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
Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke,but its safety,effectiveness,and mechanism remain to be elucidated.In this study,good m...Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke,but its safety,effectiveness,and mechanism remain to be elucidated.In this study,good manufacturing practice-grade human umbilical cord mesenchymal stem cells(5×105 and 1×106 cells)and saline were administered by cerebellomedullary cistern injection 72 hours after stroke induced by middle cerebral artery occlusion in rats.The results showed(1)no significant difference in mortality or general conditions among the three groups.There was no abnormal differentiation or tumor formation in various organs of rats in any group.(2)Compared with saline-treated animals,those treated with human umbilical cord mesenchymal stem cells showed significant functional recovery and reduced infarct volume,with no significant differences between different human umbilical cord mesenchymal stem cell doses.(3)Human umbilical cord mesenchymal stem cells were found in the ischemic brain after 14 and 28 days of follow-up,and the number of positive cells significantly decreased over time.(4)Neuronal nuclei expression in the human umbilical cord mesenchymal stem cell group was greater than that in the saline group,while glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 expression levels decreased.(5)Human umbilical cord mesenchymal stem cell treatment increased the number of CD31+microvessels and doublecortin-positive cells after ischemic stroke.Human umbilical cord mesenchymal stem cells also upregulated the expression of CD31+/Ki67+.(6)At 14 days after intrathecal administration,brain-derived neurotrophic factor expression in the peri-infarct area and the concentrations of brain-derived neurotrophic factor in the cerebrospinal fluid in both human umbilical cord mesenchymal stem cell groups were significantly greater than those in the saline group and persisted until the 28th day.Taken together,these results indicate that the intrathecal administration of human umbilical cord mesenchymal stem cells via cerebellomedullary cistern injection is safe and effective for the treatment of ischemic stroke in rats.The mechanisms may include alleviating the local inflammatory response in the peri-infarct region,promoting neurogenesis and angiogenesis,and enhancing the production of neurotrophic factors.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
BACKGROUND Research has been increasingly conducted on the connection between mesenchymal stem cell(MSC)-conditioned medium(MSC-CM)and aging.However,most studies have focused on adipose-derived MSC-CM(ADMSC-CM),result...BACKGROUND Research has been increasingly conducted on the connection between mesenchymal stem cell(MSC)-conditioned medium(MSC-CM)and aging.However,most studies have focused on adipose-derived MSC-CM(ADMSC-CM),resulting in a research bias.We hypothesized that umbilical cord-derived MSCs,being younger than adipose-derived MSCs,would be more suitable for overcoming aging-related processes.AIM To assess the efficacy and safety of umbilical cord-derived MSC-CM(UCMSCCM)for preventing and treating skin aging.METHODS In vitro and in vivo studies were conducted to compare UCMSC-CM with ADMSC-CM,the most studied active aging-preventive conditioned medium to date.Additionally,the most effective delivery method of UCMSC-CM for aged skin was identified.RESULTS UCMSC-CM had a higher content of effective factors,stimulated higher proliferation of fibroblasts,and strongly inhibited melanin production in B16F1 cells.In aged mice,UCMSC-CM application increased skin thickness,the number of Ki-67-positive cells,and the area of collagen deposition.UCMSC-CM was more effective than ADMSC-CM in preventing and treating skin aging.Additionally,a safety evaluation of UCMSC-CM performed in various animal models indicated that it was safe even when used directly on the skin.CONCLUSION UCMSC-CM is effective and safe for preventing and treating skin aging.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
BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.Th...BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.There are studies suggesting that stem cell therapy may be effective in the treatment of ASD.AIM To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell transplantation.METHODS A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with neurorehabilitation.RESULTS The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor skills.No serious side effects were encountered during the 2-year follow-up.CONCLUSION The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.展开更多
Neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease,are characterized by the progressive loss of neuronal function and structure,leading to severe morbidity and morta...Neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease,are characterized by the progressive loss of neuronal function and structure,leading to severe morbidity and mortality.Current therapeutic approaches are ineffective at stopping or reversing disease progression.Stem cell therapy has emerged as a promising candidate in research and treatment.Mesenchymal stem cells(MSCs)are considered ideal candidates for regenerative medicine because of their high proliferation rate and multi-differentiation potential.MSCs can differentiate into neurons and glial cells,modulate immune responses,and reduce inflammation,and their exosomes can promote neural repair and regulate neuronal function;thus,MSCs offer unique advantages for treating neurodegenerative diseases.However,challenges remain in optimizing cell delivery methods,ensuring the long-term survival and integration of transplanted cells,and fully understanding their therapeutic effects.This article primarily outlines the functions of MSCs in neurodegenerative diseases,with the intention that further research will fully harness their potential and translate these findings into clinical applications,offering new hope for patients suffering from neurodegenerative diseases.展开更多
Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem ce...Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived treatments.This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke.However,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical translation.To promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic stroke.We found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis.The human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor.These findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway.Finally,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety profile.Therefore,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.展开更多
Spinal cord injury has long been a prominent challenge in the trauma repair process. Spinal cord injury is a research hotspot by virtue of its difficulty to treat and its escalating morbidity. Furthermore, spinal cord...Spinal cord injury has long been a prominent challenge in the trauma repair process. Spinal cord injury is a research hotspot by virtue of its difficulty to treat and its escalating morbidity. Furthermore, spinal cord injury has a long period of disease progression and leads to complications that exert a lot of mental and economic pressure on patients. There are currently a large number of therapeutic strategies for treating spinal cord injury, which range from pharmacological and surgical methods to cell therapy and rehabilitation training. All of these strategies have positive effects in the course of spinal cord injury treatment. This review mainly discusses the problems regarding stem cell therapy for spinal cord injury, including the characteristics and action modes of all relevant cell types. Induced pluripotent stem cells, which represent a special kind of stem cell population, have gained impetus in cell therapy development because of a range of advantages. Induced pluripotent stem cells can be developed into the precursor cells of each neural cell type at the site of spinal cord injury, and have great potential for application in spinal cord injury therapy.展开更多
Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflamm...Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.展开更多
Objective Cerebral palsy(CP)is a prevalent neurodevelopmental disorder acquired during the perinatal period,with periventricular white matter injury(PWMI)serving as its primary pathological hallmark.PWMI is characteri...Objective Cerebral palsy(CP)is a prevalent neurodevelopmental disorder acquired during the perinatal period,with periventricular white matter injury(PWMI)serving as its primary pathological hallmark.PWMI is characterized by the loss of oligodendrocytes(OLs)and the disintegration of myelin sheaths,leading to impaired neural connectivity and motor dysfunction.Neural stem cells(NSCs)represent a promising regenerative source for replenishing lost OLs;however,conventional twodimensional(2D)in vitro culture systems lack the three-dimensional(3D)physiological microenvironment.Microfluidic chip technology has emerged as a powerful tool to overcome this limitation by enabling precise spatial and temporal control over 3D microenvironmental conditions,including the establishment of stable concentration gradients of bioactive molecules.Catalpol,an iridoid glycoside derived from traditional medicinal plants,exhibits dual antioxidant and anti-apoptotic properties.Despite its therapeutic potential,the capacity of catalpol to drive NSC differentiation toward OLs under biomimetic 3D conditions,as well as the underlying molecular mechanisms,remains poorly understood.This study aims to develop a microfluidic-based 3D biomimetic platform to systematically investigate the concentration-dependent effects of catalpol on promoting NSCs-to-OLs differentiation and to elucidate the role of the caveolin-1(Cav-1)signaling pathway in this process.Methods We developed a novel multiplexed microfluidic device featuring parallel microchannels with integrated gradient generators capable of establishing and maintaining