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Small extracellular vesicles from hypoxia-preconditioned bone marrow mesenchymal stem cells attenuate spinal cord injury via miR-146a-5p-mediated regulation of macrophage polarization 被引量:1
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作者 Zeyan Liang Zhelun Yang +5 位作者 Haishu Xie Jian Rao Xiongjie Xu Yike Lin Chunhua Wang Chunmei Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第10期2259-2269,共11页
Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)... Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury. 展开更多
关键词 bone marrow mesenchymal stem cells hypoxia preconditioning interleukin-1 receptor-associated kinase 1 MACROPHAGES mesenchymal stem cells small extracellular vesicles spinal cord injury
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Protective effect of thodioloside and bone marrow mesenchymal stem cells infected with HIF-1-expressing adenovirus on acute spinal cord injury 被引量:9
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作者 Xiao-Qin Ha Bo Yang +3 位作者 Huai-Jing Hou Xiao-Ling Cai Wan-Yuan Xiong Xu-Pan Wei 《Neural Regeneration Research》 SCIE CAS CSCD 2020年第4期690-696,共7页
Rhodioloside has been shown to protect cells from hypoxia injury,and bone marrow mesenchymal stem cells have a good effect on tissue repair.To study the effects of rhodioloside and bone marrow mesenchymal stem cells o... Rhodioloside has been shown to protect cells from hypoxia injury,and bone marrow mesenchymal stem cells have a good effect on tissue repair.To study the effects of rhodioloside and bone marrow mesenchymal stem cells on spinal cord injury,a rat model of spinal cord injury was established using the Infinite Horizons method.After establishing the model,the rats were randomly divided into five groups.Rats in the control group were intragastrically injected with phosphate buffered saline(PBS)(5μL).PBS was injected at 6 equidistant points around 5 mm from the injury site and at a depth of 5 mm.Rats in the rhodioloside group were intragastrically injected with rhodioloside(5 g/kg)and intramuscularly injected with PBS.Rats in the mesenchymal stem cell(MSC)group were intramuscularly injected with PBS and intramuscularly with MSCs(8×10^6/mL in a 50-μL cell suspension).Rats in the Ad-HIF-MSC group were intragastrically injected with PBS and intramuscularly injected with HIF-1 adenovirus-infected MSCs.Rats in the rhodioloside+Ad-HIF-MSC group were intramuscularly injected with MSCs infected with the HIF-1 adenovirus and intragastrically injected with rhodioloside.One week after treatment,exercise recovery was evaluated with a modified combined behavioral score scale.Hematoxylin-eosin staining and Pischingert’s methylene blue staining were used to detect any histological or pathological changes in spinal cord tissue.Levels of adenovirus IX and Sry mRNA were detected by real-time quantitative polymerase chain reaction and used to determine the number of adenovirus and mesenchymal stem cells that were transfected into the spinal cord.Immunohistochemical staining was applied to detect HIF-1 protein levels in the spinal cord.The results showed that:(1)compared with the other groups,the rhodioloside+Ad-HIF-MSC group exhibited the highest combined behavioral score(P<0.05),the most recovered tissue,and the greatest number of neurons,as indicated by Pischingert’s methylene blue staining.(2)Compared with the PBS group,HIF-1 protein expression was greater in the rhodioloside group(P<0.05).(3)Compared with the Ad-HIF-MSC group,Sry mRNA levels were higher in the rhodioloside+Ad-HIF-MSC group(P<0.05).These results confirm that rhodioloside combined with bone marrow mesenchymal stem cells can promote the recovery of spinal cord injury and activate the HIF-1 pathway to promote the survival of bone marrow mesenchymal stem cells and repair damaged neurons within spinal cord tissue.This experiment was approved by the Animal Ethics Committee of Gansu University of Traditional Chinese Medicine,China(approval No.2015KYLL029)in June 2015. 展开更多
关键词 acute spinal cord injury ADENOVIRUS ADENOVIRUS gene IX bone marrow MESENCHYMAL stem cells combined behavioral score scale HIF-1α NERVE regeneration NERVE repair RHODIOLA rosea SRY
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Effect of intravenous transplantation of bone marrow mesenchymal stem cells on neurotransmitters and synapsins in rats with spinal cord injury 被引量:5
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作者 Shaoqiang Chen Bilian Wu Jianhua Lin 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第19期1445-1453,共9页
Bone marrow mesenchymal stem cells were isolated, purified and cultured in vitro by Percoll density gradient centrifugation combined with the cell adherence method. Passages 3 5 bone marrow mesenchymal stem cells were... Bone marrow mesenchymal stem cells were isolated, purified and cultured in vitro by Percoll density gradient centrifugation combined with the cell adherence method. Passages 3 5 bone marrow mesenchymal stem cells were transplanted into rats with traumatic spinal cord injury via the caudal vein. Basso-Beattie-Bresnahan scores indicate that neurological function of experimental rats was significantly improved over transplantation time (1-5 weeks). Expressions of choline acetyltransferase, glutamic acid decarboxytase and synapsins in the damaged spinal cord of rats was significantly increased after transplantation, determined by immunofluorescence staining and laser confocal scanning microscopy. Bone marrow mesenchymal stem cells that had migrated into the damaged area of rats in the experimental group began to express choline acetyltransferase, glutamic acid decarboxylase and synapsins, 3 weeks after transplantation. The Basso-Beattie- Bresnahan scores positively correlated with expression of choline acetyltransferase and synapsins. Experimental findings indicate that intravenously transplanted bone marrow mesenchymal stem cells traverse into the damaged spinal cord of rats, promote expression of choline acetyltransferase, glutamic acid decarboxylase and synapsins, and improve nerve function in rats with spinal cord injury. 展开更多
