Bone Marrow-Derived Cells Participate in Composition of the Satellite Cell Niche in Intact and Regenerating Mouse Skeletal Muscle
Abstract
The cellular components of the satellite cell niche participate in regulation of skeletal muscle regeneration. Besides myogenic cells at different developmental stages, this niche is formed by cells of the immune system, the interstitial connective tissue and the vascular system.
Unambiguous determination of origin of these cell types could contribute to optimization of cell based therapy of skeletal muscle disorders. In our work we intravenously transplanted mouse GFP+ unseparated bone marrow cells into whole-body lethally irradiated immunocompetent mice 4 weeks before the cardiotoxin-induced injury of the recipients' skeletal muscles.
Seven and 28 days after the toxin injection, the injured regenerating and contralateral intact muscles were examined for identification of GFP+ bone marrow derived cells by direct fluorescence, protein immunohistochemistry and immunogold transmission electron microscopy. In both the intact and injured muscles GFP positivity was determined in immune cells, mainly in macrophages, and in interstitial spindle-shaped cells.
Moreover, in the injured muscles rare GFP+ endothelial cells of the blood vessels and newly formed myotubes and muscle fibers were present. Our results confirmed ability of bone marrow derived cells to contribute to the cellular component of the satellite cell niche in the intact and regenerating skeletal muscle.
These cells originated not only from the hematopoietic stem cells, but obviously, also from other stem or progenitor cells residing in the bone marrow, e.g. the multipotent mesenchymal stromal cells and the endothelial progenitors.