precise linear concentration gradients(0-3 g/L catalpol)across 3D NSCs cultures.This platform facilitated the continuous perfusion culture of NSC-derived 3D spheroids,mimicking the dynamic in vivo microenvironment.Real-time cell viability was assessed using Calcein-AM/propidium iodide(PI)dual staining,with fluorescence imaging quantifying live/dead cell ratios.Oligodendrocyte differentiation was evaluated through quantitative reverse transcription polymerase chain reaction(qRT-PCR)for MBP and SOX10 gene expression,complemented by immunofluorescence staining to visualize corresponding protein changes.To dissect the molecular mechanism,the Cav-1-specific pharmacological inhibitor methyl‑β‑cyclodextrin(MCD)was employed to perturb the pathway,and its effects on differentiation markers were analyzed.Results Catalpol demonstrated excellent biocompatibility,with cell viability exceeding 96%across the entire tested concentration range(0-3 g/L),confirming its non-cytotoxic nature.At the optimal concentration of 0-3 g/L,catalpol significantly upregulated both MBP and SOX10 expression(P<0.05,P<0.01),indicating robust promotion of oligodendroglial differentiation.Intriguingly,Cav-1 mRNA expression was progressively downregulated during NSC differentiation into OLs.Further inhibition of Cav-1 with MCD further enhanced this effect,leading to a statistically significant increase in OL-specific gene expression(P<0.05,P<0.01),suggesting Cav-1 acts as a negative regulator of OLs differentiation.Conclusion This study established an integrated microfluidic gradient chip-3D NSC spheroid culture system,which combines the advantages of precise chemical gradient control with physiologically relevant 3D cell culture.The findings demonstrate that 3 g/L catalpol effectively suppresses Cav-1 signaling to drive NSC differentiation into functional OLs.This work not only provides novel insights into the Cav-1-dependent mechanisms of myelination but also delivers a scalable technological platform for future research on remyelination therapies,with potential applications in cerebral palsy and other white matter disorders.The platform’s modular design permits adaptation for screening other neurogenic compounds or investigating additional signaling pathways involved in OLs maturation.展开更多
Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic...Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.展开更多
Mesenchymal stromal/stem cells(MSCs)are currently applied in regenerative medicine and tissue engineering.Numerous clinical studies have indicated that MSCs from different tissue sources can provide therapeutic benefi...Mesenchymal stromal/stem cells(MSCs)are currently applied in regenerative medicine and tissue engineering.Numerous clinical studies have indicated that MSCs from different tissue sources can provide therapeutic benefits for patients.MSCs derived from either human adult or perinatal tissues have their own unique advantages in their medical practices.Usually,clinical studies are conducted by using of cultured MSCs after thawing or short-term cryopreserved-then-thawed MSCs prior to administration for the treatment of a wide range of diseases and medical disorders.Currently,cryogenically banking perinatal MSCs for potential personalized medicine for later use in lifetime has raised growing interest in China as well as in many other countries.Meanwhile,this has led to questions regarding the availability,stability,consistency,multipotency,and therapeutic efficiency of the potential perinatal MSC-derived therapeutic products after longterm cryostorage.This opinion review does not minimize any therapeutic benefit of perinatal MSCs in many diseases after short-term cryopreservation.This article mainly describes what is known about banking perinatal MSCs in China and,importantly,it is to recognize the limitation and uncertainty of the perinatal MSCs stored in cryobanks for stem cell medical treatments in whole life.This article also provides several recommendations for banking of perinatal MSCs for potentially future personalized medicine,albeit it is impossible to anticipate whether the donor will benefit from banked MSCs during her/his lifetime.展开更多
This article comments on the study by Fang,which demonstrates that reduced nuclear factor erythroid-derived 2(NRF2)activity promotes endoplasmic reticulum stress and senescence in adipose-derived mesenchymal stem cell...This article comments on the study by Fang,which demonstrates that reduced nuclear factor erythroid-derived 2(NRF2)activity promotes endoplasmic reticulum stress and senescence in adipose-derived mesenchymal stem cells from hypertrophic obese mice,primarily through downregulation of mitofusin-2(MFN2).Robust methodologies,including knockdown/rescue experiments,chromatin immunoprecipitation quantitative polymerase chain reaction,coimmunoprecipitation,and transplantation assays,substantiate that NRF2 or MFN2 disruption impairs the therapeutic potential of these cells in insulin resistance.However,the proposed MFN2-binding immunoglobulin protein interaction remains indirectly supported and requires biochemical validation(e.g.,glutathione S-transferase pull-down/Forster resonance energy transfer/crosslinking mass spectrometry).Moreover,NRF2 may influence endoplasmic reticulum stress and senescence through additional unexplored targets.Future studies should clarify the structural and functional nature of the MFN2-binding immunoglobulin protein relationship and its implications for mitochondrial dynamics,endoplasmic reticulum-mitochondria tethering,and calcium signaling.展开更多
