Therapeutic effects of peripherally administrated neural crest stem cells on pain and spinal cord changes after sciatic nerve transection

Severe peripheral nerve injury significantly affects patients' quality of life and induces neuropathic pain. Neural crest stem cells (NCSCs) exhibit several attractive characteristics for cell-based therapies following peripheral nerve injury. Here, we investigate the therapeutic effect of NCSC...

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Published in:Stem cell research & therapy 2021-03, Vol.12 (1), p.180-180, Article 180
Main Authors: Zhang, Yang, Xu, Xiang, Tong, Yuxin, Zhou, Xijie, Du, Jian, Choi, In Young, Yue, Shouwei, Lee, Gabsang, Johnson, Blake N, Jia, Xiaofeng
Format: Article
Language:English
Subjects:
Analysis
Antibodies
Behavior
Brain injury
Brain-derived neurotrophic factor
Calcitonin
Calcitonin gene-related peptide
Calcium
Capsaicin receptors
Cell activation
Extracellular signal-regulated kinase
Gait
Glial activation
Glial cells
Glial fibrillary acidic protein
Health aspects
Immunofluorescence
Inflammation
Investigations
Latency
Mechanical properties
Microglia
Neural crest
Neural crest stem cells
Neuronal-glial interactions
Neuropathic pain
NF-κB protein
Pain
Pain perception
Peripheral nerve injury
Peripheral nerves
Peripheral neuropathy
Proteins
Quality of life
Sciatic nerve
Spinal cord
Spinal cord injuries
Stem cells
Transplantation
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cited_by cdi_FETCH-LOGICAL-c628t-d15b64b22eb7563516d1c97b51887670898107c4730e1b8782fab40d59f069903
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container_title Stem cell research & therapy
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creator Zhang, Yang
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Lee, Gabsang
Johnson, Blake N
Jia, Xiaofeng
description Severe peripheral nerve injury significantly affects patients' quality of life and induces neuropathic pain. Neural crest stem cells (NCSCs) exhibit several attractive characteristics for cell-based therapies following peripheral nerve injury. Here, we investigate the therapeutic effect of NCSC therapy and associated changes in the spinal cord in a sciatic nerve transection (SNT) model. Complex sciatic nerve gap injuries in rats were repaired with cell-free and cell-laden nerve scaffolds for 12 weeks (scaffold and NCSC groups, respectively). Catwalk gait analysis was used to assess the motor function recovery. The mechanical withdrawal threshold and thermal withdrawal latency were used to assess the development of neuropathic pain. Activation of glial cells was examined by immunofluorescence analyses. Spinal levels of extracellular signal-regulated kinase (ERK), NF-κB P65, brain-derived neurotrophic factor (BDNF), growth-associated protein (GAP)-43, calcitonin gene-related peptide (CGRP), and inflammation factors were calculated by western blot analysis. Catwalk gait analysis showed that animals in the NCSC group exhibited a higher stand index and Max intensity At (%) relative to those that received the cell-free scaffold (scaffold group) (p 
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Neural crest stem cells (NCSCs) exhibit several attractive characteristics for cell-based therapies following peripheral nerve injury. Here, we investigate the therapeutic effect of NCSC therapy and associated changes in the spinal cord in a sciatic nerve transection (SNT) model. Complex sciatic nerve gap injuries in rats were repaired with cell-free and cell-laden nerve scaffolds for 12 weeks (scaffold and NCSC groups, respectively). Catwalk gait analysis was used to assess the motor function recovery. The mechanical withdrawal threshold and thermal withdrawal latency were used to assess the development of neuropathic pain. Activation of glial cells was examined by immunofluorescence analyses. Spinal levels of extracellular signal-regulated kinase (ERK), NF-κB P65, brain-derived neurotrophic factor (BDNF), growth-associated protein (GAP)-43, calcitonin gene-related peptide (CGRP), and inflammation factors were calculated by western blot analysis. Catwalk gait analysis showed that animals in the NCSC group exhibited a higher stand index and Max intensity At (%) relative to those that received the cell-free scaffold (scaffold group) (p &lt; 0.05). The mechanical and thermal allodynia in the medial-plantar surface of the ipsilateral hind paw were significantly relieved in the NCSC group. Sunitinib (SNT)-induced upregulation of glial fibrillary acidic protein (GFAP) (astrocyte) and ionized calcium-binding adaptor molecule 1 (Iba-1) (microglia) in the ipsilateral L4-5 dorsal and ventral horn relative to the contralateral side. Immunofluorescence analyses revealed decreased astrocyte and microglia activation. Activation of ERK and NF-κB signals and expression of transient receptor potential vanilloid 1 (TRPV1) expression were downregulated. NCSC-laden nerve scaffolds mitigated SNT-induced neuropathic pain and improved motor function recovery after sciatic nerve repair. NCSCs also protected the spinal cord from SNT-induced glial activation and central sensitization.