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3D heterogeneous islet organoid generation from human embryonic stem cells using a novel engineered hydrogel platform
Open accessAbstract
Organoids, which exhibit spontaneous organ specific organization, function, and multi-cellular complexity, are in essence the in vitro reproduction of specific in vivo organ systems. Recent work has demonstrated human pluripotent stem cells (hPSCs) as a viable regenerative cell source for tissue-specific organoid engineering. This is especially relevant for engineering islet organoids, due to the recent advances in generating functional beta-like cells from human pluripotent stem cells. In this study, we report specific engineering of regenerative islet organoids of precise size and cellular heterogeneity, using a novel hydrogel system, Amikagel. Amikagel facilitated controlled and spontaneous aggregation of human embryonic stem cell derived pancreatic progenitor cells (hESC-PP) into robust homogeneous spheroids. This platform further allowed fine control over the integration of multiple cell populations to produce heterogeneous spheroids, which is a necessity for complex organoid engineering. Amikagel induced hESC-PP spheroid formation enhanced pancreatic islet-specific Pdx-1 and NKX6.1 gene and protein expression, while also increasing the percentage of committed population. hESC-PP spheroids were further induced towards mature beta-like cells which demonstrated increased Beta-cell specific INS1 gene and C-peptide protein expression along with functional insulin production in response to in vitro glucose challenge. Further integration of hESC-PP with biologically relevant supporting endothelial cells resulted in multicellular organoids which demonstrated spontaneous maturation towards islet-specific INS1 gene and C-peptide protein expression along with a significantly developed extracellular matrix support system. These findings establish Amikagel -facilitated platform ideal for islet organoid engineering.
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“Compared to cells grown in Matrigel, beta-like cells grown in Amikagel produced higher levels of functional beta-cell markers PDX1 and NKX6.1 and were more responsive to a glucose challenge.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [175]
In the citing paper
“The authors found that stiffer gels drove pancreatic progenitor cells to aggregate, leading to increased differentiation and maturation into beta-like cells;”
From Towards organoid culture without Matrigel (2021) · cites this paper as [175]
In the citing paper
“attendant consequences of cell viability of no more than five days.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [175]
In the citing paper
“The smallest cell aggregates reported by the authors were ca. 200 microns in diameter; the typical human islet has a diameter of ca. 130 microns176.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [175]
In the citing paper
“To our knowledge, Candiello and colleagues were the first group to use a synthetic hydrogel, amikacin hydrate crosslinked with poly(ethylene glycol) diglycidyl ether known as Amikagel, to culture hESC-derived islet organoids175.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [175]
Citations
Cites
Ueber die Berührung fester elastischer Körper.
Hertz, H. G. (1882) · Journal für die reine und angewandte Mathematik (Crelles Journal) · doi:10.1515/crll.1882.92.156 · Cited by 7,182
Cerebral organoids model human brain development and microcephaly
Lancaster, M. A., Renner, M., Martin, C.-A., Wenzel, D., Bicknell, L. S., Hurles, M. E., Homfray, T., Penninger, J. M., Jackson, A. P., & Knoblich, J. A. (2013) · Nature · doi:10.1038/nature12517 · Cited by 5,372
Calibration of atomic-force microscope tips
Hutter, J. L., & Bechhoefer, J. (1993) · Review of Scientific Instruments · doi:10.1063/1.1143970 · Cited by 4,205