BACKGROUND The proteomic signature or profile best describes the functional component of a cell during its routine metabolic and survival activities.Additional complexity in differentiation and maturation is observed ...BACKGROUND The proteomic signature or profile best describes the functional component of a cell during its routine metabolic and survival activities.Additional complexity in differentiation and maturation is observed in stem/progenitor cells.The role of functional proteins at the cellular level has long been attributed to anatomical niches,and stem cells do not deflect from this attribution.Human dental stem cells(hDSCs),on the whole,are a combination of mesenchymal and epithelial coordinates observed throughout craniofacial bones to pulp.AIM To specify the proteomic profile and compare each type of hDSC with other mesenchymal stem cells(MSCs)of various niches.Furthermore,we analyzed the characteristics of the microenvironment and preconditioning changes associated with the proteomic profile of hDSCs and their influence on committed lineage differentiation.METHODS Literature searches were performed in PubMed,EMBASE,Scopus,and Web of Science databases,from January 1990 to December 2018.An extra inquiry of the grey literature was completed on Google Scholar,ProQuest,and OpenGrey.Relevant MeSH terms(PubMed)and keywords related to dental stem cells were used independently and in combination.RESULTS The initial search resulted in 134 articles.Of the 134 full-texts assessed,96 articles were excluded and 38 articles that met the eligibility criteria were reviewed.The overall assessment of hDSCs and other MSCs suggests that differences in the proteomic profile can be due to stem cellular complexity acquired from varied tissue sources during embryonic development.However,our comparison of the proteomic profile suffered inconsistencies due to the heterogeneity of various hDSCs.We believe that the existence of a heterogeneous population of stem cells at a given niche determines the modalities of regeneration or tissue repair.Added prominences to the differences present between various hDSCs have been reasoned out.CONCLUSION Systematic review on proteomic studies of various hDSCs are promising as an eye-opener for revisiting the proteomic profile and in-depth analysis to elucidate more refined mechanisms of hDSC functionalities.展开更多
BACKGROUND Hypertrophy obesity is closely associated with obesity-related metabolic diseases.The senescence of adipose-derived mesenchymal stem cells(ASCs)is believed to play a significant role in the development of h...BACKGROUND Hypertrophy obesity is closely associated with obesity-related metabolic diseases.The senescence of adipose-derived mesenchymal stem cells(ASCs)is believed to play a significant role in the development of hypertrophy obesity.AIM To investigate the relationship between ASC senescence,endoplasmic reticulum(ER)stress,and nuclear factor erythroid-derived 2(NRF2)activity in a mouse model of hypertrophy obesity.Additionally,we explored the mechanism through which NRF2 affects ASC senescence via mitofusin-2(MFN2).METHODS We observed the senescent phenotype and ER stress(ERS)in ASCs from hypertrophic obese mouse models,and determined NRF2 activity.Chromatin immunoprecipitation-quantitative polymerase chain reaction(qPCR)was used to analyze the transcriptional activity of NRF2 on Mfn2.Additionally,co-immunoprecipitation experiments were conducted to investigate the interaction between MFN2 and binding immunoglobulin protein.The impact of NRF2 and MFN2 on the therapeutic effect of ASC transplantation against insulin resistance was explored through ASC transplantation.RESULTS The study found significant increases in senescence and ERS,accompanied by decreased NRF2 activity in ASCs from hypertrophic obese mouse models.Simultaneously,chromatin immunoprecipitation-qPCR analysis revealed a reduction in NRF2 transcriptional activity on Mfn2.The downregulation of NRF2 activity and Mfn2 expression promoted senescence and ERS in ASCs,subsequently impacting the anti-insulin resistance effect of ASC transplantation.Furthermore,there exists a direct or indirect binding between MFN2 and binding immunoglobulin protein.CONCLUSION The research outcomes suggest that NRF2 may regulate ERS and senescence in subcutaneous ASCs of hypertrophic obese mice by modulating Mfn2.These discoveries offer new insights into understanding metabolic diseases associated with hypertrophic obesity and potentially provide a foundation for intervention strategies.展开更多
