Department of Biomedical Engineering.
Biointerfaces Institute.
JCI Insight. 2023 Apr 10;8(7):e162835. doi: 10.1172/jci.insight.162835.
Volumetric muscle loss (VML) is an acute trauma that results in persistent inflammation, supplantation of muscle tissue with fibrotic scarring, and decreased muscle function. The cell types, nature of cellular communication, and tissue locations that drive the aberrant VML response have remained elusive. Herein, we used spatial transcriptomics on a mouse model of VML and observed that VML engenders a unique spatial profibrotic pattern driven by crosstalk between fibrotic and inflammatory macrophages and mesenchymal-derived cells. The dysregulated response impinged on muscle stem cell-mediated repair, and targeting this circuit resulted in increased regeneration and reductions in inflammation and fibrosis. Collectively, these results enhance our understanding of the cellular crosstalk that drives aberrant regeneration and provides further insight into possible avenues for fibrotic therapy exploration.
体积性肌肉损失（VML）是一种急性创伤，会导致持续的炎症、肌肉组织被纤维瘢痕取代以及肌肉功能下降。驱动异常 VML 反应的细胞类型、细胞间通讯的性质和组织位置仍然难以捉摸。在此，我们在 VML 的小鼠模型上使用空间转录组学，观察到 VML 引发了一种独特的空间成纤维性模式，这种模式是由纤维性和炎症性巨噬细胞以及间充质衍生细胞之间的串扰驱动的。失调的反应影响了肌肉干细胞介导的修复，针对该回路可导致再生增加，炎症和纤维化减少。总的来说，这些结果增强了我们对驱动异常再生的细胞串扰的理解，并为纤维化治疗的探索提供了进一步的见解。
