Neuromuscular Junction Formation Between Human Stem-Cell-Derived Motoneurons and Rat Skeletal Muscle in a Defined System

    Authors

    X. F. Guo; M. Das; J. Rumsey; M. Gonzalez; M. Stancescu;J. Hickman

    Comments

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    Abbreviated Journal Title

    Tissue Eng. Part C-Methods

    Keywords

    MOTOR-NEURON DISEASE; SERUM-FREE MEDIUM; SPINAL-CORD; FUNCTIONAL; MOTONEURONS; ORGANOSILANE SURFACE; HIPPOCAMPAL-NEURONS; ADULT RATS; IN-VITRO; DIFFERENTIATION; INDUCTION; Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell; Biology

    Abstract

    To date, the coculture of motoneurons (MNs) and skeletal muscle in a defined in vitro system has only been described in one study and that was between rat MNs and rat skeletal muscle. No in vitro studies have demonstrated human MN to rat muscle synapse formation, although numerous studies have attempted to implant human stem cells into rat models to determine if they could be of therapeutic use in disease or spinal injury models, although with little evidence of neuromuscular junction (NMJ) formation. In this report, MNs differentiated from human spinal cord stem cells, together with rat skeletal myotubes, were used to build a coculture system to demonstrate that NMJ formation between human MNs and rat skeletal muscles is possible. The culture was characterized by morphology, immunocytochemistry, and electrophysiology, while NMJ formation was demonstrated by immunocytochemistry and videography. This defined system provides a highly controlled reproducible model for studying the formation, regulation, maintenance, and repair of NMJs. The in vitro coculture system developed here will be an important model system to study NMJ development, the physiological and functional mechanism of synaptic transmission, and NMJ- or synapse-related disorders such as amyotrophic lateral sclerosis, as well as for drug screening and therapy design.

    Journal Title

    Tissue Engineering Part C-Methods

    Volume

    16

    Issue/Number

    6

    Publication Date

    1-1-2010

    Document Type

    Article

    Language

    English

    First Page

    1347

    Last Page

    1355

    WOS Identifier

    WOS:000284627000013

    ISSN

    1937-3384

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