Combination of chemically modified SDF-1 alpha mRNA and small skin improves wound healing in diabetic rats with full-thickness skin defects

CELL PROLIFERATION(2022)

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摘要
Objectives Diabetes mellitus is associated with refractory wound healing, yet current therapies are insufficient to accelerate the process of healing. Recent studies have indicated chemically modified mRNA (modRNA) as a promising therapeutic intervention. The present study aimed to explore the efficacy of small skin engineered to express modified mRNAs encoding the stromal cell-derived factor-1 alpha (SDF-1 alpha) facilitating wound healing in a full-thickness skin defect rat model. This study, devised therapeutic strategies for diabetic wounds by pre-treating small skin with SDF-1 alpha modRNA. Materials and Methods The in vitro transfection efficiency was evaluated using fluorescence microscopy and the content of SDF-1 alpha in the medium was determined using ELISA after the transfection of SDF-1 alpha into the small skin. To evaluate the effect of SDF-1 alpha modRNA and transplantation of the small skin cells on wound healing, an in vivo full-thickness skin defect rat model was assessed. Results The results revealed that a modRNA carrying SDF-1 alpha provided potent wound healing in the small skin lesions reducing reduced scar thickness and greater angiogenesis (CD31) in the subcutaneous layer. The SDF-1 alpha cytokines were significantly secreted by the small skin after transfection in vitro. Conclusions This study demonstrated the benefits of employing small skin combined with SDF-1 alpha modRNA in enhancing wound healing in diabetic rats having full-thickness skin defects.
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