In vitro models of axon regeneration

Al-Ali, Hassan; Beckerman, Samuel R.; Bixby, John L.; Lemmon, Vance

doi:10.1016/j.expneurol.2016.01.020

Cited by 46 publications

(41 citation statements)

References 200 publications

(201 reference statements)

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“…While GDNF has already been reported to promote neurite outgrowth of both populations, FGF-2 was described to preferentially enhance motor neurite outgrowth when measuring the length of longest neurites [15]. Since reliable measurements of neurite outgrowth analysis in organotypic cultures are complicated [21], we used a semiautomatic analysis that works as an adaption of the Sholl method [17] to improve accuracy and reproducibility as shown in other works [22, 23]. Thus, the differences in methods and variables to quantify neurite outgrowth in these studies may in fact explain some controversies.…”

Section: Resultsmentioning

confidence: 99%

Dose-Dependent Differential Effect of Neurotrophic Factors on In Vitro and In Vivo Regeneration of Motor and Sensory Neurons

et al. 2016

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Although peripheral axons can regenerate after nerve transection and repair, functional recovery is usually poor due to inaccurate reinnervation. Neurotrophic factors promote directional guidance to regenerating axons and their selective application may help to improve functional recovery. Hence, we have characterized in organotypic cultures of spinal cord and dorsal root ganglia the effect of GDNF, FGF-2, NGF, NT-3, and BDNF at different concentrations on motor and sensory neurite outgrowth. In vitro results show that GDNF and FGF-2 enhanced both motor and sensory neurite outgrowth, NGF and NT-3 were the most selective to enhance sensory neurite outgrowth, and high doses of BDNF selectively enhanced motor neurite outgrowth. Then, NGF, NT-3, and BDNF (as the most selective factors) were delivered in a collagen matrix within a silicone tube to repair the severed sciatic nerve of rats. Quantification of Fluorogold retrolabeled neurons showed that NGF and NT-3 did not show preferential effect on sensory regeneration whereas BDNF preferentially promoted motor axons regeneration. Therefore, the selective effects of NGF and NT-3 shown in vitro are lost when they are applied in vivo, but a high dose of BDNF is able to selectively enhance motor neuron regeneration both in vitro and in vivo.

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Section: Resultsmentioning

confidence: 99%

Dose-Dependent Differential Effect of Neurotrophic Factors on In Vitro and In Vivo Regeneration of Motor and Sensory Neurons

et al. 2016

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“…Organotypic cultures are multicellular in vitro models in which neurons and growing neurites share similar differentiation and development patterns with in vivo conditions [ 28 ] while they are still in contact with Schwann cells and fibroblasts. In this way, DRG explants have been long used to study axonal growth and regeneration of the sensory nervous system [ 29 , 30 ] as DRG contain the soma of pseudounipolar sensory neurons that project growing neurites outside the ganglion. On the other hand, neurites growing from the ventral areas of the spinal cord arise from motoneurons of the ventral horn instead of other interneurons [ 31 ] making this 3D culture an useful model for studying regeneration of motor neurites in vitro [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Preferential Enhancement of Sensory and Motor Axon Regeneration by Combining Extracellular Matrix Components with Neurotrophic Factors

Santos

González-Pérez

Giudetti

et al. 2016

IJMS

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After peripheral nerve injury, motor and sensory axons are able to regenerate but inaccuracy of target reinnervation leads to poor functional recovery. Extracellular matrix (ECM) components and neurotrophic factors (NTFs) exert their effect on different neuronal populations creating a suitable environment to promote axonal growth. Here, we assessed in vitro and in vivo the selective effects of combining different ECM components with NTFs on motor and sensory axons regeneration and target reinnervation. Organotypic cultures with collagen, laminin and nerve growth factor (NGF)/neurotrophin-3 (NT3) or collagen, fibronectin and brain-derived neurotrophic factor (BDNF) selectively enhanced sensory neurite outgrowth of DRG neurons and motor neurite outgrowth from spinal cord slices respectively. For in vivo studies, the rat sciatic nerve was transected and repaired with a silicone tube filled with a collagen and laminin matrix with NGF/NT3 encapsulated in poly(lactic-co-glycolic acid) (PLGA) microspheres (MP) (LM + MP.NGF/NT3), or a collagen and fibronectin matrix with BDNF in PLGA MPs (FN + MP.BDNF). Retrograde labeling and functional tests showed that LM + MP.NGF/NT3 increased the number of regenerated sensory neurons and improved sensory functional recovery, whereas FN + MP.BDNF preferentially increased regenerated motoneurons and enhanced motor functional recovery. Therefore, combination of ECM molecules with NTFs may be a good approach to selectively enhance motor and sensory axons regeneration and promote appropriate target reinnervation.

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“…This system enables isolation of the axons from the soma and dendrites of neurons by allowing axons to extend into the microgrooves. The axons reach the opposite chamber with this extension, often accelerated due to a hydrostatic pressure difference, and associated flow, between the two chambers . Cohen et al studied BDNF‐mediated dendrite‐to‐nucleus signaling and its related gene expression changes in a CMS.…”

Section: Modeling Neurodegenerative Diseases On a Chipmentioning

confidence: 99%

In Vitro Microfluidic Models for Neurodegenerative Disorders

Osaki

Shin

Sivathanu

et al. 2017

Adv Healthcare Materials

119

126

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Microfluidic devices enable novel means of emulating neurodegenerative disease pathophysiology in vitro. These organ-on-a-chip systems can potentially reduce animal testing and substitute (or augment) simple 2D culture systems. Reconstituting critical features of neurodegenerative diseases in a biomimetic system using microfluidics can thereby accelerate drug discovery and improve our understanding of the mechanisms of several currently incurable diseases. This review describes latest advances in modeling neurodegenerative diseases in the central nervous system and the peripheral nervous system. First, this study summarizes fundamental advantages of microfluidic devices in the creation of compartmentalized cell culture microenvironments for the co-culture of neurons, glial cells, endothelial cells, and skeletal muscle cells and in their recapitulation of spatiotemporal chemical gradients and mechanical microenvironments. Then, this reviews neurodegenerative-disease-on-a-chip models focusing on Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Finally, this study discusses about current drawbacks of these models and strategies that may overcome them. These organ-on-chip technologies can be useful to be the first line of testing line in drug development and toxicology studies, which can contribute significantly to minimize the phase of animal testing steps.

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In vitro models of axon regeneration

Cited by 46 publications

References 200 publications

Dose-Dependent Differential Effect of Neurotrophic Factors on In Vitro and In Vivo Regeneration of Motor and Sensory Neurons

Dose-Dependent Differential Effect of Neurotrophic Factors on In Vitro and In Vivo Regeneration of Motor and Sensory Neurons

Preferential Enhancement of Sensory and Motor Axon Regeneration by Combining Extracellular Matrix Components with Neurotrophic Factors

In Vitro Microfluidic Models for Neurodegenerative Disorders

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