The global incidence of asthma,a leading respiratory disorder affecting more than 235 million people,has dramatically increased in recent years.Characterized by chronic airway inflammation and an imbalanced response t...The global incidence of asthma,a leading respiratory disorder affecting more than 235 million people,has dramatically increased in recent years.Characterized by chronic airway inflammation and an imbalanced response to airborne irritants,this chronic condition is associated with elevated levels of inflammatory factors and symptoms such as dyspnea,cough,wheezing,and chest tightness.Conventional asthma therapies,such as corticosteroids,long-actingβ-agonists,and antiinflammatory agents,often evoke diverse adverse reactions and fail to reduce symptoms and hospitalization rates over the long term effectively.These limitations have prompted researchers to explore innovative therapeutic strategies,including stem cell-related interventions,offering hope to those afflicted with this incurable disease.In this review,we describe the characteristics of stem cells and critically assess the potential and challenges of stem cell-based therapies to improve disease management and treatment outcomes for asthma and other diseases.展开更多
Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic a...Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic analysis of human dental pulp stem cells(HDPSCs)obtained from individuals of various ages.Our findings showed that the expression of NUP62 was decreased in aged HDPSCs.We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo.Conversely,the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs.Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression,we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1.This,in turn,stimulates the transcription of the epigenetic enzyme NSD2.Finally,the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes(HMGA1,HMGA2,and SIRT6).Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.展开更多
Lupus nephritis(LN)is one of the most common and serious complications of systemic lupus erythematosus,which can lead to end-stage renal disease,and is an important cause of death in patients with systemic lupus eryth...Lupus nephritis(LN)is one of the most common and serious complications of systemic lupus erythematosus,which can lead to end-stage renal disease,and is an important cause of death in patients with systemic lupus erythematosus.Treatment options include glucocorticoids,immunosuppressive agents and the addition of biologics.Recently,the therapeutic role of mesenchymal stem cells(MSCs)in LN has received extensive attention worldwide.MSCs can suppress autoimmunity,alleviate proteinuria and restore renal function by modulating the functions of various immune cells and reducing the secretion of inflammatory cytokines.Several clinical trials have investigated MSC treatment in LN with promising but sometimes inconsistent outcomes.This review summarizes the sources of MSCs and mechanisms in immunoregulation.Furthermore,it examines clinical trials evaluating the efficacy,safety,and limitations of MSC therapy in LN.By highlighting advances and ongoing challenges,this review underscores the potential of MSCs for LN treatment.More large-scale randomized controlled trials are needed to support the effectiveness of this therapy and pave the way for personalized and combinatorial therapeutic approaches.展开更多
Epilepsy is a serious neurological disorder;however,the effectiveness of current medications is often suboptimal.Recently,stem cell technology has demonstrated remarkable therapeutic potential in addressing various ne...Epilepsy is a serious neurological disorder;however,the effectiveness of current medications is often suboptimal.Recently,stem cell technology has demonstrated remarkable therapeutic potential in addressing various neurological diseases,igniting interest in its applicability for epilepsy treatment.This comprehensive review summarizes different therapeutic approaches utilizing various types of stem cells.Preclinical experiments have explored the use and potential therapeutic effects of mesenchymal stem cells,including genetically modified variants.Clinical trials involving patientderived mesenchymal stem cells have shown promising results,with reductions in the frequency of epileptic seizures and improvements in neurological,cognitive,and motor functions reported.Another promising therapeutic strategy involves neural stem cells.These cells can be cultured outside the body and directed to differentiate into specific cell types.The transplant of neural stem cells has the potential to replace lost inhibitory interneurons,providing a novel treatment avenue for epilepsy.Embryonic stem cells are characterized by their significant capacity for self-renewal and their ability to differentiate into any type of somatic cell.In epilepsy treatment,embryonic stem cells can serve three primary functions:neuron regeneration,the maintenance of cellular homeostasis,and restorative activity.One notable strategy involves differentiating embryonic stem cells intoγ-aminobutyric acidergic neurons for transplantation into lesion sites.This