多机制协同调控成纤维细胞重编程的瘢痕治疗转化路径
Translational Pathways for Scar Treatment with Multiple Mechanisms Synergistically Regulating Fibroblast Reprogramming
摘要: 基于成纤维细胞重编程的瘢痕治疗研究已形成从机制解析到临床转化的完整链条。本综述阐明瘢痕形成的核心机制在于TGF-β1信号驱动的肌成纤维细胞转分化与ECM硬化正反馈循环，并受免疫微环境双向调节。在调控层面，表观遗传修饰、代谢重编程(糖酵解/脂质合成)共同决定细胞命运。治疗策略整合靶向干预与创新递送系统：非编码RNA调控、小分子协同药物(TiT/CRFVPTM)及光响应水凝胶等智能载体实现时序控释，联合疗法显著提升抗纤维化效能。当前仍需突破细胞身份认知局限、衰老表观屏障及基因编辑风险，未来融合单细胞解析与智能材料递送将加速转化进程。
Abstract: Research on scar therapy, grounded in the field of fibroblast reprogramming, has established a comprehensive framework encompassing mechanism analysis and clinical translation. This review elucidates that the core mechanism of scar formation lies in a positive feedback loop of myofibroblast transdifferentiation and ECM sclerosis driven by TGF-β1 signaling and regulated by the immune microenvironment in both directions. At the regulatory level, epigenetic modifications and metabolic reprogramming (glycolysis/lipid synthesis) work in concert to determine cell fate. Therapeutic strategies have been developed that integrate targeted interventions with innovative delivery systems, including non-coding RNA modulation, small molecule synergistic drugs (TiT/CRFVPTM), and smart carriers such as light-responsive hydrogels to achieve sequential controlled release. The combination of therapies has been shown to dramatically improve antifibrotic efficacy. Presently, there is an ongoing need to overcome the limitations of cell identity recognition, aging, epigenetic barriers, and gene editing risks. The integration of single-cell analysis and smart material delivery will accelerate the translational process in the future.
文章引用：段智欢. 多机制协同调控成纤维细胞重编程的瘢痕治疗转化路径[J]. 临床医学进展, 2025, 15(10): 1041-1048. https://doi.org/10.12677/acm.2025.15102853

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