Wnt7a stimulates myogenic stem cell motility and engraftment resulting in improved muscle strength.
Wnt7a stimulates myogenic stem cell motility and engraftment resulting in improved muscle strength.
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DOI：
10.1083/jcb.201310035
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发表时间：
2014-04-14
期刊：
影响因子：
--
通讯作者：
Rudnicki MA
中科院分区：
文献类型：
--
作者：
Bentzinger CF;von Maltzahn J;Dumont NA;Stark DA;Wang YX;Nhan K;Frenette J;Cornelison DD;Rudnicki MA
除了刺激骨骼肌生长和修复外，Wnt 7a/Fzd 7信号传导还增加了肌源性祖细胞的极性和定向迁移，并提高了肌肉干细胞治疗的功效。Wnt 7a/Fzd 7信号通过平面细胞极性途径诱导卫星干细胞的对称扩增和通过激活肌纤维中的Akt/mTOR生长途径来刺激骨骼肌生长和修复。在这里，我们描述了第三水平的活性，其中Wnt 7a/Fzd 7通过激活Dvl 2和小GTd 3 Rac 1增加小鼠卫星细胞和人肌源性祖细胞的极性和定向迁移。重要的是，这些作用可用于增强肌源性细胞移植到营养不良肌肉中的结果。我们观察到短时间的Wnt 7a治疗显著刺激了组织分散和植入，导致肌肉功能显著改善。此外，与Wnt 7a处理的细胞融合的远端部位的肌纤维是肥大的，这表明移植的细胞将活化的Wnt 7a/Fzd 7信号传导复合物递送至受体肌纤维。总之，我们描述了一个可行的和有效的离体细胞调节过程，深刻地提高了骨骼肌干细胞治疗的疗效。
In addition to stimulating skeletal muscle growth and repair, Wnt7a/Fzd7 signaling increases the polarity and directional migration of myogenic progenitors and improves the efficacy of muscle stem cell therapy. Wnt7a/Fzd7 signaling stimulates skeletal muscle growth and repair by inducing the symmetric expansion of satellite stem cells through the planar cell polarity pathway and by activating the Akt/mTOR growth pathway in muscle fibers. Here we describe a third level of activity where Wnt7a/Fzd7 increases the polarity and directional migration of mouse satellite cells and human myogenic progenitors through activation of Dvl2 and the small GTPase Rac1. Importantly, these effects can be exploited to potentiate the outcome of myogenic cell transplantation into dystrophic muscles. We observed that a short Wnt7a treatment markedly stimulated tissue dispersal and engraftment, leading to significantly improved muscle function. Moreover, myofibers at distal sites that fused with Wnt7a-treated cells were hypertrophic, suggesting that the transplanted cells deliver activated Wnt7a/Fzd7 signaling complexes to recipient myofibers. Taken together, we describe a viable and effective ex vivo cell modulation process that profoundly enhances the efficacy of stem cell therapy for skeletal muscle.
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影响因子：
5.2
作者：
Siegel, Ashley L.;Atchison, Kevin;Fisher, Kevin E.;Davis, George E.;Cornelison, D. D. W.
通讯作者：
Cornelison, D. D. W.
影响因子：
4.8
作者：
Subauste, MC;Von Herrath, M;Hahn, KM
通讯作者：
Hahn, KM
影响因子：
4.9
作者：
Bentzinger CF;Lin S;Romanino K;Castets P;Guridi M;Summermatter S;Handschin C;Tintignac LA;Hall MN;Rüegg MA
通讯作者：
Rüegg MA
影响因子：
16.6
作者：
von Maltzahn, Julia;Zinoviev, Radoslav;Chang, Natasha C.;Bentzinger, C. Florian;Rudnicki, Michael A.
通讯作者：
Rudnicki, Michael A.
影响因子：
12.4
作者：
Ikemoto, Madoka;Fukada, So-ichiro;Takeda, Shin'ichi
通讯作者：
Takeda, Shin'ichi