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

ABSTRACT: 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.

SUBMITTER: Larouche JA

PROVIDER: S-EPMC10132146 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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

Larouche Jacqueline A JA Wallace Emily C EC Spence Bonnie D BD Buras Eric E Aguilar Carlos A CA

JCI insight 20230410 7

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 macroph ...[more]

PMID: 36821376

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

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