关键词 bone marrow mesenchymal stem cells spinal cord injury choline acetyltransferase glutamic aciddecarboxylase SYNAPSINS neural regeneration
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Bone marrow mesenchymal stem cells with Nogo-66 receptor gene silencing for repair of spinal cord injury 被引量:5
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作者 Zhiyuan Li Zhanxiu Zhang +3 位作者 Lili Zhao Hui Li Suxia Wang Yong Shen 《Neural Regeneration Research》 SCIE CAS CSCD 2014年第8期806-814,共9页
We hypothesized that RNA interference to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells before transplantation might further improve neurological function in rats with spinal cord trans... We hypothesized that RNA interference to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells before transplantation might further improve neurological function in rats with spinal cord transection injury. After 2 weeks, the number of neurons and BrdU-positive cells in the Nogo-66 receptor gene silencing group was higher than in the bone marrow mesenchymal stem cell group, and significantly greater compared with the model group. After 4 weeks, behavioral performance was signiifcantly enhanced in the model group. Af-ter 8 weeks, the number of horseradish peroxidase-labeled nerve ifbers was higher in the Nogo-66 receptor gene silencing group than in the bone marrow mesenchymal stem cell group, and signiifcantly higher than in the model group. The newly formed nerve ifbers and myelinated ner ve ifbers were detectable in the central transverse plane section in the bone marrow mesenchymal stem cell group and in the Nogo-66 receptor gene silencing group. 展开更多
关键词 nerve regeneration spinal cord injury bone marrow mesenchymal stem cells Nogo-66receptor RNA interference horseradish peroxidase BRDU gene silencing neural regeneration
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Upregulation of UBAP2L in Bone Marrow Mesenchymal Stem Cells Promotes Functional Recovery in Rats with Spinal Cord Injury 被引量:4
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作者 Guan-lin LIN Huan WANG +5 位作者 Jun DAI Xiao LI Ming GUAN Qing DING Huai-xi WANG Huang FANG 《Current Medical Science》 SCIE CAS 2018年第6期1081-1089,共9页
Post-translational modifications of cellular proteins with ubiquitin or ubiquitin-like proteins regulate many cellular processes,such as cell proliferation,differentiation,apoptosis, signal transduction,intercellular ... Post-translational modifications of cellular proteins with ubiquitin or ubiquitin-like proteins regulate many cellular processes,such as cell proliferation,differentiation,apoptosis, signal transduction,intercellular immune recognition,inflammatory response,stress response,and DNA repair.Nice4/UBAP2L is an important member in the family of ubiquitin-like proteins,and its biological function remains unknown.This study aimed to investigate the effect of UBAP2L on spinal cord injury (SCI).At first,rat bone marrow mesenchymal stem cells (BMSCs)were infected with adeno-associated virus to induce over-expression of Nice4.Subsequently,the infected BMSCs were transplanted into rats suffering from semi-sectioned SCI.The results showed that the over-expression of Nice4 significantly promoted the proliferation and differentiation of BMSCs. In addition,the transplantation of infected BMSCs into the injured area of SCI rats improved the function repair of SCI.Importantly,the immunohistochemical and hematoxylin-eosin staining and RT-PCR results showed that the number of neuronal cells,oligodendrocytes,and astrocytes was significantly increased in the injured area,along with significantly upregulated expression ofcyclin D1 and p38 mitogen-activated protein kinase (MAPK).Meanwhile,the expression of caspase 3 protein was significantly down-regulated.In conclusion,the over-expression of Nice4 gene can promote the functional recovery in SCI rats by promoting cell proliferation and inhibiting apoptosis. The results of this study indicate an alternative option for the clinical treatment of SCI. 展开更多
关键词 bone marrow MESENCHYMAL stem cells spinal CORD injury ubiquitin-associated protein 2-like apoptosis proliferation
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Propofol injection combined with bone marrow mesenchymal stem cell transplantation better improves electrophysiological function in the hindlimb of rats with spinal cord injury than monotherapy 被引量:1
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作者 Yue-xin Wang Jing-jing Sun +4 位作者 Mei Zhang Xiao-hua Hou Jun Hong Ya-jing Zhou Zhi-yong Zhang 《Neural Regeneration Research》 SCIE CAS CSCD 2015年第4期636-643,共8页
