Comparing Scaffold-Free and Fibrin-Based Adipose-Derived Stromal Cell Constructs for Adipose Tissue Engineering: An In Vitro and In Vivo Study

Success of adipose tissue engineering for soft tissue repair has been limited by insufficient adipogenic differentiation, an unfavorable host response, and insufficient vascularization. In this study, we examined how scaffold-free spheroid and fibrin-based environments impact these parameters in human adipose-derived stromal cell (ASC)-based adipose constructs. ASCs were differentiated in spheroids or fibrin-based constructs. After 7 days, conditioned medium was collected and spheroids/fibrin-based constructs were either harvested or implanted subcutaneously in athymic mice. Following 7 days of implantation, the number of blood vessels in fibrin-based constructs was significantly higher than in spheroids (93 +/- 45 vs. 23 +/- 11 vessels/mm(2)) and the inflammatory response to fibrin-based constructs was less severe. The reasons for these results were investigated further in vitro. We found that ASCs in fibrin-based constructs secreted significantly higher levels of the angiogenic factors VEGF and HGF and lower levels of the inflammatory cytokine IL-8. Furthermore, ASCs in fibrin-based constructs secreted significantly higher levels of leptin and showed a 2.5-fold upregulation of the adipogenic transcription factor PPARG and a fourfold to fivefold upregulation of the adipocyte-specific markers FABP4, perilipin, and leptin. These results indicate that fibrin-based ASC constructs are potentially more suitable for ASC-based adipose tissue reconstruction than scaffold-free spheroids.