BACKGROUND.: One major challenge in developing cell therapy for muscle diseases is to define the best condition for the recipient’s muscle to niche donor cells. We have examined the efficiency of human myoblast transplantation in an immunodeficient animal model, after local irradiation, as well as the potential impact of laminin on myoblast behavior. METHODS.: Human myoblasts were injected into preirradiated tibialis anterior muscles from immunodeficient mice. The donor cell engraftment, proliferation, and laminin content within the transplanted muscles were evaluated by immunocytochemistry. Additionally, the effect of laminin upon myoblast proliferation, migration, and survival was ascertained in vitro. RESULTS.: Engraftment of human myoblasts into the skeletal muscle of immunodeficient Rag2/gammac/C5 mice presubjected to local irradiation provided the best niche for myoblast engraftment, as demonstrated by the number of viable and proliferating donor cells found in the host muscle. Local irradiation significantly enhanced laminin deposition within the recipient’s muscle and donor cells were preferentially located in laminin-enriched areas. The same batch of myoblasts used for in vivo injections also responded to laminin in vitro with increased proliferation and cell survival, as well as an improved migratory response. CONCLUSIONS.: We show that local irradiation enhances the laminin content in the host muscle microenvironment and provides a better engraftment of human myoblasts. In addition, laminin increases myoblast proliferation, survival, and migration in vitro. These data provide combined in vivo and in vitro evidence that laminin status should be taken into account when designing experimental and clinical cell therapy strategies for muscle disease.

Silva-Barbosa SD, Butler-Browne GS, de Mello W, Riederer I, Di Santo JP, Savino W, Mouly V.

1 UMR S 787 INSERM, Paris, France. 2 Université Pierre et Marie Curie, Paris, France. 3 Institut de Myologie, Paris, France. 4 Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. 5 Center for Bone Marrow Transplantation, National Cancer Institute, Rio de Janeiro, Brazil. 6 Unité des Cytokines et Développement Lymphoïde, Institut Pasteur, Paris, France.