(337a) Vascularization of Pancreatic Islet-Mimetic Organoids with Microvessel Fragments
AIChE Annual Meeting
2018
2018 AIChE Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Engineering the Tissue and Cell Microenvironment II: Directing Cell Behavior with Extracellular Cues
Tuesday, October 30, 2018 - 12:30pm to 12:48pm
A critical step for islet organoid engineering is the controlled synthesis of the 3-D spheroid morphology. Our lab has developed methods for engineering controlled 3-D homotypic (same cell type) and heterotypic (different cell types) aggregates from hPSC-derived cells [1]. hPSCs were differentiated towards islet lineage following the protocol reported by Melton et al. [2], which results in predominantly alpha and beta cell phenotype. Subsequently, the intra-islet vascular network were reproduced by aggregating the hPSC-derived islet-like cells with adipose-derived microvessel fragments and stromal cells. The neo-vascular network formation within the islet organoids were found to be sensitive to the culture media as well as the phenotype of the hPSC derived cell population. The resulting vascularized organoids demonstrated enhanced functionality over beta cell aggregates through the gene expression of key pancreatic maturation markers (NKX6.1, PDX1, and INS). Additionally, the intra-organoid vasculature exhibited increased expression of the islet specific endothelial gene, API, along with endothelial diaphragm fenestration indicator, PLVAP, which indicates islet-specific vascular development. With enhanced pancreatic phenotype and functioning vascular network, these organoids will be highly applicable in regenerative therapy for the treatment of type 1 diabetes. Furthermore, we are currently integrating these organoids into in-vitro body-on-chip platform for disease modeling and drug/ toxicity testing.
Ref:
[1] Candiello J, Grandhi TSP, Goh SK, Vaidya V, Lemmon-Kishi M, Kumta PN, Rege K, Banerjeea I. 3D Heterogeneous Islet Organoid Generation from Human Embryonic Stem Cells using a Novel Engineered Hydrogel Platform 2018: submitted.
[2] Pagliuca, F.W.; Millman, J.R.; Guertler, M.; Segel, M.; Dervort, A.V.; Ryu, J.H.; Peterson, Q.P.; Greiner, D.; Melton, D.A. Generation of Functional Human Pancreatic b Cells In Vitro. Cell. 2014, 159, 428-439