In Vitro Osteogenic and Chondrogenic Differentiation of Embryonic Stem Cells for Bone and Cartilage Tissue Engineering
Author(s)
Hwang, Yu-Shik
Type
Thesis or dissertation
Abstract
Regeneration of skeletal tissues represents an increasingly promising area of biological repair with a broad spectrum of potential clinical applications. Tissue engineering, which has emerged as a new discipline that amalgamates aspects from biology, engineering, materials science, and medicine, aims to produce functional replacement tissues that can be used to restore damaged ones. Furthermore, in view of the ageing population and the worldwide shortage of donor tissue, tissue engineering and regenerative medicine are expected to alter the practice of modern medicine. Recently, embryonic stem cells (ESCs) have been developed and are considered as potent cell source for skeletal tissue engineering due to several biological advantages. However, although considerable progress to direct ESC differentiation to specific lineages has been made, before ESCs may be used as a suitable cell source in cell and tissue therapy, there are still remaining obstacles which have to be resolved regarding ESC differentiation: 1) the requirement for more efficient methods for increasing the differentiation efficiency to the???? desired cell type together with reducing differentiation to undesired cell types; and 2) the requirement of developing time and cost effective culture systems for controlling ESC differentiation is essential. The overall aim of this thesis was the development of an efficient method to control mesodermal differentiation and enhance osteogenic/chondrogenic differentiation of murine ESCs (mESCs) for application to skeletal tissue engineering. The initial focus of this thesis was the investigation of the effect of the HepG2 conditioned medium on the early differentiation of mESCs to primitive streak/nascent mesoderm-like cells, which could be potent progenitor cells of osteogenic and chondrogenic differentiation. Next, the focus was to investigate the control and enhancement of osteogenic and chondrogenic differentiation from mESC-d~rived primitive streak/nascent mesoderm-like cells by modulating the culture conditions and process. Finally, the focus became the development of efficient bioprocessing for the three-dimensional (3D) osteogenic and chondrogenic differentiation of mESC in alginate hydrogels and the culture in HARV bioreactors for the purpose of achieving 3D bone/cartilage-like tissue formation, resulting in an efficient and reproducible culture system for bone and cartilage tissue engineering applications.
Version
Imperial Users only
Date Issued
2007-01
Online Publication Date
2011-10-10T13:49:46Z
Creator
Hwang, Yu-Shik
Publisher Institution
Imperial College London (University of London)
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)