Fragmin/protamine microparticles as cell carriers to enhance viability of adipose‐derived stromal cells and their subsequent effect on in vivo neovascularization

We prepared fragmin/protamine microparticles (F/P MPs) as cell carriers to enhance cell viability. Use of material consisting of a low‐molecular‐weight heparin (fragmin) mixed with protamine resulted in water‐insoluble microparticles (about 0.5–1 μm in diameter). In this study, we investigated the capability of F/P MPs to enhance the viabilities of human microvascular endothelial cells (HMVECs), human dermal fibroblasts (fibroblasts), and adipose tissue‐derived stromal cells (ATSCs) in suspension culture. F/P MPs were bound to the surfaces of these cells, and the interaction of these cells with F/P MPs induced cells/F/P MPs‐aggregate formations in vitro , and maintained viabilities of those cells for at least 3 days. The ATSCs/F/P MPs‐aggregates adhered to and grew on suspension culture plates in a fashion similar to those on type I collagen‐coated plates. The cultured ATSCs secreted significant amounts of angiogenic heparin‐binding growth factors such as FGF‐2. When the ATSCs/F/P MPs‐aggregates were subcutaneously injected into the back of nude mice, significant neovascularization and fibrous tissue formation were induced near the site of injection from day 3 to week 2. The ATSCs/F/P MPs‐aggregates were thus useful and convenient biomaterials for cell‐therapy of angiogenesis. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010