All the PNS is a Stage: Transplanted Bone Marrow Cells Play an Immunomodulatory Role in Peripheral Nerve Regeneration

Working on a Wallerian degeneration model in rats, our group has shown the beneficial effects of systemic bone marrow mononuclear cell transplant on morphological and functional parameters, as well as the prevention of neuropathic pain. The current work thus seeks to evaluate the effect of systemic...

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Main Authors: Gonzalo Piñero, Marianela Vence, Marcos L. Aranda, Magalí C. Cercato, Paula A. Soto, Vanina Usach, Patricia C. Setton-Avruj
Format: Article
Language:English
Published: SAGE Publishing 2023-09-01
Series:ASN Neuro
Online Access:https://doi.org/10.1177/17590914231167281
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author Gonzalo Piñero
Marianela Vence
Marcos L. Aranda
Magalí C. Cercato
Paula A. Soto
Vanina Usach
Patricia C. Setton-Avruj
author_facet Gonzalo Piñero
Marianela Vence
Marcos L. Aranda
Magalí C. Cercato
Paula A. Soto
Vanina Usach
Patricia C. Setton-Avruj
author_sort Gonzalo Piñero
collection DOAJ
description Working on a Wallerian degeneration model in rats, our group has shown the beneficial effects of systemic bone marrow mononuclear cell transplant on morphological and functional parameters, as well as the prevention of neuropathic pain. The current work thus seeks to evaluate the effect of systemic bone marrow cell transplant in a mouse model of sciatic nerve crush and aims to dig deeper into the mechanisms involved in bone marrow cell therapy. Adult C57BL/6J mice were subjected to 8s sciatic nerve crush and intravenously transplanted with bone marrow cells. Cells were tracked using a fluorescent probe, and the evolution of the degeneration–regeneration process was evaluated through axonal and myelin marker immunodetection at different survival times. Gene and protein expression of the main cytokines involved in the inflammatory phase and lesion-associated macrophage phenotypes were also analyzed. Initial findings corroborated the beneficial effect of bone marrow cells on the regenerative process and proved their efficiency in reducing the expression of some proinflammatory cytokines and increasing that of anti-inflammatory interleukin 10 (IL-10). In addition, transplanted animals showed a decrease in inducible nitric oxide synthase (iNOS) + macrophages, an increment in CD206 + cells, and an anticipated rise in Arg-1 + macrophages. Taken together, our results endorse bone marrow cell therapy as an alternative approach to accelerate nerve recovery and postulate bone marrow cells as potential immunomodulators. Summary Statement Bone marrow cell transplant has proven to be an effective therapeutic approach to treat peripheral nervous system injuries as it not only promoted regeneration and remyelination of the injured nerve but also had a potent effect on neuropathic pain.
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spelling doaj.art-d2df3b19a0d0474ea39f192f427c47472023-09-01T21:03:23ZengSAGE PublishingASN Neuro1759-09142023-09-011510.1177/17590914231167281All the PNS is a Stage: Transplanted Bone Marrow Cells Play an Immunomodulatory Role in Peripheral Nerve RegenerationGonzalo Piñero0Marianela Vence1Marcos L. Aranda2Magalí C. Cercato3Paula A. Soto4Vanina Usach5Patricia C. Setton-Avruj6 Department of Pathology, Mount Sinai Hospital, New York, NY, USA Universidad de Buenos Aires-CONICET, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Ciudad Autónoma de Buenos Aires, Argentina Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL, USA Universidad de Buenos Aires-CONICET, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Ciudad Autónoma de Buenos Aires, Argentina Universidad de Buenos Aires-CONICET, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Ciudad Autónoma de Buenos Aires, Argentina Universidad de Buenos Aires-CONICET, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Ciudad Autónoma de Buenos Aires, Argentina Universidad de Buenos Aires-CONICET, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Ciudad Autónoma de Buenos Aires, ArgentinaWorking on a Wallerian degeneration model in rats, our group has shown the beneficial effects of systemic bone marrow mononuclear cell transplant on morphological and functional parameters, as well as the prevention of neuropathic pain. The current work thus seeks to evaluate the effect of systemic bone marrow cell transplant in a mouse model of sciatic nerve crush and aims to dig deeper into the mechanisms involved in bone marrow cell therapy. Adult C57BL/6J mice were subjected to 8s sciatic nerve crush and intravenously transplanted with bone marrow cells. Cells were tracked using a fluorescent probe, and the evolution of the degeneration–regeneration process was evaluated through axonal and myelin marker immunodetection at different survival times. Gene and protein expression of the main cytokines involved in the inflammatory phase and lesion-associated macrophage phenotypes were also analyzed. Initial findings corroborated the beneficial effect of bone marrow cells on the regenerative process and proved their efficiency in reducing the expression of some proinflammatory cytokines and increasing that of anti-inflammatory interleukin 10 (IL-10). In addition, transplanted animals showed a decrease in inducible nitric oxide synthase (iNOS) + macrophages, an increment in CD206 + cells, and an anticipated rise in Arg-1 + macrophages. Taken together, our results endorse bone marrow cell therapy as an alternative approach to accelerate nerve recovery and postulate bone marrow cells as potential immunomodulators. Summary Statement Bone marrow cell transplant has proven to be an effective therapeutic approach to treat peripheral nervous system injuries as it not only promoted regeneration and remyelination of the injured nerve but also had a potent effect on neuropathic pain.https://doi.org/10.1177/17590914231167281
spellingShingle Gonzalo Piñero
Marianela Vence
Marcos L. Aranda
Magalí C. Cercato
Paula A. Soto
Vanina Usach
Patricia C. Setton-Avruj
All the PNS is a Stage: Transplanted Bone Marrow Cells Play an Immunomodulatory Role in Peripheral Nerve Regeneration
ASN Neuro
title All the PNS is a Stage: Transplanted Bone Marrow Cells Play an Immunomodulatory Role in Peripheral Nerve Regeneration
title_full All the PNS is a Stage: Transplanted Bone Marrow Cells Play an Immunomodulatory Role in Peripheral Nerve Regeneration
title_fullStr All the PNS is a Stage: Transplanted Bone Marrow Cells Play an Immunomodulatory Role in Peripheral Nerve Regeneration
title_full_unstemmed All the PNS is a Stage: Transplanted Bone Marrow Cells Play an Immunomodulatory Role in Peripheral Nerve Regeneration
title_short All the PNS is a Stage: Transplanted Bone Marrow Cells Play an Immunomodulatory Role in Peripheral Nerve Regeneration
title_sort all the pns is a stage transplanted bone marrow cells play an immunomodulatory role in peripheral nerve regeneration
url https://doi.org/10.1177/17590914231167281
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