VEGF released by deferoxamine preconditioned mesenchymal stem cells seeded on collagen-GAG substrates enhances neovascularization.
Hypoxia preconditioning of mesenchymal stem cells (MSCs) has been shown to promote wound healing through HIF-1α stabilization. Preconditioned MSCs can be applied to three-dimensional biomaterials to further enhance the regenerative properties. While environmentally induced hypoxia has proven difficult in clinical settings, this study compares the wound healing capabilities of adipose derived (Ad) MSCs seeded on a collagen-glycosaminoglycan (GAG) dermal substrate exposed to either environmental hypoxia or FDA approved deferoxamine mesylate (DFO) to stabilize HIF-1α for wound healing. The release of hypoxia related reparative factors by the cells on the collagen-GAG substrate was evaluated to detect if DFO produces results comparable to environmentally induced hypoxia to facilitate optimal clinical settings. VEGF release increased in samples exposed to DFO. While the SDF-1α release was lower in cells exposed to environmental hypoxia in comparison to cells cultured in DFO in vitro. The AdMSC seeded biomaterial was further evaluated in a murine model. The implants where harvested after 1 days for histological, inflammatory, and protein analysis. The application of DFO to the cells could mimic and enhance the wound healing capabilities of environmentally induced hypoxia through VEGF expression and promises a more viable option in clinical settings that is not merely restricted to the laboratory.
Department of Plastic Surgery and Hand Surgery, University Hospital rechts der Isar, Technische Universität München, Munich, 81675, Germany.
Elizabeth A
EA
Wahl
Department of Plastic Surgery and Hand Surgery, University Hospital rechts der Isar, Technische Universität München, Munich, 81675, Germany.
Thilo L
TL
Schenck
Department of Plastic Surgery and Hand Surgery, University Hospital rechts der Isar, Technische Universität München, Munich, 81675, Germany.
Hans-Günther
HG
Machens
Department of Plastic Surgery and Hand Surgery, University Hospital rechts der Isar, Technische Universität München, Munich, 81675, Germany.|Institute for Advanced Study, Technische Universität München, Garching, 85748, Germany.
Elizabeth R
ER
Balmayor
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry; D003470:Culture Media / Q000737:chemistry; D003676:Deferoxamine / Q000494:pharmacology; D005260:Female; D006025:Glycosaminoglycans / Q000737:chemistry; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D008812:Mice, Hairless; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D054457:Tissue Scaffolds / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000502:physiology; D014945:Wound Healing
D003470:Culture Media; D006025:Glycosaminoglycans; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; D003676:Deferoxamine