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Hydrogel loaded with bone marrow stromal cell-derived exosomes promotes bone regeneration by inhibiting inflammatory responses and angiogenesis 被引量:1
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作者 Shuai Zhang Chuan Lu +1 位作者 Sheng Zheng Guang Hong 《World Journal of Stem Cells》 SCIE 2024年第5期499-511,共13页
BACKGROUND Bone healing is a complex process involving early inflammatory immune regu-lation,angiogenesis,osteogenic differentiation,and biomineralization.Fracture repair poses challenges for orthopedic surgeons,neces... BACKGROUND Bone healing is a complex process involving early inflammatory immune regu-lation,angiogenesis,osteogenic differentiation,and biomineralization.Fracture repair poses challenges for orthopedic surgeons,necessitating the search for efficient healing methods.AIM To investigate the underlying mechanism by which hydrogel-loaded exosomes derived from bone marrow mesenchymal stem cells(BMSCs)facilitate the process of fracture healing.METHODS Hydrogels and loaded BMSC-derived exosome(BMSC-exo)gels were charac-terized to validate their properties.In vitro evaluations were conducted to assess the impact of hydrogels on various stages of the healing process.Hydrogels could recruit macrophages and inhibit inflammatory responses,enhance of human umbilical vein endothelial cell angiogenesis,and promote the osteogenic differen-tiation of primary cranial osteoblasts.Furthermore,the effect of hydrogel on fracture healing was confirmed using a mouse fracture model.RESULTS The hydrogel effectively attenuated the inflammatory response during the initial repair stage and subsequently facilitated vascular migration,promoted the formation of large vessels,and enabled functional vascularization during bone repair.These effects were further validated in fracture models.CONCLUSION We successfully fabricated a hydrogel loaded with BMSC-exo that modulates macrophage polarization and angiogenesis to influence bone regeneration. 展开更多
关键词 HYDROGEL bone marrow mesenchymal stem cells Macrophage polarization ANGIOGENESIS bone regeneration
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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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Bone marrow-derived mesenchymal stem cell-derived exosomeloaded miR-129-5p targets high-mobility group box 1 attenuates neurological-impairment after diabetic cerebral hemorrhage 被引量:1
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作者 Yue-Ying Wang Ke Li +5 位作者 Jia-Jun Wang Wei Hua Qi Liu Yu-Lan Sun Ji-Ping Qi Yue-Jia Song 《World Journal of Diabetes》 SCIE 2024年第9期1979-2001,共23页
BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patie... BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain. 展开更多
关键词 bone marrow mesenchymal stem cells Exosome Diabetic cerebral hemorrhage Neuroinflammation MicroRNA-129-5p High mobility group box 1
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O-linkedβ-N-acetylglucosaminylation may be a key regulatory factor in promoting osteogenic differentiation of bone marrow mesenchymal stromal cells
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作者 Xu-Chang Zhou Guo-Xin Ni 《World Journal of Stem Cells》 SCIE 2024年第3期228-231,共4页
Cumulative evidence suggests that O-linkedβ-N-acetylglucosaminylation(OGlcNAcylation)plays an important regulatory role in pathophysiological processes.Although the regulatory mechanisms of O-GlcNAcylation in tumors ... Cumulative evidence suggests that O-linkedβ-N-acetylglucosaminylation(OGlcNAcylation)plays an important regulatory role in pathophysiological processes.Although the regulatory mechanisms of O-GlcNAcylation in tumors have been gradually elucidated,the potential mechanisms of O-GlcNAcylation in bone metabolism,particularly,in the osteogenic differentiation of bone marrow mesenchymal stromal cells(BMSCs)remains unexplored.In this study,the literature related to O-GlcNAcylation and BMSC osteogenic differentiation was reviewed,assuming that it could trigger more scholars to focus on research related to OGlcNAcylation and bone metabolism and provide insights into the development of novel therapeutic targets for bone metabolism disorders such as osteoporosis. 展开更多
关键词 O-GLCNACYLATION Osteogenic differentiation bone marrow mesenchymal stromal cells OSTEOPOROSIS
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Bone marrow mesenchymal stem cells in treatment of peripheral nerve injury
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作者 Xiong-Fei Zou Bao-Zhong Zhang +1 位作者 Wen-Wei Qian Florence Mei Cheng 《World Journal of Stem Cells》 SCIE 2024年第8期799-810,共12页
