Abstract 4300: Cells and Cytokines Induce Regeneration after Cardiac Repair with a New Biodegradable Scaffold
Rationale: Following an extensive myocardial infarction (MI), patch repair of the left ventricle can restore function, but cellular engraftment is required for regeneration. Gelfoam (GF) is an ideal scaffold, but lacks strength. Therefore, we modified GF (MGF) to increase its strength, and seeded it with cells and cytokines to produce new tissue and restore ventricular elasticity and function.
Methods: GF was coated with PCL (poly ϵ-caprolactone). Adult rats underwent coronary ligation. Two weeks later, the infarct scar was resected and repaired with (1) GF, (2) MGF, (3) MGF with bone marrow cells (BMSCs; 1×106) suspended in hydrogel (MGF+C) or (4) MGF with BMSCs and SCF/SDF (30ng) in hydrogel (MGF+CC). Hydrogel was also injected into the border around the repair to reverse surgical damage. Sham surgery without patch replacement was performed as a control. Cardiac function was evaluated by echocardiography (periodic) and pressure-volume loop (P-V) analysis (4 weeks after the repair). Cardiac histology and geometry (magnetic resonance imaging; MRI) were also assessed at 4 weeks.
Results: GF animals group died of ventricular rupture. The polymer coating increased mechanical strength and permitted successful repair of the left ventricle. MGF significantly improved cardiac function (p<0.05 compared to the sham group; fractional shorting %: MGF+C=44±2, MGF+CC=43±6, MGF=32±9, Sham=20±5%). The addition of cells and cytokines enhanced healing and further reduced (p<0.05) end-diastolic volumes (MGF+C=198±44, MGF+CC=206±22, MGF=345±62, Sham=357±61 μL). Cells and cytokines also further increased (p<0.05) the number of capillaries (MGF+C=44.8±19.6, MGF+CC =43.5±14.7, MGF=23.5±9.9/mm2) and the area of α-smooth muscle actin (MGF+C=15±2.9, MGF+CC=16.7±6.5, MGF=7.8±5.2 %). MRI demonstrated that cells and cytokines induced an ellipsoid shape of the left ventricle, and maintained greater (p<0.05) wall thickness than MGF alone.
Conclusions: Chemically-modified GF permitted successful repair of the infarcted ventricle. Further, seeding the GF with cells and cytokines supported the engraftment of implanted and recruited cells to facilitate new tissue formation, and improved ventricular remodeling.