多能干细胞用于退行性肌肉疾病的基因疗法

Title:Pluripotent Stem Cells for Gene Therapy of Degenerative Muscle Diseases

Volume: 15 Issue: 4

Author(s): Mariana Loperfido, Heather B. Steele-Stallard, Francesco Saverio Tedesco and Thierry VandenDriessche

Affiliation:

关键词: 细胞治疗，核酸酶设计师 ，胚胎干细胞，基因治疗，诱导多能干细胞（iPS），肌肉干细胞，肌肉萎缩症，再生医学。

摘要: 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.

Cite this article as:

Mariana Loperfido, Heather B. Steele-Stallard, Francesco Saverio Tedesco and Thierry VandenDriessche , Pluripotent Stem Cells for Gene Therapy of Degenerative Muscle Diseases, Current Gene Therapy 2015; 15 (4) . https://dx.doi.org/10.2174/1566523215666150630121207