Influence of Stem Cell Source Gender on Endothelial Cell Differentiation

Open Access
Author:
Oddo, Michael Jack
Area of Honors:
Biomedical Engineering
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Xiaojun Lian, Thesis Supervisor
  • Nanyin Zhang, Honors Advisor
  • Justin Brown, Faculty Reader
Keywords:
  • Stem Cell
  • Endothelial
Abstract:
Essentially all tissues in the body rely on vessels supplying blood for survival. Transportation of this valuable resource would not occur without the highly adaptive lining of squamous endothelial cells known as the endothelium. [1] Their precursors, endothelial progenitor cells or EPCs are of great interest in biology and medicine. EPCs play significant roles in diseases including cancer, diabetes, and cardiovascular disorders. [2] These cells are commonly found peripherally, circulating through the blood stream, prepared to assist in angiogenesis after an ischemic or hypoxic event. This helps prevent further injury. The body’s natural use of EPCs highlights their importance, but as tissue engineering and regenerative medicine race forward, novel realizations of EPC potential are constantly being discovered. This research aims to explain and advance generating EPCs from human embryonic and induced pluripotent stem cells, ESCs and iPSCs respectively. Use of pluripotent stem cells in medicine is of great interest due to their unlimited proliferation capabilities, potentially creating an endless supply of various tissues and disease models. This study describes the development of a method for creating human EPCs from stem cells originating from a female source. It also examines the differences in cell signaling and gene expression that explain why different treatment is required for different cell source genders. Addition of vascular endothelial growth factor, VEGF, to an existing protocol involving temporal activation of the WNT β-Catenin pathway enabled EPC creation, not previously possible from female stem cells. [3] Differential expression of VEGF was identified as a potential source and genetic basis for the differences in stem cells of varying genders during this WNT activation. This protocol was developed and optimized to enable robust production of EPCs from a previously untapped source.