The rapid advancement of cell therapies underscores the importance of understanding fundamental cellular attributes. Among these, cell fitness—how transplanted cells adapt to new microenvironments and maintain functional stability in vivo—is crucial. This study identifies a chemical compound, FPH2, that enhances the fitness of human chondrocytes and the repair of articular cartilage, which is typically nonregenerative. Through drug screening, FPH2 was shown to broadly improve cell performance, especially in maintaining chondrocyte phenotype and enhancing migration. Single-cell transcriptomics indicated that FPH2 induced a super-fit cell state. The mechanism primarily involves the inhibition of carnitine palmitoyl transferase I and the optimization of metabolic homeostasis. In animal models, FPH2-treated human chondrocytes substantially improved cartilage regeneration, demonstrating well-integrated tissue interfaces in rats. In addition, an acellular FPH2-loaded hydrogel proved effective in preventing the onset of osteoarthritis. This research provides a viable and safe method to enhance chondrocyte fitness, offering insights into the self-regulatory mechanisms of cell fitness.

中文翻译：

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化学程序化的新陈代谢驱动着软骨再生的卓越细胞适应性


细胞疗法的快速发展凸显了了解基本细胞属性的重要性。其中，细胞适应性——移植细胞如何适应新的微环境并在体内保持功能稳定性——至关重要。这项研究确定了一种化合物 FPH2，它可以增强人类软骨细胞的适应性和关节软骨的修复，这通常是非再生的。通过药物筛选，FPH2 被证明可以广泛改善细胞性能，尤其是在维持软骨细胞表型和增强迁移方面。单细胞转录组学表明 FPH2 诱导超拟合细胞状态。其机制主要涉及抑制肉碱棕榈酰转移酶 I 和优化代谢稳态。在动物模型中，FPH2 处理的人软骨细胞显着改善了软骨再生，表明大鼠的组织界面整合良好。此外，无细胞 FPH2 负载的水凝胶被证明可有效预防骨关节炎的发作。这项研究提供了一种可行且安全的方法来提高软骨细胞适应性，为细胞适应性的自我调节机制提供了见解。