MMP-9 overexpression improves myogenic cell migration and engraftment

Myoblast migration requires matrix metalloproteinase (MMP) activity but the contribution of individual MMPs or tissue inhibitors of matrix metalloproteinase (TIMPs), particularly MMP‐9 and TIMP‐1, is lacking. Using two clones derived for differential regulation of MMP‐2, MMP‐9, and TIMP‐1, we correlated protein expression with cell migration. MMP/TIMP regulation was determined by zymography, western blots, and quantitative reverse transcriptase–polymerase chain reaction (qRT‐PCR). Cell migration was compared in vitro and after grafting into nude–mdx mouse muscles. C2M9 clones produced high MMP‐9 and low MMP‐2, and migrated better than C2F clones, which secreted low MMP‐9, but overexpressed MMP‐2 and TIMP‐1. Improvement of C2F invasion by MMP‐9 and inhibition of C2M9 migration by MMP‐9 inhibitor I confirmed the role of MMP‐9 and pointed to potential inhibition by TIMP‐1. Higher complementation achieved by C2M9 grafts corroborated the beneficial effect of MMP‐9 overexpression. Modulation of MMP‐9 expression opens perspectives for improved efficacy of cell therapy for muscular dystrophies. Muscle Nerve, 2010