The repair effects of bone marrow mesenchymal stem cell transplantation on nervous system damage are not satisfactory. Propofol has been shown to protect against spinal cord injury. Therefore, this study sought to exp... The repair effects of bone marrow mesenchymal stem cell transplantation on nervous system damage are not satisfactory. Propofol has been shown to protect against spinal cord injury. Therefore, this study sought to explore the therapeutic effects of their combination on spinal cord injury. Rat models of spinal cord injury were established using the weight drop method. Rats were subjected to bone marrow mesenchymal stem cell transplantationvia tail vein injection and/or propofol injectionvia tail vein using an infusion pump. Four weeks after cell transplan-tation and/or propofol treatment, the cavity within the spinal cord was reduced. The numbers of PKH-26-positive cells and horseradish peroxidase-positive nerve ifbers apparently increased in the spinal cord. Latencies of somatosensory evoked potentials and motor evoked potentials in the hindlimb were noticeably shortened, amplitude was increased and hindlimb motor function was obviously improved. Moreover, the combined effects were better than cell transplantation or propofol injection alone. The above data suggest that the combination of propofol injection and bone marrow mesenchymal stem cell transplantation can effectively improve hindlimb electro-physiological function, promote the recovery of motor funtion, and play a neuroprotective role in spinal cord injury in rats. 展开更多
关键词 nerve regeneration bone marrow mesenchymal stem cells PROPOFOL spinal cord injury cell transplantation ELECTROPHYSIOLOGY motor function stem cells NEUROPROTECTION neural regeneration
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Improvement of neurological function in rats with spinal cord injury after the transplantation of neural stem cells directly differentiated from bone marrow mesenchymal stem cells
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作者 张小宁 《外科研究与新技术》 2011年第4期290-290,共1页
Objective To study the effect and mechanism of neurological function recovery in rats with spinal cord injury ( SCI) rats after transplantation of neural stem cells which are directly differentiated from bone marrow m... Objective To study the effect and mechanism of neurological function recovery in rats with spinal cord injury ( SCI) rats after transplantation of neural stem cells which are directly differentiated from bone marrow mesenchymal stem cells ( BMSC ) ,and to investigate the suitable engraftment time. Methods BMSC at 3rd passage were differentiated into neural stem cells ( NSC) , and immunofluorescence staining was used to 展开更多
关键词 bone Improvement of neurological function in rats with spinal cord injury after the transplantation of neural stem cells directly differentiated from bone marrow mesenchymal stem cells stem
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Glial cell-derived neurotrophic factor mRNA expression in a rat model of spinal cord injury following bone marrow stromal cell transplantation 被引量:13
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作者 Lei Li Gang Lu +5 位作者 Yanfeng Wang Hong Gao XinXu Lunhao Bai Lunhao Bai Huan Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2008年第10期1056-1059,共4页
BACKGROUND: Several animal experiments utilizing bone marrow stromal cell (BMSC) transplantation for the treatment of spinal cord injury have proposed a hypothesis that BMSC transplantation effects are associated w... BACKGROUND: Several animal experiments utilizing bone marrow stromal cell (BMSC) transplantation for the treatment of spinal cord injury have proposed a hypothesis that BMSC transplantation effects are associated with increased glial cell-derived neurotrophic factor (GDNF) expression. OBJECTIVE: To confirm the effects of BMSC transplantation on GDNF mRNA expression in rats with spinal cord injury by reverse transcription-polymerase chain reaction (RT-PCR). DESIGN, TIME AND SETTING: The present molecular, cell biology experiment was performed at the Key Laboratory of Children's Congenital Malformation, Ministry of Health of China & Department of Developmental Biology, Basic Medical College, China Medical University between March 2006 and May 2007. MATERIALS: Sixty healthy Wistar rats aged 2-4-months and of either gender were included in this study. Spinal cord injury was induced in all rats by hemisection of T9 on the left side. RT-PCR kits were purchased from TaKaRa Company, China. Type 9600 RCR amplifier was provided by Perkin Elmer Company, USA. METHODS: Three rats were selected for BMSC culture and subsequent transplantation (after three passages). Of the remaining 57 rats, nine were selected for sham-operation (sham-operated group), where only the T9 spinal cord was exposed without hemisection. A total of 48 rats were randomly and evenly divided into BMSC transplantation and model groups. In the BMSC transplantation group, following spinal cord injury induction, each rat was administered a BMSC suspension tbrougb two injection sites selected on the gray and white matter boundary caudally and cephalically, seperately and near to injury site in the spinal cord. The model group received an equal volume of PBS through the identical injection sites. MAIN OUTCOME MEASURES: At 24 and 72 hours, as well as at 7 days, following spinal cord injury, the spinal cord at the T9 segment was removed. Eight rats were allocated to each time point in the BMSC transplantation and model groups, with three rats allocated to the sham-operated group. GDNF mRNA expression was semiquantitatively analyzed by RT-PCR. RESULTS: The sham-operated group exhibited extremely low GDNF mRNA expression. GDNF mRNA expression significantly increased at 24 hours after spinal cord injury, reached a peak level at 72 hours, and slowly decreased thereafter. However, it remained higher than normal levels at 7 days (P 〈 0.05). At all time points following spinal cord injury, GDNF mRNA expression was significantly greater in the BMSC transplantation group than in the model group (P 〈 0.05). CONCLUSION: Transplantation of BMSCs into the injured spinal cord up-regulated GDNF mRNA expression, thereby promoting repair of the injured spinal cord. 展开更多
