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
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
Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Altho...Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.展开更多
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
Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse ...Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.展开更多
Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke trea...Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function.Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect.Neural stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/exosomes.However,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain unresolved.In this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells.We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.展开更多
Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)...Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.展开更多
Greenblatt and his team have unveiled vertebral skeletal stem cells(vSSCs)as a critical player in the landscape of bone metastasis.This commentary delves into the transformative discoveries surrounding vSSCs,emphasizi...Greenblatt and his team have unveiled vertebral skeletal stem cells(vSSCs)as a critical player in the landscape of bone metastasis.This commentary delves into the transformative discoveries surrounding vSSCs,emphasizing their distinct role in bone metastasis compared to other stem cell lineages.We illuminate the unique properties and functions of vSSCs,which may account for the elevated susceptibility of vertebral bones to metastatic invasion.Furthermore,we explore the exciting therapeutic horizons opened by this newfound understanding.These include potential interventions targeting vSSCs,modulation of associated signaling pathways,and broader implications for the treatment and management of bone metastasis.By shedding light on these game-changing insights,we hope to pave the way for novel strategies that could revolutionize the prognosis and treatment landscape for cancer patients with metastatic bone disease.展开更多
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
BACKGROUND Colorectal cancer stem cells(CCSCs)are heterogeneous cells that can self-renew and undergo multidirectional differentiation in colorectal cancer(CRC)patients.CCSCs are generally accepted to be important sou...BACKGROUND Colorectal cancer stem cells(CCSCs)are heterogeneous cells that can self-renew and undergo multidirectional differentiation in colorectal cancer(CRC)patients.CCSCs are generally accepted to be important sources of CRC and are responsible for the progression,metastasis,and therapeutic resistance of CRC.Therefore,targeting this specific subpopulation has been recognized as a promising strategy for overcoming CRC.AIM To investigate the effect of VX-509 on CCSCs and elucidate the underlying mechanism.METHODS CCSCs were enriched from CRC cell lines by in conditioned serum-free medium.Western blot,Aldefluor,transwell and tumorigenesis assays were performed to verify the phenotypic characteristics of the CCSCs.The anticancer efficacy of VX-509 was assessed in HCT116 CCSCs and HT29 CCSCs by performing cell viability analysis,colony formation,sphere formation,flow cytometry,and western blotting assessments in vitro and tumor growth,immunohistochemistry and immunofluorescence assessments in vivo.RESULTS Compared with parental cells,sphere cells derived from HCT116 and HT29 cells presented increased expression of stem cell transcription factors and stem cell markers and were more potent at promoting migration and tumori-genesis,demonstrating that the CRC sphere cells displayed CSC features.VX-509 inhibited the tumor malignant biological behavior of CRC-stem-like cells,as indicated by their proliferation,migration and clonality in vitro,and suppressed the tumor of CCSC-derived xenograft tumors in vivo.Besides,VX-509 suppressed the CSC character-istics of CRC-stem-like cells and inhibited the progression of epithelial-mesenchymal transition(EMT)signaling in vitro.Nodal was identified as the regulatory factor of VX-509 on CRC stem-like cells through analyses of differen-tially expressed genes and CSC-related database information.VX-509 markedly downregulated the expression of Nodal and its downstream phosphorylated Smad2/3 to inhibit EMT progression.Moreover,VX-509 reversed the dedifferentiation of CCSCs and inhibited the progression of EMT induced by Nodal overexpression.CONCLUSION VX-509 prevents the EMT process in CCSCs by inhibiting the transcription and protein expression of Nodal,and inhibits the dedifferentiated self-renewal of CCSCs.展开更多
BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown...BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown that decellularized extracellular matrix(ECM)derived from autologous,allogenic,or xenogeneic mesenchymal stromal cells(MSCs)can effectively restore osteochondral integrity.AIM To determine whether the decellularized ECM of antler reserve mesenchymal cells(RMCs),a xenogeneic material from antler stem cells,is superior to the currently available treatments for osteochondral defects.METHODS We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70%confluence;50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition.Decellularized sheets of adipocyte-derived MSCs(aMSCs)and antlerogenic periosteal cells(another type of antler stem cells)were used as the controls.Three weeks after ascorbic acid stimulation,the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints.RESULTS The defects were successfully repaired by applying the ECM-sheets.The highest quality of repair was achieved in the RMC-ECM group both in vitro(including cell attachment and proliferation),and in vivo(including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues).Notably,the antler-stem-cell-derived ECM(xenogeneic)performed better than the aMSC-ECM(allogenic),while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells.CONCLUSION Decellularized xenogeneic ECM derived from the antler stem cell,particularly the active form(RMC-ECM),can achieve high quality repair/reconstruction of osteochondral defects,suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.展开更多
