Human pluripotent stem cells represent a unique source for cell-based therapies
and regenerative medicine. The intrinsic features of these cells such as their easy
accessibility and their capacity to be expanded indefinitely overcome some limitations
of conventional adult stem cells. Furthermore, the possibility to derive patient-specific
induced pluripotent stem (iPS) cells in combination with the current development of gene modification methods could be
used for autologous cell therapies of some genetic diseases. In particular, muscular dystrophies are considered to be a
good candidate due to the lack of efficacious therapeutic treatments for patients to date, and in view of the encouraging results
arising from recent preclinical studies. Some hurdles, including possible genetic instability and their efficient differentiation
into muscle progenitors through vector/transgene-free methods have still to be overcome or need further optimization.
Additionally, engraftment and functional contribution to muscle regeneration in pre-clinical models need to be
carefully assessed before clinical translation. This review offers a summary of the advanced methods recently developed
to derive muscle progenitors from pluripotent stem cells, as well as gene therapy by gene addition and gene editing methods
using ZFNs, TALENs or CRISPR/Cas9. We have also discussed the main issues that need to be addressed for successful
clinical translation of genetically corrected patient-specific pluripotent stem cells in autologous transplantation trials
for skeletal muscle disorders.
Keywords: Cell therapy, designer nucleases, embryonic stem cells, gene therapy, induced pluripotent stem (iPS) cells, muscle
stem cells, muscular dystrophies, regenerative medicine.
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