On the Contact of Elastic Solids
Hertz (1882) · Journal für die reine und angewandte Mathematik (Crelles Journal) · Cited by 3,051
Organogenesis in a dish: Modeling development and disease using organoid technologies
Lancaster, M. A., & Knoblich, J. A. (2014) · Science · doi:10.1126/science.1247125 · Cited by 2,931
Vascularized and functional human liver from an iPSC-derived organ bud transplant
Takebe, T., Sekine, K., Enomura, M., Koike, H., Kimura, M., Ogaeri, T., Zhang, R.-R., Ueno, Y., Zheng, Y.-W., Koike, N., et al. (2013) · Nature · doi:10.1038/nature12271 · Cited by 2,170
A practical guide to hydrogels for cell culture
Caliari, S. R., & Burdick, J. A. (2016) · Nature Methods · doi:10.1038/nmeth.3839 · Cited by 2,075
Generation of Functional Human Pancreatic β Cells In Vitro
Pagliuca, F. W., Millman, J. R., Gürtler, M., Segel, M., Van Dervort, A., Ryu, J. H., Peterson, Q. P., Greiner, D., & Melton, D. A. (2014) · Cell · doi:10.1016/j.cell.2014.09.040 · Cited by 2,025
Production of pancreatic hormone–expressing endocrine cells from human embryonic stem cells
D’Amour, K. A., Bang, A. G., Eliazer, S., Kelly, O., Agulnick, A. D., Smart, N. G., Moorman, M. A., KROON, E. J., Carpenter, M. K., & Baetge, E. E. (2006) · Nature Biotechnology · doi:10.1038/nbt1259 · Cited by 1,913
Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro
Spence, J. R., Mayhew, C. N., Rankin, S. A., Kuhar, M. F., Vallance, J. E., Tolle, K. A., Hoskins, E. E., Kalinichenko, V. V., Wells, S. I., Zorn, A. M., et al. (2010) · Nature · doi:10.1038/nature09691 · Cited by 1,911
Research works printed but not linked: 1
- Jaramillo, 2015, Endothelial cells mediate islet-specific maturation of human embryonic stem cell-derived pancreatic progenitor cells, Tissue Eng. A, 21, 14, 10.1089/ten.tea.2014.0013 · DOI
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Jabri, A., Alsharif, M., Taftafa, B., Abbad, T., Sibai, D., Mhannayeh, A., Elsalti, A., Saadeldin, I. M., Salma, J., Mir, T. A., et al. (2026) · Bioengineering · doi:10.3390/bioengineering13040478 · Cited by 2
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Wei, Q., Quan, Y., Gao, Y., Zhang, Y., Song, S., Lu, D., & Xu, R. (2026) · Biomacromolecules · doi:10.1021/acs.biomac.6c01538
Poklar, M., Parlow, E., Ravikumar, K., Lingenfelter, N., Stump, M., Barnes, E., Kutzer, L., Liu, W., Dai, J., McCarthy, L., et al. (2026) · Biofabrication · doi:10.1088/1758-5090/aeae75
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Metadata
- Authors
- Candiello, J., Grandhi, T. S. P., Goh, S. K., Vaidya, V., Lemmon-Kishi, M., Eliato, K. R., Ros, R., Kumta, P. N., Rege, K., & Banerjee, I.
- Affiliations
- University of Pittsburgh (US)
- Arizona State University (US)
- Corresponding author
- Banerjee, Ipsita
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 177
- Pages
- 27-39
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2804037024
- Cited by
- 146
- References
- 64
- Citations by year
- 2026: 7 · 2025: 21 · 2024: 11 · 2023: 19 · 2022: 17 · 2021: 27 · 2020: 20 · 2019: 17 · 2018: 7
- FWCI
- 18.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biomaterials (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- NSF EAGER (1547618)
- NSF CBET (1706674)
- Swanson School of Engineering, University of Pittsburgh
- NSF (0933153, 1510700)
- NIH/NIGMS (1R01GM093229-01A1)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- islet organoids, human embryonic stem cells, hydrogel scaffolds, pancreatic progenitor cells, beta-like cells, insulin production, PDX1, NKX6.1, Ins1, C-peptide, endothelial cells, extracellular matrix, spheroid formation
- MeSH terms
- Human Embryonic Stem Cells, Biocompatible Materials, Cell Aggregation, Cell Line, Humans, Islets of Langerhans, Organoids, Spheroids, Cellular, Hydrogels, Tissue Engineering, Insulin-Secreting Cells, Tissue Scaffolds
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