An Investigation Into The Nanofiber-induced Epigenetic Changes In Mesenchymal Stem Cells

Open Access
Author:
Swatski, Matthew David
Area of Honors:
Biomedical Engineering
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Justin Lee Brown, Thesis Supervisor
  • William O Hancock, Honors Advisor
  • Jian Yang, Faculty Reader
Keywords:
  • epigenetics
  • nanofibers
  • PMMA
  • biomaterials
  • regenerative medicine
  • stem cells
  • tissue engineering
  • biomedical engineering
Abstract:
Substrates, such as microgrooves and nanofibers that attempt to mimic the extracellular matrix, have been shown to direct the differentiation of mesenchymal stem cells (MSC). The shape, aspect ratio, and curvature of the substrate are all factors that can direct MSC differentiation toward a specific lineage. The diameters of the nanofibers have been shown to play a role in directing differentiation. However, the mechanism by which this occurs is still unclear. This study proposes that one of these mechanisms is the epigenetic modification of the histone H3 protein. The acetylation of the histone H3 protein expedites transcription of the DNA, while methylation may turn specific genes “on” or “off”. In this study, mesenchymal stem cells are seeded onto PMMA nanofibers, and the epigenetic proteins of dimethylated H3 K9, dimethylated H3 K4, acetylated H3 K9/K14, total acetylated H3, and Erk1/2 were examined. The PMMA Nanofibers were created by electrospinning a solution of 30% m/v PMMA in nitromethane onto a T-Glase scaffold. The fibers are relatively aligned and their diameter is approximately 3.38  0.53 m. There was a statistically significant decrease in the dimethylated H3 K9, the dimethylated H3 K4, and Erk1/2 expression. There was a significantly increase in the total acetylated H3. The changes in these epigenetic proteins point to a signaling response that is caused by the cells interacting with nanofiber scaffolds. The investigations also examined whether these epigenetic responses are heritable. The cells were found to maintain some of these modifications following removal from the PMMA nanofibers and placement onto a flat control surface.