Stromal cells help specialized cells such as those in muscle to grow, develop and survive. This supportive role is poorly understood, however. Bénédicte Chazaud and co-workers have therefore been investigating how macrophages - a recognized stromal cell type - support post-injury muscle regeneration. They report on that macrophages use a set of pro-survival cell-cell adhesion systems to rescue myoblasts and myotubes from apoptosis during this process. The authors show that entry of macrophages into regenerating mouse muscle in vivo correlates with decreased apoptosis of myogenic cells. They then demonstrate that direct cell-cell contact with human macrophages rescues these cells from apoptosis in vitro. Array analysis indicates that macrophages and myogenic cells express the ligands and receptors, respectively, for four pro-survival cell-cell adhesion systems (VCAM-1-VLA-4, ICAM-1-LFA-1, PECAM-1-PECAM-1 and CX3CL1-CX3CR1); experiments with blocking antibodies demonstrate that macrophages use all these to prevent apoptosis of myogenic cells. These results provide new insights into how stromal cells support specialized cells during tissue repair and suggest ways to improve myoblast transfer therapy, which is currently limited by massive cell death.
