Memory or amnesia: the dilemma of stem cell therapy in muscular dystrophies

Abstract

Muscular dystrophies are monogenetic diseases that are often characterized by the degeneration of both cardiac and skeletal muscle. Gene therapy to correct the mutated gene has shown promise in both animal models and clinical trials; however, current gene delivery strategies are limited to the introduction of the corrected gene into only one tissue. Strategies to target multiple striated muscle types would provide a much-needed improvement for the treatment of muscular dystrophies. In this issue of the JCI, Quattrocelli and colleagues demonstrate that induced pluripotent stem cells (iPSCs) with a myogenic propensity are able to engraft into both cardiac and skeletal muscles. The authors also identified a novel pool of mesodermal iPSC-derived progenitors (MiPs). Moreover, the authors show that these MiPs are amenable to gene correction and can restore function in murine dystrophic models. Together, the results of this study provide an important advance in improving gene delivery to treat patients with muscular dystrophy.

Figure 1. MiPs carrying the corrected DNA have the potential to repair damaged striatal muscle.

The decision regarding where MiPs migrate and engraft is greatly affected by the cell’s memory. Independent of their origin and memory, fibroblast- and mesangioblast-derived MiPs both preferentially target the heart, while only the cells that have a certain memory of the muscle environment are able to reach and engraft into skeletal muscles.