| Authors: | 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 |
| Title: | 3D heterogeneous islet organoid generation from human embryonic stem cells using a novel engineered hydrogel platform |
| Type: | Journal Article |
| Publisher: | Biomaterials
|
| Year: | 2018 |
| Volume: | 177 |
| Issue: | |
| Start Page: | 27-39 |
| End Page: | |
| DOI: | 10.1016/j.biomaterials.2018.05.031 |
| WEB-link: | http://www.sciencedirect.com/science/article/pii/S0142961218303740 |
| Abstract: | Organoids, which exhibit spontaneous organ specific organization, function, and multi-cellular complexity, are in essence the inývitro reproduction of specific inývivo 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 inývitro 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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| Keywords: | Islet |
| File: | (3211K) |
