Neuromuscular electrical stimulation promotes development in mice of mature human muscle from immortalized human myoblasts.
Neuromuscular electrical stimulation promotes development in mice of mature human muscle from immortalized human myoblasts.
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DOI：
10.1186/s13395-016-0078-6
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发表时间：
2016
期刊：
影响因子：
4.9
通讯作者：
Bloch RJ
中科院分区：
文献类型：
--
作者：
Sakellariou P;O'Neill A;Mueller AL;Stadler G;Wright WE;Roche JA;Bloch RJ
研究人类肌病和肌肉萎缩症的致病机制往往需要动物模型，但目前还没有一些人类疾病的模型。促进来自患有此类疾病的个体的肌源性细胞在小鼠体内的植入和发育的方法将加速此类研究，并为测试治疗方法提供有用的工具。在这里，我们研究了永生化人肌原性前体细胞（hMPCs）在植入非肥胖糖尿病- rag1缺失IL2rγ缺失（NOD-Rag）免疫缺陷小鼠后肢后形成成熟人肌纤维的能力。我们报道，NOD-Rag小鼠的后肢经过x射线照射，用心脏毒素处理，然后注射永生化对照hMPCs或来自面肩肱骨肌营养不良症（FSHD）患者的hMPCs，发育成熟的人肌纤维。此外，移植肢体腓神经的间歇性神经肌肉电刺激（iNMES）促进了两种永生细胞系形成的移植物中成熟纤维的发育。通过控制细胞，iNMES增加了形成的人体肌纤维的数量和大小，并促进了更紧密的纤维间堆积。移植物中的人肌纤维有神经支配，完全分化，并且很少受到鼠肌核的污染。我们的研究结果表明，移植了hMPCs的小鼠可以形成对照和FSHD人肌纤维，iNMES促进了成熟人肌肉的植入和随后的发育。
Studies of the pathogenic mechanisms underlying human myopathies and muscular dystrophies often require animal models, but models of some human diseases are not yet available. Methods to promote the engraftment and development of myogenic cells from individuals with such diseases in mice would accelerate such studies and also provide a useful tool for testing therapeutics. Here, we investigate the ability of immortalized human myogenic precursor cells (hMPCs) to form mature human myofibers following implantation into the hindlimbs of non-obese diabetic-Rag1 null IL2rγ null (NOD-Rag)-immunodeficient mice. We report that hindlimbs of NOD-Rag mice that are X-irradiated, treated with cardiotoxin, and then injected with immortalized control hMPCs or hMPCs from an individual with facioscapulohumeral muscular dystrophy (FSHD) develop mature human myofibers. Furthermore, intermittent neuromuscular electrical stimulation (iNMES) of the peroneal nerve of the engrafted limb enhances the development of mature fibers in the grafts formed by both immortal cell lines. With control cells, iNMES increases the number and size of the human myofibers that form and promotes closer fiber-to-fiber packing. The human myofibers in the graft are innervated, fully differentiated, and minimally contaminated with murine myonuclei. Our results indicate that control and FSHD human myofibers can form in mice engrafted with hMPCs and that iNMES enhances engraftment and subsequent development of mature human muscle.
影响因子：
7.8
作者：
Bader, D
通讯作者：
Bader, D