Cell Stem Cell：Wnt7a蛋白可加速肌肉组织再生

细胞海洋

加拿大渥太华医院研究所和渥太华大学的科学家找到了一种全新的刺激肌肉再生的有效方法，为找到一种新的治疗诸如肌肉营养失调等肌肉衰弱病症的方法铺平了道路。加科学家的研究首次表明，一种称为Wnt7a的蛋白质可以提高肌肉组织中干细胞的数量，进而可以加速骨骼肌的生长和修复。该项研究发表在6月5日出版的《细胞—干细胞》杂志上。. Y9 L- o6 l/ |8 D+ I. W7 A8 k
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干细胞有助于人体组织和器官的生长。卫星干细胞是特别的肌肉干细胞，生活在成年人的骨骼肌肉组织中，具有复制和分化成各种不同类型肌肉细胞的双重能力。加拿大干细胞研究网技术负责人，渥太华医院研究所干细胞研究中心主任，该项目主要研究人员迈克尔·鲁德利基教授领导的研究小组发现，当Wnt7a蛋白质被引入实验鼠肌肉组织中时，可以大大提高卫星干细胞的数量，加速组织再生过程，生长出体积更大、力量更强壮的肌肉。实验中，肌肉组织的质量增加了20%。
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4 M1 W' r1 V3 g% a2 H1 V3 `' |鲁德利基教授表示，该项发现表明，今后可以将研究目标集中于迅速增加干细胞数量，以使身体提高修复肌肉组织的能力。他认为，该项发现为开发出全新的肌肉萎缩等肌肉类疾病治疗方法指明了方向。8 q& b% i' A" X- w* h

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Cell Stem Cell,5 June 2009 doi:10.1016/j.stem.2009.03.013! ~/ [( R3 u/ L( G

# L( k3 b/ F' b" ^6 ~Wnt7a Activates the Planar Cell Polarity Pathway to Drive the Symmetric Expansion of Satellite Stem Cells- v) f" E% q1 l
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Fabien Le Grand1,2,3,Andrew E. Jones1,2,Vanessa Seale1,Anthony Scimè1,2andMichael A. Rudnicki1,2,,( l  R+ E9 V! A- \# n1 B: }
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1 Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada+ x7 X1 Y7 C) l& m' k
2 Department of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada
3 K' ?, S' w: n1 S+ G3 [- }/ Y3 Present address: Institut Cochin, INSERM U567, Université Paris Descartes, Paris 75014, France" Z- Y6 ~" X7 [

) P/ }+ _8 e8 G+ R4 `5 I* }6 QSatellite cells in skeletal muscle are a heterogeneous population of stem cells and committed progenitors. We found that quiescent satellite stem cells expressed the Wnt receptor Fzd7 and that its candidate ligand Wnt7a was upregulated during regeneration. Wnt7a markedly stimulated the symmetric expansion of satellite stem cells but did not affect the growth or differentiation of myoblasts. Silencing of Fzd7 abrogated Wnt7a binding and stimulation of stem cell expansion. Wnt7a signaling induced the polarized distribution of the planar cell polarity effector Vangl2. Silencing of Vangl2 inhibited Wnt7a action on satellite stem cell expansion. Wnt7a overexpression enhanced muscle regeneration and increased both satellite cell numbers and the proportion of satellite stem cells. Muscle lacking Wnt7a exhibited a marked decrease in satellite cell number following regeneration. Therefore, Wnt7a signaling through the planar cell polarity pathway controls the homeostatic level of satellite stem cells and hence regulates the regenerative potential of muscle.