Wintruba Kaitlyn L, Wolf Matthew J, van Berlo Jop H, Saucerman Jeffrey J
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908 USA.
Division of Cardiovascular Medicine, University of Virginia, Charlottesville, VA 22908 USA.
Curr Treat Options Cardiovasc Med. 2025;27(1):42. doi: 10.1007/s11936-025-01107-0. Epub 2025 Jul 19.
This review explores current advancements in drug discovery for promoting cardiomyocyte proliferation and highlights key challenges in translating these findings to clinical applications.
High-throughput screening platforms, including phenotypic assays using stem cell-derived or neonatal cardiomyocytes, have identified candidate compounds that modulate proliferative signaling pathways. Computational modeling and omics analysis have enabled mechanistic insights and supported the development of targeted drug discovery strategies. Emerging approaches are increasingly incorporating orthogonal screening and cross-species validation to improve translational potential.
While no therapy has yet fully translated beyond pre-clinical models, significant progress has been made in identifying candidate drugs that stimulate cardiomyocyte proliferation in animal models. Translating these findings into effective therapies requires a rigorous foundation in basic research to clarify the molecular mechanisms of cardiac repair and guide drug development.
本综述探讨了促进心肌细胞增殖的药物发现方面的当前进展,并强调了将这些发现转化为临床应用的关键挑战。
高通量筛选平台,包括使用干细胞衍生或新生心肌细胞的表型分析,已鉴定出调节增殖信号通路的候选化合物。计算建模和组学分析有助于深入了解机制,并支持靶向药物发现策略的开发。新兴方法越来越多地纳入正交筛选和跨物种验证,以提高转化潜力。
虽然尚无疗法完全超越临床前模型,但在识别动物模型中刺激心肌细胞增殖的候选药物方面已取得重大进展。将这些发现转化为有效疗法需要在基础研究方面有坚实的基础,以阐明心脏修复的分子机制并指导药物开发。