Cited by 146Pancreatic function and diabetesTissue Engineering and Regenerative MedicinePluripotent Stem Cells Research

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3D heterogeneous islet organoid generation from human embryonic stem cells using a novel engineered hydrogel platform

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Candiello, Joseph, Grandhi, Taraka Sai Pavan, Goh, Saik Kia, Vaidya, Vimal, Lemmon-Kishi, Maya, Eliato, Kiarash Rahmani, Ros, Robert, Kumta, Prashant N., Rege, Kaushal, Banerjee, Ipsita·2018·Biomaterials

DOI 10.1016/j.biomaterials.2018.05.031

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Abstract

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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Self-citation
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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: Grandhi, Taraka Sai Pavan
Lemmon-Kishi, Maya
Ros, Robert
Kumta, Prashant N.
Rege, Kaushal
Banerjee, Ipsita
Venue: Biomaterials
Publisher: Elsevier BV
Published: 2018-09
Volume: 177
Pages: 27-39
ISSN: 0142-9612 (ISSN-L)
DOI: 10.1016/j.biomaterials.2018.05.031
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (am, 277 d)
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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3D heterogeneous islet organoid generation from human embryonic stem cells using a novel engineered hydrogel platform

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