Abstract 240: Vascular Differentiation of C-kit+ Cardiac Progenitor Cells in Bioactive PEG Hydrogels

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Abstract

Ischemic heart disease is the leading cause of death in the United States. The ideal therapy would include regeneration of functional myocardial cells as well as vascularization of the regenerated cardiac tissue. In this context, c-kit+ cardiac progenitor cells (CPCs) isolated from the heart are an exciting stem cell population as they have been shown to have potential to differentiate into cells of myocardial as well as vascular (endothelial, vascular smooth muscle) lineages. Being an autologous adult stem cell source, they provide advantages of alleviation of immune-rejection and disease transmission risks and are free from ethical concerns. Driving the vascular differentiation of CPCs can enable them to be used for angiogenic cell therapy. The objective of this project is to direct CPCs to the endothelial lineage via stimulation with VEGF immobilized in a PEG-maleimide (PEG-MAL) hydrogel scaffold for better retention of grafted cells. This hydrogel has protease-cleavable sites which should enable the hydrogel to be degraded while allowing for tube formation. CPCs are encapsulated in PEG-MAL hydrogel constructs presenting 100 ng VEGF/mL hydrogel. CPCs encapsulated in these PEG-MAL hydrogels maintain high viability for up to 14 days. In hydrogels presenting immobilized VEGF, successful biochemical stimulation of the encapsulated CPCs is evidenced by downstream ERK phosphorylation, likely through VEGFR2. These immobilized-VEGF treated CPCs also demonstrate greater RNA expression of endothelial markers 7 days post-encapsulation. CPCs in VEGF presenting gels show a trend toward increasing formation of vascular structures in comparison to cells encapsulated in empty hydrogels. Together, this preliminary evidence suggests that c-kit+ cardiac progenitor cells can be driven toward the endothelial lineage when stimulated with immobilized VEGF, and may adapt a vascular phenotype. This system has the potential to be used for therapeutic angiogenesis as the PEG hydrogel scaffold should enable controlled delivery of the CPCs in vivo and is injectable and biodegradable.

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