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

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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)27-39
Number of pages13
JournalBiomaterials
Volume177
DOIs
StatePublished - Sep 1 2018

Fingerprint

Organoids
Hydrogel
Stem cells
Hydrogels
Stem Cells
Genes
C-Peptide
Pluripotent Stem Cells
Proteins
Peptides
Insulin
Endothelial cells
Glucose
Human Embryonic Stem Cells
Islets of Langerhans
Population
Agglomeration
Extracellular Matrix
Reproduction
Cells

Keywords

  • Aggregation
  • Human embryonic stem cells
  • Hydrogel
  • Islet
  • Organoid
  • Three dimensional

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Candiello, J., Grandhi, T. S. P., Goh, S. K., Vaidya, V., Lemmon-Kishi, M., Eliato, K. R., ... Banerjee, I. (2018). 3D heterogeneous islet organoid generation from human embryonic stem cells using a novel engineered hydrogel platform. Biomaterials, 177, 27-39. https://doi.org/10.1016/j.biomaterials.2018.05.031

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

In: Biomaterials, Vol. 177, 01.09.2018, p. 27-39.

Research output: Contribution to journalArticle

Candiello, J, Grandhi, TSP, Goh, SK, Vaidya, V, Lemmon-Kishi, M, Eliato, KR, Ros, R, Kumta, PN, Rege, K & Banerjee, I 2018, '3D heterogeneous islet organoid generation from human embryonic stem cells using a novel engineered hydrogel platform', Biomaterials, vol. 177, pp. 27-39. https://doi.org/10.1016/j.biomaterials.2018.05.031
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. / 3D heterogeneous islet organoid generation from human embryonic stem cells using a novel engineered hydrogel platform. In: Biomaterials. 2018 ; Vol. 177. pp. 27-39.
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