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


Type
Article
Change log
Authors
Loomans, Cindy JM 
Williams Giuliani, Nerys 
Balak, Jeetindra 
Ringnalda, Femke 
van Gurp, Léon 
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.

Description
Keywords
ALDH, beta cells, diabetes, endocrine differentiation, fetal, human, insulin, organoid, pancreas, progenitor, Adult, Animals, Cell Differentiation, Cell Proliferation, Humans, Insulin, Insulin-Secreting Cells, Mice, Organoids, Stem Cells
Journal Title
Stem Cell Reports
Conference Name
Journal ISSN
2213-6711
2213-6711
Volume Title
10
Publisher
Elsevier BV