Coronavirus disease 2019(COVID-19)is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection typically presents with fever and respiratory symptoms,whi...Coronavirus disease 2019(COVID-19)is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection typically presents with fever and respiratory symptoms,which can progress to severe respiratory distress syndrome and multiple organ failure.In severe cases,these complications may even lead to death.One of the causes of COVID-19 deaths is the cytokine storm caused by an overactive immune response.Therefore,suppressing the overactive immune response may be an effective strategy for treating COVID-19.Mesenchymal stem cells(MSCs)and their derived exosomes(MSCs-Exo)have potent homing abilities,immunomodulatory functions,regenerative repair,and antifibrotic effects,promising an effective tool in treating COVID-19.In this paper,we review the main mechanisms and potential roles of MSCs and MSCs-Exo in treating COVID-19.We also summarize relevant recent clinical trials,including the source of cells,the dosage and the efficacy,and the clinical value and problems in this field,providing more theoretical references for the clinical use of MSCs and MSCs-Exo in the treatment of COVID-19.展开更多
BACKGROUND In recent years,there has been an increase in the number of total hip arthroplasty procedures in the younger patient population.This active group has higher expectations of their prosthesis in comparison to...BACKGROUND In recent years,there has been an increase in the number of total hip arthroplasty procedures in the younger patient population.This active group has higher expectations of their prosthesis in comparison to the older population,and there is a greater physical demand for the prosthesis.Short femoral stems were in-troduced to retain proximal bone stock and joint biomechanics and became more common to implant in this specific population.Currently,the long-term survival and functional outcomes of various short stems are still being investigated in different clinics.AIM To determine the 5-year survival of the Optimys hip stem.METHODS This was a prospective multicenter cohort study of 500 patients conducted in two hospitals in the Netherlands.All patients received the Optimys short stem(Mathys Ltd,Bettlach,Switzerland).The primary outcome measure was survival of the hip stem,with revision as the endpoint.The secondary outcome measurements included patient-reported outcome measures(PROMs).Kaplan-Meier analysis was used to calculate the 5-year survival rate.Log-minus-log transformation was performed to calculate the 95%confidence interval(95%CI).Mixed model analyses were performed to assess the course of the PROMs during the 1st 2 years after surgery.Analyses were modeled separately for the 1st and 2nd years to calculate the yearly change in PROMs during both follow-up periods with accompanying 95%CIs.RESULTS The mean age of the total 500 patients was 62.3 years(standard deviation:10.6)and 202 were male(40%).At a median follow-up of 5.5 years(interquartile range:4.5-6.7),7 patients were deceased and 6 revisions were registered,for infection(n=3),subsidence(n=2)and malposition(n=1).This resulted in an overall 5-year survival of 98.8%(95%CI:97.3-99.5).If infection was left out as reason for revision,a stem survival of 99.4%(95%CI:98.1-99.8)was seen.Baseline questionnaires were completed by 471 patients(94%),317 patients(63%)completed the 1-year follow-up questionnaires and 233 patients(47%)completed the 2-year follow-up.Both outcome measures significantly improved across all domains in the 1st year after the operation(P<0.03 for all domains).In the 2nd year after surgery,no significant changes were observed in any domain in comparison to the 1-year follow-up.CONCLUSION The Optimys stem has a 5-year survival of 98.8%.Patient-reported outcome measures increased significantly in the 1st postoperative year with stabilization at the 2-year follow-up.展开更多
基金supported by the National Natural Science Foundation of China,No.82171380(to CD)Jiangsu Students’Platform for Innovation and Entrepreneurship Training Program,No.202110304098Y(to DJ)。
文摘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.
文摘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.
基金supported by the National Key Research and Development Program of China,No.2018YFA0108602the CAMS Initiative for Innovative Medicine,No.2021-1-I2M-019the National High Level Hospital Clinical Research Funding,No.2022-PUMCH-C-042(all to XB).
文摘Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.
基金supported by the National Natural Science Foundation of China,No.82171336(to XX)。
文摘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.
文摘Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.
