Basic Behavior of Migratory Schwann Cells in Peripheral Nerve Regeneration

Torigoe, Kojun; Tanaka, Hirohito-F; Takahashi, Akira; Awaya, Akira; Hashimoto, Katsufumi

doi:10.1006/exnr.1996.0030

Cited by 163 publications

(146 citation statements)

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“…A role of Cdc2 function in migration was further demonstrated in Schwann cells that were infected with Cdc2-expressing viral vectors and implanted into the sciatic nerve. Since transplanted Schwann cells expressing wt-Cdc2 migrated faster toward the distal end than those expressing dn-Cdc2, we presume that endogenous Schwann cells in which Cdc2 expression was increased by nerve crush might conduct similar motility along the Wallerian degenerated trunk (Fukaya et al, 2003;Torigoe et al, 1996).…”

Section: Discussionmentioning

confidence: 95%

“…Schwann cells in the injured nerve area proliferate and migrate into the distal end forming the band of Büngner and support axonal regrowth (Fawcett and Keynes, 1990). Schwann cell migration, which also occurs at proximal end of the injury area, provides a guide for regenerating axons by interacting with nerve fibers or basal lamina (Williams et al, 1983;Daniloff, 1991;Guenard et al, 1992;Torigoe et al, 1996). Several studies showed that Schwann cell migration is crucial for successful axonal elongation (Torigoe et al, 1996;Anton et al, 1994a).…”

Section: Introductionmentioning

confidence: 99%

“…Schwann cell migration, which also occurs at proximal end of the injury area, provides a guide for regenerating axons by interacting with nerve fibers or basal lamina (Williams et al, 1983;Daniloff, 1991;Guenard et al, 1992;Torigoe et al, 1996). Several studies showed that Schwann cell migration is crucial for successful axonal elongation (Torigoe et al, 1996;Anton et al, 1994a). Of the molecular factors responsible for Schwann cell migration, NGF and its Schwann cell receptor (low-affinity NGF receptor or LNGFR) and 4C5 Schwann cell surface antigen were reported to mediate Schwann cell migration on denervated sciatic nerve (Anton et al, 1994a;Yfanti et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Cdc2-mediated Schwann cell migration during peripheral nerve regeneration

Han

Seo

Kim

et al. 2007

Journal of Cell Science

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Schwann cell migration facilitates peripheral nerve regeneration after injury. We have recently found increased activation of Cdc2 kinase in regenerating sciatic nerves. Here we show that Cdc2 phosphorylation of caldesmon regulates Schwann cell migration and nerve regeneration. A robust but transient increase in Cdc2 expression was found in cultured Schwann cells prepared from the sciatic nerve in rats that had undergone crush injury for 7 days. These `injury-preconditioned' Schwann cells exhibited enhanced migration compared with non-preconditioned control cells and treatment with the cdk inhibitor roscovitine prevented cell migration. After transduction with recombinant Cdc2 DNA adenoviral vectors, Schwann cells were implanted into sciatic nerves; those expressing wild-type Cdc2 migrated further in the distal direction than those expressing dominant-negative Cdc2. We identified caldesmon as a downstream substrate of Cdc2 in Schwann cells and its phosphorylation by Cdc2 changed its subcellular localization. Overexpression of dominant-negative caldesmon significantly counteracted the migration effect caused by Cdc2. Finally, neurite outgrowth of cultured DRG sensory neurons, facilitated by co-culture with injury-preconditioned Schwann cells, was suppressed by roscovitine treatment. The results indicate that activation of the Cdc2-caldesmon pathway is necessary for Schwann cell migration and suggest a role for this pathway in peripheral axonal growth.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cdc2-mediated Schwann cell migration during peripheral nerve regeneration

Han

Seo

Kim

et al. 2007

Journal of Cell Science

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“…Furthermore, Schwann cells express tPA (Kalderon, 1984;Krystosek and Seeds, 1984;Clark et al, 1991). After nerve injury, Schwann cells proliferate, migrate, and align along newly regenerating nerves (Son and Thompson, 1995;Torigoe et al, 1996). Thus, it is probable that induction of tPA mRNA occurred in these reactive Schwann cells during regeneration of the sciatic nerve (Fig.…”

Section: Discussionmentioning

confidence: 99%

Induction of the Plasminogen Activator System Accompanies Peripheral Nerve Regeneration after Sciatic Nerve Crush

