title: Comparing scaffold-free and fibrin-based adipose-derived stromal cell constructs for adipose tissue engineering: an in vitro and in vivo study.
abstract: 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.
authors: Department of Plastic and Reconstructive Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. f.verseijden@erasmusmc.nl
authors: Femke
authors: F
authors: Verseijden
authors: Sandra J
authors: SJ
authors: Posthumus-van Sluijs
authors: Johan W
authors: JW
authors: van Neck
authors: Stefan O P
authors: SO
authors: Hofer
authors: Stevan E R
authors: SE
authors: Hovius
authors: Gerjo J V M
authors: GJ
authors: van Osch
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D043925:Angiogenesis Inducing Agents; D016207:Cytokines; D005337:Fibrin