Exosome-Mediated Benefits of Cell Therapy in Mouse and Human Models of Duchenne Muscular Dystrophy

被引：117

作者：

Aminzadeh, Mark A. ^{[1
]}

Rogers, Russell G. ^{[1
]}

Fournier, Mario ^{[1
]}

Tobin, Rachel E. ^{[1
]}

Guan, Xuan ^{[2
]}

Childers, Martin K. ^{[2
]}

Andres, Allen M. ^{[1
]}

Taylor, David J. ^{[1
]}

Ibrahim, Ahmed ^{[1
]}

Ding, Xiangming ^{[3
]}

Torrente, Angelo ^{[1
]}

Goldhaber, Joshua M. ^{[1
]}

Lewis, Michael ^{[1
]}

Gottlieb, Roberta A. ^{[1
]}

Victor, Ronald A. ^{[1
]}

Marban, Eduardo ^{[1
]}

机构：

[1] Cedars Sinai Med Ctr, Smidt Heart Inst, 8700 Beverly Blvd,Suite AHSP 3100, Los Angeles, CA 90048 USA

[2] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98109 USA

[3] Univ Calif Los Angeles, Technol Ctr Genom & Bioinformat, Los Angeles, CA 90095 USA

来源：

STEM CELL REPORTS | 2018年 / 10卷 / 03期

关键词：

CARDIOSPHERE-DERIVED CELLS; MYOCARDIAL-INFARCTION; CARDIAC-FUNCTION; IMPROVE FUNCTION; STEM-CELLS; RAT MODEL; MDX; CARDIOMYOPATHY; REGENERATION; EFFICACY;

D O I：

10.1016/j.stemcr.2018.01.023

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

Genetic deficiency of dystrophin leads to disability and premature death in Duchenne muscular dystrophy (DMD), affecting the heart as well as skeletal muscle. Here, we report that clinical-stage cardiac progenitor cells, known as cardiosphere-derived cells (CDCs), improve cardiac and skeletal myopathy in the mdx mouse model of DMD. Injection of CDCs into the hearts of mdx mice augments cardiac function, ambulatory capacity, and survival. Exosomes secreted by human CDCs reproduce the benefits of CDCs in mdx mice and in human induced pluripotent stem cell-derived Duchenne cardiomyocytes. Surprisingly, CDCs and their exosomes also transiently restored partial expression of full-length dystrophin in mdx mice. The findings further motivate the testing of CDCs in Duchenne patients, while identifying exosomes as next-generation therapeutic candidates.

引用

页码：942 / 955

页数：14

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