Transient cytokine treatment induces acinar cell reprogramming and regenerates functional beta cell mass in diabetic mice.
Nat Biotechnol
; 32(1): 76-83, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24240391
ABSTRACT
Reprogramming of pancreatic exocrine cells into cells resembling beta cells may provide a strategy for treating diabetes. Here we show that transient administration of epidermal growth factor and ciliary neurotrophic factor to adult mice with chronic hyperglycemia efficiently stimulates the conversion of terminally differentiated acinar cells to beta-like cells. Newly generated beta-like cells are epigenetically reprogrammed, functional and glucose responsive, and they reinstate normal glycemic control for up to 248 d. The regenerative process depends on Stat3 signaling and requires a threshold number of Neurogenin 3 (Ngn3)-expressing acinar cells. In contrast to previous work demonstrating in vivo conversion of acinar cells to beta-like cells by viral delivery of exogenous transcription factors, our approach achieves acinar-to-beta-cell reprogramming through transient cytokine exposure rather than genetic modification.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator Neurotrófico Ciliar
/
Diabetes Mellitus
/
Fator de Crescimento Epidérmico
/
Células Secretoras de Insulina
Limite:
Animals
Idioma:
En
Revista:
Nat Biotechnol
Assunto da revista:
BIOTECNOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos