Publication Date
2018
Document Type
Thesis
Committee Members
Katherine Excoffon (Committee Co-Chair) Jaime E. Ramirez-Vick (Committee Co-Chair), Barbara Hull (Committee Member), Shulin Ju (Committee Member)
Degree Name
Master of Science (MS)
Abstract
Mesenchymal stem cells (MSCs) are adult multipotent stem cell that can differentiate into mesodermal lineages such osteoblast, adipocytes, and chondrocytes, or can be transdifferentiated into clinically relevant lineages such as cardiac or neural cells using in vitro reprogramming techniques. In addition to the multilineage differentiation potential, MSCs from most tissue origins such bone marrow derived mesenchymal stem cells (BM-MSCs) or adipose derived mesenchymal stem cells (AD-MSCs) have immune modulatory functions which indicate their promise in clinical applications for cell-based therapy, tissue engineering, and regenerative medicine. In recent years, three-dimensional (3D) cell culture systems, which utilize 3D scaffolds or hydrogels to provide a physiological 3D microenvironment that mimics the native extracellular matrix, have been largely embraced to study cellular function and cell fate determination using different cell types. Although many investigators have shown that stem cell self-renewal/differentiation is modulated by the 3D scaffold chemistry and/or its surface topology, less attention has been given to undercover how such 3D scaffold affects chromatin organization and gene expression of key developmental regulators or lineage specifiers at the transcription and translation level during the course of stem cell differentiation. In this novel study, we have established a Corning PuraMatrix Peptide Hydrogel based 3D culture system for BM-MSCs and have analyzed key transcription factors regulating osteogenic (RUNX2, OSX, TWIST1) and adipogenic (PPARy, C/EBPa, CHOP10) differentiation of BM-MSCs grown in a 2D culture and a PuraMatrix peptide hydrogel-based 3D culture. BM-MSCs adopt a completely different morphology and metabolism when encapsulated in PuraMatrix peptide hydrogel. Moreover, expression of these key osteogenic (RUNX2, OSX, TWIST1) and adipogenic (PPARy, C/EBPa, CHOP10) transcription factors are differentially expressed between 2D and 3D culture system at different stages of BM-MSCs differentiation.
Page Count
113
Department or Program
Department of Biological Sciences
Year Degree Awarded
2018
Copyright
Copyright 2018, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.