approach is currently undergoing clinical trials and could be a breakthrough in the treatment of refractory epilepsy.Induced pluripotent stem cells share the same genetic background as the donor,thereby reducing the risk of immune rejection and addressing ethical concerns.However,research on induced pluripotent stem cell therapy remains in the preclinical stage.Despite the promise of stem cell therapies for epilepsy,several limitations must be addressed.Safety concerns persist,including issues such as tumor formation,and the low survival rate of transplanted cells remains a significant challenge.Additionally,the high cost of these treatments may be prohibitive for some patients.In summary,stem cell therapy shows considerable promise in managing epilepsy,but further research is needed to overcome its existing limitations and enhance its clinical applicability.展开更多
Parkinson’s disease(PD)is a progressive neurodegenerative disorder marked by the loss of dopaminergic neurons in the substantia nigra that leads to reduced dopamine levels and impaired motor function.Current treatmen...Parkinson’s disease(PD)is a progressive neurodegenerative disorder marked by the loss of dopaminergic neurons in the substantia nigra that leads to reduced dopamine levels and impaired motor function.Current treatments only provide temporary symptom relief without addressing the underlying neuronal loss.A promising new approach for treating PD is stem cell therapy,particularly induced pluripotent stem cells and human pluripotent stem cells.They have the ability to differentiate into various neural cells,offering potential for neuronal replacement and restoration of brain function.Induced pluripotent stem cells are derived from reprogramming adult cells and present advantages such as genetic compatibility and reduced immune rejection,overcoming ethical concerns associated with embryonic stem cells.Preclinical studies show promising results,demonstrating that stem cells can differentiate into dopaminergic neurons and improve motor function in animal models.These advancements pave the way for clinical trials and potential long-term solutions for patients with PD.This review highlighted the significance of stem cell therapy in neuroregeneration and addressed pre-clinical successes,challenges in long-term safety,and ethical considerations,with the hope of revolutionizing PD treatment and improving patient outcomes.展开更多
In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the c...In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.展开更多
BACKGROUND As living biodrugs,mesenchymal stem cells(MSCs)have progressed to phase 3 clinical trials for cardiovascular applications.However,their limited immediate availability hampers their routine clinical use.AIM ...BACKGROUND As living biodrugs,mesenchymal stem cells(MSCs)have progressed to phase 3 clinical trials for cardiovascular applications.However,their limited immediate availability hampers their routine clinical use.AIM To validate our hypothesis that cryopreserved MSCs(CryoMSCs)are as safe and effective as freshly cultured MSC counterparts but carry logistical advantages.METHODS Four databases were systematically reviewed for relevant randomized controlled trials(RCTs)evaluating the safety and efficacy of CryoMSCs from various tissue sources in treating patients with heart disease.A subgroup analysis was performed based on MSC source and post-thaw cell viability to determine treatment effects across different CryoMSCs sources and viability status.Weighted mean differences(WMDs)and odds ratios were calculated to measure changes in the estimated treatment effects.All statistical analyses were performed using RevMan version 5.4.1 software.RESULTS Seven RCTs(285 patients)met the eligibility criteria for inclusion in the metaanalysis.During short-term follow-up,^(Cryo)MSCs demonstrated a significant 2.11%improvement in left ventricular ejection fraction(LVEF)[WMD(95%CI)=2.11(0.66-3.56),P=0.004,I2=1%],with umbilical cord-derived MSCs being the most effective cell type.However,the significant effect on LVEF was not sustained over the 12 months of follow-up.Subgroup analysis demonstrated a substantial 3.44%improvement in LVEF[WMD(95%CI)=3.44(1.46-5.43),P=0.0007,I2=0%]when using MSCs with post-thaw viability exceeding 80%.There was no statistically significant difference in the frequency of major cardiac adverse events observed in rehospitalization or mortality in patients treated with ^(Cryo)MSCs vs the control group.CONCLUSION ^(Cryo)MSCs are a promising option for heart failure patients,particularly considering the current treatment options for cardiovascular diseases.Our data suggest that ^(Cryo)MSCs could be a viable alternative or complementary treatment to the current options,potentially improving patient outcomes.展开更多
Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within t...Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within the ischemic brain,these mechanisms are often insufficient to restore neuronal functionality.This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option.This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events,with focus on the impact of stem cell-based therapies on neural stem cells.Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-tocell contact and through the secretion of growth factors and exosomes.Additionally,implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called“biobridges.”Furthermore,xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects,thereby supporting endogenous neuroregeneration.Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment,we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types.These approaches include:(1)co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis;(2)synergistic administration of stem cells and their exosomes to amplify paracrine effects;and(3)integration of stem cells within hydrogels,which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits.This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.展开更多
Skeletal muscle atrophy results from disruptions in the growth and metabolism of striated muscle,leading to a reduction or loss of muscle fibers.This condition not only significantly impacts patients’quality of life ...Skeletal muscle atrophy results from disruptions in the growth and metabolism of striated muscle,leading to a reduction or loss of muscle fibers.This condition not only significantly impacts patients’quality of life but also imposes substantial socioeconomic burdens.The complex molecular mechanisms driving skeletal muscle atrophy contribute to the absence of effective treatment options.Recent advances in stem cell therapy have positioned it as a promising approach for addressing this condition.This article reviews the molecular mechanisms of muscle atrophy and outlines current therapeutic strategies,focusing on mesenchymal stem cells,induced pluripotent stem cells,and their derivatives.Additionally,the challenges these stem cells face in clinical applications are discussed.A deeper understanding of the regenerative potential of various stem cells could pave the way for breakthroughs in the prevention and treatment of muscle atrophy.展开更多
Mesenchymal stem cells are highly regarded for their potential in tissue repair and regenerative medicine due to their multipotency and self-renewal abilities.Recently,mesenchymal stem cells have been redefined as“me...Mesenchymal stem cells are highly regarded for their potential in tissue repair and regenerative medicine due to their multipotency and self-renewal abilities.Recently,mesenchymal stem cells have been redefined as“medical signaling cells,”with their primary biological effects mediated through exosome secretion.These exosomes,which contain lipids,proteins,RNA,and metabolites,are crucial in regulating various biological processes and enhancing regenerative therapies.Exosomes replicate the effects of their parent cells while offering benefits such as reduced side effects,low immunogenicity,excellent biocompatibility,and high drug-loading capacity.Dental stem cells,including those from apical papilla,gingiva,dental pulp,and other sources,are key contributors to exosome-mediated regenerative effects,such as tumor cell apoptosis,neuroprotection,angiogenesis,osteogenesis,and immune modulation.Despite their promise,clinical application of exosomes is limited by challenges in isolation techniques.Current methods face issues of complexity,inefficiency,and insufficient purity,hindering detailed analysis.Recent advancements,such as micro-electromechanical systems,alternating current electroosmosis,and serum-free three-dimensional cell cultures,have improved exosome isolation efficacy.This review synthesizes nearly 200 studies on dental stem cell-derived exosomes,highlighting their potential in treating a wide range of conditions,including periodontal diseases,cancer,neurodegenerative disorders,diabetes,and more.Optimized isolation methods offer a path forward for overcoming current limitations and advancing the clinical use of exosome-based therapies.展开更多
Diabetes mellitus,a global epidemic,represents a major public health threat.Stem cell therapy,with its regenerative capacity,has emerged as a promising approach for diabetes mellitus management.This paper reviews rece...Diabetes mellitus,a global epidemic,represents a major public health threat.Stem cell therapy,with its regenerative capacity,has emerged as a promising approach for diabetes mellitus management.This paper reviews recent advancements,prospects,and challenges in stem cell-based treatments for diabetes mellitus,focusing on the applications of induced pluripotent stem cells and mesenchymal stem cells,the development of pancreatic islet organoids,and the potential for personalized medicine.The review critically assesses the efficacy and safety of stem cell therapies in clinical trials and examines their applications in both type 1 and type 2 diabetes mellitus.Despite the promising potential,challenges such as safety concerns,transplantation efficiency,ethical considerations,and immune rejection remain prevalent.Lastly,the paper discusses future directions,including the integration of stem cell therapy with other treatments and the advancement of personalized therapeutic strategies,offering new perspectives and hope for dia-betes mellitus management.展开更多
