinsulinemia in rats","volume":"27","author":"Guan","year":"1995","journal-title":"Transplant Proc"},{"key":"2022031211292985700_B21","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.2337\/diabetes.47.7.1020","article-title":"Glucose turnover and insulin sensitivity in rats with pancreatic islet transplants","volume":"47","author":"Guan","year":"1998","journal-title":"Diabetes"},{"key":"2022031211292985700_B22"},{"key":"2022031211292985700_B23","doi-asserted-by":"crossref","first-page":"203","DOI":"10.3346\/jkms.2010.25.2.203","article-title":"Comparison of four pancreatic islet implantation sites","volume":"25","author":"Kim","year":"2010","journal-title":"J Korean Med Sci"},{"key":"2022031211292985700_B24","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1007\/s00125-011-2091-y","article-title":"The anterior chamber of the eye as a clinical transplantation site for the treatment of diabetes: a study in a baboon model of diabetes","volume":"54","author":"Perez","year":"2011","journal-title":"Diabetologia"},{"key":"2022031211292985700_B25","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1097\/01.tp.0000203858.41105.88","article-title":"Reversal of diabetes by pancreatic islet transplantation into a subcutaneous, neovascularized device","volume":"81","author":"Pileggi","year":"2006","journal-title":"Transplantation"},{"key":"2022031211292985700_B26"},{"key":"2022031211292985700_B27","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.3727\/096368911X623853","article-title":"Beneficial effects of ischemic preconditioning on pancreas cold preservation","volume":"21","author":"Hogan","year":"2012","journal-title":"Cell Transplant"},{"key":"2022031211292985700_B28","doi-asserted-by":"crossref","first-page":"413","DOI":"10.2337\/diab.37.4.413","article-title":"Automated method for isolation of human pancreatic islets","volume":"37","author":"Ricordi","year":"1988","journal-title":"Diabetes"},{"key":"2022031211292985700_B29","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.2337\/diabetes.52.7.1595","article-title":"Islet transplantation: a brave new world","volume":"52","author":"Ricordi","year":"2003","journal-title":"Diabetes"},{"key":"2022031211292985700_B30"},{"key":"2022031211292985700_B31","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1097\/TP.0b013e3181a36b1e","article-title":"Impact of pancreatic cold preservation on rat islet recovery and function","volume":"87","author":"Pileggi","year":"2009","journal-title":"Transplantation"},{"key":"2022031211292985700_B32","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1097\/TP.0b013e3181fe1377","article-title":"Islet transplantation in type 1 diabetic patients using calcineurin inhibitor-free immunosuppressive protocols based on T-cell adhesion or costimulation blockade","volume":"90","author":"Posselt","year":"2010","journal-title":"Transplantation"},{"key":"2022031211292985700_B33","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.2337\/db09-1264","article-title":"A novel clinically relevant strategy to abrogate autoimmunity and regulate alloimmunity in NOD mice","volume":"59","author":"Vergani","year":"2010","journal-title":"Diabetes"},{"key":"2022031211292985700_B34"},{"key":"2022031211292985700_B35","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/xen.12086","article-title":"Encapsulated piscine (tilapia) islets for diabetes therapy: studies in diabetic NOD and NOD-SCID mice","volume":"21","author":"Safley","year":"2014","journal-title":"Xenotransplantation"},{"key":"2022031211292985700_B36","first-page":"76","article-title":"Local immumosuppression modulates islet allograft rejection into a biohybrid device","volume":"10","author":"Brady","year":"2010","journal-title":"Am J Transplant"},{"key":"2022031211292985700_B37","doi-asserted-by":"crossref","first-page":"3433","DOI":"10.1016\/j.transproceed.2005.09.090","article-title":"C-peptide and glucose values in the peritransplant period after intraportal islet infusions in type 1 diabetes","volume":"37","author":"Faradji","year":"2005","journal-title":"Transplant Proc"},{"key":"2022031211292985700_B38"},{"key":"2022031211292985700_B39","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1097\/00007890-198308000-00014","article-title":"A new site for islet transplantation--a peritoneal-omental pouch","volume":"36","author":"Yasunami","year":"1983","journal-title":"Transplantation"},{"key":"2022031211292985700_B40","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/icb.1986.4","article-title":"A comparative study of transplant sites for endocrine tissue transplantation in the pig","volume":"64","author":"Simeonovic","year":"1986","journal-title":"Aust J Exp Biol Med Sci"},{"key":"2022031211292985700_B41","first-page":"2789","article-title":"Development of an omental pouch site for islet