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 C 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

doi:10.1016/j.stemcr.2018.02.005

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 C 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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

117 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 ALDHlocells. Interestingly, gene expression profiling revealed that ALDHhicells 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 ALDHhicells formed INS+cells. We conclude that adult human pancreatic tissue has potential for expansion into 3D structures harboring progenitor cells with endocrine differentiation potential.

Original language	English
Pages (from-to)	712-724
Number of pages	13
Journal	Stem Cell Reports
Volume	10
Issue number	3
DOIs	https://doi.org/10.1016/j.stemcr.2018.02.005
Publication status	Published - 13 Mar 2018

Keywords

Journal Article

Access to Document

10.1016/j.stemcr.2018.02.005

Cite this

Loomans, C. J. M., Williams Giuliani, N., Balak, J., Ringnalda, F. C., 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

@article{41c0e56140fc4ab4a047a05b80773389,

title = "Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential",

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 ALDHlocells. Interestingly, gene expression profiling revealed that ALDHhicells 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 ALDHhicells 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 = "Journal Article",

author = "Loomans, {Cindy J M} and {Williams Giuliani}, Nerys and Jeetindra Balak and Ringnalda, {Femke C} and {van Gurp}, L{\'e}on and Meritxell Huch and Boj, {Sylvia F} and Toshiro Sato and Lennart Kester and {de Sousa Lopes}, {Susana M Chuva} and Roost, {Matthias S} and Susan Bonner-Weir and Engelse, {Marten A} and Rabelink, {Ton J} and Harry Heimberg and Vries, {Robert G J} and {van Oudenaarden}, Alexander and Fran{\c c}oise Carlotti and Hans Clevers and {de Koning}, {Eelco J P}",

year = "2018",

month = mar,

day = "13",

doi = "10.1016/j.stemcr.2018.02.005",

language = "English",

volume = "10",

pages = "712--724",

journal = "Stem Cell Reports",

issn = "2213-6711",

publisher = "Cell Press",

number = "3",

}

Loomans, CJM, Williams Giuliani, N, Balak, J, Ringnalda, FC, van Gurp, L, Huch, M, Boj, SF, Sato, T, Kester, L, de Sousa Lopes, SMC, Roost, MS, Bonner-Weir, S, Engelse, MA, Rabelink, TJ, Heimberg, H, Vries, RGJ, van Oudenaarden, A, Carlotti, F, Clevers, H & de Koning, EJP 2018, 'Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential', Stem Cell Reports, vol. 10, no. 3, pp. 712-724. https://doi.org/10.1016/j.stemcr.2018.02.005

TY - JOUR

T1 - Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential

AU - Loomans, Cindy J M

AU - Williams Giuliani, Nerys

AU - Balak, Jeetindra

AU - Ringnalda, Femke C

AU - van Gurp, Léon

AU - Huch, Meritxell

AU - Boj, Sylvia F

AU - Sato, Toshiro

AU - Kester, Lennart

AU - de Sousa Lopes, Susana M Chuva

AU - Roost, Matthias S

AU - Bonner-Weir, Susan

AU - Engelse, Marten A

AU - Rabelink, Ton J

AU - Heimberg, Harry

AU - Vries, Robert G J

AU - van Oudenaarden, Alexander

AU - Carlotti, Françoise

AU - Clevers, Hans

AU - de Koning, Eelco J P

PY - 2018/3/13

Y1 - 2018/3/13

N2 - 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 ALDHlocells. Interestingly, gene expression profiling revealed that ALDHhicells 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 ALDHhicells formed INS+cells. We conclude that adult human pancreatic tissue has potential for expansion into 3D structures harboring progenitor cells with endocrine differentiation potential.

AB - 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 ALDHlocells. Interestingly, gene expression profiling revealed that ALDHhicells 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 ALDHhicells formed INS+cells. We conclude that adult human pancreatic tissue has potential for expansion into 3D structures harboring progenitor cells with endocrine differentiation potential.

KW - Journal Article

U2 - 10.1016/j.stemcr.2018.02.005

DO - 10.1016/j.stemcr.2018.02.005

M3 - Article

C2 - 29539434

SN - 2213-6711

VL - 10

SP - 712

EP - 724

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 3

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this