Siconolfi

Seeds

2001

J. Neurosci.

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Peripheral nerve regeneration is dependent on the ability of regenerating neurites to migrate through cellular debris and altered extracellular matrix at the injury site, grow along the residual distal nerve sheath conduit, and reinnervate synaptic targets. In cell culture, growth cones of regenerating axons secrete proteases, specifically plasminogen activators (PAs), which are believed to facilitate growth cone movement by digesting extracellular matrices and cell adhesions. In this study, the PA system was shown to be specifically activated in sensory neurons after sciatic nerve crush in adult mice. The number of sensory neurons expressing urokinase PA receptor (uPAR) mRNA levels increased above sham levels by 8 hr after crush, whereas the number of sensory neurons expressing uPA and tissue PA (tPA) mRNAs was significantly increased by 3 d after crush. PA mRNA levels were also increased at the crush site, with uPA mRNA elevated by 8 hr after crush and tPA and uPAR mRNA levels markedly increased by 7 d. PA-dependent enzymatic activity was significantly increased from 1 to 7 d after crush in nerves that had been crushed compared with uncrushed nerves. Immunohistochemistry showed that tPA was localized within regenerating axons of the sciatic nerve. There were no significant changes in plasminogen activator inhibitor 1 activity between crush and sham after the injury. These results clearly demonstrated that after injury the PA system was rapidly induced in sensory neurons, where it may play an important role in nerve regeneration in vivo.

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“…SCs exhibit substantial potential for the repair of the injured spinal cord [28,29] . Injury to the PNS produces a cascade of cellular and molecular events, which promote the proliferation and activation of SCs within the distal nerve stump [24,30] . Activated SCs (ASCs) express various neurotrophic factors and cell adhesion molecules and supply the extracellular matrix, which plays an important role in remyelination and interactions between SCs and axons [31][32][33][34][35] .…”

Section: Introductionmentioning

confidence: 99%

Multichannel polymer scaffold seeded with activated Schwann cells and bone mesenchymal stem cells improves axonal regeneration and functional recovery after rat spinal cord injury

Yang

Zhang

et al. 2017

Acta Pharmacol Sin

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The adult mammalian CNS has a limited capacity to regenerate after traumatic injury. In this study, a combinatorial strategy to promote axonal regeneration and functional recovery after spinal cord injury (SCI) was evaluated in adult rats. The rats were subjected to a complete transection in the thoracic spinal cord, and multichannel scaffolds seeded with activated Schwann cells (ASCs) and/or rat bone marrow-derived mesenchymal stem cells (MSCs) were acutely grafted into the 3-mm-wide transection gap. At 4 weeks posttransplantation and thereafter, the rats receiving scaffolds seeded with ASCs and MSCs exhibited significant recovery of nerve function as shown by the Basso, Beattie and Bresnahan (BBB) score and electrophysiological test results. Immunohistochemical analyses at 4 and 8 weeks after transplantation revealed that the implanted MSCs at the lesion/graft site survived and differentiated into neuron-like cells and co-localized with host neurons. Robust bundles of regenerated fibers were identified in the lesion/graft site in the ASC and MSC co-transplantation rats, and neurofilament 200 (NF) staining confirmed that these fibers were axons. Furthermore, myelin basic protein (MBP)-positive myelin sheaths were also identified at the lesion/graft site and confirmed via electron microscopy. In addition to expressing mature neuronal markers, sparse MSC-derived neuron-like cells expressed choline acetyltransferase (ChAT) at the injury site of the ASC and MSC co-transplantation rats. These findings suggest that co-transplantation of ASCs and MSCs in a multichannel polymer scaffold may represent a novel combinatorial strategy for the treatment of spinal cord injury.

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Basic Behavior of Migratory Schwann Cells in Peripheral Nerve Regeneration

Cited by 163 publications

References 0 publications

Cdc2-mediated Schwann cell migration during peripheral nerve regeneration

Cdc2-mediated Schwann cell migration during peripheral nerve regeneration

Induction of the Plasminogen Activator System Accompanies Peripheral Nerve Regeneration after Sciatic Nerve Crush

Multichannel polymer scaffold seeded with activated Schwann cells and bone mesenchymal stem cells improves axonal regeneration and functional recovery after rat spinal cord injury

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