Cancer is a highly heterogeneous pathology that poses a significant threat to millions of lives worldwide.In recent decades,there has been a substantial advancement in our understanding of the mechanisms underlying on...Cancer is a highly heterogeneous pathology that poses a significant threat to millions of lives worldwide.In recent decades,there has been a substantial advancement in our understanding of the mechanisms underlying oncogenesis.Contemporary models now take into account the intricate interplay between cancer cells,immune cells,and other non-pathological cells during oncogenesis.The identification of small subpopulations of cancer stem cells has emerged as a crucial area of research,as these cells have been associated with cancer progression and resistance to various therapeutic interventions.The ability to distinguish between cancer stem cells and non-pathological stem cells is paramount for effective diagnostics and treatment.The stem state is associated with a cell’s ability to survive under harmful conditions.Evidence has recently emerged that non-pathological stem cells possess immune privileges.The ability of stem cells to evade surveillance of the immune system could be utilized by oncogenesis.This is of particular significance due to the rising role of anti-cancer immune therapies.Moreover,the immune privileges of stem cells could be exploited by cancer before any treatment,emphasizing the importance of their integration into cancer models.This review elucidates the functional comparison of cancer stem cells with non-pathological stem cells and the associated challenges in diagnostics and treatment.展开更多
BACKGROUND Tumors characterized by high cellular stemness often have unfavorable clinical outcomes,primarily due to their heightened potential for metastasis and resistance to chemotherapy.Among the model genes,the cl...BACKGROUND Tumors characterized by high cellular stemness often have unfavorable clinical outcomes,primarily due to their heightened potential for metastasis and resistance to chemotherapy.Among the model genes,the clinical relevance and prognostic significance of Niemann-Pick type C2(NPC2)in gastric cancer(GC)remained largely unexplored.AIM To identify stemness-associated genes in GC.METHODS In this study,epithelial cells were categorized as either tumor or normal epithelial cells using the infer copy number variation method.Stemness scores were calculated for both cell types.The hierarchical Weighted Gene Co-expression Network Analysis identified two gene modules with the strongest association with stemness.Prognostically significant stemness-related genes were pinpointed using univariate Cox regression based on The Cancer Genome Atlas dataset.A predictive model related to stemness was constructed using Least Absolute Shrinkage and Selection Operator regression followed by multivariate Cox analysis.RESULTS Functional roles of NPC2 were validated using single-cell and bulk RNA sequencing data.Further experimental validation revealed that elevated NPC2 expression promoted tumor cell stemness,invasiveness,migratory ability,and resistance to standard chemotherapeutic agents.Importantly,high NPC2 expression correlated with poorer overall survival in GC patients.CONCLUSION In summary,the proposed model offers prognostic insights that outperform traditional clinical staging and may inform more tailored therapeutic approaches for gastric cancer management.展开更多
BACKGROUND Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)can traverse the blood-brain barrier due to their small size.This characteristic makes them a research hotspot for the treatment of Parkinson’s ...BACKGROUND Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)can traverse the blood-brain barrier due to their small size.This characteristic makes them a research hotspot for the treatment of Parkinson’s disease(PD)and is expected to be a potentially revolutionary strategy for treating PD.Despite this,no summary of clinical trial results has been reported.AIM To assess the efficacy and durability of MSC-EVs in treating PD.METHODS Systematic searches were conducted in four electronic databases until June 2024 to collect studies on the use of MSC-EVs for this purpose.Thirteen relevant randomized controlled trials,encompassing 16 experiments,were selected for inclusion.RESULTS Behavioral assessments,including the rotarod and apomorphine turning behavior tests,indicated improvements in motor coordination(P<0.00001);the Pole test and the Wire-hang test showed enhanced limb motor agility and synchronization(P=0.003 and P<0.00001,respectively).Histopathologically,there was a reduction in inflammatory markers such as tumor necrosis factor-αand interleukin-6(P=0.03 and P=0.01,respectively)and an increase in tyrosine hydroxylase-positive cells in the lesion areas(P<0.00001).CONCLUSION MSC-EV therapy for PD is a gradual process,with significant improvements observable more than 2 weeks after administration and lasting at least 8 weeks.This study is the first to demonstrate the efficacy and durability of MSC-EV treatment in PD.展开更多
基金the Joint Innovation Project Funds of Huaqiao University,No.2022YX001.
