Schwann cell regulation of axonal regeneration

In the mammalian nervous system, the regenerative capabilities of neurons show regional variability. In the peripheral nervous system (PNS), axons efficiently regenerate after nerve damage associated to the pro-regenerative effect of Schwann cells. In contrast, in the central nervous system the regenerative capability is poor due to both neuronal intrinsic limitations and glial responses that restrict regeneration. Although, axonal regeneration in the periphery show good regenerative capacity in preclinical models, it still represents a clinical problem associated to delayed repair of peripheral nerves, and the negative effects of aging and other conditions, including diabetes, for axonal regeneration and functional recovery. In the lab, we study how Schwann cells reprogramming regulates axonal regeneration after nerve damage, in order to manipulate this response to enhance axonal regeneration.

Longitudinal section of a sciatic nerve, with regenerating axons crossing a surgically repaired region, axons are labelled using an antibody against the protein SCG10.

Schwann cell exosomes enhance axonal regeneration

In the peripheral nervous system, regeneration of injured axons depends on the reprogramming of Schwann cell from a differentiated phenotype into a phenotype known as repair Schwann cells. Our lab was the first to demonstrate that Schwann cell exosomes enhanced axonal regeneration in vitro and in vivo in laboratory animals, an effect we later showed was dependent on the reprogramming of Schwann cells into a repair phenotype, and associated with the loading of specific miRNA into exosomes and their transfer to axons. In addition, we are exploring the effects of aging, chronic denervation and diabetes in Schwann cell reprograming and axonal regeneration, in order to develop interventions to enhance axonal regeneration in these conditions.

People involved

Nicole Letelier

Postdoctoral Fellow

Biochemist and master in Biochemistry from University of Chile. PhD in Biomedicine by University of Barcelona with strong knowledge in immunology. My doctoral thesis focused on the mechanisms of LXR-mediated control of obesity-induced metaflammation and insulin-resistance.

Andrés Fuentes

PhD Student

Biotechnologist and PhD in Integrative Genomics from the Mayor University, Chile. Currently working in the characterization and indiction of senescence over Schwann cells in the context of chronic denervation and aging. Aiming to assess the clinical impact of senescent Schwann cells over axonal regeneration in the peripheral nervous system after mechanical damage.

David Necuñir

Research Assistant

Biotechnology Engineer and Master from Universidad Nacional Andrés Bello, Santiago de Chile. I’m currently working on the role of necroptosis in axonal degeneration in mesencephalic neurons primary culture, RNA transference and glial cells-neurons communication mediated by exosomes using Schwann cells and evaluating regeneration of peripheral neurons.

Related Publications

New insights on the molecular mechanisms of collateral sprouting after peripheral nerve injury.

Lemaitre D, Court FA.

Neural Regen Res. 2021 Sep;16(9):1760-1761. doi: 10.4103/1673-5374.306069.

PMID: 33510065

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Collateral Sprouting of Peripheral Sensory Neurons Exhibits a Unique Transcriptomic Profile.

Lemaitre D, Hurtado ML, De Gregorio C, Oñate M, Martínez G, Catenaccio A, Wishart TM, Court FA.

Mol Neurobiol. 2020 Oct;57(10):4232-4249. doi: 10.1007/s12035-020-01986-3. Epub 2020 Jul 21.

PMID: 32696431

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Schwann Cell Reprogramming Into Repair Cells Increases Exosome-Loaded miRNA-21 Promoting Axonal Growth.

López-Leal R, Díaz-Viraqué F, Catalán RJ, Saquel C, Enright A, Iraola G, Court FA.

J Cell Sci. 2020 Jun 15;133(12):jcs239004. doi: 10.1242/jcs.239004.

PMID: 32409566

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The p75NTR neurotrophin receptor is required to organize the mature neuromuscular synapse by regulating synaptic vesicle availability.

Pérez V, Bermedo-Garcia F, Zelada D, Court FA, Pérez MÁ, Fuenzalida M, Ábrigo J, Cabello-Verrugio C, Moya-Alvarado G, Tapia JC, Valenzuela V, Hetz C, Bronfman FC, Henríquez JP.

Acta Neuropathol Commun. 2019 Sep 12;7(1):147. doi: 10.1186/s40478-019-0802-7.

PMID: 31514753

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