关键词 bone marrow stromal cells neurotrophic factors spinal cord injury TRANSPLANTATION
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Chondroitinase ABC plus bone marrow mesenchymal stem cells for repair of spinal cord injury 被引量:10
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作者 Chun Zhang Xijing He +1 位作者 Haopeng Li Guoyu Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2013年第11期965-974,共10页
As chondroitinase ABC can improve the hostile microenvironment and cell transplantation is proven to be effective after spinal cord injury, we hypothesized that their combination would be a more effective treatment op... As chondroitinase ABC can improve the hostile microenvironment and cell transplantation is proven to be effective after spinal cord injury, we hypothesized that their combination would be a more effective treatment option. At 5 days after T8 spinal cord crush injury, rats were injected with bone marrow mesenchymal stem cell suspension or chondroitinase ABC 1 mm from the edge of spinal cord damage zone. Chondroitinase ABC was first injected, and bone marrow mesenchymal stem cell suspension was injected on the next day in the combination group. At 14 days, the mean Basso, Beattie and Bresnahan score of the rats in the combination group was higher than other groups. Hematoxylin-eosin staining showed that the necrotic area was significantly reduced in the combination group compared with other groups. Glial fibrillary acidic protein-chondroitin sulfate proteoglycan double staining showed that the damage zone of astrocytic scars was significantly reduced without the cavity in the combination group. Glial fibrillary acidic protein/growth associated protein-43 double immunostaining revealed that positive fibers traversed the damage zone in the combination group. These results suggest that the combination of chondroitinase ABC and bone marrow mesenchymal stem cell transplantation contributes to the repair of spinal cord injury. 展开更多
关键词 neural regeneration spinal cord injury stem cells chondroitin sulfate proteoglycans ASTROCYTES glial scar chondroitinase ABC bone marrow mesenchymal stem cells TRANSPLANTATION chemicalbarrier NEUROREGENERATION
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Electrophysiological functional recovery in a rat model of spinal cord hemisection injury following bone marrow-derived mesenchymal stem cell transplantation under hypothermia 被引量:8
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作者 Dong Wang Jianjun Zhang 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第10期749-755,共7页
Following successful establishment of a rat model of spinal cord hemisection injury by resecting right spinal cord tissues, bone marrow stem cells were transplanted into the spinal cord lesions via the caudal vein whi... Following successful establishment of a rat model of spinal cord hemisection injury by resecting right spinal cord tissues, bone marrow stem cells were transplanted into the spinal cord lesions via the caudal vein while maintaining rectal temperature at 34 ± 0.5°C for 6 hours (mild hypothermia). Hematoxylin-eosin staining showed that astrocytes gathered around the injury site and formed scars at 4 weeks post-transplantation. Compared with rats transplanted with bone marrow stem cells under normal temperature, rats transplanted with bone marrow stem cells under hypothermia showed increased numbers of proliferating cells (bromodeoxyuridine-positive cells), better recovery of somatosensory-evoked and motor-evoked potentials, greater Basso, Beattie, and Bresnahan locomotor rating scores, and an increased degree of angle in the incline plate test. These findings suggested that hypothermia combined with bone marrow mesenchymal stem cells transplantation effectively promoted electrical conduction and nerve functional repair in a rat model of spinal cord hemisection injury. 展开更多
关键词 bone marrow mesenchymal stem cells electrophysiological function HYPOTHERMIA spinal cord hemisection injury TRANSPLANTATION
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Cell transplantation for the treatment of spinal cord injury–bone marrow stromal cells and choroid plexus epithelial cells 被引量:9
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作者 Chizuka Ide Norihiko Nakano Kenji Kanekiyo 《Neural Regeneration Research》 SCIE CAS CSCD 2016年第9期1385-1388,共4页
Transplantation of bone marrow stromal cells (BMSCs) enhanced the outgrowth of regenerating axons and promoted locomotor improvements of rats with spinal cord injury (SCI). BMSCs did not survive long-term, disappe... Transplantation of bone marrow stromal cells (BMSCs) enhanced the outgrowth of regenerating axons and promoted locomotor improvements of rats with spinal cord injury (SCI). BMSCs did not survive long-term, disappearing from the spinal cord within 2-3 weeks after transplantation. Astrocyte-devoid areas, in which no astrocytes or oligodendrocytes were found, formed at the epicenter of the lesion. It was remarkable that numerous regenerating axons extended through such astrocyte-devoid areas. Regenerating axons were associated with Schwann cells embedded in extracellular matrices. Transplantation of choroid plexus epithelial cells (CPECs) also enhanced axonal regeneration and locomotor improvements in rats with SCI. Although CPECs disappeared from the spinal cord shortly after transplantation, an extensive outgrowth of regenerating axons occurred through astrocyte-devoid areas, as in the case of BMSC transplantation. These findings suggest that BMSCs and CPECs secret neurotrophic factors that promote tissue repair of the spinal cord, including axonal regeneration and reduced cavity formation. This means that transplantation of BMSCs and CPECs promotes "intrinsic" ability of the spinal cord to regenerate. The treatment to stimu- late the intrinsic regeneration ability of the spinal cord is the safest method of clinical application for SCI. It should be emphasized that the generally anticipated long-term survival, proliferation and differentiation of transplanted cells are not necessarily desirable from the clinical point of view of safety. 展开更多
关键词 bone marrow stromal cell choroid plexus epithelial cell spinal cord injury axonal regeneration locomotor improvement intrinsic regeneration ability
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Bone marrow mesenchymal stem cells and exercise restore motor function following spinal cord injury by activating PI3K/AKT/mTOR pathway 被引量:8
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作者 Xin Sun Li-Yi Huang +8 位作者 Hong-Xia Pan Li-Juan Li Lu Wang Gai-Qin Pei Yang Wang Qing Zhang Hong-Xin Cheng Cheng-Qi He Quan Wei 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第5期1067-1075,共9页
Although many therapeutic interventions have shown promise in treating spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following spinal cord ... Although many therapeutic interventions have shown promise in treating spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following spinal cord injury. In this study, we applied a combinatorial approach for treating spinal cord injury involving neuroprotection and rehabilitation, exploiting cell transplantation and functional sensorimotor training to promote nerve regeneration and functional recovery. Here, we used a mouse model of thoracic contusive spinal cord injury to investigate whether the combination of bone marrow mesenchymal stem cell transplantation and exercise training has a synergistic effect on functional restoration. Locomotor function was evaluated by the Basso Mouse Scale, horizontal ladder test, and footprint analysis. Magnetic resonance imaging, histological examination, transmission electron microscopy observation, immunofluorescence staining, and western blotting were performed 8 weeks after spinal cord injury to further explore the potential mechanism behind the synergistic repair effect. In vivo, the combination of bone marrow mesenchymal stem cell transplantation and exercise showed a better therapeutic effect on motor function than the single treatments. Further investigations revealed that the combination of bone marrow mesenchymal stem cell transplantation and exercise markedly reduced fibrotic scar tissue, protected neurons, and promoted axon and myelin protection. Additionally, the synergistic effects of bone marrow mesenchymal stem cell transplantation and exercise on spinal cord injury recovery occurred via the PI3 K/AKT/mTOR pathway. In vitro, experimental evidence from the PC12 cell line and primary cortical neuron culture also demonstrated that blocking of the PI3 K/AKT/mTOR pathway would aggravate neuronal damage. Thus, bone marrow mesenchymal stem cell transplantation combined with exercise training can effectively restore motor function after spinal cord injury by activating the PI3 K/AKT/mTOR pathway. 展开更多
关键词 axon growth bone marrow mesenchymal stem cell exercise training mTOR neuroprotection NEUROTROPHIN REMYELINATION scar formation spinal cord injury synaptic plasticity
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The future of bone marrow stromal cell transplantation for the treatment of spinal cord injury 被引量:6
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作者 Mitsuhiro Enomoto 《Neural Regeneration Research》 SCIE CAS CSCD 2015年第3期383-384,共2页
Bone marrow stromal cell (BMSC) transplantation therapy is a promising approach for treating spinal cord injury (SCI), based on a number of experimental and clinical reports (Wright et al., 2011). BMSCs are a so... Bone marrow stromal cell (BMSC) transplantation therapy is a promising approach for treating spinal cord injury (SCI), based on a number of experimental and clinical reports (Wright et al., 2011). BMSCs are a source of neuroregenerative somatic stem cells that are without the potential for tumorigenicity. Although clinical studies of autologous BMSC transplantation have been reported in Asia (fiang et al., 2013; Yoon et al., 2007), in Japan, it is currently an uncommon procedure and highly controversial as well. This perspective paper provides an overview of the clinical effectiveness of BMSC trans- 191antation and a proposal to enhance its use as a viable therapy. 展开更多
关键词 BMSCS The future of bone marrow stromal cell transplantation for the treatment of spinal cord injury SCI bone cell
