Micro-environmental factors directing differentiation of murine embryonic stem cells down osteogenic and chondrogenic lineages
Date
2013-02-15
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Abstract
The field of bone tissue engineering (BTE) aims to develop graft substitutes for diseased or difficult to heal fractures. We used a BTE construct made of collagen type I and murine embryonic stem cells (mESCs) which has been shown to trigger mESCs differentiation into osteoblasts, and successfully contribute to fracture repair in vivo within a mouse model system.
Bone healing is a complex process involving the interplay of biochemical and biomechanical cues. Therefore, this project aimed to systematically emulate the roles of chemical and mechanical cues present during fracture repair on the differentiation of mESCs in vitro in order to optimize treatment strategies for BTE.
Further characterization of this cell/gel construct revealed that mESCs differentiate into a heterogeneous cell population of chondrocytes and osteoblasts, replicating the process of endochondral ossification that normally occurs during fracture repair. To study the effect of biomechanical cues, a loading system was specifically designed and characterized to apply confined compressive load to a soft, viscoelastic cell/gel construct. Mechanical stimuli enhanced chondrogenic differentiation but had no effect on osteogenic differentiation. Moreover, the role of integrins in directing mESCs differentiation and transducing mechanical signals was evaluated. Finally, the synergistic effect between extracellular matrix mediated differentiation, mechanical stimulation and BMP-2 delivery to the system using nano-particles was studied.
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Engineering--Biomedical
Citation
Hazenbiller, O. (2013). Micro-environmental factors directing differentiation of murine embryonic stem cells down osteogenic and chondrogenic lineages (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/26906