CD13 Regulates Anchorage and Differentiation of the Skeletal Muscle Satellite Stem Cell Population in Ischemic Injury

• Published in: Stem cells (Dayton, Ohio) Vol. 32; no. 6; pp. 1564 - 1577
• Main Authors: Rahman, M. Mamunur, Ghosh, Mallika, Subramani, Jaganathan, Fong, Guo‐Hua, Carlson, Morgan E., Shapiro, Linda H.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.06.2014
• Subjects: Angiogenesis; Animals; Arterial Occlusive Diseases - metabolism; Arterial Occlusive Diseases - pathology; Arterial Occlusive Diseases - physiopathology; Arteries - metabolism; Arteries - pathology; Bone marrow; CD13; CD13 Antigens - metabolism; Cell Adhesion; Cell Count; Cell Differentiation; Cytokines - metabolism; Hind limb ischemia; Inflammation - pathology; Ischemia - metabolism; Ischemia - pathology; Ischemia - physiopathology; Mice; Mice, Knockout; Muscle stem cells; Musculoskeletal system; Neovascularization, Physiologic; Recovery of Function; Regeneration; Rodents; Satellite Cells, Skeletal Muscle - pathology; Satellites; Signal Transduction; Stem cells; Stem Cells - metabolism; Stem Cells - pathology; Transplants & implants; Wound Healing; Angiogenesis; Hind limb ischemia; CD13; Muscle stem cells
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1002/stem.1610

CD13 is a multifunctional cell surface molecule that regulates inflammatory and angiogenic mechanisms in vitro, but its contribution to these processes in vivo or potential roles in stem cell biology remains unexplored. We investigated the impact of loss of CD13 on a model of ischemic skeletal muscle injury that involves angiogenesis, inflammation, and stem cell mobilization. Consistent with its role as an inflammatory adhesion molecule, lack of CD13 altered myeloid trafficking in the injured muscle, resulting in cytokine profiles skewed toward a prohealing environment. Despite this healing‐favorable context, CD13KO animals showed significantly impaired limb perfusion with increased necrosis, fibrosis, and lipid accumulation. Capillary density was correspondingly decreased, implicating CD13 in skeletal muscle angiogenesis. The number of CD45−/Sca1−/α7‐integrin+/β1‐integrin+ satellite cells was markedly diminished in injured CD13KO muscles and adhesion of isolated CD13KO satellite cells was impaired while their differentiation was accelerated. Bone marrow transplantation studies showed contributions from both host and donor cells to wound healing. Importantly, CD13 was coexpressed with Pax7 on isolated muscle‐resident satellite cells. Finally, phosphorylated‐focal adhesion kinase and ERK levels were reduced in injured CD13KO muscles, consistent with CD13 regulating satellite cell adhesion, potentially contributing to the maintenance and renewal of the satellite stem cell pool and facilitating skeletal muscle regeneration. Stem Cells 2014;32:1564–1577