期刊
STEM CELL REPORTS
卷 10, 期 3, 页码 712-724出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2018.02.005
关键词
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资金
- DON foundation
- Dutch Diabetes Research Foundation
- Tjanka Foundation
- Diabetes Cell Therapy Initiative
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK036836] Funding Source: NIH RePORTER
Generating an unlimited source of human insulin-producing cells is a prerequisite to advance beta 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.
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