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Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment
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作者 Sumei Liu Baoguo Liu +4 位作者 Qian Li Tianqi Zheng Bochao Liu Mo Li Zhiguo Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第2期440-446,共7页
Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells a... Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats. 展开更多
关键词 biomaterial FIBRINOGEN functional recovery induced neural stem cell transplantation MICROENVIRONMENT MICROGLIA spinal cord injury THROMBIN
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Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina
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作者 María Norte-Muñoz David García-Bernal +2 位作者 Diego García-Ayuso Manuel Vidal-Sanz Marta Agudo-Barriuso 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第3期542-547,共6页
Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the und... Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation. 展开更多
关键词 adaptive immunity cell therapy central nervous system immune system innate immunity mesenchymal stromal cells NEUROREGENERATION preclinical studies RETINA transplantation
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Controversies regarding transplantation of mesenchymal stem cells
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作者 Tsvetelina Velikova Tereza Dekova Dimitrina Georgieva Miteva 《World Journal of Transplantation》 2024年第2期48-61,共14页
Mesenchymal stem cells(MSCs)have tantalized regenerative medicine with their therapeutic potential,yet a cloud of controversies looms over their clinical tran-splantation.This comprehensive review navigates the intric... Mesenchymal stem cells(MSCs)have tantalized regenerative medicine with their therapeutic potential,yet a cloud of controversies looms over their clinical tran-splantation.This comprehensive review navigates the intricate landscape of MSC controversies,drawing upon 15 years of clinical experience and research.We delve into the fundamental properties of MSCs,exploring their unique immuno-modulatory capabilities and surface markers.The heart of our inquiry lies in the controversial applications of MSC transplantation,including the perennial debate between autologous and allogeneic sources,concerns about efficacy,and lingering safety apprehensions.Moreover,we unravel the enigmatic mechanisms surro-unding MSC transplantation,such as homing,integration,and the delicate balance between differentiation and paracrine effects.We also assess the current status of clinical trials and the ever-evolving regulatory landscape.As we peer into the future,we examine emerging trends,envisioning personalized medicine and innovative delivery methods.Our review provides a balanced and informed perspective on the controversies,offering readers a clear understanding of the complexities,challenges,and potential solutions in MSC transplantation. 展开更多
关键词 Mesenchymal stem cells transplantation controversies Regenerative medicine Autoimmune diseases Chronic inflammatory illnesses Tumor growth METASTASIS Therapeutic potential Clinical use of mesenchymal stem cell
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Transplantation of human placental chorionic plate-derived mesenchymal stem cells for repair of neurological damage in neonatal hypoxic-ischemic encephalopathy
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作者 Lulu Xue Ruolan Du +8 位作者 Ning Bi Qiuxia Xiao Yifei Sun Ruize Niu Yaxin Tan Li Chen Jia Liu Tinghua Wang Liulin Xiong 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第9期2027-2035,共9页
Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ische... Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function. 展开更多
关键词 behavioral evaluations gene knockout human neuroblastoma cells(SH-SY5Y) human placental chorionic derived mesenchymal stem cells INTERLEUKIN-3 neonatal hypoxic-ischemic encephalopathy nerve injury oxygen-glucose deprivation protein chip small interfering RNA
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Understanding host-graft crosstalk for predicting the outcome of stem cell transplantation
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作者 Luminita Labusca Florin Zugun-Eloae 《World Journal of Stem Cells》 SCIE 2024年第3期232-236,共5页
