Abstract 145: Microcapsule Delivery of Mesenchymal Stem Cell for Myocardial Regeneration

Following myocardial injury, 1 in 3 patients will have irreversible cardiac damage and develop congestive heart failure. The paracrine factors secreted by mesenchymal stem cells (MSCs) have shown promise in regenerating damaged heart tissue through their pro-angiogenic and anti-inflammatory properties. The beneficial effect of MSCs can be further optimized by their targeted delivery and increased retention within the damaged myocardium. Objective: To develop a novel cell therapy approach which allows direct infusion of encapsulated mesenchymal stem cells into the coronary circulation without compromising cardiac function. Methods: Mesenchymal stem cells were encapsulated into polyethylene glycol (PEG) based microparticles (MPs) using microfluidics technology. These encapsulated MSCs were infused ex vivo into the rat coronaries using retrograde perfusion in a Langendorff - isolated heart setup. Rat hearts infused with fluorescently tagged MPs were imaged using Xtreme Optical imaging (Bruker, MA) to evaluate for MP distribution within the tissue. Frozen sections of the MP infused hearts were evaluated for distribution within the coronary microvasculature. To evaluate cardiac function after iterative MP infusion, pressure volume curves were generated using a Millar catheter and recorded on Powerlab (ADI instruments, Australia). Results: The microfluidics encapsulation process generates microparticles of 30-60 μm diameter with up to 59.7% encapsulation efficiency. Encapsulated MSCs distribute evenly throughout the heart as assessed by whole-organ fluorescence imaging. Systolic function of the rat heart was not compromised when up to 100,000 encapsulated MSCs were infused by retrograde coronary perfusion. Histological sections post infusion showed that the MPs localized to terminal blood vessels as small as 10 μm in diameter, suggesting that these microparticles are compressible and are trapped within small coronary vessels, thereby improving retention. Conclusion: Intra-coronary perfusion of encapsulated MSCs is a viable and promising approach for the delivery of MSCs after myocardial injury.