基金supported by the National Natural Science Foundation of China,No.81971105(to ZNG)the Science and Technology Department of Jilin Province,No.YDZJ202201ZYTS677(to ZNG)+3 种基金Talent Reserve Program of the First Hospital of Jilin University,No.JDYYCB-2023002(to ZNG)the Norman Bethune Health Science Center of Jilin University,No.2022JBGS03(to YY)Science and Technology Department of Jilin Province,Nos.YDZJ202302CXJD061,20220303002SF(to YY)Jilin Provincial Key Laboratory,No.YDZJ202302CXJD017(to YY).
文摘Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function.Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect.Neural stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/exosomes.However,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain unresolved.In this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells.We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.
基金supported by the Fujian Minimally Invasive Medical Center Foundation,No.2128100514(to CC,CW,HX)the Natural Science Foundation of Fujian Province,No.2023J01640(to CC,CW,ZL,HX)。
文摘Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.
文摘Greenblatt and his team have unveiled vertebral skeletal stem cells(vSSCs)as a critical player in the landscape of bone metastasis.This commentary delves into the transformative discoveries surrounding vSSCs,emphasizing their distinct role in bone metastasis compared to other stem cell lineages.We illuminate the unique properties and functions of vSSCs,which may account for the elevated susceptibility of vertebral bones to metastatic invasion.Furthermore,we explore the exciting therapeutic horizons opened by this newfound understanding.These include potential interventions targeting vSSCs,modulation of associated signaling pathways,and broader implications for the treatment and management of bone metastasis.By shedding light on these game-changing insights,we hope to pave the way for novel strategies that could revolutionize the prognosis and treatment landscape for cancer patients with metastatic bone disease.
文摘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.
基金National Natural Science Foundation of China,No.82074298Chengdu Science and Technology Bureau Project,No.2021-YF05-01726-SN“Xinglin Scholars”Research Promotion Program of Chengdu University of Traditional Chinese Medicine,No.QJRC2022007.
文摘BACKGROUND Colorectal cancer stem cells(CCSCs)are heterogeneous cells that can self-renew and undergo multidirectional differentiation in colorectal cancer(CRC)patients.CCSCs are generally accepted to be important sources of CRC and are responsible for the progression,metastasis,and therapeutic resistance of CRC.Therefore,targeting this specific subpopulation has been recognized as a promising strategy for overcoming CRC.AIM To investigate the effect of VX-509 on CCSCs and elucidate the underlying mechanism.METHODS CCSCs were enriched from CRC cell lines by in conditioned serum-free medium.Western blot,Aldefluor,transwell and tumorigenesis assays were performed to verify the phenotypic characteristics of the CCSCs.The anticancer efficacy of VX-509 was assessed in HCT116 CCSCs and HT29 CCSCs by performing cell viability analysis,colony formation,sphere formation,flow cytometry,and western blotting assessments in vitro and tumor growth,immunohistochemistry and immunofluorescence assessments in vivo.RESULTS Compared with parental cells,sphere cells derived from HCT116 and HT29 cells presented increased expression of stem cell transcription factors and stem cell markers and were more potent at promoting migration and tumori-genesis,demonstrating that the CRC sphere cells displayed CSC features.VX-509 inhibited the tumor malignant biological behavior of CRC-stem-like cells,as indicated by their proliferation,migration and clonality in vitro,and suppressed the tumor of CCSC-derived xenograft tumors in vivo.Besides,VX-509 suppressed the CSC character-istics of CRC-stem-like cells and inhibited the progression of epithelial-mesenchymal transition(EMT)signaling in vitro.Nodal was identified as the regulatory factor of VX-509 on CRC stem-like cells through analyses of differen-tially expressed genes and CSC-related database information.VX-509 markedly downregulated the expression of Nodal and its downstream phosphorylated Smad2/3 to inhibit EMT progression.Moreover,VX-509 reversed the dedifferentiation of CCSCs and inhibited the progression of EMT induced by Nodal overexpression.CONCLUSION VX-509 prevents the EMT process in CCSCs by inhibiting the transcription and protein expression of Nodal,and inhibits the dedifferentiated self-renewal of CCSCs.
基金National Natural Science Foundation of China,No.U20A20403This study was conducted in accordance with the Animal Ethics Committee of the Institute of Antler Science and Product Technology,Changchun Sci-Tech University(AEC No:CKARI202309).