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Combination of bone marrow mesenchymal stem cells and brain-derived neurotrophic factor for treating spinal cord injury 被引量:3
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作者 Dengliang Wang Dezhi Kang +3 位作者 Jianhua Lin Lianghong YU Zhangya Lin Zhaoyang Wu 《Neural Regeneration Research》 SCIE CAS CSCD 2010年第7期491-495,共5页
BACKGROUND: Because bone marrow mesenchymal stem cells (BMSCs) do not secrete sufficient brain-derived neurotrophic factor (BDNF), the use of exogenous BDNF could improve microenvironments in injured regions for ... BACKGROUND: Because bone marrow mesenchymal stem cells (BMSCs) do not secrete sufficient brain-derived neurotrophic factor (BDNF), the use of exogenous BDNF could improve microenvironments in injured regions for BMSCs differentiation. OBJECTIVE: To analyze recovery of the injured spinal cord following BMSCs venous transplantation in combination with consecutive injections of BDNF. DESIGN, TIME AND SETTING: A randomized, controlled animal experiment was performed at the Central Laboratory of First Hospital and Anatomical Laboratory, Fujian Medical University from October 2004 to May 2006. MATERIALS: Human BDNF was purchased from Sigma, USA. METHODS: A total of 44 New Zealand rabbits were randomly assigned to model (n = 8), BDNF (n = 12), BMSC (n= 12), and BMSC+BDNF (n= 12) groups. Spinal cord (I-2)injury was established with the dropping method. The model group rabbits were injected with 1 mL normal saline via the ear margin vein; the BDNF group was subdurally injected with 100 μg/d human BDNF for 1 week; the BMSC group was injected with 1 mL BMSCs suspension (2 × 10^6/mL) via the ear margin vein; and the BMSC+BDNF group rabbits were subdurally injected with 100 μg/d BDNF for 1 week, in addition to BMSCs suspension via the ear margin vein. MAIN OUTCOME MEASURES: BMSCs surface markers were detected by flow cytometry. BMSCs differentiation in the injured spinal cord was detected by immunofluorescence histochemistry. Functional and structural recovery, as well as morphological changes, in the injured spinal cord were respectively detected by Tarlov score, horseradish peroxidase retrograde tracing, and hematoxylin & eosin staining methods at 1, 3, and 5 weeks following transplantation. RESULTS: Transplanted BMSCs differentiated into neuronal-like cells in the injured spinal cord at 3 and 5 weeks following transplantation. Neurological function and pathological damage improved following BMSC + BDNF treatment compared with BDNF or BMSC alone (P 〈 0.01 or P 〈 0.05). CONCLUSION: BMSCs venous transplantation in combination with BDNF subdural injection benefits neuronal-like cell differentiation and significantly improves structural and function of injured spinal cord compared with BMSCs or BDNF alone. 展开更多
关键词 bone marrow mesenchymal stem cells brain-derived neurotrophic factor cell transplantation DIFFERENTIATION nerve factors spinal cord injury neural regeneration
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Does vitamin C have the ability to augment the therapeutic effect of bone marrow-derived mesenchymal stem cells on spinal cord injury? 被引量:2
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作者 Nesrine Salem Mohamed Y.Salem +7 位作者 Mohammed M.Elmaghrabi Moataz A.Elawady Mona A.Elawady Dina Sabry Ashraf Shamaa Abdel-Haleem H.Elkasapy Noha Ibrhim Azza Elamir 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第12期2050-2058,共9页
Methylprednisolone(MP) is currently the only drug confirmed to exhibit a neuroprotective effect on acute spinal cord injury(SCI). Vitamin C(VC) is a natural water-soluble antioxidant that exerts neuroprotective ... Methylprednisolone(MP) is currently the only drug confirmed to exhibit a neuroprotective effect on acute spinal cord injury(SCI). Vitamin C(VC) is a natural water-soluble antioxidant that exerts neuroprotective effects through eliminating free radical damage to nerve cells. Bone marrow mesenchymal stem cells(BMMSCs), as multipotent stem cells, are promising candidates in SCI repair. To evaluate the therapeutic effects of MP, VC and BMMSCs on traumatic SCI, 80 adult male rats were randomly divided into seven groups: control, SCI(SCI induction by weight-drop method), MP(SCI induction, followed by administration of 30 mg/kg MP via the tail vein, once every other 6 hours, for five times), VC(SCI induction, followed by intraperitoneal administration of 100 mg/kg VC once a day, for 28 days), MP + VC(SCI induction, followed by administration of MP and VC as the former), BMMSCs(SCI induction, followed by injection of 3 × 10~6 BMMSCs at the injury site), and BMMSCs + VC(SCI induction, followed by BMMSCs injection and VC administration as the former). Locomotor recovery was assessed using the Basso Mouse Scale. Injured spinal cord tissue was evaluated using hematoxylin-eosin staining and immunohistochemical staining. Expression of transforming growth factor-beta, tumor necrosis factor-alpha, and matrix metalloproteinase-2 genes was determined using real-time quantitative PCR. BMMSCs intervention better promoted recovery of nerve function of rats with SCI, mitigated nerve cell damage, and decreased expression of transforming growth factor-beta, tumor necrosis factor-alpha, and matrix metalloproteinase-2 genes than MP and/or VC. More importantly, BMMSCs in combination with VC induced more obvious improvements. These results suggest that VC can enhance the neuroprotective effects of BMMSCs against SCI. 展开更多
