BMP-7 induces adult human pancreatic exocrine-to-endocrine conversion

Dagmar Klein, Silvia Álvarez-Cubela, Giacomo Lanzoni, Nancy Vargas, Kamalaveni R. Prabakar, Maria Boulina, Camillo Ricordi, Luca A Inverardi, Ricardo Pastori, Juan Dominguez-Bendala

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24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4123-4134
Number of pages12
JournalDiabetes
Volume64
Issue number12
DOIs
StatePublished - Dec 1 2015

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Klein, D., Álvarez-Cubela, S., Lanzoni, G., Vargas, N., Prabakar, K. R., Boulina, M., Ricordi, C., Inverardi, L. A., Pastori, R., & Dominguez-Bendala, J. (2015). BMP-7 induces adult human pancreatic exocrine-to-endocrine conversion. Diabetes, 64(12), 4123-4134. https://doi.org/10.2337/db15-0688