文摘The global incidence of asthma,a leading respiratory disorder affecting more than 235 million people,has dramatically increased in recent years.Characterized by chronic airway inflammation and an imbalanced response to airborne irritants,this chronic condition is associated with elevated levels of inflammatory factors and symptoms such as dyspnea,cough,wheezing,and chest tightness.Conventional asthma therapies,such as corticosteroids,long-actingβ-agonists,and antiinflammatory agents,often evoke diverse adverse reactions and fail to reduce symptoms and hospitalization rates over the long term effectively.These limitations have prompted researchers to explore innovative therapeutic strategies,including stem cell-related interventions,offering hope to those afflicted with this incurable disease.In this review,we describe the characteristics of stem cells and critically assess the potential and challenges of stem cell-based therapies to improve disease management and treatment outcomes for asthma and other diseases.
基金supported by the National Natural Science Foundation of China(32171347)the Foundation of Leading Talents from Shanghai Health Commission(2022XD038)+1 种基金Training Program for Research Physicians in Innovation,the Funda-mental Research Funds for the Central Universities(YG2023QNA23)Transforma-tion from shanghai hospital development center(SHDC2022CRD002).
文摘Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic analysis of human dental pulp stem cells(HDPSCs)obtained from individuals of various ages.Our findings showed that the expression of NUP62 was decreased in aged HDPSCs.We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo.Conversely,the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs.Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression,we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1.This,in turn,stimulates the transcription of the epigenetic enzyme NSD2.Finally,the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes(HMGA1,HMGA2,and SIRT6).Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
基金Supported by Natural Science Foundation of Zhejiang Province,No.LY23H050005Zhejiang Medical Technology Project,No.2020KY439,No.2022RC009,No.2024KY645,and No.2024KY697.
文摘Lupus nephritis(LN)is one of the most common and serious complications of systemic lupus erythematosus,which can lead to end-stage renal disease,and is an important cause of death in patients with systemic lupus erythematosus.Treatment options include glucocorticoids,immunosuppressive agents and the addition of biologics.Recently,the therapeutic role of mesenchymal stem cells(MSCs)in LN has received extensive attention worldwide.MSCs can suppress autoimmunity,alleviate proteinuria and restore renal function by modulating the functions of various immune cells and reducing the secretion of inflammatory cytokines.Several clinical trials have investigated MSC treatment in LN with promising but sometimes inconsistent outcomes.This review summarizes the sources of MSCs and mechanisms in immunoregulation.Furthermore,it examines clinical trials evaluating the efficacy,safety,and limitations of MSC therapy in LN.By highlighting advances and ongoing challenges,this review underscores the potential of MSCs for LN treatment.More large-scale randomized controlled trials are needed to support the effectiveness of this therapy and pave the way for personalized and combinatorial therapeutic approaches.
基金supported by the National Natural Science Foundation of China,Nos.82471471(to WJ),82471485(to FY)Shaanxi Province Special Support Program for Leading Talents in Scientific and Technological Innovation,No.tzjhjw(to WJ)+1 种基金Shaanxi Key Research and Development Plan Project,No.2023-YBSF-353(to XW)the Joint Fund Project of Innovation Research Institute of Xijing Hospital,No.LHJJ24JH13(to ZS)。
文摘Epilepsy is a serious neurological disorder;however,the effectiveness of current medications is often suboptimal.Recently,stem cell technology has demonstrated remarkable therapeutic potential in addressing various neurological diseases,igniting interest in its applicability for epilepsy treatment.This comprehensive review summarizes different therapeutic approaches utilizing various types of stem cells.Preclinical experiments have explored the use and potential therapeutic effects of mesenchymal stem cells,including genetically modified variants.Clinical trials involving patientderived mesenchymal stem cells have shown promising results,with reductions in the frequency of epileptic seizures and improvements in neurological,cognitive,and motor functions reported.Another promising therapeutic strategy involves neural stem cells.These cells can be cultured outside the body and directed to differentiate into specific cell types.The transplant of neural stem cells has the potential to replace lost inhibitory interneurons,providing a novel treatment avenue for epilepsy.Embryonic stem cells are characterized by their significant capacity for self-renewal and their ability to differentiate into any type of somatic cell.In epilepsy treatment,embryonic stem cells can serve three primary functions:neuron regeneration,the maintenance of cellular homeostasis,and restorative activity.One notable strategy involves differentiating embryonic stem cells intoγ-aminobutyric acidergic neurons for transplantation into lesion sites.This approach is currently undergoing clinical trials and could be a breakthrough in the treatment of refractory epilepsy.Induced pluripotent stem cells share the same genetic background as the donor,thereby reducing the risk of immune rejection and addressing ethical concerns.However,research on induced pluripotent stem cell therapy remains in the preclinical stage.Despite the promise of stem cell therapies for epilepsy,several limitations must be addressed.Safety concerns persist,including issues such as tumor formation,and the low survival rate of transplanted cells remains a significant challenge.Additionally,the high cost of these treatments may be prohibitive for some patients.In summary,stem cell therapy shows considerable promise in managing epilepsy,but further research is needed to overcome its existing limitations and enhance its clinical applicability.
