ABSTRACT
Adipose-derived multipotent stem/progenitor cells (ASPCs) were shown to be ideal candidates for cell-based regenerative therapies. Yet, despite their huge potential, successful clinical applications are still rare. It was suggested that the efficacy of ASPCs at the recipient site depends on the vehicle of cell delivery. In this study, for preparation of a murine critical-size nerve defect model, we assessed the commercially available fibrin gel (ARTISS) as a potential cell carrier. In a thorough in vitro analysis, we investigated cell-fibrin interactions and analyzed the distribution and the long-term behavior of ASPCs cultivated in fibrin gel under normoxic and hypoxic conditions. ASPCs attached to the surface of a thin fibrin layer (two-dimensional condition) and spread with the abundant formation of actin stress fibers. Cells cultured within a fibrin matrix (three-dimensional condition) displayed a uniform distribution and formed interconnected networks while exhibiting strong cell-matrix interactions. Using time-lapse analysis, cells were found to migrate out of the gel and subsequently proliferated robustly both under hypoxic and normoxic conditions. During 14 days of culture in fibrin gel, ASPCs showed high viability, metabolic, and remodeling activities. At the end of the culture period, the fibrin matrix was degraded entirely accompanied by an upregulation of matrix metalloproteinases. In conclusion, fibrin gel stands out as a valuable biomaterial for delivering vital and active cells to damaged tissues. As a direct proof, ASPCs carried in a fibrin matrix will be evaluated in a murine critically sized peripheral nerve repair model.
