Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China.
Cell Prolif. 2022 Dec;55(12):e13318. doi: 10.1111/cpr.13318. Epub 2022 Aug 6.
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-1α (SDF-1α) 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-1α modRNA.
The in vitro transfection efficiency was evaluated using fluorescence microscopy and the content of SDF-1α in the medium was determined using ELISA after the transfection of SDF-1α into the small skin. To evaluate the effect of SDF-1α modRNA and transplantation of the small skin cells on wound healing, an in vivo full-thickness skin defect rat model was assessed.
The results revealed that a modRNA carrying SDF-1α provided potent wound healing in the small skin lesions reducing reduced scar thickness and greater angiogenesis (CD31) in the subcutaneous layer. The SDF-1α cytokines were significantly secreted by the small skin after transfection in vitro.
This study demonstrated the benefits of employing small skin combined with SDF-1α modRNA in enhancing wound healing in diabetic rats having full-thickness skin defects.
糖尿病与难治性伤口愈合有关,但目前的治疗方法不足以加速愈合过程。最近的研究表明,化学修饰的 mRNA(modRNA)是一种很有前途的治疗干预手段。本研究旨在探讨经工程化设计的小型皮肤表达修饰的 mRNAs 编码基质细胞衍生因子-1α(SDF-1α),以促进全层皮肤缺损大鼠模型中伤口愈合的疗效。本研究通过用 SDF-1α modRNA 预处理小型皮肤,为糖尿病伤口制定了治疗策略。
通过荧光显微镜评估 SDF-1α 转染小型皮肤后的转染效率,并通过 ELISA 测定转染后 SDF-1α 在培养基中的含量。为了评估 SDF-1α modRNA 和小型皮肤细胞移植对伤口愈合的影响,评估了体内全层皮肤缺损大鼠模型。
结果表明,携带 SDF-1α 的 modRNA 可有效治疗小型皮肤损伤,减少疤痕厚度,增加皮下层的血管生成(CD31)。体外转染后,小型皮肤中明显分泌了 SDF-1α 细胞因子。
本研究表明,在糖尿病大鼠全层皮肤缺损模型中,使用小型皮肤联合 SDF-1α modRNA 可增强伤口愈合。