文摘Parkinson’s disease(PD)is a progressive neurodegenerative disorder marked by the loss of dopaminergic neurons in the substantia nigra that leads to reduced dopamine levels and impaired motor function.Current treatments only provide temporary symptom relief without addressing the underlying neuronal loss.A promising new approach for treating PD is stem cell therapy,particularly induced pluripotent stem cells and human pluripotent stem cells.They have the ability to differentiate into various neural cells,offering potential for neuronal replacement and restoration of brain function.Induced pluripotent stem cells are derived from reprogramming adult cells and present advantages such as genetic compatibility and reduced immune rejection,overcoming ethical concerns associated with embryonic stem cells.Preclinical studies show promising results,demonstrating that stem cells can differentiate into dopaminergic neurons and improve motor function in animal models.These advancements pave the way for clinical trials and potential long-term solutions for patients with PD.This review highlighted the significance of stem cell therapy in neuroregeneration and addressed pre-clinical successes,challenges in long-term safety,and ethical considerations,with the hope of revolutionizing PD treatment and improving patient outcomes.
基金supported by Ohio State Start Up FundNational Institutes of Health(NIH)+12 种基金Department of Defense(DoD)Wings for Life Spinal Cord Research Foundation,Wings for Life Spinal Cord Research Foundation(Austria)California Institute of Regenerative Medicine(CIRM)International Spinal Research Trust(United Kingdom)Stanford University Bio-X Program Interdisciplinary Initiatives Seed Grant IIP-7Dennis Chan FoundationKlein Family FundLucile Packard Foundation for Children's HealthStanford Institute for Neuro-Innovation and Translational Neurosciences(SINTN)Saunders Family Neuroscience FundJames Doty Neurosurgery FundHearst Neuroscience FundEileen Bond Research Fund(to GP)。
文摘In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.
文摘BACKGROUND As living biodrugs,mesenchymal stem cells(MSCs)have progressed to phase 3 clinical trials for cardiovascular applications.However,their limited immediate availability hampers their routine clinical use.AIM To validate our hypothesis that cryopreserved MSCs(CryoMSCs)are as safe and effective as freshly cultured MSC counterparts but carry logistical advantages.METHODS Four databases were systematically reviewed for relevant randomized controlled trials(RCTs)evaluating the safety and efficacy of CryoMSCs from various tissue sources in treating patients with heart disease.A subgroup analysis was performed based on MSC source and post-thaw cell viability to determine treatment effects across different CryoMSCs sources and viability status.Weighted mean differences(WMDs)and odds ratios were calculated to measure changes in the estimated treatment effects.All statistical analyses were performed using RevMan version 5.4.1 software.RESULTS Seven RCTs(285 patients)met the eligibility criteria for inclusion in the metaanalysis.During short-term follow-up,^(Cryo)MSCs demonstrated a significant 2.11%improvement in left ventricular ejection fraction(LVEF)[WMD(95%CI)=2.11(0.66-3.56),P=0.004,I2=1%],with umbilical cord-derived MSCs being the most effective cell type.However,the significant effect on LVEF was not sustained over the 12 months of follow-up.Subgroup analysis demonstrated a substantial 3.44%improvement in LVEF[WMD(95%CI)=3.44(1.46-5.43),P=0.0007,I2=0%]when using MSCs with post-thaw viability exceeding 80%.There was no statistically significant difference in the frequency of major cardiac adverse events observed in rehospitalization or mortality in patients treated with ^(Cryo)MSCs vs the control group.CONCLUSION ^(Cryo)MSCs are a promising option for heart failure patients,particularly considering the current treatment options for cardiovascular diseases.Our data suggest that ^(Cryo)MSCs could be a viable alternative or complementary treatment to the current options,potentially improving patient outcomes.
