Cell therapy for muscular dystrophies: advances and challenges

Abstract

Purpose of review: Cell therapy is considered a potential therapeutic avenue for the treatment of skeletal muscle diseases. Heterologous and autologous approaches have been attempted in the context, respectively, of generalized degenerative disease and of localized repairs. Cell transplantation trials, however, have been hampered by poor survival and limited migratory ability of the cells. This article reviews recent problems including the identification of new putative cellular candidates, the combination of complementary genetic or pharmacological therapeutic approaches, and the set up of clinical trials.

Recent findings: Deeper investigations identified anoikis, oxidative stress, fusion inability and some administration methodologies as causes of early massive cell death. It was proposed to adapt the injection strategies or to combine them with genetic modifications of the cells or pharmacological interventions on the environment to improve the success of implantation. New myogenic cell types have been identified, mainly in the family of perivascular cells, which can be administered systemically. New concepts have emerged regarding the correction of gene expression (use of lentiviral vectors, set-up of exon skipping, direct DNA repair, etc.).

Summary: Initial cell transplantation trials dedicated to the repair of striated muscles in muscular dystrophies produced mitigated results and underlined some limitations of cellular candidates under study. The research and identification of new stem cell candidates, the invention of new molecular strategies for correction of gene expression, the development of complementary approaches to improve transplantation success, have been justified by the unmet medical needs. These efforts led to new preclinical and clinical trials based on these concepts.