{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T11:06:47Z","timestamp":1778584007300,"version":"3.51.4"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2016,7,12]],"date-time":"2016-07-12T00:00:00Z","timestamp":1468281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>\u03b2-Cell replacement therapy represents the most promising approach to restore \u03b2-cell mass and glucose homeostasis in patients with type 1 diabetes. Safety and ethical issues associated with pluripotent stem cells stimulated the search for adult progenitor cells with endocrine differentiation capacities. We have already described a model for expansion and differentiation of human pancreatic duct-derived cells (HDDCs) into insulin-producing cells. Here we show an innovative and robust in vitro system for large-scale production of \u03b2-like cells from HDDCs using a nonintegrative RNA-based reprogramming technique. Synthetic modified RNAs for pancreatic transcription factors (pancreatic duodenal homeobox 1, neurogenin3, and V-Maf musculoaponeurotic fibrosarcoma oncogene homolog A [MAFA]) were manufactured and daily transfected in HDDCs without strongly affecting immune response and cell viability. MAFA overexpression was efficient and sufficient to induce \u03b2-cell differentiation of HDDCs, which acquired a broad repertoire of mature \u03b2-cell markers while downregulating characteristic epithelial-mesenchymal transition markers. Within 7 days, MAFA-reprogrammed HDDC populations contained 37% insulin-positive cells and a proportion of endocrine cells expressing somatostatin and pancreatic polypeptide. Ultrastructure analysis of differentiated HDDCs showed both immature and mature insulin granules with light-backscattering properties. Furthermore, in vitro HDDC-derived \u03b2 cells (called \u03b2-HDDCs) secreted human insulin and C-peptide in response to glucose, KCl, 3-isobutyl-1-methylxanthine, and tolbutamide stimulation. Transplantation of \u03b2-HDDCs into diabetic SCID-beige mice confirmed their functional glucose-responsive insulin secretion and their capacity to mitigate hyperglycemia. Our data describe a new, reliable, and fast procedure in adult human pancreatic cells to generate clinically relevant amounts of new \u03b2 cells with potential to reverse diabetes.<\/jats:p>\n               <jats:sec>\n                  <jats:title>Significance<\/jats:title>\n                  <jats:p>\u03b2-Cell replacement therapy represents the most promising approach to restore glucose homeostasis in patients with type 1 diabetes. This study shows an innovative and robust in vitro system for large-scale production of \u03b2-like cells from human pancreatic duct-derived cells (HDDCs) using a nonintegrative RNA-based reprogramming technique. V-Maf musculoaponeurotic fibrosarcoma oncogene homolog A overexpression was efficient and sufficient to induce \u03b2-cell differentiation and insulin secretion from HDDCs in response to glucose stimulation, allowing the cells to mitigate hyperglycemia in diabetic SCID-beige mice. The data describe a new, reliable, and fast procedure in adult human pancreatic cells to generate clinically relevant amounts of new \u03b2 cells with the potential to reverse diabetes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.5966\/sctm.2015-0318","type":"journal-article","created":{"date-parts":[[2016,7,13]],"date-time":"2016-07-13T02:43:32Z","timestamp":1468377812000},"page":"1525-1537","source":"Crossref","is-referenced-by-count":14,"title":["V-Maf Musculoaponeurotic Fibrosarcoma Oncogene Homolog A Synthetic Modified mRNA Drives Reprogramming of Human Pancreatic Duct-Derived Cells Into Insulin-Secreting Cells"],"prefix":"10.1093","volume":"5","author":[{"given":"Elisa","family":"Corritore","sequence":"first","affiliation":[{"name":"Pediatric Research Laboratory, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 Catholique de Louvain, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Syu","family":"Lee","sequence":"additional","affiliation":[{"name":"Pediatric Research Laboratory, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 Catholique de Louvain, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Pasquale","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, Istituti di Ricovero e Cura a Carattere Scientifico, San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Liberati","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, Istituti di Ricovero e Cura a Carattere Scientifico, San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei-Ju","family":"Hsu","sequence":"additional","affiliation":[{"name":"Pediatric Research Laboratory, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 Catholique de Louvain, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine Anne","family":"Lombard","sequence":"additional","affiliation":[{"name":"Pediatric Research Laboratory, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 Catholique de Louvain, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Van Der Smissen","sequence":"additional","affiliation":[{"name":"de Duve Institute, Universit\u00e9 Catholique de Louvain, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amedeo","family":"Vetere","sequence":"additional","affiliation":[{"name":"Chemical Biology Program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Bonner-Weir","sequence":"additional","affiliation":[{"name":"Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Piemonti","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, Istituti di Ricovero e Cura a Carattere Scientifico, San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Etienne","family":"Sokal","sequence":"additional","affiliation":[{"name":"Pediatric Research Laboratory, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 Catholique de Louvain, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe A.","family":"Lysy","sequence":"additional","affiliation":[{"name":"Pediatric Research Laboratory, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 Catholique de Louvain, Brussels, Belgium"},{"name":"Pediatric Endocrinology Unit, Cliniques Universitaires Saint Luc, Universit\u00e9 Catholique de Louvain, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,7,12]]},"reference":[{"key":"2021122705130573400_R1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1152\/physrev.00003.2010","article-title":"Type 1 diabetes: Etiology, immunology, and therapeutic strategies","volume":"91","author":"van Belle","year":"2011","journal-title":"Physiol Rev"},{"key":"2021122705130573400_R2","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.2337\/dc12-0063","article-title":"Improvement in outcomes of clinical islet transplantation: 1999-2010","volume":"35","author":"Barton","year":"2012","journal-title":"Diabetes 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