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

Research output: Contribution to journalArticle

36 Citations (Scopus)

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. 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.

Original languageEnglish
Pages (from-to)712-724
Number of pages13
JournalStem cell reports
Volume10
Issue number3
DOIs
Publication statusPublished - 2018 Mar 13

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Loomans, C. J. M., Williams Giuliani, N., Balak, J., Ringnalda, F., van Gurp, L., Huch, M., Boj, S. F., Sato, T., Kester, L., de Sousa Lopes, S. M. C., Roost, M. S., Bonner-Weir, S., Engelse, M. A., Rabelink, T. J., Heimberg, H., Vries, R. G. J., van Oudenaarden, A., Carlotti, F., Clevers, H., & de Koning, E. J. P. (2018). Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential. Stem cell reports, 10(3), 712-724. https://doi.org/10.1016/j.stemcr.2018.02.005