Current understanding of dystrophin-related muscular dystrophy and therapeutic challenges ahead

Objective To review the recent research progress in dystrophin-related muscular dystrophy includes X-linked hereditary Duchenne and Becker muscular dystrophies （DMD and BMD）. Data sources Information included in this article was identified by searches of PUBMED and other online resources using the key terms DMD, dystrophin, mutations, animal models, pathophysiology, gene expression, stem cells, gene therapy, cell therapy, and pharmacological. Study selection Mainly original milestone articles and timely reviews written by major pioneer investigators of the field were selected. Results The key issues related to the genetic basis and pathophysiological factors of the diseases were critically addressed. The availabilities and advantages of various animal models for the diseases were described. Major molecular and cellular therapeutic approaches were also discussed, many of which have indeed exhibited some success in pre-clinical studies but at the same time encountered a number of technical hurdles, including the efficient and systemic delivery of a functional gene and myogenic precursor/stem cells to repair genetic defects. Conclusions Further understanding of pathophysiological mechanisms at molecular levels and regenerative properites of myogenic precursor/stem cells will promote the development of multiple therapeutic strategies. The combined use of multiple strategies may represent the major challenge as well as the greatest hope for the therapy of these diseases in coming years.

Synergistic stimulation of surface topography and biphasic electric current promotes muscle regeneration

Developing a universal culture platform that manipulates cell fate is one of the most important tasks in the investigation of the role of the cellular microenvironment.This study focuses on the application of topographical and electrical field stimuli to human myogenic precursor cell(hMPC)cultures to assess the influences of the adherent direction,proliferation,and differentiation,and induce preconditioning-induced therapeutic benefits.First,a topographical surface of commercially available culture dishes was achieved by femtosecond laser texturing.The detachable biphasic electrical current system was then applied to the hMPCs cultured on laser-textured culture dishes.Laser-textured topographies were remarkably effective in inducing the assembly of hMPC myotubes by enhancing the orientation of adherent hMPCs compared with flat surfaces.Furthermore,electrical field stimulation through laser-textured topographies was found to promote the expression of myogenic regulatory factors compared with nonstimulated cells.As such,we successfully demonstrated that the combined stimulation of topographical and electrical cues could effectively enhance the myogenic maturation of hMPCs in a surface spatial and electrical field-dependent manner,thus providing the basis for therapeutic strategies.