A New Model for Specific Visualization of Skin Graft Neoangiogenesis Using Flt1-tdsRed BAC Transgenic Mice
| Autor: | Mizuho Yamato, Mohamed Abdelhakim, Atsushi Sakai, Masatsugu Ema, Teruyuki Dohi, Rei Ogawa, Hiroya Takada, Shigetomo Fukuhara, Hidenori Suzuki |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Genetically modified mouse Bac transgenic Pathology medicine.medical_specialty Intravital Microscopy Transgene Vascular Endothelial Growth Factor Receptor Mice Nude Neovascularization Physiologic Mice Transgenic 030230 surgery Neovascularization Mice 03 medical and health sciences 0302 clinical medicine Cell Movement Genes Reporter medicine Animals Skin Wound Healing Microscopy Confocal Vascular Endothelial Growth Factor Receptor-1 business.industry Graft Survival Endothelial Cells Skin Transplantation Molecular Imaging Transplantation Luminescent Proteins 030220 oncology & carcinogenesis Models Animal Female Surgery medicine.symptom business Reticular Dermis Sprouting |
| Zdroj: | Plastic & Reconstructive Surgery. 148:89-99 |
| ISSN: | 0032-1052 |
| DOI: | 10.1097/prs.0000000000008039 |
| Popis: | BACKGROUND Neovascularization plays a critical role in skin graft survival. Up to date, the lack of specificity to solely track the newly sprouting blood vessels has remained a limiting factor in skin graft transplantation models. Therefore, the authors developed a new model by using Flt1-tdsRed BAC transgenic mice. Flt1 is a vascular endothelial growth factor receptor expressed by sprouting endothelial cells mediating neoangiogenesis. The authors determined whether this model reliably visualizes neovascularization by quantifying tdsRed fluorescence in the graft over 14 days. METHODS Cross-transplantation of two full-thickness 1 × 1-cm dorsal skin grafts was performed between 6- to 8-week-old male Flt1 mice and KSN/Slc nude mice (n = 5). The percentage of graft area occupied by tdsRed fluorescence in the central and lateral areas of the graft on days 3, 5, 9, and 14 was determined using confocal-laser scanning microscopy. RESULTS Flt1+ endothelial cells migrating from the transgenic wound bed into the nude graft were first visible in the reticular dermis of the graft center on day 3 (0.5 ± 0.1; p < 0.05). Peak neovascularization was observed on day 9 in the lateral and central parts, increasing by 2- to 4-fold (4.6 ± 0.8 and 4.2 ± 0.9; p < 0.001). Notably, some limited neoangiogenesis was displayed within the Flt grafts on nude mice, particularly in the center. No neovascularization was observed from the wound margins. CONCLUSION The ability of the Flt1-tdsRed transgenic mouse model to efficiently identify the origin of the skin-graft vasculature and visualize graft neovascularization over time suggests its potential utility for developing techniques that promote graft neovascularization. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|