ABSTRACT
Regeneration of volume-stable adipose tissue is required for treatment of soft-tissue loss due to cancer, trauma, burns and for correctional cosmetic surgery. In this study, we hypothesized that transplantation of human adipose-derived stromal cells (hADSCs) using polycaprolactone (PCL) scaffolds fabricated with a solid free-form fabrication method would better maintain the volume of regenerated adipose tissues, as compared with the use of fibrin gel. Six weeks after implantation into the dorsal subcutaneous pockets of athymic mice, the volumes and adipose tissue areas of hADSC-PCL scaffold implants were significantly larger than those of hADSC-fibrin implants. In addition, the mRNA expression of adipogenic genes was more extensive in the hADSC-PCL scaffold implants.
Subject(s)
Guided Tissue Regeneration/methods , Lipogenesis , Polyesters , Stromal Cells/transplantation , Subcutaneous Fat/physiology , Tissue Scaffolds , Adipogenesis/genetics , Animals , Cells, Cultured , Female , Fibrin , Genetic Markers , Humans , Lipogenesis/genetics , Mice , Mice, Inbred BALB C , Microscopy, Electron, Scanning , Reverse Transcriptase Polymerase Chain Reaction , Subcutaneous Fat/cytologyABSTRACT
Stem cell transplantation can induce neovascularization. Regenerated blood vessels should remain stable for a long-term period in order to function as new blood vessels in ischemic tissues. Here we show that local delivery of FGF2 enhances the long-term (12weeks) angiogenic efficacy of human adipose-derived stem cells (hADSCs) implanted into mouse ischemic hindlimbs. Following transplantation of hADSCs into ischemic hindlimbs of mice, hADSC viability was significantly higher in the hADSC+FGF2 group at 4 and 12weeks post-transplantation than in the hADSC only group. Furthermore, hADSCs produced higher levels of angiogenic growth factors (i.e., fibroblast growth factor 2, vascular endothelial growth factor, hepatocyte growth factor, and platelet-derived growth factor) at both time points. As a result, the density of arterioles in the ischemic hindlimb muscle was significantly higher in the hADSC+FGF2 group than in either hADSC or FGF2 only group at both time points. The number of arterioles with larger diameters was significantly greater in the hADSC+FGF2 group than in the other groups at 12weeks, and increased in the hADSC+FGF2 group as the time period increased from 4weeks to 12weeks post-transplantation. This suggests that FGF2 delivery to hADSC transplantation sites enhances long-term angiogenic efficacy of hADSCs transplanted into ischemic tissues.
Subject(s)
Adipose Tissue/cytology , Fibroblast Growth Factors/administration & dosage , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/cytology , Neovascularization, Physiologic/physiology , Animals , Arterioles/drug effects , Arterioles/pathology , Biomarkers/metabolism , Cell Survival , Cells, Cultured , Female , Fibroblast Growth Factors/metabolism , Hindlimb/pathology , Ischemia/therapy , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/ultrastructure , Mice , Mice, Nude , Microscopy, Electron, Scanning , Muscles/blood supply , Muscles/pathology , Transplantation, HeterologousABSTRACT
Implantation of chondrocytes isolated from patients and expanded in number in vitro is being used to treat patients with cartilage injuries. However, chondrocytes de-differentiate during culture with several passages, and cartilage regenerated by implantation of de-differentiated chondrocytes may be suboptimal. Here, we show that a spinner-flask culture system induces formation of chondrocyte aggregates and redifferentiate de-differentiated chondrocytes. Spinner-flask cultures induced the aggregate formation of chondrocytes with passage 1 or 4. Importantly, spinner-flask cultures induced redifferentiation of the de-differentiated chondrocytes, as type I collagen expression was significantly lower and type II collagen expression was significantly higher in spinner flask-cultured chondrocytes than in monolayer-cultured chondrocytes. This system is easily scalable and could be feasible for clinical setting.
