De novo formation of insulin-producing "neo-ß cell islets" from intestinal crypts.
Cell Rep
; 6(6): 1046-1058, 2014 Mar 27.
Article
em En
| MEDLINE
| ID: mdl-24613355
ABSTRACT
The ability to interconvert terminally differentiated cells could serve as a powerful tool for cell-based treatment of degenerative diseases, including diabetes mellitus. To determine which, if any, adult tissues are competent to activate an islet ß cell program, we performed an in vivo screen by expressing three ß cell "reprogramming factors" in a wide spectrum of tissues. We report that transient intestinal expression of these factors-Pdx1, MafA, and Ngn3 (PMN)-promotes rapid conversion of intestinal crypt cells into endocrine cells, which coalesce into "neoislets" below the crypt base. Neoislet cells express insulin and show ultrastructural features of ß cells. Importantly, intestinal neoislets are glucose-responsive and able to ameliorate hyperglycemia in diabetic mice. Moreover, PMN expression in human intestinal "organoids" stimulates the conversion of intestinal epithelial cells into ß-like cells. Our results thus demonstrate that the intestine is an accessible and abundant source of functional insulin-producing cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ilhotas Pancreáticas
/
Células Secretoras de Insulina
/
Insulina
/
Intestinos
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article