Cultured human skeletal muscle satellite cells exhibit characteristics of mesenchymal stem cells and play anti-inflammatory roles through prostaglandin E2 and hepatocyte growth factors

Abstract

Skeletal muscle satellite cells (SkMSCs) play crucial roles in muscle fiber maintenance, repair, and remodeling; however, it remains unknown if these properties are preserved in cultured SkMSCs. In this study, we investigated the characteristics of cultured SkMSCs and their ability to regulate the activity of M1 macrophages. SkMSCs grew well with an average population doubling time of 26.26 ± 6.85 h during 10 passages (P). At P5, Pax7, MyoD, cluster of differentiation (CD)34, and CD56 were not expressed in SkMSCs, but the MSC markers CD73, CD105, and CD90 were expressed and the cells were differentiated into adipocytes and osteoblasts. When SkMSCs were cocultured with macrophages, interleukin (IL)‐1β secretion was decreased, prostaglandin (PG)E2 was produced in coculture, and cyclooxygenase‐2 protein was induced in an SkMSC‐dependent manner. Hepatocyte growth factor (HGF) was highly secreted by monocultured SkMSCs; interferon‐γ and lipopolysaccharide reduced its expression level. However, HGF expression recovered when SkMSCs and macrophages were cocultured. Although exogenous PGE2 upregulated macrophage pro‐IL‐1β expression, it suppressed the secretion of cleaved IL‐1β. In contrast, HGF decreased active IL‐1β secretion without affecting pro‐IL‐1β expression. Co‐treatment of macrophages with HGF and PGE2 reduced pro‐IL‐ 1β expression level and active IL‐1β secretion. Our results suggest that SkMSCs lose their satellite cell properties during serial passaging but acquire mesenchymal stem cell properties including the ability to exert an antiinflammatory response for macrophages through PGE2 and HGF.