Mesenchymal stromal cells(MSCs)hold great promise for tissue regeneration in debilitating disorders.Despite reported improvements,the short-term outcomes of MSC transplantation,which is possibly linked to poor cell su... Mesenchymal stromal cells(MSCs)hold great promise for tissue regeneration in debilitating disorders.Despite reported improvements,the short-term outcomes of MSC transplantation,which is possibly linked to poor cell survival,demand extensive investigation.Disease-associated stress microenvironments further complicate outcomes.This debate underscores the need for a deeper understanding of the phenotypes of transplanted MSCs and their environment-induced fluctuations.Additionally,questions arise about how to predict,track,and comprehend cell fate post-transplantation.In vivo cellular imaging has emerged as a critical requirement for both short-and long-term safety and efficacy studies.However,translating preclinical imaging methods to clinical settings remains challenging.The fate and function of transplanted cells within the host environment present intricate challenges,including MSC engraftment,variability,and inconsistencies between preclinical and clinical data.The study explored the impact of high glucose concentrations on MSC survival in diabetic environments,emphasizing mitochondrial factors.Preserving these factors may enhance MSC survival,suggesting potential strategies involving genetic modification,biomaterials,and nanoparticles.Understanding stressors in diabetic patients is crucial for predicting the effects of MSC-based therapies.These multifaceted challenges call for a holistic approach involving the incorporation of large-scale data,computational disease modeling,and possibly artificial intelligence to enable deterministic insights. 展开更多
关键词 Mesenchymal stem cells PHENOTYPE transplantation Host MICROENVIRONMENT cellular imaging Diabetes mellitus
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Long-term outcome of stem cell transplantation with and without anti-tumor necrotic factor therapy in perianal fistula with Crohn’s disease
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作者 Min Young Park Yong Sik Yoon +2 位作者 Jae Ha Park Jong Lyul Lee Chang Sik Yu 《World Journal of Stem Cells》 SCIE 2024年第3期257-266,共10页
BACKGROUND Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn’s disease(CD).Anti-tumor necrotic factor(TNF)therapy combined with drainage procedure is effective as well.H... BACKGROUND Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn’s disease(CD).Anti-tumor necrotic factor(TNF)therapy combined with drainage procedure is effective as well.However,previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula closure.AIM This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn’s perianal fistula(CPF)closure rates after stem cell transplantation with and without anti-TNF therapy,and to identify the factors affecting CPF closure and recurrence.METHODS The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were enrolled.Clinical data were compared according to anti-TNF therapy and CPF closure.RESULTS A total of 65 patients were included.The median age of females was 26 years(range:21-31)and that of males was 29(44.6%).The mean follow-up duration was 65.88±32.65 months,and complete closure was observed in 50(76.9%)patients.The closure rates were similar after stem cell transplantation with and without anti-TNF therapy(66.7%vs 81.6%at 3 year,P=0.098).The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture(P=0.027,0.002,and 0.008,respectively).Clinical factors such as complexity,number of fistulas,presence of concurrent abscess,and medication were not significant for closure.The cumulative 1-,2-,and 3-year closure rates were 66.2%,73.8%,and 75.4%,respectively.CONCLUSION Anti-TNF therapy does not increase CPF closure rates in patients with stem cell transplantation.However,both refractory and non-refractory CPF have similar closure rates after additional anti-TNF therapy.Fistulous tract length,proctitis,and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation. 展开更多
关键词 Crohn’s disease ANUS FISTULA stem cell transplantation Tumor necrosis factor-alpha inhibitors INFLIXIMAB
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One-step cell biomanufacturing platform:porous gelatin microcarrier beads promote human embryonic stem cell-derived midbrain dopaminergic progenitor cell differentiation in vitro and survival after transplantation in vivo
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作者 Lin Feng Da Li +10 位作者 Yao Tian Chengshun Zhao Yun Sun Xiaolong Kou Jun Wu Liu Wang Qi Gu Wei Li Jie Hao Baoyang Hu Yukai Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第2期458-464,共7页
Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a p... Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation. 展开更多
关键词 axonal integrity cell cryopreservation cellular environment cellular niche cell replacement therapy dopaminergic progenitors human pluripotent stem cell mechanical damage neuronal cell delivery Parkinson’s disease small-aperture gelatin microcarriers
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Current status and future perspectives on stem cell transplantation for spinal cord injury