文摘BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown that decellularized extracellular matrix(ECM)derived from autologous,allogenic,or xenogeneic mesenchymal stromal cells(MSCs)can effectively restore osteochondral integrity.AIM To determine whether the decellularized ECM of antler reserve mesenchymal cells(RMCs),a xenogeneic material from antler stem cells,is superior to the currently available treatments for osteochondral defects.METHODS We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70%confluence;50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition.Decellularized sheets of adipocyte-derived MSCs(aMSCs)and antlerogenic periosteal cells(another type of antler stem cells)were used as the controls.Three weeks after ascorbic acid stimulation,the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints.RESULTS The defects were successfully repaired by applying the ECM-sheets.The highest quality of repair was achieved in the RMC-ECM group both in vitro(including cell attachment and proliferation),and in vivo(including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues).Notably,the antler-stem-cell-derived ECM(xenogeneic)performed better than the aMSC-ECM(allogenic),while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells.CONCLUSION Decellularized xenogeneic ECM derived from the antler stem cell,particularly the active form(RMC-ECM),can achieve high quality repair/reconstruction of osteochondral defects,suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.
基金Supported by Science and Technology Department Project of Jilin Province,China,No.20230101163JCthe Outstanding Youth Fund Project of Jilin Provincial Department of Education,China,No.JJKH20241324KJ.
文摘Coronavirus disease 2019(COVID-19)is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection typically presents with fever and respiratory symptoms,which can progress to severe respiratory distress syndrome and multiple organ failure.In severe cases,these complications may even lead to death.One of the causes of COVID-19 deaths is the cytokine storm caused by an overactive immune response.Therefore,suppressing the overactive immune response may be an effective strategy for treating COVID-19.Mesenchymal stem cells(MSCs)and their derived exosomes(MSCs-Exo)have potent homing abilities,immunomodulatory functions,regenerative repair,and antifibrotic effects,promising an effective tool in treating COVID-19.In this paper,we review the main mechanisms and potential roles of MSCs and MSCs-Exo in treating COVID-19.We also summarize relevant recent clinical trials,including the source of cells,the dosage and the efficacy,and the clinical value and problems in this field,providing more theoretical references for the clinical use of MSCs and MSCs-Exo in the treatment of COVID-19.
文摘BACKGROUND In recent years,there has been an increase in the number of total hip arthroplasty procedures in the younger patient population.This active group has higher expectations of their prosthesis in comparison to the older population,and there is a greater physical demand for the prosthesis.Short femoral stems were in-troduced to retain proximal bone stock and joint biomechanics and became more common to implant in this specific population.Currently,the long-term survival and functional outcomes of various short stems are still being investigated in different clinics.AIM To determine the 5-year survival of the Optimys hip stem.METHODS This was a prospective multicenter cohort study of 500 patients conducted in two hospitals in the Netherlands.All patients received the Optimys short stem(Mathys Ltd,Bettlach,Switzerland).The primary outcome measure was survival of the hip stem,with revision as the endpoint.The secondary outcome measurements included patient-reported outcome measures(PROMs).Kaplan-Meier analysis was used to calculate the 5-year survival rate.Log-minus-log transformation was performed to calculate the 95%confidence interval(95%CI).Mixed model analyses were performed to assess the course of the PROMs during the 1st 2 years after surgery.Analyses were modeled separately for the 1st and 2nd years to calculate the yearly change in PROMs during both follow-up periods with accompanying 95%CIs.RESULTS The mean age of the total 500 patients was 62.3 years(standard deviation:10.6)and 202 were male(40%).At a median follow-up of 5.5 years(interquartile range:4.5-6.7),7 patients were deceased and 6 revisions were registered,for infection(n=3),subsidence(n=2)and malposition(n=1).This resulted in an overall 5-year survival of 98.8%(95%CI:97.3-99.5).If infection was left out as reason for revision,a stem survival of 99.4%(95%CI:98.1-99.8)was seen.Baseline questionnaires were completed by 471 patients(94%),317 patients(63%)completed the 1-year follow-up questionnaires and 233 patients(47%)completed the 2-year follow-up.Both outcome measures significantly improved across all domains in the 1st year after the operation(P<0.03 for all domains).In the 2nd year after surgery,no significant changes were observed in any domain in comparison to the 1-year follow-up.CONCLUSION The Optimys stem has a 5-year survival of 98.8%.Patient-reported outcome measures increased significantly in the 1st postoperative year with stabilization at the 2-year follow-up.
