Encapsulation as a 3D model for human embryonic stem cell propagation and differentiation
type: CreativeWork
description: Type 1 diabetes is a chronic disease caused by the destruction of the beta cells of the pancreas. Current treatments for are whole pancreas or islet transplantation, which is limited by scarcity of cadaveric pancreata. Therefore, developing a cell replacement therapy with renewable sources of surrogate beta cells is essential. Human embryonic stem cells (hESCs) have an indefinite replication capacity and can be directed to differentiate into many types of specialized cells. Currently, efficient protocols to generate beta cells rely on a step-wise ontogenic approach which mimics the in vivo pancreatic development. This approach requires a three dimensional (3D) culture system that can induce cell-cell and cell-matrix interactions which are essential for functional maturation. This project investigated the use of cell encapsulation technology to maintain hESC propagation and enhance their differentiation into beta cells in a 3D system. This system also offers potential for immune-isolation and prevention of teratoma formation by hESCs during transplantation. For the first time conditions were optimized for encapsulation of single cell population of the hESCs in alginate microcapsules with an extended proliferation. A 5-stage ontogeny-based protocol for differentiation to beta cells was then applied to these cells. Encapsulated hESCs were successfully differentiated into definitive endoderm (DE); however, this 3D model was not efficient to derive functional beta cells due to low cell viability maintained during the latter differentiation stages. To enhance this differentiation process, further investigation was performed by using glucagon-like peptide-1 (GLP-1) which has been shown to stimulate differentiation of stem and progenitor cells to an endocrine phenotype, induce insulin expression and prevent beta cell apoptosis. The present study demonstrated that undifferentiated and differentiated hESCs expressed GLP-1 receptor (GLP-1R). Attempts were made by supplementing…
abstract: Type 1 diabetes is a chronic disease caused by the destruction of the beta cells of the pancreas. Current treatments for are whole pancreas or islet transplantation, which is limited by scarcity of cadaveric pancreata. Therefore, developing a cell replacement therapy with renewable sources of surrogate beta cells is essential. Human embryonic stem cells (hESCs) have an indefinite replication capacity and can be directed to differentiate into many types of specialized cells. Currently, efficient protocols to generate beta cells rely on a step-wise ontogenic approach which mimics the in vivo pancreatic development. This approach requires a three dimensional (3D) culture system that can induce cell-cell and cell-matrix interactions which are essential for functional maturation. This project investigated the use of cell encapsulation technology to maintain hESC propagation and enhance their differentiation into beta cells in a 3D system. This system also offers potential for immune-isolation and prevention of teratoma formation by hESCs during transplantation. For the first time conditions were optimized for encapsulation of single cell population of the hESCs in alginate microcapsules with an extended proliferation. A 5-stage ontogeny-based protocol for differentiation to beta cells was then applied to these cells. Encapsulated hESCs were successfully differentiated into definitive endoderm (DE); however, this 3D model was not efficient to derive functional beta cells due to low cell viability maintained during the latter differentiation stages. To enhance this differentiation process, further investigation was performed by using glucagon-like peptide-1 (GLP-1) which has been shown to stimulate differentiation of stem and progenitor cells to an endocrine phenotype, induce insulin expression and prevent beta cell apoptosis. The present study demonstrated that undifferentiated and differentiated hESCs expressed GLP-1 receptor (GLP-1R). Attempts were made by supplementing…
author: Chayosumrit, Methichit
language: EN
keywords: Type 1 diabetes, treatment, Pancreas
license: https://purl.org/coar/access_right/c_abf2
license: https://creativecommons.org/licenses/by-nc-nd/3.0/au/
date published: 2010
date modified: 2026-07-24T05:32:27Z
provider: University of New South Wales
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: UNSW, Sydney

PropertyValue
property ID: Handle
value: http://hdl.handle.net/1959.4/45355

PropertyValue
property ID: DOI
value: 10.26190/unsworks/23160