Title

Neuromuscular junction formation between human stem cell-derived motoneurons and human skeletal muscle in a defined system

Authors

Authors

X. F. Guo; M. Gonzalez; M. Stancescu; H. H. Vandenburgh;J. J. Hickman

Comments

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Abbreviated Journal Title

Biomaterials

Keywords

Stem cell; Co-culture; In vitro; Nerve tissue engineering; Skeletal; muscle; In vitro test; RAT SPINAL-CORD; INNERVATED HUMAN MUSCLE; IN-VITRO; MOTOR-NEURONS; DIRECTED DIFFERENTIATION; FUNCTIONAL MOTONEURONS; SYNAPSE FORMATION; DRUG DISCOVERY; NERVE; CULTURE; Engineering, Biomedical; Materials Science, Biomaterials

Abstract

Functional in vitro models composed of human cells will constitute an important platform in the next generation of system biology and drug discovery. This study reports a novel human-based in vitro Neuromuscular Junction (NMJ) system developed in a defined serum-free medium and on a patternable non-biological surface. The motoneurons and skeletal muscles were derived from fetal spinal stem cells and skeletal muscle stem cells. The motoneurons and skeletal myotubes were completely differentiated in the co-culture based on morphological analysis and electrophysiology. NMJ formation was demonstrated by phase contrast microscopy, immunocytochemistry and the observation of motoneuron-induced muscle contractions utilizing time-lapse recordings and their subsequent quenching by D-Tubocurarine. Generally, functional human based systems would eliminate the issue of species variability during the drug development process and its derivation from stem cells bypasses the restrictions inherent with utilization of primary human tissue. This defined human-based NMJ system is one of the first steps in creating functional in vitro systems and will play an important role in understanding NMJ development, in developing high information content drug screens and as test beds in preclinical studies for spinal or muscular diseases/injuries such as muscular dystrophy, Amyotrophic lateral sclerosis and spinal cord repair. (C) 2011 Elsevier Ltd. All rights reserved.

Journal Title

Biomaterials

Volume

32

Issue/Number

36

Publication Date

1-1-2011

Document Type

Article

Language

English

First Page

9602

Last Page

9611

WOS Identifier

WOS:000296821800006

ISSN

0142-9612

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