Exosome-Mediated Benefits of Cell Therapy in Mouse and Human Models of Duchenne Muscular Dystrophy.
Exosome-Mediated Benefits of Cell Therapy in Mouse and Human Models of Duchenne Muscular Dystrophy.
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DOI：
10.1016/j.stemcr.2018.01.023
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发表时间：
2018-03-13
影响因子：
5.9
通讯作者：
Marbán E
中科院分区：
文献类型：
--
作者：
Aminzadeh MA;Rogers RG;Fournier M;Tobin RE;Guan X;Childers MK;Andres AM;Taylor DJ;Ibrahim A;Ding X;Torrente A;Goldhaber JM;Lewis M;Gottlieb RA;Victor RA;Marbán E
在杜氏肌营养不良症（DMD）中，肌营养不良蛋白的遗传缺陷导致残疾和过早死亡，影响心脏和骨骼肌。在这里，我们报告说，临床阶段的心脏祖细胞，称为心球衍生细胞（CDC），改善心脏和骨骼肌病变的mdx小鼠模型的DMD。将CDC注射到mdx小鼠的心脏中可增强心脏功能、行走能力和存活率。人CDC分泌的外泌体在mdx小鼠和人诱导多能干细胞衍生的Duchenne心肌细胞中再现CDC的益处。令人惊讶的是，CDC和它们的外来体也瞬时恢复了mdx小鼠中全长肌营养不良蛋白的部分表达。这些发现进一步激发了在Duchenne患者中测试CDC，同时将外泌体确定为下一代治疗候选者。CDC改善DMD mdx小鼠模型中的心脏和骨骼肌病变CDC外泌体再现CDC的益处CDC及其外泌体瞬时恢复肌营养不良蛋白的部分表达在这篇文章中，Marbán及其同事表明，外泌体介导了杜氏肌营养不良症小鼠和人类模型中细胞治疗的益处。
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. CDCs improve cardiac and skeletal myopathy in the mdx mouse model of DMD CDC exosomes reproduce the benefits of CDCs CDCs and their exosomes transiently restored partial expression of dystrophin In this article, Marbán and colleagues show that exosomes mediate benefits of cell therapy in mouse and human models of Duchenne muscular dystrophy.
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影响因子：
3.7
作者：
Davis DR;Zhang Y;Smith RR;Cheng K;Terrovitis J;Malliaras K;Li TS;White A;Makkar R;Marbán E
通讯作者：
Marbán E
影响因子：
16
作者：
Lötvall J;Hill AF;Hochberg F;Buzás EI;Di Vizio D;Gardiner C;Gho YS;Kurochkin IV;Mathivanan S;Quesenberry P;Sahoo S;Tahara H;Wauben MH;Witwer KW;Théry C
通讯作者：
Théry C
影响因子：
168.9
作者：
Makkar, Raj R.;Smith, Rachel R.;Cheng, Ke;Malliaras, Konstantinos;Thomson, Louise E. J.;Berman, Daniel;Czer, Lawrence S. C.;Marban, Linda;Mendizabal, Adam;Johnston, Peter V.;Russell, Stuart D.;Schuleri, Karl H.;Lardo, Albert C.;Gerstenblith, Gary;Marban, Eduardo
通讯作者：
Marban, Eduardo
影响因子：
5.2
作者：
Li, Tao-Sheng;Cheng, Ke;Lee, Shuo-Tsan;Matsushita, Satoshi;Davis, Darryl;Malliaras, Konstantinos;Zhang, Yiqiang;Matsushita, Noriko;Smith, Rachel Ruckdeschel;Marban, Eduardo
通讯作者：
Marban, Eduardo
影响因子：
39.3
作者：
Aminzadeh, Mohammad A.;Tseliou, Eleni;Marban, Eduardo
通讯作者：
Marban, Eduardo