Schwann cells and neurite outgrowth from embryonic dorsal root ganglions are highly mechanosensitive

Rosso, Gonzalo; Liashkovich, Ivan; Young, Peter; Röhr, Dominik; Shahin, Victor

doi:10.1016/j.nano.2016.06.011

Cited by 45 publications

(68 citation statements)

References 46 publications

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“…The selected stiffness range corresponds to early, intermediate and adult developmental stages, respectively [4]. Putting the observations together: We have previously shown that outgrowth length of neurites from embryonic DRG explants is substrate stiffness-sensitive [4]. Here we show that also extension pattern, directionality and presumably fasciculation of embryonic DRG neurites strongly depend on substrate stiffness.…”

Section: Discussionsupporting

confidence: 63%

“…The substrates were coated with laminin, a major constituent of SCs basal lamina and a key mediator of SCs actions [14]. The selected stiffness range corresponds to early, intermediate and adult developmental stages, respectively [4]. Putting the observations together: We have previously shown that outgrowth length of neurites from embryonic DRG explants is substrate stiffness-sensitive [4].…”

Section: Discussionmentioning

confidence: 99%

“…DRG explants were dissected from embryonic mice as described in our recent publication [4]. Basically, DRGs explants were isolated from day 12.5 to 13.5 C57BL6/J mice embryos and plated on PA substrates which were previously coated with poly-D-Lysine (Sigma-Aldrich) and 10 µg/ mL laminin (Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

“…This so called mechanosensitivity is crucial for central nervous system development and repair [2], and recent studies demonstrate that isolated peripheral nervous system (PNS) neurons and Schwann cells (SCs) are mechanosensitive [3, 4]. SCs perform numerous tasks crucial for PNS development, maintenance, survival, protection and regeneration [5].…”

Section: Introductionmentioning

confidence: 99%

“…The gradual deposition of ECM dynamically increases the stiffness around SCs and axons during PNS development. Substrate stiffness strongly modulates gene expression in purified SCs [8] and we have shown that morphology and motility of the same cells are highly substrate stiffness-sensitive [4]. Hence, the question is pressing as to whether ECM stiffness acts in concert with biochemical signaling to promote SCs progenitors migration.…”

Section: Introductionmentioning

confidence: 99%

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Mechanosensitivity of Embryonic Neurites Promotes Their Directional Extension and Schwann Cells Progenitors Migration

Rosso

Young²,

Shahin³

2017

Cell Physiol Biochem

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Background/Aims: Migration of Schwann cells (SCs) progenitors and neurite outgrowth from embryonic dorsal root ganglions (DRGs) are two central events during the development of the peripheral nervous system (PNS). How these two enthralling events preceding myelination are promoted is of great relevance from basic research and clinical aspects alike. Recent evidence demonstrates that biophysical cues (extracellular matrix stiffness) and biochemical signaling act in concert to regulate PNS myelination. Microenvironment stiffness of SCs progenitors and embryonic neurites dynamically changes during development. Methods: DRG explants were isolated from day 12.5 to 13.5 mice embryos and plated on laminin-coated substrates with varied stiffness values. After 4 days in culture and immunostaining with specific markers, neurite outgrowth pattern, SCs progenitors migration, and growth cone shape and advance were analyzed with confocal fluorescence microscopy. Results: We found out that growing substrate stiffness promotes directional neurite outgrowth, SCs progenitors migration, growth cone advance and presumably axons fasciculation. Conclusions: DRG explants are in vitro models for the research of PNS development, myelination and regeneration. Consequently, we conclude the following: Our observations point out the importance of mechanosensitivity for the PNS. At the same time, they prompt the investigation of the important yet unclear links between PNS biomechanics and inherited neuropathies with myelination disorders such as Charcot-Marie-Tooth 1A and hereditary neuropathy with liability to pressure palsies. Finally, they encourage the consideration of mechanosensitivity in bioengineering of scaffolds to aid nerve regeneration after injury.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mechanosensitivity of Embryonic Neurites Promotes Their Directional Extension and Schwann Cells Progenitors Migration

Rosso

Young²,

Shahin³

2017

Cell Physiol Biochem

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The Use of Genipin as an Effective, Biocompatible, Anti‐Inflammatory Cross‐Linking Method for Nerve Guidance Conduits

et al. 2020

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A number of natural polymer biomaterial‐based nerve guidance conduits (NGCs) are developed to facilitate repair of peripheral nerve injuries. Cross‐linking ensures mechanical integrity and desired degradation properties of the NGCs; however, common methods such as formaldehyde are associated with cellular toxicity. Hence, there is an unmet clinical need for alternative nontoxic cross‐linking agents. In this study, collagen‐based NGCs with a collagen/chondroitin sulfate luminal filler are used to study the effect of cross‐linking on mechanical and structural properties, degradation, biocompatibility, and immunological response. A simplified manufacturing method of genipin cross‐linking is developed, by incorporating genipin into solution prior to freeze‐drying the NGCs. This leads to successful cross‐linking as demonstrated by higher cross‐linking degree and similar tensile strength of genipin cross‐linked conduits compared to formaldehyde cross‐linked conduits. Genipin cross‐linking also preserves NGC macro and microstructure as observed through scanning electron microscopy and spectral analysis. Most importantly, in vitro cell studies show that genipin, unlike the formaldehyde cross‐linked conduits, supports the viability of Schwann cells. Moreover, genipin cross‐linked conduits direct macrophages away from a pro‐inflammatory and toward a pro‐repair state. Overall, genipin is demonstrated to be an effective, safe, biocompatible, and anti‐inflammatory alternative to formaldehyde for cross‐linking clinical grade NGCs.

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Tissue‐Engineered Peripheral Nerve Interfaces

Spearman

Desai

Mobini

et al. 2017

Adv Funct Materials

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Research on neural interfaces has historically concentrated on development of systems for the brain; however, there is increasing interest in peripheral nerve interfaces (PNIs) that could provide benefit when peripheral nerve function is compromised, such as for amputees. Efforts focus on designing scalable and high-performance sensory and motor peripheral nervous system interfaces. Current PNIs face several design challenges such as undersampling of signals from the thousands of axons, nerve-fiber selectivity, and device-tissue integration. To improve PNIs, several researchers have turned to tissue engineering. Peripheral nerve tissue engineering has focused on designing regeneration scaffolds that mimic normal nerve extracellular matrix composition, provide advanced microarchitecture to stimulate cell migration, and have mechanical properties like native nerve. By combining PNIs with tissue engineering, the goal is to promote natural axon regeneration into the devices to facilitate close contact with electrodes; in contrast, traditional PNIs rely on insertion or placement of electrodes into or around existing nerve, or do not utilize materials to actively facilitate axon regeneration. This review presents the state-of-the-art of PNIs and nerve tissue engineering, highlights recent approaches to combine neural interface technology and tissue engineering, and addresses remaining challenges with foreign body response.

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Schwann cells and neurite outgrowth from embryonic dorsal root ganglions are highly mechanosensitive

Cited by 45 publications

References 46 publications

Mechanosensitivity of Embryonic Neurites Promotes Their Directional Extension and Schwann Cells Progenitors Migration

Mechanosensitivity of Embryonic Neurites Promotes Their Directional Extension and Schwann Cells Progenitors Migration

The Use of Genipin as an Effective, Biocompatible, Anti‐Inflammatory Cross‐Linking Method for Nerve Guidance Conduits

Tissue‐Engineered Peripheral Nerve Interfaces

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