transplantation","volume":"24","author":"Ao","year":"1992","journal-title":"Transplant Proc"},{"key":"2022031211292985700_B42","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1097\/00007890-199309000-00007","article-title":"Survival and function of purified islets in the omental pouch site of outbred dogs","volume":"56","author":"Ao","year":"1993","journal-title":"Transplantation"},{"key":"2022031211292985700_B43","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1007\/s00125-010-1721-0","article-title":"Human islet cell implants in a nude rat model of diabetes survive better in omentum than in liver with a positive influence of beta cell number and purity","volume":"53","author":"Jacobs-Tulleneers-Thevissen","year":"2010","journal-title":"Diabetologia"},{"key":"2022031211292985700_B44","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1097\/TP.0b013e3182a6ee41","article-title":"Omentum is better site than kidney capsule for growth, differentiation, and vascularization of immature porcine \u03b2-cell implants in immunodeficient rats","volume":"96","author":"Bartholomeus","year":"2013","journal-title":"Transplantation"},{"key":"2022031211292985700_B45","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.3727\/096368912X657440","article-title":"Macroporous three-dimensional PDMS scaffolds for extrahepatic islet transplantation","volume":"22","author":"Pedraza","year":"2013","journal-title":"Cell Transplant"},{"key":"2022031211292985700_B46","first-page":"135","article-title":"Thrombin use in surgery: an evidence-based review of its clinical use","volume":"1","author":"Ham","year":"2010","journal-title":"J Blood Med"},{"key":"2022031211292985700_B47","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jss.2008.11.842","article-title":"Omental roll-up: a technique for islet engraftment in a large animal model","volume":"161","author":"Hefty","year":"2010","journal-title":"J Surg Res"},{"key":"2022031211292985700_B48","first-page":"517","article-title":"Acute phase response in animals: a review","volume":"59","author":"Cray","year":"2009","journal-title":"Comp Med"},{"key":"2022031211292985700_B49","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3389\/fimmu.2014.00143","article-title":"Neuro-endocrine networks controlling immune system in health and disease","volume":"5","author":"Procaccini","year":"2014","journal-title":"Front Immunol"},{"key":"2022031211292985700_B50","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.2337\/diabetes.51.6.1779","article-title":"Inhibition of thrombin abrogates the instant blood-mediated inflammatory reaction triggered by isolated human islets: possible application of the thrombin inhibitor melagatran in clinical islet transplantation","volume":"51","author":"Ozmen","year":"2002","journal-title":"Diabetes"},{"key":"2022031211292985700_B51","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/labinvest.2008.87","article-title":"Characterization of pancreatic ductal cells in human islet preparations","volume":"88","author":"Ichii","year":"2008","journal-title":"Lab Invest"},{"key":"2022031211292985700_B52","first-page":"3382","article-title":"Long-term in vivo function of human mantled islets obtained by incomplete pancreatic dissociation and purification","volume":"27","author":"Ricordi","year":"1995","journal-title":"Transplant Proc"},{"key":"2022031211292985700_B53","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.2337\/diabetes.53.12.3107","article-title":"Islet graft assessment in the Edmonton Protocol: implications for predicting long-term clinical outcome","volume":"53","author":"Street","year":"2004","journal-title":"Diabetes"},{"key":"2022031211292985700_B54","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1097\/SLA.0000000000000569","article-title":"Total pancreatectomy and islet autotransplantation in children for chronic pancreatitis: indication, surgical techniques, postoperative management, and long-term outcomes","volume":"260","author":"Chinnakotla","year":"2014","journal-title":"Ann Surg"},{"key":"2022031211292985700_B55"}],"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/diabetes.diabetesjournals.org\/syndication\/doi\/10.2337\/db15-1525","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/65\/5\/1350\/582907\/db151525.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/65\/5\/1350\/582907\/db151525.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:48:58Z","timestamp":1667407738000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/65\/5\/1350\/17453\/Bioengineering-the-Endocrine-Pancreas-Intraomental"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,25]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2016,2,25]]},"published-print":{"date-parts":[[2016,5,1]]}},"URL":"https:\/\/doi.org\/10.2337\/db15-1525","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,25]]}}}