In vivo generation of a mature and functional artificial skeletal muscle.

In vivo generation of a mature and functional artificial skeletal muscle.
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DOI:
10.15252/emmm.201404062
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发表时间:
2015-04
影响因子:
11.1
通讯作者:
Gargioli C
Gargioli C
中科院分区:
医学1区
文献类型:
--
作者:
Fuoco C;Rizzi R;Biondo A;Longa E;Mascaro A;Shapira-Schweitzer K;Kossovar O;Benedetti S;Salvatori ML;Santoleri S;Testa S;Bernardini S;Bottinelli R;Bearzi C;Cannata SM;Seliktar D;Cossu G;Gargioli C

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骨骼肌组织的大量丧失会导致肢体残缺和严重功能丧失。在体内移植时,体外生成的人工肌肉在宿主血管生成之前经历坏死,可以为纤维存活提供氧气。在这里,我们报告了一种新的策略的基础上使用的小鼠或人类mesoangioblast封装内PEG-纤维蛋白原水凝胶。一旦被工程化以表达胎盘源性生长因子,成中血管细胞吸引宿主血管和神经,有助于新形成的肌纤维的体内存活和成熟。当移植物植入胫骨前肌表面的皮肤下时,成熟和排列的肌纤维在几周内形成完整的功能性额外肌肉。此外,用PEG-纤维蛋白原包埋的中成血管细胞代替消融的胫骨前肌也导致了与正常胫骨前肌非常相似的人工肌肉。该策略为针对大量涉及肌肉组织萎缩的病理状况的患者特异性肌肉创建打开了可能性。
Extensive loss of skeletal muscle tissue results in mutilations and severe loss of function. In vitro-generated artificial muscles undergo necrosis when transplanted in vivo before host angiogenesis may provide oxygen for fibre survival. Here, we report a novel strategy based upon the use of mouse or human mesoangioblasts encapsulated inside PEG-fibrinogen hydrogel. Once engineered to express placental-derived growth factor, mesoangioblasts attract host vessels and nerves, contributing to in vivo survival and maturation of newly formed myofibres. When the graft was implanted underneath the skin on the surface of the tibialis anterior, mature and aligned myofibres formed within several weeks as a complete and functional extra muscle. Moreover, replacing the ablated tibialis anterior with PEG-fibrinogen-embedded mesoangioblasts also resulted in an artificial muscle very similar to a normal tibialis anterior. This strategy opens the possibility for patient-specific muscle creation for a large number of pathological conditions involving muscle tissue wasting.
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