基金supported by the National Key Research and Development Program of China,No.2018YFA0108602the CAMS Initiative for Innovative Medicine,No.2021-1-I2M-019National High-Level Hospital Clinical Research Funding,No.2022-PUMCH-C-042(all to XB)。
文摘Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within the ischemic brain,these mechanisms are often insufficient to restore neuronal functionality.This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option.This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events,with focus on the impact of stem cell-based therapies on neural stem cells.Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-tocell contact and through the secretion of growth factors and exosomes.Additionally,implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called“biobridges.”Furthermore,xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects,thereby supporting endogenous neuroregeneration.Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment,we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types.These approaches include:(1)co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis;(2)synergistic administration of stem cells and their exosomes to amplify paracrine effects;and(3)integration of stem cells within hydrogels,which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits.This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.
基金Suzhou Science and Technology Development Planning Project,No.SYW2024048National Natural Science Foundation of China,No.81901933Major Natural Science Research Projects in Universities of Jiangsu Province,No.24KJA310007.
文摘Skeletal muscle atrophy results from disruptions in the growth and metabolism of striated muscle,leading to a reduction or loss of muscle fibers.This condition not only significantly impacts patients’quality of life but also imposes substantial socioeconomic burdens.The complex molecular mechanisms driving skeletal muscle atrophy contribute to the absence of effective treatment options.Recent advances in stem cell therapy have positioned it as a promising approach for addressing this condition.This article reviews the molecular mechanisms of muscle atrophy and outlines current therapeutic strategies,focusing on mesenchymal stem cells,induced pluripotent stem cells,and their derivatives.Additionally,the challenges these stem cells face in clinical applications are discussed.A deeper understanding of the regenerative potential of various stem cells could pave the way for breakthroughs in the prevention and treatment of muscle atrophy.
文摘Mesenchymal stem cells are highly regarded for their potential in tissue repair and regenerative medicine due to their multipotency and self-renewal abilities.Recently,mesenchymal stem cells have been redefined as“medical signaling cells,”with their primary biological effects mediated through exosome secretion.These exosomes,which contain lipids,proteins,RNA,and metabolites,are crucial in regulating various biological processes and enhancing regenerative therapies.Exosomes replicate the effects of their parent cells while offering benefits such as reduced side effects,low immunogenicity,excellent biocompatibility,and high drug-loading capacity.Dental stem cells,including those from apical papilla,gingiva,dental pulp,and other sources,are key contributors to exosome-mediated regenerative effects,such as tumor cell apoptosis,neuroprotection,angiogenesis,osteogenesis,and immune modulation.Despite their promise,clinical application of exosomes is limited by challenges in isolation techniques.Current methods face issues of complexity,inefficiency,and insufficient purity,hindering detailed analysis.Recent advancements,such as micro-electromechanical systems,alternating current electroosmosis,and serum-free three-dimensional cell cultures,have improved exosome isolation efficacy.This review synthesizes nearly 200 studies on dental stem cell-derived exosomes,highlighting their potential in treating a wide range of conditions,including periodontal diseases,cancer,neurodegenerative disorders,diabetes,and more.Optimized isolation methods offer a path forward for overcoming current limitations and advancing the clinical use of exosome-based therapies.
基金Supported by the Faculty Development Grants of Xiangyang No.1 People’s Hospital Affiliated to Hubei University of Medicine,No.XYY2025D05,No.2024QDJZR037 and No.2024QDJZR015.
文摘Diabetes mellitus,a global epidemic,represents a major public health threat.Stem cell therapy,with its regenerative capacity,has emerged as a promising approach for diabetes mellitus management.This paper reviews recent advancements,prospects,and challenges in stem cell-based treatments for diabetes mellitus,focusing on the applications of induced pluripotent stem cells and mesenchymal stem cells,the development of pancreatic islet organoids,and the potential for personalized medicine.The review critically assesses the efficacy and safety of stem cell therapies in clinical trials and examines their applications in both type 1 and type 2 diabetes mellitus.Despite the promising potential,challenges such as safety concerns,transplantation efficiency,ethical considerations,and immune rejection remain prevalent.Lastly,the paper discusses future directions,including the integration of stem cell therapy with other treatments and the advancement of personalized therapeutic strategies,offering new perspectives and hope for dia-betes mellitus management.
