Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering.
Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering.
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DOI：
10.1016/j.celrep.2018.03.091
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发表时间：
2018-04-17
期刊：
影响因子：
8.8
通讯作者：
Tedesco FS
中科院分区：
文献类型：
--
作者：
Maffioletti SM;Sarcar S;Henderson ABH;Mannhardt I;Pinton L;Moyle LA;Steele-Stallard H;Cappellari O;Wells KE;Ferrari G;Mitchell JS;Tyzack GE;Kotiadis VN;Khedr M;Ragazzi M;Wang W;Duchen MR;Patani R;Zammit PS;Wells DJ;Eschenhagen T;Tedesco FS
生成人体骨骼肌模型是研究肌肉病理和治疗的工具。在这里，我们报告了从人多能干细胞生成三维（3D）人工骨骼肌组织，包括来自杜氏症、肢带症和先天性肌肉营养不良症患者的诱导多能干细胞（iPSCs）。水凝胶在张力作用下诱导多能细胞的三维骨骼肌分化，以提供肌纤维排列。人工肌肉再现了人类骨骼肌组织的特征，可植入免疫缺陷小鼠体内。使用该3D平台，可以高保真地模拟无法治愈的严重肌肉萎缩症的病理细胞特征。最后，我们展示了生成完全人类ipsc衍生的、复杂的、多谱系肌肉模型，其中包含骨骼肌的关键等基因细胞成分，包括血管内皮细胞、周细胞和运动神经元。这些结果为疾病建模、再生医学和治疗发展的人类骨骼肌类器官平台奠定了基础。多能干细胞衍生的3D人造肌肉显示正常骨骼肌的特征多种肌营养不良iPSC系可以在3D人造肌肉中分化人工肌肉构建模型严重的、无法治愈的肌肉营养不良形式等基因血管样网络和运动神经元在人造肌肉中发育Maffioletti等人从健康供体和患者特异性多能干细胞中生成人类3D人造骨骼肌。这些人造肌肉准确地模拟了严重的遗传性肌肉疾病。它们可以被改造成包括骨骼肌中存在的其他细胞类型，如血管细胞和运动神经元。
Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development. Human iPSC-derived 3D artificial muscles show features of normal skeletal muscle Multiple muscular dystrophy iPSC lines can be differentiated in 3D artificial muscles Artificial muscle constructs model severe, incurable forms of muscular dystrophy Isogenic vascular-like networks and motor neurons develop within artificial muscles Maffioletti et al. generate human 3D artificial skeletal muscles from healthy donors and patient-specific pluripotent stem cells. These human artificial muscles accurately model severe genetic muscle diseases. They can be engineered to include other cell types present in skeletal muscle, such as vascular cells and motor neurons.
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DOI：
10.1083/jcb.103.3.995
发表时间：
1986-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ecob-Prince MS;Jenkison M;Butler-Browne GS;Whalen RG
通讯作者：
Whalen RG
影响因子：
--
作者：
Kirschner, Janbernd;Lochmuller, Hanns
通讯作者：
Lochmuller, Hanns
DOI：
10.5435/00124635-201102001-00007
发表时间：
2011-01-01
影响因子：
3.2
作者：
Grogan, Brian F.;Hsu, Joseph R.
通讯作者：
Hsu, Joseph R.
影响因子：
4.1
作者：
Machingal, Masood A.;Corona, Benjamin T.;Christ, George J.
通讯作者：
Christ, George J.
影响因子：
4
作者：
Bertrand, Anne T.;Ziaei, Simindokht;Coirault, Catherine
通讯作者：
Coirault, Catherine