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Stem Cell Reports. 2018 Mar 13;10(3):712-724. doi: 10.1016/j.stemcr.2018.02.005.

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

Author information

1
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.
2
Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
3
Hubrecht Institute/KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands.
4
Hubrecht Institute/KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands; Wellcome Trust/Cancer Research UK, Gurdon Institute, Cambridge CB2 1QN, UK.
5
Department of Gastroenterology, Keio University, Tokyo 108-8345, Japan.
6
Department of Anatomy and Embryology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
7
Islet Cell & Regenerative Biology, Joslin Diabetes Center, Boston, MA 02215, USA.
8
Beta Cell Neogenesis (BENE), Vrije Universiteit Brussel, 1050 Brussels, Belgium.
9
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.

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 ALDHlo cells. Interestingly, gene expression profiling revealed that ALDHhi 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 ALDHhi 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.

KEYWORDS:

ALDH; beta cells; diabetes; endocrine differentiation; fetal; human; insulin; organoid; pancreas; progenitor

PMID:
29539434
PMCID:
PMC5918840
DOI:
10.1016/j.stemcr.2018.02.005
[Indexed for MEDLINE]
Free PMC Article

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