{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T12:55:58Z","timestamp":1774788958031,"version":"3.50.1"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2008,3,5]],"date-time":"2008-03-05T00:00:00Z","timestamp":1204675200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0001734","type":"journal-article","created":{"date-parts":[[2008,3,4]],"date-time":"2008-03-04T22:56:25Z","timestamp":1204671385000},"page":"e1734","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["Nonvirally Modified Autologous Primary Hepatocytes Correct Diabetes and Prevent Target Organ Injury in a Large Preclinical Model"],"prefix":"10.1371","volume":"3","author":[{"given":"Nelson K. F.","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jen San","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene H. C.","family":"Kee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siang Hui","family":"Lai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Choon Hua","family":"Thng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wai Har","family":"Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert T. H.","family":"Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo Yong","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu Yen","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark E. H.","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaichandran","family":"Sivalingam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierce K. H.","family":"Chow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oi Lian","family":"Kon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2008,3,5]]},"reference":[{"key":"ref1","first-page":"313","article-title":"Correction of hyperbilirubinemia in the glucuronyltransferase-deficient rat by intraportal hepatocyte transplantation.","volume":"9","author":"CG Groth","year":"1977","journal-title":"Transplant Proc"},{"key":"ref2","first-page":"1546","article-title":"Human liver cell transplantation. Prolonged function in athymic-Gunn and athymic-analbuminemic hybrid rats.","volume":"96","author":"AD Moscioni","year":"1989","journal-title":"Gastroenterology"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1073\/pnas.89.1.89","article-title":"Expression of human alpha 1-antitrypsin in dogs after autologous transplantation of retroviral transduced hepatocytes.","volume":"89","author":"MA Kay","year":"1992","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"ref4","first-page":"171","article-title":"Therapeutic liver repopulation for the treatment of metabolic liver diseases.","volume":"12","author":"M Grompe","year":"1999","journal-title":"Hum Cell"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1016\/S0041-1345(97)00252-2","article-title":"Transplantation of human hepatocytes.","volume":"29","author":"SC Strom","year":"1997","journal-title":"Transplant Proc"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1097\/01.tp.0000231689.44266.ac","article-title":"Human hepatocyte transplantation: worldwide results.","volume":"82","author":"RA Fisher","year":"2006","journal-title":"Transplantation"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1023\/A:1010375203539","article-title":"Liver repopulation for the treatment of metabolic diseases.","volume":"24","author":"M Grompe","year":"2001","journal-title":"J Inherit Metab Dis"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.jhep.2006.11.006","article-title":"Liver transplantation in children.","volume":"46","author":"P Muiesan","year":"2007","journal-title":"J Hepatol."},{"key":"ref9","doi-asserted-by":"crossref","first-page":"S135","DOI":"10.1097\/01.tp.0000186905.10088.e5","article-title":"Liver transplantation for inborn errors of metabolism.","volume":"80","author":"J Meyburg","year":"2005","journal-title":"Transplantation"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nrg1066","article-title":"Progress and problems with the use of viral vectors for gene therapy.","volume":"4","author":"CE Thomas","year":"2003","journal-title":"Nat Rev Genet"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/nm867","article-title":"NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice.","volume":"9","author":"H Kojima","year":"2003","journal-title":"Nat Med"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"7964","DOI":"10.1073\/pnas.0405277102","article-title":"Cell-replacement therapy for diabetes: generating functional insulin-producing tissue from adult human liver cells.","volume":"102","author":"T Sapir","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1038\/nbt1145","article-title":"A human \u03b2-cell line for transplantation therapy to control type 1 diabetes.","volume":"23","author":"M Narushima","year":"2005","journal-title":"Nat Biotechnol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1038\/sj.mt.6300117","article-title":"Engineered enteroendocrine cells secrete insulin in response to glucose and reverse hyperglycemia in diabetic mice.","volume":"15","author":"J Han","year":"2007","journal-title":"Mol Ther"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s00125-006-0509-8","article-title":"Adult rat liver cells transdifferentiated with lentiviral IPF1 vectors reverse diabetes in mice: an ex vivo gene therapy approach.","volume":"50","author":"A Fodor","year":"2007","journal-title":"Diabetologia"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev.nutr.17.1.405","article-title":"Regulation of the expression of lipogenic enzyme genes by carbohydrate.","volume":"17","author":"HC Towle","year":"1997","journal-title":"Annu Rev Nutr"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.2337\/diabetes.50.10.2181","article-title":"Gene