BMP-7 Induces Adult Human Pancreatic Exocrine-to-Endocrine Conversion

Overview

Journal Diabetes

Specialty Endocrinology

Date 2015 Aug 27

PMID 26307584

Citations 29

Authors

Dagmar Klein

Silvia Alvarez-Cubela

Giacomo Lanzoni

Nancy Vargas

Kamalaveni R Prabakar

Maria Boulina

Camillo Ricordi

Luca Inverardi

Ricardo L Pastori

Juan Dominguez-Bendala

Affiliations

Soon will be listed here.

Abstract

The exocrine pancreas can give rise to endocrine insulin-producing cells upon ectopic expression of key transcription factors. However, the need for genetic manipulation remains a translational hurdle for diabetes therapy. Here we report the conversion of adult human nonendocrine pancreatic tissue into endocrine cell types by exposure to bone morphogenetic protein 7. The use of this U.S. Food and Drug Administration-approved agent, without any genetic manipulation, results in the neogenesis of clusters that exhibit high insulin content and glucose responsiveness both in vitro and in vivo. In vitro lineage tracing confirmed that BMP-7-induced insulin-expressing cells arise mainly from extrainsular PDX-1(+), carbonic anhydrase II(-) (mature ductal), elastase 3a (acinar)(-) , and insulin(-) subpopulations. The nongenetic conversion of human pancreatic exocrine cells to endocrine cells is novel and represents a safer and simpler alternative to genetic reprogramming.

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