Abstract 2060: Enhanced in situ Recellularization by Fibronectin and Stromal Cell Derived Factor-1alpha Coating of Heart Valves Acquires a Quasi-Native Valve Composition of Cell Phenotypes.
Spontaneous recellularization of bioprosthetic valves is limited and characterized by cellular phenotypes distinctly different from those of native valves. To recellularize by in situ attraction of appropriate circulating cells, valves constructed from slowly degradable photooxidized pericardium were coated with fibronectin (800μg FN) in combination with stromal cell derived factor 1α (80μg FN-SDF; n=7) and implanted in pulmonary position in sheep for 5 months. Uncoated (C: n=8) and FN coated (n=6) valves served as controls. All valves functioned normally (echocardiography at 3 & 5 months). Recellularization of coated valves (cells/valve section: 4682±1715 in control vs. 6940±1917 (p=.020) in FN and 7032±2839 (p=.094) in FN-SDF) was increased to values within the range of native valves (7482±2863). In coated valves, the majority of interstitial cells were vimentin+ (69±13 % in FN, 58±11 % in FN-SDF vs. 47±15 % in C). In FN-SDF coated valves the ASMA+ (9±4 %) and desmin+ (5±3 %) fraction was significantly lower than in FN (resp. 25±10 & 11±2 %; p=.008) or C (resp. 39±16 %; p<.001 & 6±8%; NS) valves and emulating the interstitial cells of native valves (resp. 1±1 & 0±0 %). Smoothelin+ or heavy chain myosin+ cells were scarce to absent in all groups and no difference in endothelialization (eNOS+) was observed. Because the SDF-receptor is expressed by many inflammatory cells we stained for CD45 (leukocytes) and CD11b (macrophages). The CD45+ fraction in FN (23±17 %) or FN-SDF (16±9 %) equaled controls (16±8 %), but CD11b+ fraction was less in FN-SDF valves (3±3 %) than in controls (9±8 %; p=.029). No differences in leaflet thickness, stiffness and strength were found. Compared to unimplanted material (26±9 N), force at breakage was decreased in controls (15±7 N; p=.004) but preserved in the FN-SDF group (30±13 N). Recellularization induced by FN-SDF coating resulted in less contractile cell phenotypes, a quasi-native valve interstitial cell composition. Although leucocytes are still present, the macrophage fraction was low. Nevertheless the biomechanical properties were perfectly preserved.