Brain-Derived Neurotrophic Factor from Bone Marrow-Derived Cells Promotes Post-Injury Repair of Peripheral Nerve

Takemura, Y; Imai, Shunsuke; Kojima, Hideto; Katagi, Munehiro; Yamakawa, Isamu; Kasahara, Toshiyuki; Urabe, Hiroshi; Terashima, Tomoya; Yasuda, Hitoshi; Kimura, Hiroshi; Matsusue, Yoshitaka

doi:10.1371/journal.pone.0044592

Cited by 41 publications

(24 citation statements)

References 32 publications

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“…In sensory neurons, NGF promotes primary survival and axonal outgrowth [52,53]. BDNF promotes motor neuron survival and differentiation [54,55]. NT-3 supports myelin formation by enhancing SC motility and migration [56,57].…”

Section: Discussionmentioning

confidence: 99%

Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth

Sugimura‐Wakayama

Katagiri

Osugi

et al. 2015

Stem Cells and Development

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Peripheral nerve regeneration across nerve gaps is often suboptimal, with poor functional recovery. Stem cell transplantation-based regenerative therapy is a promising approach for axon regeneration and functional recovery of peripheral nerve injury; however, the mechanisms remain controversial and unclear. Recent studies suggest that transplanted stem cells promote tissue regeneration through a paracrine mechanism. We investigated the effects of conditioned media derived from stem cells from human exfoliated deciduous teeth (SHED-CM) on peripheral nerve regeneration. In vitro, SHED-CM-treated Schwann cells exhibited significantly increased proliferation, migration, and the expression of neuron-, extracellular matrix (ECM)-, and angiogenesis-related genes. SHED-CM stimulated neuritogenesis of dorsal root ganglia and increased cell viability. Similarly, SHED-CM enhanced tube formation in an angiogenesis assay. In vivo, a 10-mm rat sciatic nerve gap model was bridged by silicon conduits containing SHED-CM or serum-free Dulbecco's modified Eagle's medium. Light and electron microscopy confirmed that the number of myelinated axons and axon-to-fiber ratio (G-ratio) were significantly higher in the SHED-CM group at 12 weeks after nerve transection surgery. The sciatic functional index (SFI) and gastrocnemius (target muscle) wet weight ratio demonstrated functional recovery. Increased compound muscle action potentials and increased SFI in the SHED-CM group suggested sciatic nerve reinnervation of the target muscle and improved functional recovery. We also observed reduced muscle atrophy in the SHED-CM group. Thus, SHEDs may secrete various trophic factors that enhance peripheral nerve regeneration through multiple mechanisms. SHED-CM may therefore provide a novel therapy that creates a more desirable extracellular microenvironment for peripheral nerve regeneration.

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Section: Discussionmentioning

confidence: 99%

Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth

Sugimura‐Wakayama

Katagiri

Osugi

et al. 2015

Stem Cells and Development

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“…Most availableevidence suggests that endogenous NGF does not promote regeneration (Diamond et al, 1987; Gloster and Diamond, 1992; Shoemaker et al, 2006; Lankford et al, 2013). On the other hand, heterozygote knockout animals indicate that endogenous BDNF and NT3 in non-neuronal cells do promote regeneration (Sahenk et al, 2008; Takemura et al, 2012). …”

Section: The Biology Of Wallerian Degenerationmentioning

confidence: 99%

The neuroimmunology of degeneration and regeneration in the peripheral nervous system

et al. 2015

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Peripheral nerves regenerate following injury due to the effective activation of the intrinsic growth capacity of the neurons and the formation of a permissive pathway for outgrowth due to Wallerian degeneration. Wallerian degeneration and subsequent regeneration are significantly influenced by various immune cells and the cytokines they secrete. Although macrophages have long been known to play a vital role in the degenerative process, recent work has pointed to their importance in influencing the regenerative capacity of peripheral neurons. In this review, we focus on the various immune cells, cytokines, and chemokines that make regeneration possible in the peripheral nervous system, with specific attention placed on the role macrophages play in this process.

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“…Administration of neurotrophic factors results in post-injury repair of peripheral nerves and their functional recovery. 20 Successful corneal nerve regeneration following the use of autologous plasma in neurotrophic keratopathy, 21 as well as with autologous serum tears ( AST ) in dry eye patients, prompted us to consider the possible application of AST in patients suffering from corneal neuropathy-induced photoallodynia. 22 …”

Section: Introductionmentioning

confidence: 99%

Autologous Serum Tears for Treatment of Photoallodynia in Patients with Corneal Neuropathy: Efficacy and Evaluation with In Vivo Confocal Microscopy

et al. 2015

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Objective Patients suffering from corneal neuropathy may present with photoallodynia; i.e., increased light sensitivity, frequently with a normal slit-lamp examination. This study aimed to evaluate the efficacy of autologous serum tears (AST) for treatment of severe photoallodynia in corneal neuropathy and correlate with corneal subbasal nerve alterations by in vivo confocal microscopy (IVCM). Methods Retrospective case control study with 16 patients with neuropathy-induced severe photoallodynia compared to 16 normal controls. Symptom severity, clinical examination and bilateral corneal IVCM scans were recorded. Results All patients suffered from extreme photoallodynia (8.8±1.1) with no concurrent ocular surface disease. Subbasal nerves were significantly decreased at baseline in patients compared to controls; total nerve length (9208 ±1264 vs 24714 ±1056 μm/mm2; p<.0001) and total nerve number (9.6±1.4 vs 28.6±2.0; p<.0001), respectively. Morphologically, significantly increased reflectivity (2.9±0.2 vs 1.8±0.1; p<.0001), beading (in 93.7%), and neuromas (in 62.5%) were seen. AST (3.6±2.1 months) resulted in significantly decreased symptom severity (1.6±1.7; p=.02). IVCM demonstrated significantly improved nerve parameters (p< .005), total nerve length (15451±1595 μm/mm2), number (13.9±2.1), and reflectivity (1.9±0.1). Beading and neuromas were seen in only 56.2% and 7.6% of patients. Conclusion Patients with corneal neuropathy-induced photoallodynia show profound alterations in corneal nerves. AST restores nerve topography through nerve regeneration, and this correlated with improvement in patient-reported photoallodynia. The data support the notion that corneal nerve damage results in alterations in afferent trigeminal pathways to produce photoallodynia.

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Brain-Derived Neurotrophic Factor from Bone Marrow-Derived Cells Promotes Post-Injury Repair of Peripheral Nerve

Cited by 41 publications

References 32 publications

Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth

Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth

The neuroimmunology of degeneration and regeneration in the peripheral nervous system

Autologous Serum Tears for Treatment of Photoallodynia in Patients with Corneal Neuropathy: Efficacy and Evaluation with In Vivo Confocal Microscopy

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