title: Reprogramming of mice primary hepatocytes into insulin-producing cells by transfection with multicistronic vectors.
abstract: The neogenesis of insulin-producing cells (IPCs) from non-beta-cells has emerged as a potential method for treating diabetes mellitus (DM). Many groups have documented that activation of pancreatic transcription factor(s) in hepatocytes can improve the hyperglycemia in diabetic mice. In the present study, we explored a novel protocol that reprogrammed primary hepatocytes into functional IPCs by using multicistronic vectors carrying pancreatic and duodenal homeobox-1 (Pdx1), neurogenin 3 (Ngn3), and v-musculoaponeurotic fibrosarcoma oncogene homolog A (MafA). These triple-transfected cells activated multiple beta-cell genes, synthesized and stored considerable amounts of insulin, and released the hormone in a glucose-regulated manner in vitro. Furthermore, when transplanted into streptozotocin-induced diabetic mice, the cells markedly ameliorated glucose tolerance. Our results indicated that ectopic expression of Pdx1, Ngn3, and MafA facilitated hepatocytes-to-IPCs reprogramming. This approach may offer opportunities for treatment of DM.
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, No. 253 Gong Ye Road, Guangzhou 510282, China ; Department of Endocrinology, Nanhai Hospital, Southern Medical University, No. 40 Foping Road, Foshan 528200, China.
authors.forename: Haizhao
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, No. 253 Gong Ye Road, Guangzhou 510282, China.
authors.forename: Rongping
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, No. 253 Gong Ye Road, Guangzhou 510282, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, No. 253 Gong Ye Road, Guangzhou 510282, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Nanhai Hospital, Southern Medical University, No. 40 Foping Road, Foshan 528200, China.
authors.forename: Youping
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Nanhai Hospital, Southern Medical University, No. 40 Foping Road, Foshan 528200, China.
authors.forename: Yi
authors.identifier: 0000-0003-4811-3621
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, No. 253 Gong Ye Road, Guangzhou 510282, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D018149:Glucose Intolerance / Q000097:blood; D005951:Glucose Tolerance Test; D022781:Hepatocytes / Q000166:cytology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D051473:Maf Transcription Factors, Large / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001786:Blood Glucose; D018398:Homeodomain Proteins; D007328:Insulin; D051473:Maf Transcription Factors, Large; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; C485160:Mafa protein, mouse; C407737:Neurog3 protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein