Stem cell route to neuromuscular therapies

Abstract

As applied to skeletal muscle, stem cell therapy is a reincarnation of myoblast transfer therapy that has resulted from recent advances in the cell biology of skeletal muscle. Both strategies envisage the reconstruction of damaged muscle from its precursors, but stem cell therapy employs precursors that are earlier in the developmental hierarchy. It is founded on demonstrations of apparently multipotential cells in a wide variety of tissues that can assume, among others, a myogenic phenotype. The main demonstrated advantage of such cells is that they are capable of colonizing many tissues, including skeletal and cardiac muscle via the blood vascular system, thereby providing the potential for a body-wide distribution of myogenic progenitors. From a practical viewpoint, the chief disadvantage is that such colonization has been many orders of magnitude too inefficient to be useful. Proposals for overcoming this drawback are the subject of much speculation but, so far, relatively little experimentation. This review attempts to give some perspective to the status of the stem cell as a therapeutic instrument for neuromuscular disease and to identify issues that need to be addressed for application of this technology.

Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles

“…The classic strategies are gene or cell therapies. However, these treatments have met with a number of difficulties (14). Naked plasmid DNA gene transfer by either direct intramuscular injection or systemic delivery has been too inefficient so far (15).…”

“…Similarly, the therapeutic effectiveness of cell therapy is still far short of practical utility on the whole-body scale (14).…”

Migration of adult myogenic precursor cells as revealed by GFP/nLacZ labelling of mouse transplantation chimeras

“…Solid transplanted muscle tissue (Füchtbauer et al, 1988;Fan et al, 1996;Smythe and Grounds, 2001) may act as a source of muscle precursor cells for an extended period of time and may thus circumvent the low yields in myoblast and stem cell colonization of muscle (Hodgetts et al, 2000;Ferrari et al, 2001;Partridge, 2002) as a route for therapeutical improvement.…”

MMP1 gene expression enhances myoblast migration and engraftment following implanting into mdx/SCID mice

“…1,6,31 In essence, myogenic cells carrying wt dystrophin fuse and provide preexisting dystrophic muscle fibers with functional dystrophin protein expression. Myogenic cell transplantation (including stem cells, satellite cells, and myoblasts) has been well studied and considered as a potential strategy to rescue damaged skeletal muscle from injury and/or disease; it may be particularly effective in patients suffering from Duchenne and Becker Muscular Dystrophies.…”