Expression of Functional CXCR4 by Muscle Satellite Cells and Secretion of SDF-1 by Muscle-Derived Fibroblasts is Associated with the Presence of Both Muscle Progenitors in Bone Marrow and Hematopoietic Stem/Progenitor Cells in Muscles

May 14, 2003Stem cells (Dayton, Ohio)

Muscle stem cells with CXCR4 and muscle fibroblasts releasing SDF-1 are linked to muscle-making cells in bone marrow and blood stem cells in muscles

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Abstract

Murine muscle cell lines express the functional CXCR4 receptor and respond to the ligand SDF-1.

Muscle satellite cells and human hematopoietic stem/progenitor cells are chemoattracted by muscle fibroblast supernatants.
Bone marrow fibroblast supernatants also attract CXCR4(+) satellite cells, similar to CD34(+) cells.
Preincubation with a CXCR4 inhibitor significantly reduces chemotaxis of both muscle satellite cells and CD34(+) cells.
The SDF-1-CXCR4 axis may facilitate the movement of circulating stem cells to muscle and bone marrow tissues.

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We found that the murine cell lines C2C12 and G7 derived from muscle satellite cells, which are essential for muscle regeneration, express the functional CXCR4 receptor on their surface and that the specific ligand for this receptor, alpha-chemokine stromal-derived factor 1 (SDF-1), is secreted in muscle tissue. These cell lines responded to SDF-1 stimulation by chemotaxis, phosphorylation of mitogen-activated protein kinase (MAPK) p42/44 and AKT serine-threonine kinase, and calcium flux, confirming the functionality of the CXCR4 receptor. Moreover, supernatants derived from muscle fibroblasts chemoattracted both satellite cells and human CD34(+) hematopoietic stem/progenitor cells. In a similar set of experiments, supernatants from bone marrow fibroblasts were found to chemoattract CXCR4(+) satellite cells just as they chemoattract CD34(+) cells. Moreover, preincubation of both muscle satellite cells and hematopoietic stem/progenitor CD34(+) cells before chemotaxis with T140, a specific CXCR4 inhibitor, resulted in a significantly lower chemotaxis to media conditioned by either muscle- or bone marrow-derived fibroblasts. Based on these observations, we postulate that the SDF-1-CXCR4 axis is involved in chemoattracting circulating CXCR4(+) muscle stem/progenitor and circulating CXCR4(+) hematopoietic CD34(+) cells to both muscle and bone marrow tissues. Thus, it appears that tissue-specific stem cells circulating in peripheral blood could compete for SDF-1(+) niches, and this would explain, without invoking the concept of stem cell plasticity, why hematopoietic colonies can be cultured from muscles and early muscle progenitors can be cultured from bone marrow.

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Expression of Functional CXCR4 by Muscle Satellite Cells and Secretion of SDF-1 by Muscle-Derived Fibroblasts is Associated with the Presence of Both Muscle Progenitors in Bone Marrow and Hematopoietic Stem/Progenitor Cells in Muscles

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