title: Beta Cells Secrete Significant and Regulated Levels of Insulin for Long Periods when Seeded onto Acellular Micro-Scaffolds.
abstract: The aim of this work is to obtain significant and regulated insulin secretion from human beta cells ex vivo. Long-term culture of human pancreatic islets and attempts at expanding human islet cells normally result in loss of beta-cell phenotype. We propose that to obtain proper ex vivo beta cell function, there is a need to develop three-dimensional structures that mimic the natural islet tissue microenvironment. We here describe the preparation of endocrine micro-pancreata (EMPs) that are made up of acellular organ-derived micro-scaffolds seeded with human intact or enzymatically dissociated islets. We show that EMPs constructed by seeding whole islets, freshly enzymatically-dissociated islets or even dissociated islets grown first in standard monolayer cultures express high levels of key beta-cell specific genes and secrete quantities of insulin per cell similar to freshly isolated human islets in a glucose-regulated manner for more than 3 months in vitro.
authors.affiliation: Department of Cell and Developmental Biology, The Hebrew University of Jerusalem , The Alexander Silberman Institute of Life Sciences, Jerusalem, Israel .
authors.forename: Ronit Vogt
authors.initials: RV
authors.lastname: Sionov
authors.affiliation: Department of Cell and Developmental Biology, The Hebrew University of Jerusalem , The Alexander Silberman Institute of Life Sciences, Jerusalem, Israel .
authors.forename: Gershon
authors.initials: G
authors.lastname: Finesilver
authors.affiliation: Department of Cell and Developmental Biology, The Hebrew University of Jerusalem , The Alexander Silberman Institute of Life Sciences, Jerusalem, Israel .
authors.forename: Lena
authors.initials: L
authors.lastname: Sapozhnikov
authors.affiliation: Department of Cell and Developmental Biology, The Hebrew University of Jerusalem , The Alexander Silberman Institute of Life Sciences, Jerusalem, Israel .
authors.forename: Avigail
authors.initials: A
authors.lastname: Soroker
authors.affiliation: Department of Cell and Developmental Biology, The Hebrew University of Jerusalem , The Alexander Silberman Institute of Life Sciences, Jerusalem, Israel .
authors.forename: Efrat
authors.initials: E
authors.lastname: Zlotkin-Rivkin
authors.affiliation: Department of Cell and Developmental Biology, The Hebrew University of Jerusalem , The Alexander Silberman Institute of Life Sciences, Jerusalem, Israel .
authors.forename: Yocheved
authors.initials: Y
authors.lastname: Saad
authors.affiliation: Department of Cell and Developmental Biology, The Hebrew University of Jerusalem , The Alexander Silberman Institute of Life Sciences, Jerusalem, Israel .
authors.forename: Meygal
authors.initials: M
authors.lastname: Kahana
authors.affiliation: Department of Cell and Developmental Biology, The Hebrew University of Jerusalem , The Alexander Silberman Institute of Life Sciences, Jerusalem, Israel .
authors.forename: Matan
authors.initials: M
authors.lastname: Bodaker
authors.affiliation: Department of Cell and Developmental Biology, The Hebrew University of Jerusalem , The Alexander Silberman Institute of Life Sciences, Jerusalem, Israel .
authors.forename: Evgenia
authors.initials: E
authors.lastname: Alpert
authors.affiliation: Department of Cell and Developmental Biology, The Hebrew University of Jerusalem , The Alexander Silberman Institute of Life Sciences, Jerusalem, Israel .
authors.forename: Eduardo
authors.initials: E
authors.lastname: Mitrani
mesh_terms: D000293:Adolescent; D000328:Adult; D021522:Bioartificial Organs; D002474:Cell-Free System; D002478:Cells, Cultured; D019544:Equipment Failure Analysis; D005109:Extracellular Matrix / Q000737:chemistry*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D008137:Longitudinal Studies; D008168:Lung / Q000737:chemistry / Q000166:cytology; D008297:Male; D008875:Middle Aged; D019397:Pancreas, Artificial; D011474:Prosthesis Design; D054457:Tissue Scaffolds; D055815:Young Adult
chemical_list: D007328:Insulin; D005947:Glucose