We here address the question whether the unique capacity of mesenchymal stem cells to re-establish tissue homeostasis depends on their potential to sense pathogen-associated molecular pattern and, in consequence, mount an adaptive response in the interest of tissue repair. After injection of MSCs primed with the bacterial wall component LPS into murine wounds, an unexpected acceleration of healing occurs, clearly exceeding that of non-primed MSCs. This correlates with a fundamental reprogramming of the transcriptome in LPS-treated MSCs as deduced from RNAseq analysis and its validation. A network of genes mediating the adaptive response through the Toll-like receptor 4 (TLR4) pathway responsible for neutrophil and macrophage recruitment and their activation profoundly contributes to enhanced wound healing. In fact, injection of LPS-primed MSCs silenced for TLR4 fails to accelerate wound healing. These unprecedented findings hold substantial promise to refine current MSC-based therapies for difficult-to-treat wounds.

中文翻译：

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MSCs 对伤口部位的 TLR4 依赖性塑造可加速伤口愈合。

我们在这里解决的问题是间充质干细胞重建组织稳态的独特能力是否取决于它们感知病原体相关分子模式的潜力，并因此产生有利于组织修复的适应性反应。在将用细菌壁成分 LPS 引发的 MSCs 注射到小鼠伤口中后，会出现意想不到的愈合加速，明显超过未引发的 MSCs。这与从 RNAseq 分析及其验证推断的 LPS 处理的 MSC 中转录组的基本重编程相关。通过负责中性粒细胞和巨噬细胞募集的 Toll 样受体 4 (TLR4) 通路介导适应性反应的基因网络及其激活对促进伤口愈合具有重要意义。实际上，注射 LPS 引发的对 TLR4 沉默的 MSC 不能加速伤口愈合。这些史无前例的发现为改进目前基于 MSC 的难治伤口疗法提供了巨大的希望。