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作者 Edoardo Agosti Marco Zeppieri +4 位作者 Andrea Pagnoni Marco Maria Fontanella Alessandro Fiorindi Tamara Ius Pier Paolo Panciani 《World Journal of Transplantation》 2024年第1期189-209,共21页
BACKGROUND Previous assessments of stem cell therapy for spinal cord injuries(SCI)have encountered challenges and constraints.Current research primarily emphasizes safety in early-phase clinical trials,while systemati... BACKGROUND Previous assessments of stem cell therapy for spinal cord injuries(SCI)have encountered challenges and constraints.Current research primarily emphasizes safety in early-phase clinical trials,while systematic reviews prioritize effectiveness,often overlooking safety and translational feasibility.This situation prompts inquiries regarding the readiness for clinical adoption.AIM To offer an up-to-date systematic literature review of clinical trial results concerning stem cell therapy for SCI.METHODS A systematic search was conducted across major medical databases[PubMed,Embase,Reference Citation Analysis(RCA),and Cochrane Library]up to October 14,2023.The search strategy utilized relevant Medical Subject Heading(MeSH)terms and keywords related to"spinal cord","injury","clinical trials","stem cells","functional outcomes",and"adverse events".Studies included in this review consisted of randomized controlled trials and non-randomized controlled trials reporting on the use of stem cell therapies for the treatment of SCI.RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,496 papers were initially identified,with 237 chosen for full-text analysis.Among them,236 were deemed eligible after excluding 170 for various reasons.These studies encompassed 1086 patients with varying SCI levels,with cervical injuries being the most common(42.2%).Bone marrow stem cells were the predominant stem cell type used(71.1%),with various administration methods.Follow-up durations averaged around 84.4 months.The 32.7%of patients showed functional improvement from American spinal injury association Impairment Scale(AIS)A to B,40.8%from AIS A to C,5.3%from AIS A to D,and 2.1%from AIS B to C.Sensory improvements were observed in 30.9%of patients.A relatively small number of adverse events were recorded,including fever(15.1%),headaches(4.3%),muscle tension(3.1%),and dizziness(2.6%),highlighting the potential for SCI recovery with stem cell therapy.CONCLUSION In the realm of SCI treatment,stem cell-based therapies show promise,but clinical trials reveal potential adverse events and limitations,underscoring the need for meticulous optimization of transplantation conditions and parameters,caution against swift clinical implementation,a deeper understanding of SCI pathophysiology,and addressing ethical,tumorigenicity,immunogenicity,and immunotoxicity concerns before gradual and careful adoption in clinical practice. 展开更多
关键词 Spinal cord injury stem cell therapy Adverse events Functional outcomes Systematic review
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COVID-19 impact in Crohn’s disease patients submitted to autologous hematopoietic stem cell transplantation
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作者 Milton Artur Ruiz Roberto Luiz Kaiser Junior +3 位作者 Lilian Piron-Ruiz Tainara Souza Pinho Lilian Castiglioni Luiz Gustavo de Quadros 《World Journal of Hematology》 2024年第1期1-8,共8页
BACKGROUND Severe acute respiratory syndrome coronavirus 2 is the virus responsible for coronavirus disease 2019(COVID-19),a disease that has been blamed for inducing or exacerbating symptoms in patients with autoimmu... BACKGROUND Severe acute respiratory syndrome coronavirus 2 is the virus responsible for coronavirus disease 2019(COVID-19),a disease that has been blamed for inducing or exacerbating symptoms in patients with autoimmune diseases.Crohn's disease(CD)is an inflammatory bowel disease that affects genetically susceptible patients who develop an abnormal mucosal immune response to the intestinal microbiota.Patients who underwent hematopoietic stem cell transplantation(HSCT)are considered at risk for COVID-19.AIM To describe for the first time the impact of COVID-19 in CD patients who had undergone autologous,non-myeloablative HSCT.METHODS In this descriptive study a series of 19 patients were diagnosed with positive COVID-19.For two patients there were reports of the occurrence of two infectious episodes.Parameters related to HSCT,such as time elapsed since the procedure,vaccination status,CD status before and after infection,and clinical manifestations resulting from COVID-19,were evaluated.RESULTS Among the patients with COVID-19,three,who underwent Auto HSCT less than six months ago,relapsed and one,in addition to the