and cell-replacement therapy in the treatment of type 1 diabetes: how high must the standards be set?","volume":"50","author":"PA Halban","year":"2001","journal-title":"Diabetes"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/sj.gt.3302412","article-title":"Gene therapy progress and prospects: gene therapy for diabetes mellitus.","volume":"12","author":"V Yechoor","year":"2005","journal-title":"Gene Ther"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/sj.gt.3302446","article-title":"Plasmid-electroporated primary hepatocytes acquire quasi-physiological secretion of human insulin and restore euglycemia in diabetic mice.","volume":"12","author":"NKF Chen","year":"2005","journal-title":"Gene Ther"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.tem.2005.10.003","article-title":"Glucose as a regulator of eukaryotic gene transcription.","volume":"16","author":"HC Towle","year":"2005","journal-title":"Trends Endocrinol Metab"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.yasu.2005.04.010","article-title":"Comparison of whole organ pancreas and isolated islet transplantation for type 1 diabetes.","volume":"39","author":"AM Frank","year":"2005","journal-title":"Adv Surg"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1097\/01.mpa.0000203961.16630.2f","article-title":"Prospective and challenges of islet transplantation for the therapy of autoimmune diabetes.","volume":"32","author":"AN Balamurugan","year":"2006","journal-title":"Pancreas"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1740-2557-1-3","article-title":"Insulin expressing hepatocytes not destroyed in transgenic NOD mice.","volume":"1","author":"MT Tabiin","year":"2004","journal-title":"J. Autoimmune Dis"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1007\/s00125-006-0434-x","article-title":"Embryonic stem cell-based diabetes therapy\u2013a long road to travel.","volume":"49","author":"P Serup","year":"2006","journal-title":"Diabetologia"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1016\/S0002-9440(10)62488-1","article-title":"Teratoma formation leads to failure of treatment for type 1 diabetes using embryonic stem cell-derived insulin-producing cells.","volume":"166","author":"T Fujikawa","year":"2005","journal-title":"Am J Pathol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1080\/14653240500363216","article-title":"Outgrowth of a transformed cell population derived from normal human BM mesenchymal stem cell culture.","volume":"7","author":"Y Wang","year":"2005","journal-title":"Cytotherapy"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1634\/stemcells.2005-0403","article-title":"Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation.","volume":"24","author":"M Miura","year":"2006","journal-title":"Stem Cells"},{"key":"ref28","first-page":"4.2.1","article-title":"Guanidine methods for total RNA preparation.","author":"RE Kingston","year":"1996"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1055\/s-2007-978631","article-title":"Ammonium chloride potentiation of streptozotocin-induced diabetes in juvenile pigs.","volume":"32","author":"FL Korompai","year":"2000","journal-title":"Horm Metab Res"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1006\/jsre.1997.5120","article-title":"Serial ultrasound-guided percutaneous liver biopsy in a partial hepatectomy porcine model: a new technique in the study of liver regeneration.","volume":"70","author":"PK Chow","year":"1997","journal-title":"J Surg Res"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.tplants.2006.05.010","article-title":"Microarray data analysis made easy.","volume":"11","author":"GJ Beckers","year":"2006","journal-title":"Trends Plant Sci"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"5116","DOI":"10.1073\/pnas.091062498","article-title":"Significance analysis of microarrays applied to the ionizing radiation response.","volume":"A.98","author":"VG Tusher","year":"2001","journal-title":"Proc Natl Acad Sci U S"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.2527\/1993.71113020x","article-title":"Growth and plasma zinc responses of young pigs fed pharmacologic levels of zinc.","volume":"71","author":"JD Hahn","year":"1993","journal-title":"J Anim Sci"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.2337\/diabetes.50.9.2001","article-title":"Decrease in beta-cell mass leads to impaired pulsatile insulin secretion, reduced postprandial hepatic insulin clearance, and relative hyperglucagonemia in the minipig.","volume":"50","author":"LL Kjems","year":"2001","journal-title":"Diabetes"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"743","DOI":"10.2337\/diab.31.9.743","article-title":"Glycosylated hemoglobin in human and animal red cells. Role of glucose permeability.","volume":"31","author":"PJ Higgins","year":"1982","journal-title":"Diabetes"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1152\/jappl.1981.51.3.762","article-title":"Total plasma creatinine: an accurate measure of total striated muscle mass.","volume":"51","author":"JE Schutte","year":"1981","journal-title":"J Appl Physiol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1093\/ajcn\/56.2.320","article-title":"Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis.","volume":"56","author":"AM Dattilo","year":"1992","journal-title":"Am J Clin Nutr"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1097\/00000478-200604000-00012","article-title":"Glycogenic hepatopathy: an underrecognized hepatic complication of diabetes mellitus.","volume":"30","author":"M Torbenson","year":"2006","journal-title":"Am