Peripheral nerve injury(PNI)is a common neurological disorder and complete functional recovery is difficult to achieve.In recent years,bone marrow mesenchymal stem cells(BMSCs)have emerged as ideal seed cells for PNI ... Peripheral nerve injury(PNI)is a common neurological disorder and complete functional recovery is difficult to achieve.In recent years,bone marrow mesenchymal stem cells(BMSCs)have emerged as ideal seed cells for PNI treatment due to their strong differentiation potential and autologous trans-plantation ability.This review aims to summarize the molecular mechanisms by which BMSCs mediate nerve repair in PNI.The key mechanisms discussed include the differentiation of BMSCs into multiple types of nerve cells to promote repair of nerve injury.BMSCs also create a microenvironment suitable for neuronal survival and regeneration through the secretion of neurotrophic factors,extracellular matrix molecules,and adhesion molecules.Additionally,BMSCs release pro-angiogenic factors to promote the formation of new blood vessels.They modulate cytokine expression and regulate macrophage polarization,leading to immunomodulation.Furthermore,BMSCs synthesize and release proteins related to myelin sheath formation and axonal regeneration,thereby promoting neuronal repair and regeneration.Moreover,this review explores methods of applying BMSCs in PNI treatment,including direct cell trans-plantation into the injured neural tissue,implantation of BMSCs into nerve conduits providing support,and the application of genetically modified BMSCs,among others.These findings confirm the potential of BMSCs in treating PNI.However,with the development of this field,it is crucial to address issues related to BMSC therapy,including establishing standards for extracting,identifying,and cultivating BMSCs,as well as selecting application methods for BMSCs in PNI such as direct transplantation,tissue engineering,and genetic engineering.Addressing these issues will help translate current preclinical research results into clinical practice,providing new and effective treatment strategies for patients with PNI. 展开更多
关键词 bone marrow mesenchymal stem cells Peripheral nerve injury Schwann cells Myelin sheath Tissue engineering
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Effects of interleukin-10 treated macrophages on bone marrow mesenchymal stem cells via signal transducer and activator of transcription 3 pathway
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作者 Meng-Hao Lyu Ce Bian +3 位作者 Yi-Ping Dou Kang Gao Jun-Ji Xu Pan Ma 《World Journal of Stem Cells》 SCIE 2024年第5期560-574,共15页
BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can sign... BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process.AIM To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory environment.METHODS IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment.In this study,we investigated its impact on the proliferation,migration,and osteogenesis of BMSCs.The expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated macrophages.Subsequently,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling.RESULTS IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs.Mechanistically,STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages.Specifically,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of BMSCs.CONCLUSION Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs.The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation. 展开更多
关键词 MACROPHAGES INTERLEUKIN-10 bone marrow mesenchymal stem cells Signal transducer and activator of transcription 3 Inflammatory response
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Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis
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作者 Xiahong Tang Nan Zheng +8 位作者 Qingming Lin Yan You Zheng Gong Yangping Zhuang Jiali Wu Yu Wang Hanlin Huang Jun Ke Feng Chen 《Neural Regeneration Research》 SCIE CAS 2025年第4期1103-1123,共21页
Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to impr... Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning. 展开更多
关键词 bone marrow–derived mesenchymal stem cells cardiac arrest cardiac resuscitation hypoxic preconditioning liver isoform of phosphofructokinase mitochondria NEUROINFLAMMATION oxidative stress PYROPTOSIS reactive oxygen species
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Ecthyma Gangrenosum in Patient with Bone Marrow Aplasia: A Case Report and Review of the Literature
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作者 Hanane Hajaj Hanae Bahari +4 位作者 Hind Zahiri Ayyad Ghanam Aziza El Ouali Abdeladim Babakhouya Maria Rkain 《Open Journal of Pediatrics》 2024年第2期272-278,共7页
Background: Ecthyma gangrenosum (EG) is an infrequent and discernible cutaneous disease caused by Pseudomonas aeruginosa. In situations where it is associated with septicemia in debilitated patients, the prognosis is ... Background: Ecthyma gangrenosum (EG) is an infrequent and discernible cutaneous disease caused by Pseudomonas aeruginosa. In situations where it is associated with septicemia in debilitated patients, the prognosis is usually unfavorable. Objective: In this case, we aim to verify risk factors, clinical, bacteriological and therapeutic characteristics of ecthyma gangrenosum and we review the literature to highlight the features of this rare condition and discuss the role of early diagnosis and treatment. Case Report: We describe the clinical case of a 4-year-old male with bone marrow aplasia who was presented with characteristic skin lesions of EG and developed sepsis later. Conclusion: EG is a cutaneous disease characterized by its aggressive nature. The presence of delayed diagnosis and therapy, along with sepsis, is closely linked to a high mortality rate. Treatment is empirically founded on an aggressive initial approach. 展开更多
关键词 Ecthyma Gangrenosum CHILD bone marrow Aplasia
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Exosomes from bone marrow mesenchymal stem cells are a potential treatment for ischemic stroke 被引量:10
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作者 Chang Liu Tian-Hui Yang +3 位作者 Hong-Dan Li Gong-Zhe Li Jia Liang Peng Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第10期2246-2251,共6页
Exosomes derived from human bone marrow mesenchymal stem cells(MSC-Exo)are characterized by easy expansion and storage,low risk of tumor formation,low immunogenicity,and anti-inflammatory effects.The therapeutic effec... Exosomes derived from human bone marrow mesenchymal stem cells(MSC-Exo)are characterized by easy expansion and storage,low risk of tumor formation,low immunogenicity,and anti-inflammatory effects.The therapeutic effects of MSC-Exo on ischemic stroke have been widely explored.However,the underlying mechanism remains unclear.In this study,we established a mouse model of ischemic brain injury induced by occlusion of the middle cerebral artery using the thread bolt method and injected MSC-Exo into the tail vein.We found that administration of MSC-Exo reduced the volume of cerebral infarction in the ischemic brain injury mouse model,increased the levels of interleukin-33(IL-33)and suppression of tumorigenicity 2 receptor(ST2)in the penumbra of cerebral infarction,and improved neurological function.In vitro results showed that astrocyte-conditioned medium of cells deprived of both oxygen and glucose,to simulate ischemia conditions,combined with MSC-Exo increased the survival rate of primary cortical neurons.However,after transfection by IL-33 siRNA or ST2 siRNA,the survival rate of primary cortical neurons was markedly decreased.These results indicated that MSC-Exo inhibited neuronal death induced by oxygen and glucose deprivation through the IL-33/ST2 signaling pathway in astrocytes.These findings suggest that MSC-Exo may reduce ischemia-induced brain injury through regulating the IL-33/ST2 signaling pathway.Therefore,MSC-Exo may be a potential therapeutic method for ischemic stroke. 展开更多
关键词 ASTROCYTES bone marrow mesenchymal stem cells brain injury EXOSOME IL-33 inflammation ischemic stroke neurological function NEURON ST2
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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:7
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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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Exosomal miR-23b from bone marrow mesenchymal stem cells alleviates oxidative stress and pyroptosis after intracerebral hemorrhage 被引量:5
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作者 Liu-Ting Hu Bing-Yang Wang +2 位作者 Yu-Hua Fan Zhi-Yi He Wen-Xu Zheng 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第3期560-567,共8页
Our previous studies showed that miR-23b was downregulated in patients with intracerebral hemorrhage(ICH). This indicates that miR-23b may be closely related to the patho-physiological mechanism of ICH, but this hypot... Our previous studies showed that miR-23b was downregulated in patients with intracerebral hemorrhage(ICH). This indicates that miR-23b may be closely related to the patho-physiological mechanism of ICH, but this hypothesis lacks direct evidence. In this study, we established rat models of ICH by injecting collagenase Ⅶ into the right basal ganglia and treating them with an injection of bone marrow mesenchymal stem cell(BMSC)-derived exosomal miR-23b via the tail vein. We found that edema in the rat brain was markedly reduced and rat behaviors were improved after BMSC exosomal miR-23b injection compared with those in the ICH groups. Additionally, exosomal miR-23b was transported to the microglia/macrophages, thereby reducing oxidative stress and pyroptosis after ICH. We also used hemin to mimic ICH conditions in vitro. We found that phosphatase and tensin homolog deleted on chromosome 10(PTEN) was the downstream target gene of miR-23b, and exosomal miR-23b exhibited antioxidant effects by regulating the PTEN/Nrf2 pathway. Moreover, miR-23b reduced PTEN binding to NOD-like receptor family pyrin domain containing 3(NLRP3) and NLRP3 inflammasome activation, thereby decreasing the NLRP3-dependent pyroptosis level. These findings suggest that BMSC-derived exosomal miR-23b exhibits antioxidant effects through inhibiting PTEN and alleviating NLRP3 inflammasome-mediated pyroptosis, thereby promoting neurologic function recovery in rats with ICH. 展开更多
关键词 bone marrow mesenchymal stem cells exosomal miRNAs intracerebral hemorrhage miR-23b NEUROINFLAMMATION NLRP3 inflammasome Nrf2 oxidative stress PTEN PYROPTOSIS
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Overexpression of vascular endothelial growth factor enhances the neuroprotective effects of bone marrow mesenchymal stem cell transplantation in ischemic stroke 被引量:5
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作者 Cui Liu Zhi-Xiang Yang +6 位作者 Si-Qi Zhou Ding Ding Yu-Ting Hu Hong-Ning Yang Dong Han Shu-Qun Hu Xue-Mei Zong 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第6期1286-1292,共7页
Although bone marrow mesenchymal stem cells(BMSCs)might have therapeutic potency in ischemic stroke,the benefits are limited.The current study investigated the effects of BMSCs engineered to overexpress vascular endot... Although bone marrow mesenchymal stem cells(BMSCs)might have therapeutic potency in ischemic stroke,the benefits are limited.The current study investigated the effects of BMSCs engineered to overexpress vascular endothelial growth factor(VEGF)on behavioral defects in a rat model of transient cerebral ischemia,which was induced by middle cerebral artery occlusion.VEGF-BMSCs or control grafts were injected into the left striatum of the infarcted hemisphere 24 hours after stroke.We found that compared with the stroke-only group and the vehicle-and BMSCs-control groups,the VEGF-BMSCs treated animals displayed the largest benefits,as evidenced by attenuated behavioral defects and smaller infarct volume 7 days after stroke.Additionally,VEGF-BMSCs greatly inhibited destruction of the blood-brain barrier,increased the regeneration of blood vessels in the region of ischemic penumbra,and reducedneuronal degeneration surrounding the infarct core.Further mechanistic studies showed that among all transplant groups,VEGF-BMSCs transplantation induced the highest level of brain-derived neurotrophic factor.These results suggest that BMSCs transplantation with vascular endothelial growth factor has the potential to treat ischemic stroke with better results than are currently available. 展开更多
关键词 bone marrow mesenchymal stem cell brain-derived neurotrophic factor CD31 microtubule associated protein 2 middle cerebral artery occlusion stroke transplantation vascular endothelial growth factor
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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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Communication between bone marrow mesenchymal stem cells and multiple myeloma cells:Impact on disease progression 被引量:1
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作者 Daniel García-Sánchez Alberto González-González +2 位作者 Ana Alfonso-Fernández Mónica Del Dujo-Gutiérrez Flor M Pérez-Campo 《World Journal of Stem Cells》 SCIE 2023年第5期421-437,共17页
Multiple myeloma(MM)is a hematological malignancy characterized by the accumulation of immunoglobulin-secreting clonal plasma cells at the bone marrow(BM).The interaction between MM cells and the BM microenvironment,a... Multiple myeloma(MM)is a hematological malignancy characterized by the accumulation of immunoglobulin-secreting clonal plasma cells at the bone marrow(BM).The interaction between MM cells and the BM microenvironment,and specifically BM mesenchymal stem cells(BM-MSCs),has a key role in the pathophysiology of this disease.Multiple data support the idea that BM-MSCs not only enhance the proliferation and survival of MM cells but are also involved in the resistance of MM cells to certain drugs,aiding the progression of this hematological tumor.The relation of MM cells with the resident BM-MSCs is a two-way interaction.MM modulate the behavior of BM-MSCs altering their expression profile,proliferation rate,osteogenic potential,and expression of senescence markers.In turn,modified BM-MSCs can produce a set of cytokines that would modulate the BM microenvironment to favor disease progression.The interaction between MM cells and BM-MSCs can be mediated by the secretion of a variety of soluble factors and extracellular vesicles carrying microRNAs,long non-coding RNAs or other molecules.However,the communication between these two types of cells could also involve a direct physical interaction through adhesion molecules or tunneling nanotubes.Thus,understanding the way this communication works and developing strategies to interfere in the process,would preclude the expansion of the MM cells and might offer alternative treatments for this incurable disease. 展开更多
关键词 Multiple myeloma Mesenchymal stem cells bone marrow microenvironment Soluble factors Extra-cellular vesicles Cells adhesion molecules Tunnellingnanotubes
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Role of Vascular Endothelial Growth Factor-C during Stem Cell Therapy Using Autologous Bone Marrow Mononuclear Cells in Patients with Lower Limb Lymphedema 被引量:1
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作者 Ahmed M. Ismail Said M. Abdou +7 位作者 Amira Yousef Yousra Sameh M. Attia Ahmed Badran Mohamed I. Adel El Eissawy Asmaa E. Bedeer Wesam M. Salama Ahmed O. Korany 《Stem Cell Discovery》 CAS 2023年第1期1-16,共16页
Introduction: Vascular endothelial growth factor-C (VEGF-C) is the primary lymphangiogenic factor that stimulates lymphangiogenesis by signaling via specific receptor, vascular endothelial growth factor receptor 3 (VE... Introduction: Vascular endothelial growth factor-C (VEGF-C) is the primary lymphangiogenic factor that stimulates lymphangiogenesis by signaling via specific receptor, vascular endothelial growth factor receptor 3 (VEGFR3). This study was conducted to evaluate the change in the level of VEGF-C before and after autologous bone marrow mononuclear cell transplantation for treatment of Lower limb lymphedema. Patient and methods: Forty patients with lower limb lymphedema were divided into two groups. Group I included 20 patients with chronic lower limb lymphedema who underwent autologous bone marrow mononuclear cell transplantation. Group II included 20 patients with chronic lower limb lymphedema who were exposed only to compression therapy as a control group. VEGF-C level in the diseased limbs was measured in both groups at the beginning of the study then 3 and 6 months respectively. Results: Group I included 20 patients, 8 patients were male (40%) and 12 patients were females (60%) with mean age 29.5 ± 12.15 while group II included 20, 10 patients were male (50%) and 10 patients were females (50%) with mean age 39.5 ± 11.5. In group I, the specimens were taken at 3 and 6 months after transplantation showed a marked decrease in the VEGF-C level with statistically significant p value, 0.02 and 0.001 respectively. In group II the level of VEGF-C after compression therapy alone at 3 and 6 months interval showed fluctuation with statistically non-significant p value, 0.64 and 0.55 respectively. Conclusion: VEGF-C is essential for regulation of lymphangiogenesis. The level of VEGF-C was found elevated in patients with lymphedema and decrease after autologous mononuclear bone marrow cells, however these results were statically non-significant. 展开更多
关键词 LYMPHANGIOGENESIS VEGF-C bone marrow Mononuclear Cells
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Preliminary delivery efficiency prediction of nanotherapeutics into crucial cell populations in bone marrow niche
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作者 Huijuan Chen Anzhi Hu +6 位作者 Mengdi Xiao Shiyi Hong Jing Liang Quanlong Zhang Yang Xiong Mancang Gu Chaofeng Mu 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2023年第6期113-125,共13页
Several crucial stromal cell populations regulate hematopoiesis and malignant diseases in bone marrow niches.Precise regulation of these cell types can remodel niches and develop new therapeutics.Multiple nanocarriers... Several crucial stromal cell populations regulate hematopoiesis and malignant diseases in bone marrow niches.Precise regulation of these cell types can remodel niches and develop new therapeutics.Multiple nanocarriers have been developed to transport drugs into the bone marrow selectively.However,the delivery efficiency of these nanotherapeutics into crucial niche cells is still unknown,and there is no method available for predicting delivery efficiency in these cell types.Here,we constructed a three-dimensional bone marrow niche composed of three crucial cell populations:endothelial cells(ECs),mesenchymal stromal cells(MSCs),and osteoblasts(OBs).Mimetic niches were used to detect the cellular uptake of three typical drug nanocarriers into