Abstract 138: Thermo-Responsive, Self-Adhesive Injectable Heart Scaffold for Pluripotent Stem Cell-Derived Cardiomyocyte Delivery
Introduction: Regeneration of heart tissue post-infarction is hampered by the limited proliferation of cardiomyocytes. Due to their expandability and pluripotency, human induced pluripotent stem cells (iPSCs) are considered an ideal cell source to produce cardiomyocytes and regenerate heart tissue. However, previous clinical trials revealed the quick loss of injected cells (> 90%) after delivery in aqueous solutions (e.g. phosphate buffered saline, PBS), which significantly limited the clinical outcome. To enhance the retention of cells and promote tissue regeneration, we synthesized a temperature-responsive polymer which is water-soluble to encapsulate cardiomyocytes at room temperature, following injection into epicardium, it quickly forms a gel and holds the cells in situ at body temperature. Functional peptides can be conjugated to this material and facilitate its adhesion to cardiac tissue for optimal cell integration and cardiac regeneration.
Materials and Methods: The polymers monomethoxypoly(ethylene glycol) (mPEG) and poly(ε-caprolactone) (PCL) were copolymerized to produce mPEG-PCL. The polymer was further modified with decorin-derived peptide, which can firmly bind to collagenous tissue. The solution-to-gel transition temperature (Ts) was determined by dissolving the polymer in PBS, slowly increasing the temperature from 4 to 40°C and checking the fluidity of the solution. The viability of cardiomyocytes encapsulated in polymer gel at 37°C for 2 weeks was determined by calcein AM. Peptide-modified polymer solution was injected to the epithelium of adult rat heart. Echocardiography was performed to evaluate the heart functions before and two weeks post injection. The tissue response to this material was studied by histological staining.
Results and Conclusion: The material successfully underwent solution-to-gel transition at 37°C. Human iPSCs-derived cardiomyocytes encapsulated in the gel were still viable after 2 weeks. There was no heart dysfunction 2 weeks post-injection. No significant inflammatory response was induced in vivo. These demonstrate the safety and feasibility of this material to delivery cardiomyocytes to infarct heart.
- © 2013 by American Heart Association, Inc.