Extracellular vesicles from a muscle cell line (C2C12) enhance cell survival and neurite outgrowth of a motor neuron cell line (NSC-34).

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Date

2014-01

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Abstract

Introduction

There is renewed interest in extracellular vesicles over the past decade or 2 after initially being thought of as simple cellular garbage cans to rid cells of unwanted components. Although there has been intense research into the role of extracellular vesicles in the fields of tumour and stem cell biology, the possible role of extracellular vesicles in nerve regeneration is just in its infancy.

Background

When a peripheral nerve is damaged, the communication between spinal cord motor neurons and their target muscles is disrupted and the result can be the loss of coordinated muscle movement. Despite state-of-the-art surgical procedures only approximately 10% of adults will recover full function after peripheral nerve repair. To improve upon such results will require a better understanding of the basic mechanisms that influence axon outgrowth and the interplay between the parent motor neuron and the distal end organ of muscle. It has previously been shown that extracellular vesicles are immunologically tolerated, display targeting ligands on their surface, and can be delivered in vivo to selected cell populations. All of these characteristics suggest that extracellular vesicles could play a significant role in nerve regeneration.

Methods

We have carried out studies using 2 very well characterized cell lines, the C2C12 muscle cell line and the motor neuron cell line NSC-34 to ask the question: Do extracellular vesicles from muscle influence cell survival and/or neurite outgrowth of motor neurons?

Conclusion

Our results show striking effects of extracellular vesicles derived from the muscle cell line on the motor neuron cell line in terms of neurite outgrowth and survival.

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Subjects

extracellular vesicles, motor neuron, muscle, neurite outgrowth

Citation

Published Version (Please cite this version)

10.3402/jev.v3.22865

Publication Info

Madison, Roger D, Christopher McGee, Renee Rawson and Grant A Robinson (2014). Extracellular vesicles from a muscle cell line (C2C12) enhance cell survival and neurite outgrowth of a motor neuron cell line (NSC-34). Journal of extracellular vesicles, 3(1). pp. 1–9. 10.3402/jev.v3.22865 Retrieved from https://hdl.handle.net/10161/34002.

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Scholars@Duke

Roger D. Madison

Associate Professor Emeritus in Neurosurgery

Neuronal Plasticity: especially as related to the accuracy of peripheral nerve regeneration. My laboratory is currently involved in studying the efficacy of prosthetic "nerve guides" in rodents and non-human primates. The results suggest that such nerve guides can be as effective as a nerve graft to repair transected peripheral nerves. Limited clinical trials of the nerve guide prostheses are underway, in collaboration with a colleague in Denmark. The nerve regeneration work has more recently taken a molecular turn, and my laboratory is currently looking at the differential expression of genes that may underlie the accuracy of peripheral nerve regeneration. We have developed a double labeling technique which allows us to assess the accuracy of nerve regeneration at the single neuron level. We are finding that motor axons and sensory afferents to muscle display a greater than chance level to grow back to muscle as opposed to skin (ie. regeneration specificity). To identify genes and gene products that may be involved in this process, we are using classical subtractive hybridization, the PCR-based differential display of mRNAs, and amplified antisense RNA (aRNA) for Êexpression profilingË.

Robinson

Grant Alan Robinson

Associate Professor Emeritus in Neurosurgery

My research interests are in central and peripheral nervous system regeneration.


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