ECs/MSCs/OBs in vitro.Less than 5%of nanocarriers were taken up by three stromal cell types,and most of themwere located in the extracellular matrix.Delivery efficiency in sinusoidal ECs,arteriole ECs,MSCs,and OBs in vivo was analyzed.The correlation analysis showed that the cellular uptake of three nanocarriers in crucial cell types in vitro is positively linear correlated with its delivery efficiency in vivo.The delivery efficiency into MSCs was remarkably higher than that into ECs and OBs,no matterwhat kind of nanocarrier.The overall efficiency into sinusoidal ECswas greatly lower than that into arteriole ECs.All nanocarriers were hard to be delivered into OBs(<1%).Our findings revealed that cell tropisms of nanocarriers with different compositions and ligand attachments in vivo could be predicted via detecting their cellular uptake in bone marrow niches in vitro.This study provided the methodology for niche-directed nanotherapeutics development. 展开更多
关键词 bone marrow niche mimicking Drug delivery prediction Nanotherapeutics bone marrow stromal cells
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Diagnostic Efficacy of^(18)F-FDG PET/CT in Detecting Bone Marrow Infiltration in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma
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作者 GUO Bo QIN Ran +3 位作者 GU Zhen Yang LI Yan Fen GAO Lei HUANG Wen Rong 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2023年第6期510-516,共7页
Objective Diffuse large B-cell lymphoma(DLBCL)is often associated with bone marrow infiltration,and 2-deoxy-2-(18F)fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG PET/CT)has potential di... Objective Diffuse large B-cell lymphoma(DLBCL)is often associated with bone marrow infiltration,and 2-deoxy-2-(18F)fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG PET/CT)has potential diagnostic significance for bone marrow infiltration in DLBCL.Methods A total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were included.Bone marrow biopsy and^(18)F-FDG PET/CT examinations were performed at the time of initial diagnosis.Kappa tests were used to evaluate the agreement of^(18)F-FDG PET/CT with the gold standard,and the imaging features of DLBCL bone marrow infiltration on PET/CT were described.Results The total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy(P=0.302)or between the two bone marrow biopsies(P=0.826).The sensitivity,specificity,and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923(95%CI,0.759-0.979),0.934(95%CI,0.855-0.972),and 0.857,respectively.Conclusion^(18)F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow infiltration.PET/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration. 展开更多
关键词 Diffuse large B-cell lymphoma bone marrow infiltration Positron emission computed tomography(PET/CT) bone marrow biopsy Diagnostic efficacy
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Treatment of postherpetic neuralgia by bone marrow aspirate injection:A case report
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作者 Takahiro Honda Pazili 《World Journal of Clinical Cases》 SCIE 2023年第15期3619-3624,共6页
BACKGROUND Postherpetic neuralgia(PHN)is the most frequent and a difficult-to-treat complication of herpes zoster(HZ).Its symptoms include allodynia,hyperalgesia,burning,and an electric shock-like sensation stemming f... BACKGROUND Postherpetic neuralgia(PHN)is the most frequent and a difficult-to-treat complication of herpes zoster(HZ).Its symptoms include allodynia,hyperalgesia,burning,and an electric shock-like sensation stemming from the hyperexcitability of damaged neurons and varicella-zoster virus-mediated inflammatory tissue damage.HZ-related PHN has an incidence of 5%–30%,and in some patients,the pain is intolerable and can lead to insomnia or depression.In many cases,the pain is resistant to pain-relieving drugs,necessitating radical therapy.CASE SUMMARY We present the case of a patient with PHN whose pain was not cured by conventional treatments,such as analgesics,block injections,or Chinese medicines,but by bone marrow aspirate concentrate(BMAC)injection containing bone marrow mesenchymal stem cells.BMAC has already been used for joint pains.However,this is the first report on its use for PHN treatment.CONCLUSION This report reveals that bone marrow extract can be a radical therapy for PHN. 展开更多
关键词 bone marrow aspirate concentrate Postherpetic neuralgia Herpes zoster bone marrow mesenchymal stem cells Pain syndrome Case report
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Senescent mesenchymal stem/stromal cells in pre-metastatic bone marrow of untreated advanced breast cancer patients