This article discusses the study by Xiao et al,which investigated the therapeutic efficacy of serum-free cultured human umbilical cord mesenchymal stem cells(NhUCMSCs)in a mouse model of knee osteoarthritis.The result...This article discusses the study by Xiao et al,which investigated the therapeutic efficacy of serum-free cultured human umbilical cord mesenchymal stem cells(NhUCMSCs)in a mouse model of knee osteoarthritis.The results showed that NhUCMSCs alleviated osteoarthritis-related cartilage damage and inflammation comparably to both serum-cultured hUCMSCs and hyaluronic acid.While these findings broaden the potential clinical utility of N-hUCMSCs by circumventing certain drawbacks of serum-based cultures,the equivalence in efficacy raises important questions.First,how do N-hUCMSCs differ phenotypically from serum-cultured hUCMSCs,particularly in terms of proliferation rate,replicative capacity,and senescence profile?Second,what advantages might N-hUCMSCs offer over hyaluronic acid-a well-established therapy-beyond avoiding xenogeneic components and ethical concerns?Future research should focus on longterm phenotypic stability,sustained functional benefits,safety profiles,and mechanistic insights to ascertain whether N-hUCMSCs can surpass current standards of care.展开更多
BACKGROUND While acute exposure to high-altitude hypoxic environments can lead to increased thrombosis risk,preventive measures are currently limited.Recently,human umbilical cord mesenchymal stem cell(hUC-MSC)transpl...BACKGROUND While acute exposure to high-altitude hypoxic environments can lead to increased thrombosis risk,preventive measures are currently limited.Recently,human umbilical cord mesenchymal stem cell(hUC-MSC)transplantation has been found effective in preventing and treating various clinical conditions,including thro-mbotic diseases.Platelets are crucial for thrombus formation,and theirα-granules are key determinants of platelet function.However,little is known about the influence of hUC-MSCs on plateletα-granules.METHODS Rats were assigned to three groups,namely,low-altitude,high-altitude,and hUC-MSC-treated groups.The low-altitude group was pretreated with normal saline and housed at an altitude of 1500 m.Rats in the high-altitude group received similar pretreatment and were housed in a simulated hypobaric hypoxia chamber with an altitude of 6500 m and oxygen partial pressure of 7.7 kPa.hUC-MSC-treated rats were pretreated with hUC-MSCs and exposed to hypoxic conditions.Aortic blood was collected after three days to assess platelet counts and mor-phology andα-granule release.RESULTS Compared to the low-altitude group,the high-altitude group exhibited significantly higher platelet counts,plasma levels of von Willebrand factor,platelet factor 4,beta-thromboglobulin,as well as surface P-selectin(CD62p)and p-protein kinase B,p-mitogen-activated protein kinase,and p-extracellular-signal regulated kinase expression in platelets.Platelet morphology in the high-altitude group was irregular,with extended pseudopodia and increasedα-granule densities.However,these changes were not apparent in the hUC-MSC-treated group.CONCLUSION Acute exposure to high-altitude hypoxia increased platelet counts,altered platelet morphology,and increasedα-granule density and release.These effects were mitigated by hUC-MSC treatment,mediated by the protein kinase B/mitogen-activated protein kinase/extracellular-signal regulated kinase pathway.The results indicate that hUC-MSCs may represent a promising and effective approach for the prevention and treatment of acute high-altitude-associated thrombosis,providing an experimental foundation for the development of clinical applications.展开更多
MicroRNAs(miRNAs)are small non-coding RNAs of 20-22 nucleotides in length.They have been identified as major regulators in the secretome of mesenchymal stem cells(MSCs)including adipose tissue,bone marrow,Wharton’s j...MicroRNAs(miRNAs)are small non-coding RNAs of 20-22 nucleotides in length.They have been identified as major regulators in the secretome of mesenchymal stem cells(MSCs)including adipose tissue,bone marrow,Wharton’s jelly,and dental pulp.These MSCs and their secretome with specific miRNAs are known modulators of the immune response,angiogenesis,inflammation,and apoptosis.In this review,the application of MSC-derived miRNAs in treating several ocular conditions including dry eye,glaucoma,and retinal degenerative diseases has been compiled.In addition,the emerging role of MSC-derived extracellular vesicles carrying miRNAs as a major cargo,regulating the target cells in the human eye has been reviewed.Finally,the bioengineering of nanovesicles with specific MSC-derived miRNAs as novel drug therapy has been discussed.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 Medicine-Engineering Interdisciplinary Project of Sun Yat-sen Memorial Hospital,China,No.YXYGRH202203(to YW)Key-Area Research and Development Program of Guangdong Province,China,No.2023B1111050003(to HC)Guangzhou Science and Technology Talent Project of China,No.201909020006(to HC).
