Biomaterial Database

Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells. 2013

Jonghyeob Lee, and Takuya Sugiyama, and Yinghua Liu, and Jing Wang, and Xueying Gu, and Ji Lei, and James F Markmann, and Satsuki Miyazaki, and Jun-Ichi Miyazaki, and Gregory L Szot, and Rita Bottino, and Seung K Kim

Department of Developmental Biology, Stanford University School of Medicine, Stanford, United States.

Pancreatic islet β-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional β-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native β-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark β-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes. DOI: http://dx.doi.org/10.7554/eLife.00940.001.

UI	MeSH Term	Description	Entries
D007328	Insulin	A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).	Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D010183	Pancreatic Ducts	Ducts that collect PANCREATIC JUICE from the PANCREAS and supply it to the DUODENUM.	Duct of Santorini,Duct of Wirsung,Duodenal Papilla, Minor,Wirsung's Duct,Accessory Pancreatic Duct,Accessory Pancreatic Duct of Santorini,Main Pancreatic Duct,Santorini's Duct,Accessory Pancreatic Ducts,Duct, Accessory Pancreatic,Duct, Main Pancreatic,Duct, Pancreatic,Duct, Santorini's,Duct, Wirsung's,Ducts, Pancreatic,Main Pancreatic Ducts,Minor Duodenal Papilla,Minor Duodenal Papillas,Pancreatic Duct,Pancreatic Duct, Accessory,Pancreatic Duct, Main,Pancreatic Ducts, Accessory,Papilla, Minor Duodenal,Santorini Duct,Wirsung Duct,Wirsungs Duct
D002454	Cell Differentiation	Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.	Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002469	Cell Separation	Techniques for separating distinct populations of cells.	Cell Isolation,Cell Segregation,Isolation, Cell,Cell Isolations,Cell Segregations,Cell Separations,Isolations, Cell,Segregation, Cell,Segregations, Cell,Separation, Cell,Separations, Cell
D004702	Endocrine Glands	Ductless glands that secrete HORMONES directly into the BLOOD CIRCULATION. These hormones influence the METABOLISM and other functions of cells in the body.	Endocrine Gland,Gland, Endocrine
D005260	Female		Females
D005434	Flow Cytometry	Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.	Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man