An Induced Adipocyte Sheet Reduces Inflammatory Reactions During Remodeling of Xenogeneic Scaffolds In Vivo.

Surgical therapy of cardiovascular diseases frequently requires replacement of diseased tissues with prosthetic devices or grafts. Calcification is the main reason for the degeneration of implanted grafts. However, some factors reduce stenosis and attenuate calcification of implanted grafts. In this study, we used an autologous induced adipocyte cell-sheet (IACS) as a drug delivery system to determine whether its secretion ability has a beneficial effect on the remodeling process of grafts in a rat subcutaneous model. IACSs were generated from rat adipose tissue-derived cells that secreted abundant adiponectin (APN), hepatocyte growth factor, and vascular endothelial growth factor in vitro. Two types of grafts were used in the rat subcutaneous model: decellularized and IACS-wrapped decellularized porcine vascular grafts. Transplanted IACSs secreted APN into the decellularized porcine vascular graft in rats at 4 weeks. After explanting from the rat subcutaneous model at 1, 2, 4, and 8 weeks, immunofluorescence staining showed that IACS-wrapped grafts had a dominant M2 phenotype of macrophages (p < 0.001) at all time points and showed constructive remodeling and less calcification at 8 weeks. The decellularized graft showed a predominately CCR7+ cell response (M1 phenotype) (p < 0.001) and was characterized by chronic inflammation and severe calcification at 8 weeks. Furthermore, the IACS-wrapped side of the graft showed less cell infiltration compared with the other side, which may have reduced inflammation in the area. Transplantation of IACSs with a biological scaffold had a profound influence on the macrophage phenotype and downstream remodeling processes. The method might reduce inflammatory reactions during remodeling of xenogeneic scaffolds and result in less calcification.