文摘Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke,but its safety,effectiveness,and mechanism remain to be elucidated.In this study,good manufacturing practice-grade human umbilical cord mesenchymal stem cells(5×105 and 1×106 cells)and saline were administered by cerebellomedullary cistern injection 72 hours after stroke induced by middle cerebral artery occlusion in rats.The results showed(1)no significant difference in mortality or general conditions among the three groups.There was no abnormal differentiation or tumor formation in various organs of rats in any group.(2)Compared with saline-treated animals,those treated with human umbilical cord mesenchymal stem cells showed significant functional recovery and reduced infarct volume,with no significant differences between different human umbilical cord mesenchymal stem cell doses.(3)Human umbilical cord mesenchymal stem cells were found in the ischemic brain after 14 and 28 days of follow-up,and the number of positive cells significantly decreased over time.(4)Neuronal nuclei expression in the human umbilical cord mesenchymal stem cell group was greater than that in the saline group,while glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 expression levels decreased.(5)Human umbilical cord mesenchymal stem cell treatment increased the number of CD31+microvessels and doublecortin-positive cells after ischemic stroke.Human umbilical cord mesenchymal stem cells also upregulated the expression of CD31+/Ki67+.(6)At 14 days after intrathecal administration,brain-derived neurotrophic factor expression in the peri-infarct area and the concentrations of brain-derived neurotrophic factor in the cerebrospinal fluid in both human umbilical cord mesenchymal stem cell groups were significantly greater than those in the saline group and persisted until the 28th day.Taken together,these results indicate that the intrathecal administration of human umbilical cord mesenchymal stem cells via cerebellomedullary cistern injection is safe and effective for the treatment of ischemic stroke in rats.The mechanisms may include alleviating the local inflammatory response in the peri-infarct region,promoting neurogenesis and angiogenesis,and enhancing the production of neurotrophic factors.
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.
文摘BACKGROUND Research has been increasingly conducted on the connection between mesenchymal stem cell(MSC)-conditioned medium(MSC-CM)and aging.However,most studies have focused on adipose-derived MSC-CM(ADMSC-CM),resulting in a research bias.We hypothesized that umbilical cord-derived MSCs,being younger than adipose-derived MSCs,would be more suitable for overcoming aging-related processes.AIM To assess the efficacy and safety of umbilical cord-derived MSC-CM(UCMSCCM)for preventing and treating skin aging.METHODS In vitro and in vivo studies were conducted to compare UCMSC-CM with ADMSC-CM,the most studied active aging-preventive conditioned medium to date.Additionally,the most effective delivery method of UCMSC-CM for aged skin was identified.RESULTS UCMSC-CM had a higher content of effective factors,stimulated higher proliferation of fibroblasts,and strongly inhibited melanin production in B16F1 cells.In aged mice,UCMSC-CM application increased skin thickness,the number of Ki-67-positive cells,and the area of collagen deposition.UCMSC-CM was more effective than ADMSC-CM in preventing and treating skin aging.Additionally,a safety evaluation of UCMSC-CM performed in various animal models indicated that it was safe even when used directly on the skin.CONCLUSION UCMSC-CM is effective and safe for preventing and treating skin aging.
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.
文摘BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.There are studies suggesting that stem cell therapy may be effective in the treatment of ASD.AIM To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell transplantation.METHODS A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with neurorehabilitation.RESULTS The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor skills.No serious side effects were encountered during the 2-year follow-up.CONCLUSION The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.
基金Supported by Natural Science Foundation of Henan Province,No.242300421199 and No.252300421395Henan Province Joint Fund for Science and Technology Research and Development,No.235101610002+1 种基金Key Technologies R&D Program of Henan Province,No.242102310134Henan Province Foundation for University Key Teacher,No.2024GGJS088.
