Unsaturated Long-Chain Fatty Acids Activate Resident Macrophages and Stem Cells in a Human Skeletal Muscle Tissue Model

Phenotypically heterogeneous populations of tissue-resident macrophages and stem cells play important roles in the regeneration of the skeletal muscle tissue. Previous studies using animal and cell culture models implied a beneficial effect of fatty acid (FA) species on tissue regeneration. Here, we applied a human experimental model using excised muscle tissues from reconstructive surgeries to study the effects of FAs on resident macrophages and stem cells in the natural environment of human skeletal muscle tissue. Muscle tissue samples from 20 donors were included in this study. The expression of 34 cytokines/chemokines was determined, using multiplex protein analysis. The phenotypes of macrophages and stem cells were determined immunohistochemically. The numbers of CD80+ macrophages correlated with the expression levels of IL-1α, IL-1RA, IL-8, IL-17A, and MCP-1, while the PAX7+ and MyoD+ stem cell counts were positively correlated with the expression level of CXCL12α, a recognized chemoattractant for muscle stem cells. Treatment of additional tissue sections with FAs revealed that CD80+ or MARCO+ macrophages- and PAX7+ or MyoD+ stem cells were simultaneously increased by unsaturated long-chain FAs. Taken together, this is the first experimental demonstration of a coordinated activation of macrophages and stem cells in human skeletal muscle tissue.