Investigating mesenchymal stem cell therapy for ischemic repair
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Cardiovascular diseases are the leading cause of death globally and continue to be a growing health concern. The currently available therapies are not suitable or effective for all patients, which has prompted investigation into stem cell-based therapies for vascular regeneration and ischemic repair. Clinical trials using stem cell therapy have shown promising outcomes for patients with cardiovascular diseases. However, the mechanisms of repair, and the contribution of stem cells to wound healing, are poorly understood. The objective of this dissertation is to evaluate the use of bone marrow-derived mesenchymal stem cells (MSCs) delivered within a PEGylated fibrin gel for revascularization therapies. Demonstrated in this dissertation is the design of nanoparticle contrast agents which are capable of labeling and tracking stem cells and infiltrating macrophages in vivo. In addition, the effect of hypoxia on MSC function and the resulting interaction with macrophages was studied. Hypoxia was shown to modulate MSCs to have pro-regenerative and angiogenic-promoting properties, which subsequently affected the interaction with macrophages. Lastly, functional recovery and vascular regeneration in an in vivo ischemia model were shown to be enhanced in response to MSCs delivered within PEGylated fibrin gels. The results of this work provide insights into the mechanisms of stem cell therapy in combination with PEGylated fibrin matrices and can contribute to the advancement of the field of regenerative medicine.