CD symptoms,started to present thyroid impairment with positive anti-TPO.Only one of the patients required hospitalization for five days to treat COVID-19 and remained in CD clinical remission.Nine patients reported late symptoms that may be related to COVID-19.There were no deaths,and a statistical evaluation of the series of COVID-19 patients compared to those who did not present any infectious episode did not identify significant differences regarding the analyzed parameters.CONCLUSION Despite the change in CD status in three patients and the presence of nine patients with late symptoms,we can conclude that there was no significant adverse impact concerning COVID-19 in the evaluated patients who underwent HSCT to treat CD. 展开更多
关键词 Inflammatory bowel disease Crohn disease SARS-CoV-2 COVID-19 Autologous hematopoietic stem cell transplantation stem cell therapy
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Cell transplantation therapies for spinal cord injury focusing on bone marrow mesenchymal stem cells:Advances and challenges
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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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Metabolic and proteostatic differences in quiescent and active neural stem cells 被引量:1
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作者 Jiacheng Yu Gang Chen +4 位作者 Hua Zhu Yi Zhong Zhenxing Yang Zhihong Jian Xiaoxing Xiong 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第1期43-48,共6页
Adult neural stem cells are neurogenesis progenitor cells that play an important role in neurogenesis.Therefore,neural regeneration may be a promising target for treatment of many neurological illnesses.The regenerati... Adult neural stem cells are neurogenesis progenitor cells that play an important role in neurogenesis.Therefore,neural regeneration may be a promising target for treatment of many neurological illnesses.The regenerative capacity of adult neural stem cells can be chara cterized by two states:quiescent and active.Quiescent adult neural stem cells are more stable and guarantee the quantity and quality of the adult neural stem cell pool.Active adult neural stem cells are chara cterized by rapid proliferation and differentiation into neurons which allow for integration into neural circuits.This review focuses on diffe rences between quiescent and active adult neural stem cells in nutrition metabolism and protein homeostasis.Furthermore,we discuss the physiological significance and underlying advantages of these diffe rences.Due to the limited number of adult neural stem cells studies,we refe rred to studies of embryonic adult neural stem cells or non-mammalian adult neural stem cells to evaluate specific mechanisms. 展开更多
关键词 adult neurogenesis cell metabolic pathway cellular proliferation neural stem cell niches neural stem cells neuronal differentiation nutrient sensing pathway PROTEOSTASIS
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The MORC2 p.S87L mutation reduces proliferation of pluripotent stem cells derived from a patient with the spinal muscular atrophy-like phenotype by inhibiting proliferation-related signaling pathways 被引量:1
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作者 Sen Zeng Honglan Yang +8 位作者 Binghao Wang Yongzhi Xie Ke Xu Lei Liu Wanqian Cao Xionghao Liu Beisha Tang Mujun Liu Ruxu Zhang 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第1期205-211,共7页
Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal mus... Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction. 展开更多
关键词 antisense oligonucleotides cell cycle arrest Charcot-Marie-Tooth disease 2Z induced pluripotent stem cells MAPK/ERK PI3K/Akt PROLIFERATION spinal muscular atrophy-like
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Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury 被引量:1
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作者 Mou Gao Qin Dong +4 位作者 Zhijun Yang Dan Zou Yajuan Han Zhanfeng Chen Ruxiang Xu 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第4期872-880,共9页
Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regen... Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury. 展开更多
关键词 closed head injury Ctbp2 induced neural stem cell lncRNA H19 miR-325-3p NEUROGENESIS
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Cell replacement with stem cell-derived retinal ganglion cells from different protocols
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作者 Ziming Luo Kun-Che Chang 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第4期807-810,共4页
Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness worldwide.There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not r... Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness worldwide.There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after injury.Human stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative diseases.In this review,we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture,including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation outcomes.Next,we discuss using 3D retinal organoids for retinal ganglion cell transplantation,comparing cell suspensions and clusters.This review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation,with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies. 展开更多
关键词 cell clumps cell suspension cell transplantation DIFFERENTIATION direct-induced protocol GLAUCOMA optic neuropathy regenerative medicine retinal ganglion cell retinal organoids stem cells
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The combined application of stem cells and three-dimensional bioprinting scaffolds for the repair of spinal cord injury
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作者 Dingyue Ju Chuanming Dong 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第8期1751-1758,共8页
Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and t... Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural functionality.Traditional treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal cord.Consequently,there is a critical need to develop new treatments to promote functional repair after spinal cord injury.Over recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord injury.Alongside significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex structures.This led to the loading of three-dimensional bioprinting scaffolds which provided precise cell localization.These three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal cord.In this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting scaffolds.In particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury. 展开更多
关键词 BIOMATERIALS embryonic stem cells induced pluripotent stem cells mesenchymal stem cells nerve regeneration spinal cord injury stem cell therapy stem cells three-dimensional bioprinting
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Therapeutic and regenerative potential of different sources of mesenchymal stem cells for cardiovascular diseases
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作者 YARA ALZGHOUL HALA J.BANI ISSA +8 位作者 AHMAD K.SANAJLEH TAQWA ALABDUH FATIMAH RABABAH MAHA AL-SHDAIFAT EJLAL ABU-EL-RUB FATIMAH ALMAHASNEH RAMADA R.KHASAWNEH AYMAN ALZU’BI HUTHAIFA MAGABLEH 《BIOCELL》 SCIE 2024年第4期559-569,共11页
Mesenchymalstemcells(MSCs)areidealcandidatesfortreatingmanycardiovasculardiseases.MSCscanmodify the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essent... Mesenchymalstemcells(MSCs)areidealcandidatesfortreatingmanycardiovasculardiseases.MSCscanmodify the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essential to restore heart function.MSCs can be easily isolated from different sources,including bone marrow,adipose tissues,umbilical cord,and dental pulp.MSCs from various sources differ in their regenerative and therapeutic abilities for cardiovascular disorders.In this review,we will summarize the therapeutic potential of each MSC source for heart diseases and highlight the possible molecular mechanisms of each source to restore cardiac function. 展开更多
关键词 Bone marrow mesenchymal stem cells Adipose tissue mesenchymal stem cells Dental pulp stem cells Umbilical cord mesenchymal stem cells CARDIOMYOCYTES REGENERATION Myocardial infarction Mesenchymal stem cells Differentiation IMMUNOMODULATION
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Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives
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作者 Yubo Wang Tingli Yuan +5 位作者 Tianjie Lyu Ling Zhang Meng Wang Zhiying He Yongjun Wang Zixiao Li 《Neural Regeneration Research》 SCIE CAS 2025年第1期67-81,共15页
Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflamm... Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment. 展开更多
关键词 cell therapy immune cell INFLAMMATORY ischemic stroke stem cell
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Mesenchymal stem cells’“garbage bags”at work:Treating radial nerve injury with mesenchymal stem cell-derived exosomes
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作者 Mazhar Mushtaq Doaa Hussein Zineldeen +1 位作者 Muhammad Abdul Mateen Khawaja Husnain Haider 《World Journal of Stem Cells》 SCIE 2024年第5期467-478,共12页
Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal regeneration.However,structural and functional recovery is a senile process involving mul... Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal regeneration.However,structural and functional recovery is a senile process involving multifaceted cellular and molecular processes.The contemporary treatment options are limited,with surgical intervention as the gold-standard method;however,each treatment option has its associated limitations,especially when the injury is severe with a large gap.Recent advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic PNI.The recent pilot study is a leap forward in the field,which is expected to pave the way for more enormous,systematic,and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach,in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration. 展开更多
关键词 EXOSOME Mesenchymal stem cells Nerve injury stem cells SECRETOME Regeneration
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Allogeneic mesenchymal stem cells may be a viable treatment modality in cerebral palsy
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作者 Osman Boyalı Serdar Kabatas +5 位作者 ErdinçCivelek Omer Ozdemir Yeliz Bahar-Ozdemir Necati Kaplan Eyüp Can Savrunlu Erdal Karaöz 《World Journal of Clinical Cases》 SCIE 2024年第9期1585-1596,共12页
BACKGROUND Cerebral palsy(CP)describes a group of disorders affecting movement,balance,and posture.Disturbances in motor functions constitute the main body of CP symptoms.These symptoms surface in early childhood and ... BACKGROUND Cerebral palsy(CP)describes a group of disorders affecting movement,balance,and posture.Disturbances in motor functions constitute the main body of CP symptoms.These symptoms surface in early childhood and patients are affected for the rest of their lives.Currently,treatment involves various pharmacotherapies for different types of CP,including antiepileptics for epilepsy and Botox A for focal spasticity.However,none of these methods can provide full symptom relief.This has prompted researchers to look for new treatment modalities,one of which is mesenchymal stem cell therapy(MSCT).Despite being a promising tool and offering a wide array of possibilities,mesenchymal stem cells(MSCs)still need to be investigated for their efficacy and safety.AIM To analyze the efficacy and safety of MSCT in CP patients.METHODS Our sample consists of four CP patients who cannot stand or walk without external support.All of these cases received allogeneic MSCT six times as 1×106/kg intrathecally,intravenously,and intramuscularly using umbilical cord-derived MSCs(UC-MSC).We monitored and assessed the patients pre-and post-treatment using the Wee Functional Independence Measure(WeeFIM),Gross Motor Function Classification System(GMFCS),and Manual Ability Classification Scale(MACS)instruments.We utilized the Modified Ashworth Scale(MAS)to measure spasticity.RESULTS We found significant improvements in MAS scores after the intervention on both sides.Two months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;four months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;12 months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046.However,there was no significant difference in motor functions based on WeeFIM results(P>0.05).GMFCS and MACS scores differed significantly at 12 months after the intervention(P=0.046,P=0.046).Finally,there was no significant change in cognitive functions(P>0.05).CONCLUSION In light of our findings,we believe that UC-MSC therapy has a positive effect on spasticity,and it partially improves motor functions. 展开更多
关键词 Cerebral palsy Mesenchymal stem cell transplantation Wharton’s jelly Muscle spasticity
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Unlocking the versatile potential:Adipose-derived mesenchymal stem cells in ocular surface reconstruction and oculoplastics
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作者 Pier Luigi Surico Anna Scarabosio +5 位作者 Giovanni Miotti Martina Grando Carlo Salati Pier Camillo Parodi Leopoldo Spadea Marco Zeppieri 《World Journal of Stem Cells》 SCIE 2024年第2期89-101,共13页
This review comprehensively explores the versatile potential of mesenchymal stem cells(MSCs)with a specific focus on adipose-derived MSCs.Ophthalmic and oculoplastic surgery,encompassing diverse procedures for ocular ... This review comprehensively explores the versatile potential of mesenchymal stem cells(MSCs)with a specific focus on adipose-derived MSCs.Ophthalmic and oculoplastic surgery,encompassing diverse procedures for ocular and periocular enhancement,demands advanced solutions for tissue restoration,functional and aesthetic refinement,and aging.Investigating immunomodulatory,regenerative,and healing capacities of MSCs,this review underscores the potential use of adipose-derived MSCs as a cost-effective alternative from bench to bedside,addressing common unmet needs in the field of reconstructive and regenerative surgery. 展开更多
关键词 stem cells Adipose stem cell Ocular therapy Oculoplastics REGENERATIVE
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