</description><identifier>ISSN: 1757-6512</identifier><identifier>EISSN: 1757-6512</identifier><identifier>DOI: 10.1186/s13287-021-02200-4</identifier><identifier>PMID: 33722287</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Analysis ; Antibodies ; Behavior ; Brain injury ; Brain-derived neurotrophic factor ; Calcitonin ; Calcitonin gene-related peptide ; Calcium ; Capsaicin receptors ; Cell activation ; Extracellular signal-regulated kinase ; Gait ; Glial activation ; Glial cells ; Glial fibrillary acidic protein ; Health aspects ; Immunofluorescence ; Inflammation ; Investigations ; Latency ; Mechanical properties ; Microglia ; Neural crest ; Neural crest stem cells ; Neuronal-glial interactions ; Neuropathic pain ; NF-κB protein ; Pain ; Pain perception ; Peripheral nerve injury ; Peripheral nerves ; Peripheral neuropathy ; Proteins ; Quality of life ; Sciatic nerve ; Spinal cord ; Spinal cord injuries ; Stem cells ; Transplantation</subject><ispartof>Stem cell research &amp; therapy, 2021-03, Vol.12 (1), p.180-180, Article 180</ispartof><rights>COPYRIGHT 2021 BioMed Central Ltd.</rights><rights>2021. 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Neural crest stem cells (NCSCs) exhibit several attractive characteristics for cell-based therapies following peripheral nerve injury. Here, we investigate the therapeutic effect of NCSC therapy and associated changes in the spinal cord in a sciatic nerve transection (SNT) model. Complex sciatic nerve gap injuries in rats were repaired with cell-free and cell-laden nerve scaffolds for 12 weeks (scaffold and NCSC groups, respectively). Catwalk gait analysis was used to assess the motor function recovery. The mechanical withdrawal threshold and thermal withdrawal latency were used to assess the development of neuropathic pain. Activation of glial cells was examined by immunofluorescence analyses. Spinal levels of extracellular signal-regulated kinase (ERK), NF-κB P65, brain-derived neurotrophic factor (BDNF), growth-associated protein (GAP)-43, calcitonin gene-related peptide (CGRP), and inflammation factors were calculated by western blot analysis. 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therapy</jtitle><addtitle>Stem Cell Res Ther</addtitle><date>2021-03-15</date><risdate>2021</risdate><volume>12</volume><issue>1</issue><spage>180</spage><epage>180</epage><pages>180-180</pages><artnum>180</artnum><issn>1757-6512</issn><eissn>1757-6512</eissn><abstract>Severe peripheral nerve injury significantly affects patients' quality of life and induces neuropathic pain. Neural crest stem cells (NCSCs) exhibit several attractive characteristics for cell-based therapies following peripheral nerve injury. Here, we investigate the therapeutic effect of NCSC therapy and associated changes in the spinal cord in a sciatic nerve transection (SNT) model. Complex sciatic nerve gap injuries in rats were repaired with cell-free and cell-laden nerve scaffolds for 12 weeks (scaffold and NCSC groups, respectively). Catwalk gait analysis was used to assess the motor function recovery. The mechanical withdrawal threshold and thermal withdrawal latency were used to assess the development of neuropathic pain. Activation of glial cells was examined by immunofluorescence analyses. Spinal levels of extracellular signal-regulated kinase (ERK), NF-κB P65, brain-derived neurotrophic factor (BDNF), growth-associated protein (GAP)-43, calcitonin gene-related peptide (CGRP), and inflammation factors were calculated by western blot analysis. Catwalk gait analysis showed that animals in the NCSC group exhibited a higher stand index and Max intensity At (%) relative to those that received the cell-free scaffold (scaffold group) (p &lt; 0.05). The mechanical and thermal allodynia in the medial-plantar surface of the ipsilateral hind paw were significantly relieved in the NCSC group. Sunitinib (SNT)-induced upregulation of glial fibrillary acidic protein (GFAP) (astrocyte) and ionized calcium-binding adaptor molecule 1 (Iba-1) (microglia) in the ipsilateral L4-5 dorsal and ventral horn relative to the contralateral side. Immunofluorescence analyses revealed decreased astrocyte and microglia activation. Activation of ERK and NF-κB signals and expression of transient receptor potential vanilloid 1 (TRPV1) expression were downregulated. NCSC-laden nerve scaffolds mitigated SNT-induced neuropathic pain and improved motor function recovery after sciatic nerve repair. NCSCs also protected the spinal cord from SNT-induced glial activation and central sensitization.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>33722287</pmid><doi>10.1186/s13287-021-02200-4</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-1445-8525</orcidid><oa>free_for_read</oa></addata></record>
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subjects Analysis
Antibodies
Behavior
Brain injury
Brain-derived neurotrophic factor
Calcitonin
Calcitonin gene-related peptide
Calcium
Capsaicin receptors
Cell activation
Extracellular signal-regulated kinase
Gait
Glial activation
Glial cells
Glial fibrillary acidic protein
Health aspects
Immunofluorescence
Inflammation
Investigations
Latency
Mechanical properties
Microglia
Neural crest
Neural crest stem cells
Neuronal-glial interactions
Neuropathic pain
NF-κB protein
Pain
Pain perception
Peripheral nerve injury
Peripheral nerves
Peripheral neuropathy
Proteins
Quality of life
Sciatic nerve
Spinal cord
Spinal cord injuries
Stem cells
Transplantation
title Therapeutic effects of peripherally administrated neural crest stem cells on pain and spinal cord changes after sciatic nerve transection
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