New insights into peripheral nerve regeneration: The role of secretomes

Contreras, Estefanía; Bolívar, Sara; Navarro, Xavier; Udina, Esther

doi:10.1016/j.expneurol.2022.114069

“…Schwann cells play an essential role in regulating the phenomena of axonal extension, protein synthesis, and remyelination, and it is now well established that the secretome of these cells plays an essential role in modulating Wallerian degeneration and sustaining axonal regeneration [ 41 ]. Thus, it is essential that the secretome selected as a therapeutic approach has in its constitution a set of biofactors also identified in the secretome of Schwann cells and that are known to actively participate in the regenerative process.…”

Section: Discussionmentioning

confidence: 99%

“…IL-6 is secreted by Schwann cells a few hours after nerve injury, which indicates its importance in the acute phase of regeneration and in the local inflammatory response. Simultaneously, some anti-inflammatory cytokines such as IL-10 are also upregulated at this stage, probably contributing to the balance in the immune response and preventing deleterious inflammatory reactions [ 41 ]. Fractalkine participates in a signaling pathway in neuron-to-microglia communication and is related to the development of neuropathic pain phenomena after nerve injury [ 46 ], and the cytokine GRO/KC shows upregulation in dorsal root ganglion after nerve injury, appearing to have a pro-nociceptive effect by increasing neuronal excitability in small diameter sensory neurons [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Olfactory Mucosa Stem/Stromal Cell and Olfactory Ensheating Cells Secretome on Peripheral Nerve Regeneration

Alvites

¹

,

Branquinho

²

,

Sousa

³

et al. 2022

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Cell secretome has been explored as a cell-free technique with high scientific and medical interest for Regenerative Medicine. In this work, the secretome produced and collected from Olfactory Mucosa Mesenchymal Stem Cells and Olfactory Ensheating Cells was analyzed and therapeutically applied to promote peripheral nerve regeneration. The analysis of the conditioned medium revealed the production and secretion of several factors with immunomodulatory functions, capable of intervening beneficially in the phases of nerve regeneration. Subsequently, the conditioned medium was applied to sciatic nerves of rats after neurotmesis, using Reaxon® as tube-guides. Over 20 weeks, the animals were subjected to periodic functional assessments, and after this period, the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed to confirm the beneficial effects resulting from the application of this therapeutic combination. The administration of conditioned medium from Olfactory Mucosal Mesenchymal Stem Cells led to the best results in motor performance, sensory recovery, and gait patterns. Stereological and histomorphometric evaluation also revealed the ability of this therapeutic combination to promote nervous and muscular histologic reorganization during the regenerative process. The therapeutic combination discussed in this work shows promising results and should be further explored to clarify irregularities found in the outcomes and to allow establishing the use of cell secretome as a new therapeutic field applied in the treatment of peripheral nerves after injury.

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“…Schwann cells play an essential role in regulating the phenomena of axonal extension, protein synthesis and remyelination, and it is now well established that the secretome of these cells plays an essential role in modulating Wallerian Degeneration and sustaining axonal regeneration [39]. Thus, it is essential that the secretome selected as a therapeutic approach has in its constitution a set of biofactors also identified in the secretome of Schwann cells and that are known to actively participate in the regenerative process.…”

Section: Discussionmentioning

confidence: 99%

“…IL-6 is secreted by Schwann cells a few hours after nerve injury, which indicates its importance in the acute phase of regeneration and in the local inflammatory response. Simultaneously, some anti-inflammatory cytokines such as IL-10 are also upregulated at this stage, probably contributing to the balance in the immune response and preventing deleterious inflammatory reactions [39]. Fractalkine participates in a signaling pathway in neuron-to-microglia communication and is related to the development of neuropathic pain phenomena after nerve injury [44], and the cytokine GRO/KC shows upregulation in dorsal root ganglion after nerve injury, appearing to have a pro-nociceptive effect by increasing neuronal excitability in small diameter sensory neurons [45].…”

Section: Discussionmentioning

confidence: 99%

Effects of Olfactory Mucosa Stem/Stromal Cell and Olfactory Ensheating Cells Secretome on Peripheral Nerve Regeneration

