title: BMP-7 Induces Adult Human Pancreatic Exocrine-to-Endocrine Conversion.
abstract: The exocrine pancreas can give rise to endocrine insulin-producing cells upon ectopic expression of key transcription factors. However, the need for genetic manipulation remains a translational hurdle for diabetes therapy. Here we report the conversion of adult human nonendocrine pancreatic tissue into endocrine cell types by exposure to bone morphogenetic protein 7. The use of this U.S. Food and Drug Administration-approved agent, without any genetic manipulation, results in the neogenesis of clusters that exhibit high insulin content and glucose responsiveness both in vitro and in vivo. In vitro lineage tracing confirmed that BMP-7-induced insulin-expressing cells arise mainly from extrainsular PDX-1(+), carbonic anhydrase II(-) (mature ductal), elastase 3a (acinar)(-) , and insulin(-) subpopulations. The nongenetic conversion of human pancreatic exocrine cells to endocrine cells is novel and represents a safer and simpler alternative to genetic reprogramming.
authors: Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL.
authors: Dagmar
authors: D
authors: Klein
authors: Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL.
authors: Silvia
authors: S
authors: Álvarez-Cubela
authors: Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL.
authors: Giacomo
authors: G
authors: Lanzoni
authors: Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL.
authors: Nancy
authors: N
authors: Vargas
authors: Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL.
authors: Kamalaveni R
authors: KR
authors: Prabakar
authors: Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL.
authors: Maria
authors: M
authors: Boulina
authors: Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL Department of Biomedical Engineering, Miller School of Medicine, University of Miami, Miami, FL.
authors: Camillo
authors: C
authors: Ricordi
authors: Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL.
authors: Luca
authors: L
authors: Inverardi
authors: Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL rpastori@med.miami.edu jdominguez2@med.miami.edu.
authors: Ricardo L
authors: RL
authors: Pastori
authors: Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL Department of Cell Biology and Anatomy, Miller School of Medicine, University of Miami, Miami, FL rpastori@med.miami.edu jdominguez2@med.miami.edu.
authors: Juan
authors: J
authors: Domínguez-Bendala
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002096:C-Peptide / Q000097:blood / Q000378:metabolism; D019070:Cell Lineage; D054338:Cell Transdifferentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D005455:Fluorescent Antibody Technique; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D007668:Kidney; D008297:Male; D008819:Mice, Nude; D046790:Pancreas, Exocrine / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism; D014183:Transplantation, Heterologous; D016042:Transplantation, Heterotopic
chemical_list: C525819:BMP7 protein, human; D015415:Biomarkers; D055419:Bone Morphogenetic Protein 7; D002096:C-Peptide; D018398:Homeodomain Proteins; D007328:Insulin; D011994:Recombinant Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein