Serum exosomes can restore cellular function in vitro and be used for diagnosis in dysferlinopathy.
Serum exosomes can restore cellular function in vitro and be used for diagnosis in dysferlinopathy.
复制标题
血清外泌体可以在体外恢复细胞功能并用于诊断铁蛋白病
作者：
Dong X;Gao X;Dai Y;Ran N;Yin H
目的：递送全长dysferlin基因或蛋白质以恢复dysferlin病中dysferlin缺陷（DYSF-/-）肌纤维的细胞功能是具有挑战性的，dysferlin病是由dysferlin缺乏引起的疾病，目前没有有效的治疗。外泌体是一种有效的膜状纳米级生物货物载体，可能是有用的。实验设计：研究了肌管和人血清来源的外泌体在鼠和人DYSF-/-细胞中恢复dysferlin蛋白和细胞功能的能力。此外，评估了dysferlinopathy患者血清和尿来源的外泌体作为dysferlinopathy诊断工具的能力。结果如下：在这里，我们表明，来自dysferlin表达肌管的外泌体携带丰富的dysferlin，并使全长dysferlin蛋白转移到DYSF-/-肌管。外源性dysferlin正确地定位在DYSF-/-肌管膜上，使膜响应于损伤而重新密封。人血清外泌体还携带dysferlin蛋白并改善人DYSF-/-肌管的膜修复能力，而与突变无关。在dysferlinopathy患者血清和尿外泌体中缺乏dysferlin使得能够区分健康对照和dysferlinopathy患者。结论：我们的研究结果提供了证据，外泌体是dysferlin的有效载体，可用于dysferlin病的治疗和非侵入性诊断。
Purpose: It is challenging to deliver the full-length dysferlin gene or protein to restore cellular functions of dysferlin-deficient (DYSF-/-) myofibres in dysferlinopathy, a disease caused by the absence of dysferlin, which is currently without effective treatment. Exosomes, efficient membranous nanoscale carriers of biological cargoes, could be useful. Experimental design: Myotube- and human serum-derived exosomes were investigated for their capabilities of restoring dysferlin protein and cellular functions in murine and human DYSF-/- cells. Moreover, dysferlinopathic patient serum- and urine-derived exosomes were assessed for their abilities as diagnostic tools for dysferlinopathy. Results: Here we show that exosomes from dysferlin-expressing myotubes carry abundant dysferlin and enable transfer of full-length dysferlin protein to DYSF-/- myotubes. Exogenous dysferlin correctly localizes on DYSF-/- myotube membranes, enabling membrane resealing in response to injury. Human serum exosomes also carry dysferlin protein and improve membrane repair capabilities of human DYSF-/- myotubes irrespective of mutations. Lack of dysferlin in dysferlinopathic patient serum and urine exosomes enables differentiation between healthy controls and dysferlinopathic patients. Conclusions: Our findings provide evidence that exosomes are efficient carriers of dysferlin and can be employed for the treatment and non-invasive diagnosis of dysferlinopathy.
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影响因子：
15.1
作者：
Danzer KM;Kranich LR;Ruf WP;Cagsal-Getkin O;Winslow AR;Zhu L;Vanderburg CR;McLean PJ
通讯作者：
McLean PJ
DOI：
10.1073/pnas.1307960110
发表时间：
2013-12-17
影响因子：
11.1
作者：
Kerr, Jaclyn P.;Ziman, Andrew P.;Bloch, Robert J.
通讯作者：
Bloch, Robert J.
影响因子：
3.7
作者：
Lostal W;Bartoli M;Roudaut C;Bourg N;Krahn M;Pryadkina M;Borel P;Suel L;Roche JA;Stockholm D;Bloch RJ;Levy N;Bashir R;Richard I
通讯作者：
Richard I
影响因子：
1.4
作者：
Krahn, Martin;Labelle, Veronique;Levy, Nicolas
通讯作者：
Levy, Nicolas
影响因子：
13.6
作者：
Gonzales, Patricia A.;Pisitkun, Trairak;Knepper, Mark A.
通讯作者：
Knepper, Mark A.