Alvites¹,

Branquinho²,

Silva³

et al. 2022

Preprint

1

0

View full text Add to dashboard Cite

Cell secretome has been explored as a cell-free technique with high scientific and medical interest for Regenerative Medicine. In this work, the secretome produced and collected from Olfactory Mucosa Mesenchymal Stem Cells and Olfactory Ensheating Cells was analyzed and therapeutically applied to promote peripheral nerve regeneration. The analysis of the conditioned medium revealed the production and secretion of several factors with immunomodulatory functions, capable of intervening beneficially in the phases of nerve regeneration. Subsequently, the conditioned medium was applied to sciatic nerves of rats after neurotmesis, using Reaxon® as tube-guides. Over 20 weeks, the animals were subjected to periodic functional assessments, and after this period, the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed to confirm the beneficial effects resulting from the application of this therapeutic combination. The administration of conditioned medium from Olfactory Mucosal Mesenchymal Stem Cells led to the best results in motor performance, sensory recovery, and gait patterns. Stereological and histomorphometric evaluation also revealed the ability of this therapeutic combination to promote nervous and muscular histologic reorganization during the regenerative process. The therapeutic combination discussed in this work shows promising results and should be further explored to clarify irregularities found in the outcomes and to allow establishing the use of cell secretome as a new therapeutic field applied in the treatment of peripheral nerves after injury.

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“…Ferroptosis May Occur in Macrophages after Peripheral Nerve Injury. During the Wallerian degeneration, activation of SCs is accompanied by recruitment of immune cells into the lesion site such as lymphocytes, macrophages and neutrophils [98]. Among these different cells, macrophages not only play a key role in promoting SCs activation and removing myelin debris but also contributing to the creation of permissive environment for axonal regeneration by releasing different proregenerative factors such as growth factors, chemokines, cytokines, and extracellular matrix (ECM) molecules [99].…”

Section: Ferroptosis In the Schwann Cells After Peripheral Nervementioning

confidence: 99%

Iron Metabolism and Ferroptosis in Peripheral Nerve Injury

Huang

¹

,

Bian

²

,

Zhang

³

et al. 2022

Oxidative Medicine and Cellular Longevity

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Peripheral nerve injury (PNI) is a major clinical problem that may lead to different levels of sensory and motor dysfunction including paralysis. Due to the high disability rate and unsatisfactory prognosis, the exploration and revealment of the mechanisms involved in the PNI are urgently required. Ferroptosis, a recently identified novel form of cell death, is an iron-dependent process. It is a unique modality of cell death, closely associated with iron concentrations, generation of reactive oxygen species, and accumulation of the lipid reactive oxygen species. These processes are regulated by multiple cellular metabolic pathways, including iron overloading, lipid peroxidation, and the glutathione/glutathione peroxidase 4 pathway. Furthermore, ferroptosis is accompanied by morphological changes in the mitochondria, such as increased membrane density and shrunken mitochondria; this association between ferroptosis and mitochondrial damage has been detected in various diseases, including spinal cord injury and PNI. The inhibition of ferroptosis can promote the repair of damaged peripheral nerves, reduce mitochondrial damage, and promote the recovery of neurological function. In this review, we intend to discuss the detailed mechanisms of ferroptosis and summarize the current researches on ferroptosis with respect to nerve injury. This review also aims at providing new insights on targeting ferroptosis for PNI treatment.

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New insights into peripheral nerve regeneration: The role of secretomes

Cited by 31 publications

References 122 publications

Effects of Olfactory Mucosa Stem/Stromal Cell and Olfactory Ensheating Cells Secretome on Peripheral Nerve Regeneration

Effects of Olfactory Mucosa Stem/Stromal Cell and Olfactory Ensheating Cells Secretome on Peripheral Nerve Regeneration

Effects of Olfactory Mucosa Stem/Stromal Cell and Olfactory Ensheating Cells Secretome on Peripheral Nerve Regeneration

Iron Metabolism and Ferroptosis in Peripheral Nerve Injury

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