The paracrine effects of adipose-derived stem cells on neovascularization and biocompatibility of a macroencapsulation device.

The foreign-body response to biomaterials compromises the performance of many biomedical devices by severe fibrosis and limited neovascularization. Mesenchymal stem cells are known to secrete cytokines for treating inflammatory conditions. In this study, we aim to investigate whether the paracrine products of adipose-derived mesenchymal stem cells (ADSCs) can affect the microenvironment of biomaterials and improve tissue responses to biomaterial implants. A model system was built by loading ADSC spheroids into a macroencapsulation device composed of polytetrafluoroethylene (PTFE) filtration membranes. Soluble ADSC factors that diffused out of the device in vitro promoted the angiogenetic activity of endothelial cells and affected the secretion pattern of macrophages. In vivo study was carried out by subcutaneously embedding blank or ADSC-laden devices in rats. Following a 4 week implantation, the ADSC-laden devices were better vascularized and induced significantly less fibrotic tissue formation in comparison to the non-cellular controls. This study may facilitate our understanding of foreign-body responses and suggest new ways to improve the tissue reaction of biomedical devices for cell-based therapy.