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.
“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]
Stiffer Amikagel gels drove pancreatic progenitor cells to aggregate, leading to increased differentiation and maturation into beta-like cells.
“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]
Cell viability in Amikagel was no more than five days.
“attendant consequences of cell viability of no more than five days.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [175]
The smallest cell aggregates reported by the authors were ca. 200 microns in diameter; the typical human islet has a diameter of ca. 130 microns.
“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]
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 organoids.
“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]
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- 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 › Surgery › 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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