J Surg Pathol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.1007\/s001250051393","article-title":"Mitogenic properties of insulin and insulin analogues mediated by the insulin receptor.","volume":"40","author":"D Ish-Shalom","year":"1997","journal-title":"Diabetologia"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1158\/0008-5472.CAN-05-2787","article-title":"Hepatocellular neoplasms induced by low-number pancreatic islet transplants in autoimmune diabetic BB\/Pfd rats.","volume":"66","author":"F Dombrowski","year":"2006","journal-title":"Cancer Res"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"F913","DOI":"10.1152\/ajprenal.00323.2003","article-title":"Adipose differentiation-related protein and regulators of lipid homeostasis identified by gene expression profiling in the murine db\/db diabetic kidney.","volume":"286","author":"R Mishra","year":"2004","journal-title":"Am J Physiol Renal Physiol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1172\/JCI115779","article-title":"Effects of hemipancreatectomy on pancreatic alpha and beta cell function in healthy human donors.","volume":"89","author":"ER Seaquist","year":"1992","journal-title":"J Clin Invest"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1097\/01.TP.0000146386.77076.47","article-title":"Hepatocyte transplantation for inherited factor VII deficiency.","volume":"78","author":"A Dhawan","year":"2004","journal-title":"Transplantation"},{"key":"ref44","first-page":"467","article-title":"Gene therapy for type 1 diabetes: a proposal to move to the next level.","volume":"7","author":"N Giannoukakis","year":"2005","journal-title":"Curr Opin Mol Ther"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1056\/NEJMoa061267","article-title":"International trial of the Edmonton protocol for islet transplantation.","volume":"355","author":"AM Shapiro","year":"2006","journal-title":"N Engl J Med"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"102","DOI":"10.2337\/diabetes.52.1.102","article-title":"Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes.","volume":"52","author":"AE Butler","year":"2003","journal-title":"Diabetes"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1126\/science.276.5309.60","article-title":"Liver regeneration.","volume":"276","author":"GK Michalopoulos","year":"1997","journal-title":"Science"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1002\/hep.510290213","article-title":"Entry and integration of transplanted hepatocytes in rat liver plates occur by disruption of hepatic sinusoidal endothelium.","volume":"29","author":"S Gupta","year":"1999","journal-title":"Hepatology"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1006\/jsre.1996.0291","article-title":"Factors influencing hepatocyte trafficking during allogeneic hepatocyte transplantation: improved liver sequestration with isolated perfusion.","volume":"63","author":"A Picardo","year":"1996","journal-title":"J Surg Res"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1097\/00007890-200203270-00010","article-title":"Intraportal hepatocyte transplantation in the pig: hemodynamic and histopathological study.","volume":"73","author":"M Muraca","year":"2002","journal-title":"Transplantation"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/0022-3468(92)90853-Y","article-title":"Intrahepatic hepatocyte transplantation following subtotal hepatectomy in the recipient: a possible model in the treatment of hepatic enzyme deficiency.","volume":"27","author":"H Zhang","year":"1992","journal-title":"J Pediatr Surg"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1034\/j.1399-5448.2003.00025.x","article-title":"Hypoglycemia in children with type 1 diabetes: current issues and controversies.","volume":"4","author":"TW Jones","year":"2003","journal-title":"Pediatr Diabetes"},{"key":"ref53","first-page":"1155","article-title":"The endocrine system.","author":"A Maitra","year":"2005"},{"key":"ref54","first-page":"779","article-title":"Retinal and choroidal circulation.","author":"S Roh","year":"2004"},{"key":"ref55","first-page":"3","article-title":"The mechanism of naked DNA uptake and expression.","volume":"54","author":"JA Wolff","year":"2005","journal-title":"Adv Genet"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/sj.gt.3302213","article-title":"Detection of integration of plasmid DNA into host genomic DNA following intramuscular injection and electroporation.","volume":"11","author":"Z Wang","year":"2004","journal-title":"Gene Ther"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/sj.gt.3302700","article-title":"Sustained expression after nonviral ocular gene transfer using mammalian promoters.","volume":"13","author":"S Kachi","year":"2006","journal-title":"Gene Ther"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1089\/dna.1990.9.293","article-title":"Introduction of stable high-copy-number DNA into Chinese hamster ovary cells by electroporation.","volume":"9","author":"J Barsoum","year":"1990","journal-title":"DNA Cell Biol"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0001734","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,8]],"date-time":"2019-05-08T16:44:54Z","timestamp":1557333894000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0001734"}},"subtitle":[],"editor":[{"given":"David M.","family":"Harlan","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2008,3,5]]},"references-count":58,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2008,3,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0001734","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,3,5]]}}}