文摘Cancer is a highly heterogeneous pathology that poses a significant threat to millions of lives worldwide.In recent decades,there has been a substantial advancement in our understanding of the mechanisms underlying oncogenesis.Contemporary models now take into account the intricate interplay between cancer cells,immune cells,and other non-pathological cells during oncogenesis.The identification of small subpopulations of cancer stem cells has emerged as a crucial area of research,as these cells have been associated with cancer progression and resistance to various therapeutic interventions.The ability to distinguish between cancer stem cells and non-pathological stem cells is paramount for effective diagnostics and treatment.The stem state is associated with a cell’s ability to survive under harmful conditions.Evidence has recently emerged that non-pathological stem cells possess immune privileges.The ability of stem cells to evade surveillance of the immune system could be utilized by oncogenesis.This is of particular significance due to the rising role of anti-cancer immune therapies.Moreover,the immune privileges of stem cells could be exploited by cancer before any treatment,emphasizing the importance of their integration into cancer models.This review elucidates the functional comparison of cancer stem cells with non-pathological stem cells and the associated challenges in diagnostics and treatment.
文摘BACKGROUND Tumors characterized by high cellular stemness often have unfavorable clinical outcomes,primarily due to their heightened potential for metastasis and resistance to chemotherapy.Among the model genes,the clinical relevance and prognostic significance of Niemann-Pick type C2(NPC2)in gastric cancer(GC)remained largely unexplored.AIM To identify stemness-associated genes in GC.METHODS In this study,epithelial cells were categorized as either tumor or normal epithelial cells using the infer copy number variation method.Stemness scores were calculated for both cell types.The hierarchical Weighted Gene Co-expression Network Analysis identified two gene modules with the strongest association with stemness.Prognostically significant stemness-related genes were pinpointed using univariate Cox regression based on The Cancer Genome Atlas dataset.A predictive model related to stemness was constructed using Least Absolute Shrinkage and Selection Operator regression followed by multivariate Cox analysis.RESULTS Functional roles of NPC2 were validated using single-cell and bulk RNA sequencing data.Further experimental validation revealed that elevated NPC2 expression promoted tumor cell stemness,invasiveness,migratory ability,and resistance to standard chemotherapeutic agents.Importantly,high NPC2 expression correlated with poorer overall survival in GC patients.CONCLUSION In summary,the proposed model offers prognostic insights that outperform traditional clinical staging and may inform more tailored therapeutic approaches for gastric cancer management.
基金Supported by the National Natural Science Foundation of China,No.32060232and the Natural Science Foundation of Jiangxi Province,No.20212BAB206075.
文摘BACKGROUND Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)can traverse the blood-brain barrier due to their small size.This characteristic makes them a research hotspot for the treatment of Parkinson’s disease(PD)and is expected to be a potentially revolutionary strategy for treating PD.Despite this,no summary of clinical trial results has been reported.AIM To assess the efficacy and durability of MSC-EVs in treating PD.METHODS Systematic searches were conducted in four electronic databases until June 2024 to collect studies on the use of MSC-EVs for this purpose.Thirteen relevant randomized controlled trials,encompassing 16 experiments,were selected for inclusion.RESULTS Behavioral assessments,including the rotarod and apomorphine turning behavior tests,indicated improvements in motor coordination(P<0.00001);the Pole test and the Wire-hang test showed enhanced limb motor agility and synchronization(P=0.003 and P<0.00001,respectively).Histopathologically,there was a reduction in inflammatory markers such as tumor necrosis factor-αand interleukin-6(P=0.03 and P=0.01,respectively)and an increase in tyrosine hydroxylase-positive cells in the lesion areas(P<0.00001).CONCLUSION MSC-EV therapy for PD is a gradual process,with significant improvements observable more than 2 weeks after administration and lasting at least 8 weeks.This study is the first to demonstrate the efficacy and durability of MSC-EV treatment in PD.
