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

Autor:	Loomans CJM; Hubrecht Institute/KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands; Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands., Williams Giuliani N; Hubrecht Institute/KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands; Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands., Balak J; Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands., Ringnalda F; Hubrecht Institute/KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., van Gurp L; Hubrecht Institute/KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., Huch M; Hubrecht Institute/KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands; Wellcome Trust/Cancer Research UK, Gurdon Institute, Cambridge CB2 1QN, UK., Boj SF; Hubrecht Institute/KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., Sato T; Department of Gastroenterology, Keio University, Tokyo 108-8345, Japan., Kester L; Hubrecht Institute/KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., de Sousa Lopes SMC; Department of Anatomy and Embryology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands., Roost MS; Department of Anatomy and Embryology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands., Bonner-Weir S; Islet Cell & Regenerative Biology, Joslin Diabetes Center, Boston, MA 02215, USA., Engelse MA; Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands., Rabelink TJ; Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands., Heimberg H; Beta Cell Neogenesis (BENE), Vrije Universiteit Brussel, 1050 Brussels, Belgium., Vries RGJ; Hubrecht Institute/KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., van Oudenaarden A; Hubrecht Institute/KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., Carlotti F; Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands., Clevers H; Hubrecht Institute/KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., de Koning EJP; Hubrecht Institute/KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands; Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands. Electronic address: e.koning@hubrecht.eu.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2018 Mar 13; Vol. 10 (3), pp. 712-724.
DOI:	10.1016/j.stemcr.2018.02.005
Abstrakt:	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 (ALDH hi ), express pancreatic progenitors markers (PDX1, PTF1A, CPA1, and MYC), and can form new organoids in contrast to ALDH lo cells. Interestingly, gene expression profiling revealed that ALDH hi cells 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 ALDH hi cells formed INS + cells. We conclude that adult human pancreatic tissue has potential for expansion into 3D structures harboring progenitor cells with endocrine differentiation potential. (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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