Spatiotemporal mapping of immune and stem cell dysregulation after volumetric muscle loss.

Autor: Larouche JA; Department of Biomedical Engineering.; Biointerfaces Institute., Wallace EC; Department of Biomedical Engineering., Spence BD; Department of Molecular, Cellular and Developmental Biology., Buras E; Biointerfaces Institute.; Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, and., Aguilar CA; Department of Biomedical Engineering.; Biointerfaces Institute.; Program in Cellular and Molecular Biology, University of Michigan (UM), Ann Arbor, Michigan, USA.
Jazyk: angličtina
Zdroj: JCI insight [JCI Insight] 2023 Apr 10; Vol. 8 (7). Date of Electronic Publication: 2023 Apr 10.
DOI: 10.1172/jci.insight.162835
Abstrakt: 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.
Databáze: MEDLINE