公开(公告)号：US20160256681A1

公开(公告)日：2016-09-08

申请号：US15029191

申请日：2014-10-17

申请人： THE UNIVERSITY OF MARYLAND, BALTIMORE

发明人： Robert J. Bloch ,  Andrea O'Neill ,  Joseph A. Roche ,  Paraskevi Sakellariou

IPC分类号： A61N1/32 ,  A61F2/08 ,  A61N1/36 ,  A61K35/34 ,  A01K67/027

CPC分类号： A61N1/326 ,  A01K67/0271 ,  A01K2207/12 ,  A01K2227/105 ,  A01K2267/035 ,  A61F2/08 ,  A61F2002/0894 ,  A61K35/34 ,  A61N1/36003

摘要： 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. The present invention provides methods to promote the engraftment and development of myogenic cells from individuals with such diseases into mature muscle tissue in mice to treat muscle diseases, muscle injury and reduced muscle function. Immortalized human myogenic precursor cells (hMPCs) form mature human myofibers following implantation into the hindlimbs of immunodeficient mice. The engraftment of the cells and their development into mature muscle myofibers is promoted by intermittent neuromuscular electrical stimulation (iNMES) of the peroneal nerve of the engrafted limb. The human myofibers that form are innervated, their contractile apparatus is fully differentiated, and they are comprised of human myonuclei, with minimal contamination by murine myonuclei.

摘要翻译： 研究人类肌病和肌营养不良的致病机制通常需要动物模型，但是一些人类疾病的模型尚不可用。 本发明提供了促进从这些疾病个体的肌原细胞植入和发育成小鼠成熟肌肉组织以治疗肌肉疾病，肌肉损伤和减少肌肉功能的方法。 永生化的人源性前体细胞（hMPCs）在植入免疫缺陷小鼠的后肢后形成成熟的人肌纤维。 通过间接神经肌肉电刺激（iNMES）促进移植肢体的腓神经，促进细胞的移植及其发育成熟肌肉肌纤维。 形成的人体肌纤维是神经支配的，它们的收缩装置是完全分化的，并且它们由人类的肌核组成，其中小鼠的核膜被最少的污染。