Methods of Generating Mature Human Muscle Fibers

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.

主权项

1. A method of treating a subject having a muscle disorder comprising the steps of:
a) identifying a subject having a muscle disorder in need of treatment; b) injecting human myogenic precursor cells in an amount capable of forming mature muscle tissue into a portion of a limb of the subject; d) subjecting a nerve of the limb to therapeutic stimulation configured to enhance engraftment of the human myogenic precursor cells and; e) creating a graft of the human myogenic precursor cells to promote generation of mature muscle tissue;wherein the generation of mature muscle tissue improves muscle function.