Stem cells migration during skeletal muscle regeneration - the role of Sdf-1/Cxcr4 and Sdf-1/Cxcr7 axis

Abstract

The skeletal muscle regeneration occurs due to the presence of tissue specific stem cells - satellite cells. These cells, localized between sarcolemma and basal lamina, are bound to muscle fibers and remain quiescent until their activation upon muscle injury. Due to pathological conditions, such as extensive injury or dystrophy, skeletal muscle regeneration is diminished. Among the therapies aiming to ameliorate skeletal muscle diseases are transplantations of the stem cells. In our previous studies we showed that Sdf-1 (stromal derived factor −1) increased migration of stem cells and their fusion with myoblasts in vitro. Importantly, we identified that Sdf-1 caused an increase in the expression of tetraspanin CD9 - adhesion protein involved in myoblasts fusion. In the current study we aimed to uncover the details of molecular mechanism of Sdf-1 action. We focused at the Sdf-1 receptors - Cxcr4 and Cxcr7, as well as signaling pathways induced by these molecules in primary myoblasts, as well as various stem cells - mesenchymal stem cells and embryonic stem cells, i.e. the cells of different migration and myogenic potential. We showed that Sdf-1 altered actin organization via FAK (focal adhesion kinase), Cdc42 (cell division control protein 42), and Rac-1 (Ras-Related C3 Botulinum Toxin Substrate 1). Moreover, we showed that Sdf-1 modified the transcription profile of genes encoding factors engaged in cells adhesion and migration. As the result, cells such as primary myoblasts or embryonic stem cells, became characterized by more effective migration when transplanted into regenerating muscle.

Induction of bone marrow-derived cells myogenic identity by their interactions with the satellite cell niche

“…3a, b ). As we have previously documented, Sdf-1 did not influence proliferation of cells [ 48 ]. After 5 days of coculture, 56.7% of CXCR4 + BMCs(β-gal + ) expressed Myf5 and 83% expressed Myod1 (Fig.…”

“…Previously, we have shown that Sdf-1 injection improved skeletal muscle regeneration and stem cell mobilization [ 49 , 50 ]. We also documented that pretreatment of cells with Sdf-1 induced migration of these cells after their transplantation into regenerating muscles [ 48 ]. Here, we tested whether the overexpression of Sdf-1 in injured and regenerating muscles would improve colonization of this tissue with transplanted cells.…”

“…As a result, Sdf-1-treated CXCR4 + BMCs or embryonic stem cells fused more efficiently with myoblasts. Sdf-1 also altered cell migration and actin organization via focal adhesion kinase (FAK), cell division control protein 42 (Cdc42), and Ras-related C3 botulinum toxin substrate (Rac-1), as well as matrix metalloproteinase (MMP) activity [ 48 , 49 ]. Currently, using a new in-vitro model, we were able to test the influence of the satellite cell niche on the differentiation of bone marrow-derived cells.…”

Identification of key pathways and hub genes in the myogenic process of pluripotent stem cell: A bioinformatics study

“…[11][12][13] Meanwhile, couples of pathways were veri ed to be correlated to myogenic differentiation as PI3K-MAPK, p38, p53 and actin pathway. [14][15][16][17] To up-regulate the differentiation e cacy and contribute to the repair of degenerated muscular tissues, it is especially important to clarify the differentiation mechanism at genetic level.…”

Generation and Characterization of Skeletal Muscle Cell based Model for GNE Myopathy: Implications in Actin Dynamics

“…Thus, coordination between sarcomere and other cytoskeletal proteins is critical for the contractile activity of skeletal muscle cell 24 . It is also reported that migration of muscle stem cells promote rapid tissue regeneration during tissue damage and muscle atrophy 25 . Disturbances in actin dynamics had been observed in different myopathic disorders where mutations in actin or actin-binding proteins lead to alteration in assembly and disassembly of actin 26,27 .…”