Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells.
Elife
; 2: e00940, 2013 Nov 19.
Article
em En
| MEDLINE
| ID: mdl-24252877
ABSTRACT
Pancreatic islet ß-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional ß-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 ß-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 ß-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ductos Pancreáticos
/
Diferenciação Celular
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Glândulas Endócrinas
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Insulina
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Elife
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos