In vivo migration of mesenchymal stem cells to burn injury sites and their therapeutic effects in a living mouse model

• Published in: Journal of controlled release 2018-06, Vol.279, p.79-88
• Main Authors: Oh, Eun Jung, Lee, Ho Won, Kalimuthu, Senthilkumar, Kim, Tae Jung, Kim, Hyun Mi, Baek, Se Hwan, Zhu, Liya, Oh, Ji Min, Son, Seung Hyun, Chung, Ho Yun, Ahn, Byeong-Cheol
• Format: Article
• Language: English
• Subjects: Animals; Bioluminescence imaging (BLI); Blotting, Western; Burn injury; Burns - genetics; Burns - therapy; Cell Movement - physiology; Disease Models, Animal; Green Fluorescent Proteins - genetics; In vivo cell tracking; Luciferases, Firefly - genetics; Luminescent Measurements; Male; Mesenchymal stem cell (MSC); Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stem Cells - cytology; Mice; Mice, Inbred C57BL; Molecular imaging; Neovascularization, Physiologic - genetics; Skin - injuries; Time Factors; Transforming Growth Factor beta1 - genetics; Vascular Endothelial Growth Factor A - genetics; Wound Healing - genetics
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2018.04.020

Mesenchymal stem cell (MSC)-based therapy has emerged as a promising therapeutic strategy for tissue regeneration and repair. In this study, we non-invasively monitored the tracking of MSCs toward burn injury sites using MSCs expressing firefly luciferase (Fluc) gene in living mice, and evaluated the effects of the MSCs at the injury site. Murine MSCs co-expressing Fluc and green fluorescent protein (GFP) were established using a retroviral system (referred to as MSC/Fluc). To evaluate the ability of MSC migration toward burn injury sites, cutaneous burn injury was induced in the dorsal skin of mice. MSC/Fluc was intravenously administrated into the mice model and bioluminescence imaging (BLI) was performed to monitor MSC tracking at designated time points. BLI signals of MSC/Fluc appeared in burn injury lesions at 4 days after the cell injection and then gradually decreased. Immunoblotting analysis was conducted to determine the expression of neovascularization-related genes such as TGF-β1 and VEGF in burnt skin. The levels of TGF-β1 and VEGF were higher in the MSC/Fluc-treated group than in the burn injury group. Our observations suggested that MSCs might assist burn wound healing and that MSCs expressing Fluc could be a useful tool for optimizing MSC-based therapeutic strategies for burn wound healing. [Display omitted]