Extracellular matrix protein anosmin-1 regulates Schwann cell-astrocyte interaction for regenerative axon targeting in dorsal root crush injury model

Schwann cell (SC) transplantation is considered as a promising strategy for spinal cord injury. However, SCs show less capability in assisting the regenerative axons to penetrate through astrocyte (AS)-formed scar barrier. Anosmin-1, an extracellular matrix glycosylated adhesion protein expressed in...

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Main Authors: Xichen Xuan, Xuechun Chu, Ruiliang Wang, Lu Liu, Daqing Li, Pierre Marc Bouloux, Ying Li, Youli Hu
Format: Article
Language:English
Published: SAGE Publishing 2025-08-01
Series:Cell Transplantation
Online Access:https://doi.org/10.1177/09636897251362107
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author Xichen Xuan
Xuechun Chu
Ruiliang Wang
Lu Liu
Daqing Li
Pierre Marc Bouloux
Ying Li
Youli Hu
author_facet Xichen Xuan
Xuechun Chu
Ruiliang Wang
Lu Liu
Daqing Li
Pierre Marc Bouloux
Ying Li
Youli Hu
author_sort Xichen Xuan
collection DOAJ
description Schwann cell (SC) transplantation is considered as a promising strategy for spinal cord injury. However, SCs show less capability in assisting the regenerative axons to penetrate through astrocyte (AS)-formed scar barrier. Anosmin-1, an extracellular matrix glycosylated adhesion protein expressed in the olfactory bulb, is involved in olfactory ensheathing cells and reborn olfactory nerve axons continually penetrating the glial barrier and targeting the olfactory bulb. In this study, we employ a dorsal root crush injury model treated with anosmin-1. A vertical climbing test was used for behavioral analysis and immunohistochemical study for SC/AS interaction in regenerative axon targeting. Anosmin-1 improved rat forepaw grasping as revealed by forelimb proprioception assessment. After treated with anosmin-1, p75+ immature SCs and P0+ mature SCs mingled well with ASs at the peripheral/central glial interface, reforming the glial barrier from a tight to loose structure. Furthermore, regenerated axons traced by BDA staining revealed proper axonal targeting to the dorsal horn of the spinal cord. These results suggest that anosmin-1 can regulate SC/AS interactions at the peripheral/central boundary site to open the glial barrier for regenerating axons crossing, targeting, and establishing functional neuronal circuits. Anosmin-1 might have a potential application in repair of spinal cord injuries, particularly in combination with SCs for autologous cell transplantation.
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issn 1555-3892
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publishDate 2025-08-01
publisher SAGE Publishing
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series Cell Transplantation
spelling doaj-art-8c735fc44f4745dd840cc2e5f784ba712025-08-20T03:03:12ZengSAGE PublishingCell Transplantation1555-38922025-08-013410.1177/09636897251362107Extracellular matrix protein anosmin-1 regulates Schwann cell-astrocyte interaction for regenerative axon targeting in dorsal root crush injury modelXichen Xuan0Xuechun Chu1Ruiliang Wang2Lu Liu3Daqing Li4Pierre Marc Bouloux5Ying Li6Youli Hu7Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Anesthesiology, Chengdu Seventh People’s Hospital (Affiliated Cancer Hospital of Chengdu Medical College), Chengdu, ChinaDepartment of Anesthesiology and Pain Medicine, Jiangnan University Medical Center, Wuxi No.2 People’s Hospital, Wuxi, ChinaSpinal Repair Unit, Department of Brain Repair and Rehabilitation, University College London Institute of Neurology, London, UKCentre for Neuroendocrinology, Royal Free Campus, University College Medical School, University College London, London, UKSpinal Repair Unit, Department of Brain Repair and Rehabilitation, University College London Institute of Neurology, London, UKDepartment of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaSchwann cell (SC) transplantation is considered as a promising strategy for spinal cord injury. However, SCs show less capability in assisting the regenerative axons to penetrate through astrocyte (AS)-formed scar barrier. Anosmin-1, an extracellular matrix glycosylated adhesion protein expressed in the olfactory bulb, is involved in olfactory ensheathing cells and reborn olfactory nerve axons continually penetrating the glial barrier and targeting the olfactory bulb. In this study, we employ a dorsal root crush injury model treated with anosmin-1. A vertical climbing test was used for behavioral analysis and immunohistochemical study for SC/AS interaction in regenerative axon targeting. Anosmin-1 improved rat forepaw grasping as revealed by forelimb proprioception assessment. After treated with anosmin-1, p75+ immature SCs and P0+ mature SCs mingled well with ASs at the peripheral/central glial interface, reforming the glial barrier from a tight to loose structure. Furthermore, regenerated axons traced by BDA staining revealed proper axonal targeting to the dorsal horn of the spinal cord. These results suggest that anosmin-1 can regulate SC/AS interactions at the peripheral/central boundary site to open the glial barrier for regenerating axons crossing, targeting, and establishing functional neuronal circuits. Anosmin-1 might have a potential application in repair of spinal cord injuries, particularly in combination with SCs for autologous cell transplantation.https://doi.org/10.1177/09636897251362107
spellingShingle Xichen Xuan
Xuechun Chu
Ruiliang Wang
Lu Liu
Daqing Li
Pierre Marc Bouloux
Ying Li
Youli Hu
Extracellular matrix protein anosmin-1 regulates Schwann cell-astrocyte interaction for regenerative axon targeting in dorsal root crush injury model
Cell Transplantation
title Extracellular matrix protein anosmin-1 regulates Schwann cell-astrocyte interaction for regenerative axon targeting in dorsal root crush injury model
title_full Extracellular matrix protein anosmin-1 regulates Schwann cell-astrocyte interaction for regenerative axon targeting in dorsal root crush injury model
title_fullStr Extracellular matrix protein anosmin-1 regulates Schwann cell-astrocyte interaction for regenerative axon targeting in dorsal root crush injury model
title_full_unstemmed Extracellular matrix protein anosmin-1 regulates Schwann cell-astrocyte interaction for regenerative axon targeting in dorsal root crush injury model
title_short Extracellular matrix protein anosmin-1 regulates Schwann cell-astrocyte interaction for regenerative axon targeting in dorsal root crush injury model
title_sort extracellular matrix protein anosmin 1 regulates schwann cell astrocyte interaction for regenerative axon targeting in dorsal root crush injury model
url https://doi.org/10.1177/09636897251362107
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