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作者 FRANCISCO RAÚL BORZONE MARÍA BELÉN GIORELLO +6 位作者 LEANDRO MARCELO MARTINEZ MARÍA CECILIA SANMARTIN LEONARDO FELDMAN FEDERICO DIMASE EMILIO BATAGELJ GUSTAVO YANNARELLI NORMA ALEJANDRA CHASSEING 《Oncology Research》 SCIE 2023年第3期361-374,共14页
Breast cancer is the predominant form of carcinoma among women worldwide,with 70%of advanced patients developing bone metastases,with a high mortality rate.In this sense,the bone marrow(BM)mesenchymal stem/stromal cel... Breast cancer is the predominant form of carcinoma among women worldwide,with 70%of advanced patients developing bone metastases,with a high mortality rate.In this sense,the bone marrow(BM)mesenchymal stem/stromal cells(MSCs)are critical for BM/bone homeostasis,and failures in their functionality,transform the BM into a premetastatic niche(PMN).We previously found that BM-MSCs from advanced breast cancer patients(BCPs,infiltrative ductal carcinoma,stage III-B)have an abnormal profile.This work aims to study some of the metabolic and molecular mechanisms underlying MSCs shift from a normal to an abnormal profile in this group of patients.A comparative analysis was undertaken,which included self-renewal capacity,morphology,proliferation capacity,cell cycle,reactive oxygen species(ROS)levels,and senescence-associatedβ‑galactosidase(SA‑β‑gal)staining of BMderived MSCs isolated from 14 BCPs and 9 healthy volunteers(HVs).Additionally,the expression and activity of the telomerase subunit TERT,as well as telomere length,were measured.Expression levels of pluripotency,osteogenic,and osteoclastogenic genes(OCT-4,SOX-2,M-CAM,RUNX-2,BMP-2,CCL-2,M-CSF,and IL-6)were also determined.The results showed that MSCs from BCPs had reduced,self-renewal and proliferation capacity.These cells also exhibited inhibited cell cycle progression and phenotypic changes,such as an enlarged and flattened appearance.Additionally,there was an increase in ROS and senescence levels and a decrease in the functional capacity of TERT to preserve telomere length.We also found an increase in pro-inflammatory/pro-osteoclastogenic gene expression and a decrease in pluripotency gene expression.We conclude that these changes could be responsible for the abnormal functional profile that MSCs show in this group of patients. 展开更多
关键词 Mesenchymal stem/stromal cells Senescence Breast cancer bone marrow Pre-metastatic niche bone metastasis
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Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells 被引量:1
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作者 Tong Wu Fu Zheng +7 位作者 Hong-Yi Tang Hua-Zhi Li Xin-Yu Cui Shuai Ding Duo Liu Cui-Ying Li Jiu-Hui Jiang Rui-Li Yang 《World Journal of Stem Cells》 SCIE 2024年第3期267-286,共20页
BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or to... BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or tooth root resorption.Low-intensity pulsed ultrasound(LIPUS),a noninvasive physical therapy,has been shown to promote bone fracture healing.It is also reported that LIPUS could reduce the duration of orthodontic treatment;however,how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.AIM To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement(OTM)model and explore the underlying mechanisms.METHODS A rat model of OTM was established,and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections.In vitro,human bone marrow mesenchymal stem cells(hBMSCs)were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction,Western blot,alkaline phosphatase(ALP)staining,and Alizarin red staining.The expression of Yes-associated protein(YAP1),the actin cytoskeleton,and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA(siRNA)application via immunofluorescence.RESULTS The force treatment inhibited the osteogenic differentiation potential of hBMSCs;moreover,the expression of osteogenesis markers,such as type 1 collagen(COL1),runt-related transcription factor 2,ALP,and osteocalcin(OCN),decreased.LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force.Mechanically,the expression of LaminA/C,F-actin,and YAP1 was downregulated after force treatment,which could be rescued by LIPUS.Moreover,the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment.Consistently,LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo.The decreased expression of COL1,OCN,and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS.CONCLUSION LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis,which may be a promising strategy to reduce the orthodontic treatment process. 展开更多
关键词 Low-intensity pulsed ultrasound bone resorption OSTEOGENESIS Cytoskeleton-Lamin A/C-Yes-associated protein axis bone marrow mesenchymal stem cells Orthodontic tooth movement
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