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 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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

106 Citaten (Scopus)

Samenvatting

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. In the context of β cell replacement therapy for diabetes, de Koning and colleagues describe a 3D culture platform that supports ex vivo expansion of human pancreatic tissue as organoids. These organoids harbor a subpopulation of ALDHhi cells that display proliferative capacity and can differentiate to an endocrine fate.

Originele taal-2Engels
Pagina's (van-tot)712-724
Aantal pagina's13
TijdschriftStem Cell Reports
Volume10
Nummer van het tijdschrift3
DOI's
StatusGepubliceerd - 13 mrt. 2018
Extern gepubliceerdJa

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