Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential

Cindy J M Loomans, Nerys Williams Giuliani, Jeetindra Balak, Femke C Ringnalda, Léon van Gurp, Meritxell Huch, Sylvia F Boj, Toshiro Sato, Lennart Kester, Susana M Chuva de Sousa Lopes, Matthias S Roost, Susan Bonner-Weir, Marten A Engelse, Ton J Rabelink, Harry Heimberg, Robert G J Vries, Alexander van Oudenaarden, Françoise Carlotti, Hans Clevers, Eelco J P de Koning

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

Generating an unlimited source of human insulin-producing cells is a prerequisite to advance β cell replacement therapy for diabetes. Here, we describe a 3D culture system that supports the expansion of adult human pancreatic tissue and the generation of a cell subpopulation with progenitor characteristics. These cells display high aldehyde dehydrogenase activity (ALDHhi), express pancreatic progenitors markers (PDX1, PTF1A, CPA1, and MYC), and can form new organoids in contrast to ALDHlocells. Interestingly, gene expression profiling revealed that ALDHhicells are closer to human fetal pancreatic tissue compared with adult pancreatic tissue. Endocrine lineage markers were detected upon in vitro differentiation. Engrafted organoids differentiated toward insulin-positive (INS+) cells, and circulating human C-peptide was detected upon glucose challenge 1 month after transplantation. Engrafted ALDHhicells formed INS+cells. We conclude that adult human pancreatic tissue has potential for expansion into 3D structures harboring progenitor cells with endocrine differentiation potential.

Original languageEnglish
Pages (from-to)712-724
Number of pages13
JournalStem Cell Reports
Volume10
Issue number3
DOIs
Publication statusPublished - 13 Mar 2018

Keywords

  • Journal Article

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