关键词 nerve regeneration spinal cord injury vitamin C METHYLPREDNISOLONE bone marrow mesenchymalstern cells locotmotor neural regeneration
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Co-transplantation of Schwann cells and bone marrow stromal cells versus single cell transplantation on repairing hemisected spinal cord injury of rats 被引量:2
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作者 Jifei Zhang Geng Wu +1 位作者 Fusheng Zhao Xiudong Jin 《Neural Regeneration Research》 SCIE CAS CSCD 2010年第11期805-813,共9页
BACKGROUND: Bone marrow stromal cells (BMSCs) or Schwann cells (SCs) transplantation alone can treat spinal cord injury. However, the transplantation either cell-type alone has disadvantages. The co-transplantati... BACKGROUND: Bone marrow stromal cells (BMSCs) or Schwann cells (SCs) transplantation alone can treat spinal cord injury. However, the transplantation either cell-type alone has disadvantages. The co-transplantation of both cells may benefit structural reconstruction and functional recovery of spinal nerves. OBJECTIVE: To verify spinal cord repair and related mechanisms after co-transplantation of BMSCs and SCs in a rat model of hemisected spinal cord injury. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Department of Histology and Embryology, Mudanjiang Medical College from January 2008 to May 2009. MATERIALS: Rabbit anti-S-100, glial fibrillary acidic protein, neuron specific enolase and neurofilament-200 monoclonal antibodies were purchased from Sigma, USA. METHODS: A total of 100 Wistar rats were used in a model of hemisected spinal cord injury. The rats were randomly assigned to vehicle control, SCs transplantation, BMSCs transplantation, and co-transplantation groups; 25 rats per group. At 1 week after modeling, SCs or BMSCs cultured in vitro were labeled and injected separately into the hemisected spinal segment of SCs and BMSCs transplantation groups through three injection points [5 μL (1 x 107 cells/mL)] cell suspension in each point). In addition, a 15 μL 1 × 10^7 cells/mL SCs suspension and a 15 μL 1 × 10^7 cells/mL BMSC suspension were injected into co-transplantation group by the above method. MAIN OUTCOME MEASURES: The Basso-Beattie-Bresnahan (BBB) locomotor rating scale and somatosensory evoked potential (SEP) tests were used to assess the functional recovery of rat hind limbs following operation. Structural repair of injured nerve tissue was observed by light microscopy, electron microscopy, immunohistochemistry, and magnetic resonance imaging (MRI). In vivo differentiation, survival and migration of BMSCs were evaluated by immunofluorescence. RESULTS: BBB scores were significantly greater in all three transplantation groups compared with vehicle control group 8 weeks after transplantation. In particular, the co-transplantation group displayed the highest scores among the groups (P 〈 0.05). Moreover, recovery of SEP latency and amplitude was observed in all the transplantation groups, particularly after 8 weeks. Again, the co-transplantation group exhibited the greatest improvement (P 〈 0.05). In the co-transplantation group, imaging showed a smooth surface and intact inner structure at the injury site, with no scar formation, and a large number of orderly cells at the injured site. Axonal regeneration, new myelination, and a large amount of cell division were detected in the co-transplantation group by electron microscopy. Neuron specific enolase (NSE)- and glial fibriilary acidic protein (GFAP)-positive cells were observed in the spinal cord sections 1 week following co-transplantation by immunofluorescence staining. CONCLUSION: Co-transplantation of SCs and BMSCs effectively promoted functional recovery of injured spinal cord in rats compared with SCs or BMSCs transplantation alone. This repair effect is probably achieved because of neuronal-like cells derived from BMSCs to supplement dead neurons in vivo. 展开更多
关键词 bone marrow stromal cells Schwann cells CO-TRANSPLANTATION spinal cord injury neural regeneration
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Adenovirus-mediated human brain-derived neurotrophic factor gene-modified bone marrow mesenchymal stem cell transplantation for spinal cord injury 被引量:2
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作者 ChangshengWang Jianhua Lin Chaoyang Wu Rongsheng Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2011年第16期1211-1216,共6页
Rat bone marrow mesenchymal stem cells expressing brain-derived neurotrophic factor were successfully obtained using a gene transfection method, then intravenously transplanted into rats with spinal cord injury. At 1,... Rat bone marrow mesenchymal stem cells expressing brain-derived neurotrophic factor were successfully obtained using a gene transfection method, then intravenously transplanted into rats with spinal cord injury. At 1,3, and 5 weeks after transplantation, the expression of brain-derived neurotrophic factor and neurofilament-200 was upregulated in the injured spinal cord, spinal cord injury was alleviated, and Basso-Beattie-Bresnahan scores of hindlimb motor function were significantly increased. This evidence suggested that intravenous transplantation of adenovirus- mediated brain-derived neurotrophic factor gene-modified rat bone marrow mesenchymal stem cells could play a dual role, simultaneously providing neural stem cells and neurotrophic factors. 展开更多
关键词 brain-derived neurotrophic factor bone marrow mesenchymal stem cells gene modification intravenous transplantation spinal cord injury neural regeneration
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Minimally manipulated autologous adherent bone marrow cells (ABMCs):a promising cell therapy of spinal cord injury 被引量:3
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作者 Kamana Misra Hatem E.Sabaawy 《Neural Regeneration Research》 SCIE CAS CSCD 2015年第7期1058-1060,共3页
Spinal cord injury(SCI)is a devastating ailment that results in drastic life style alterations for the patients and their family members(Mc Donald and Sadowsky,2002).Damage post injury causes necrosis,edema,hemorr... Spinal cord injury(SCI)is a devastating ailment that results in drastic life style alterations for the patients and their family members(Mc Donald and Sadowsky,2002).Damage post injury causes necrosis,edema,hemorrhage and vasospasm.Post injury,secondary damage is caused by ischemia, 展开更多
关键词 bone CELL Minimally manipulated autologous adherent bone marrow cells a promising cell therapy of spinal cord injury ABMCs MSCS
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Combined administration of platelet rich plasma and autologous bone marrow aspirate concentrate for spinal cord injury: a descriptive case series 被引量:3
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作者 Joseph A.Shehadi Steven M.Elzein +2 位作者 Paul Beery M.Chance Spalding Michelle Pershing 《Neural Regeneration Research》 SCIE CAS CSCD 2021年第2期362-366,共5页
Administration of platelet rich plasma(PRP) and bone marrow aspirate concentrate(BMAC) has shown some promise in the treatment of neurological conditions;however, there is limited information on combined administratio... Administration of platelet rich plasma(PRP) and bone marrow aspirate concentrate(BMAC) has shown some promise in the treatment of neurological conditions;however, there is limited information on combined administration. As such, the purpose of this study was to assess safety and functional outcomes for patients administered combined autologous PRP and BMAC for spinal cord injury(SCI). This retrospective case series included seven patients who received combined treatment of autologous PRP and BMAC via intravenous and intrathecal administration as salvage therapy for SCI. Patients were reviewed for adverse reactions and clinical outcomes using the Oswestry Disability Index(ODI) for up to 1 year, as permitted by availability of follow-up data. Injury levels ranged from C3 through T11, and elapsed time between injury and salvage therapy ranged from 2.4 months to 6.2 years. Post-procedure complications were mild and rare, consisting only of self-limited headache and subjective memory impairment in one patient. Four patients experienced severe disability prior to PRP combined with BMAC injection, as evidenced by high(> 48/100) Oswestry Disability Index scores. Longitudinal Oswestry Disability Index scores for two patients with incomplete SCI at C6 and C7, both of whom had cervical spine injuries, demonstrated a decrease of 28–40% following salvage therapy, representing an improvement from severe to minimal disability. In conclusion, intrathecal/intravenous co-administration of PRP and BMAC resulted in no significant complications and may have had some clinical benefits. Larger clinical studies are needed to further test this method of treatment for patients with SCI who otherwise have limited meaningful treatment options. This study was reviewed and approved by the Ohio Health Institutional Review Board(IRB No. 1204946) on May 16, 2018. 展开更多
关键词 bone marrow aspirate concentrate cell-based therapy neural regeneration Oswestry Disability Index platelet rich plasma spinal cord injury stem cells
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Cell transplantation therapies for spinal cord injury focusing on bone marrow mesenchymal stem cells:Advances and challenges 被引量:3
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作者 Li-Yi Huang Xin Sun +3 位作者 Hong-Xia Pan Lu Wang Cheng-Qi He Quan Wei 《World Journal of Stem Cells》 SCIE 2023年第5期385-399,共15页
Spinal cord injury(SCI)is a devastating condition with complex pathological mechanisms that lead to sensory,motor,and autonomic dysfunction below the site of injury.To date,no effective therapy is available for the tr... Spinal cord injury(SCI)is a devastating condition with complex pathological mechanisms that lead to sensory,motor,and autonomic dysfunction below the site of injury.To date,no effective therapy is available for the treatment of SCI.Recently,bone marrow-derived mesenchymal stem cells(BMMSCs)have been considered to be the most promising source for cellular therapies following SCI.The objective of the present review is to summarize the most recent insights into the cellular and molecular mechanism using BMMSC therapy to treat SCI.In this work,we review the specific mechanism of BMMSCs in SCI repair mainly from the following aspects:Neuroprotection,axon sprouting and/or regeneration,myelin regeneration,inhibitory microenvironments,glial scar formation,immunomodulation,and angiogenesis.Additionally,we summarize the latest evidence on the application of BMMSCs in clinical trials and further discuss the challenges and future directions for stem cell therapy in SCI models. 展开更多
关键词 spinal cord injury bone marrow derived mesenchymal stem cells Neuroprotection AXON MYELIN Inhibitory microenvironment
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