文摘Neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease,are characterized by the progressive loss of neuronal function and structure,leading to severe morbidity and mortality.Current therapeutic approaches are ineffective at stopping or reversing disease progression.Stem cell therapy has emerged as a promising candidate in research and treatment.Mesenchymal stem cells(MSCs)are considered ideal candidates for regenerative medicine because of their high proliferation rate and multi-differentiation potential.MSCs can differentiate into neurons and glial cells,modulate immune responses,and reduce inflammation,and their exosomes can promote neural repair and regulate neuronal function;thus,MSCs offer unique advantages for treating neurodegenerative diseases.However,challenges remain in optimizing cell delivery methods,ensuring the long-term survival and integration of transplanted cells,and fully understanding their therapeutic effects.This article primarily outlines the functions of MSCs in neurodegenerative diseases,with the intention that further research will fully harness their potential and translate these findings into clinical applications,offering new hope for patients suffering from neurodegenerative diseases.
基金supported by the National Nature Science Foundation of China,No.81471308(to JL)the Innovative Leading Talents of Liaoning Province,No.XLYC1902031(to JL)+2 种基金Science and Technology Projects in Liaoning Province,No.2022-BS-238(to CH)Young Top Talents of Liaoning Province,No.XLYC1907009(to LW)Dalian Science and Technology Innovation Fund,No.2018J11CY025(to JL)。
文摘Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived treatments.This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke.However,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical translation.To promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic stroke.We found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis.The human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor.These findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway.Finally,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety profile.Therefore,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.
基金supported by the National Key Research and Development Program of China,No. 2017YFA0104304 (to BW),2017YFA0205400 (to PPS),and 2017YFA0506000 (to PPS)the National Natural Science Foundation of China,No. 81571213 (to BW)+2 种基金the Nanjing Medical Science and Technique Development Foundation of China,No. QRX17006 (to BW)the Nanjing Medical Science and Innovation Platform,No. ZDX16005 (to BW)the Innovation and Entrepreneurship Plan of Jiangsu Province (2019)(to BW)。
文摘Spinal cord injury has long been a prominent challenge in the trauma repair process. Spinal cord injury is a research hotspot by virtue of its difficulty to treat and its escalating morbidity. Furthermore, spinal cord injury has a long period of disease progression and leads to complications that exert a lot of mental and economic pressure on patients. There are currently a large number of therapeutic strategies for treating spinal cord injury, which range from pharmacological and surgical methods to cell therapy and rehabilitation training. All of these strategies have positive effects in the course of spinal cord injury treatment. This review mainly discusses the problems regarding stem cell therapy for spinal cord injury, including the characteristics and action modes of all relevant cell types. Induced pluripotent stem cells, which represent a special kind of stem cell population, have gained impetus in cell therapy development because of a range of advantages. Induced pluripotent stem cells can be developed into the precursor cells of each neural cell type at the site of spinal cord injury, and have great potential for application in spinal cord injury therapy.
基金supported by grants from the Major Program of National Key Research and Development Project,Nos.2020YFA0112600(to ZH)the National Natural Science Foundation of China,No.82171270(to ZL)+5 种基金Public Service Platform for Artificial Intelligence Screening and Auxiliary Diagnosis for the Medical and Health Industry,Ministry of Industry and Information Technology of the People’s Republic of China,No.2020-0103-3-1(to ZL)the Natural Science Foundation of Beijing,No.Z200016(to ZL)Beijing Talents Project,No.2018000021223ZK03(to ZL)Beijing Municipal Committee of Science and Technology,No.Z201100005620010(to ZL)CAMS Innovation Fund for Medical Sciences,No.2019-I2M-5-029(to YW)Shanghai Engineering Research Center of Stem Cells Translational Medicine,No.20DZ2255100(to ZH).
文摘Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.
基金supported by grants from the Liaoning Province Excellent Talent Program Project(XLYC1902031)Dalian Science and Technology Talent Innovation Plan Grant(2022RG18)Basic Research Project of the Department of Education of Liaoning Province(LJKQZ20222395)。
文摘Objective Cerebral palsy(CP)is a prevalent neurodevelopmental disorder acquired during the perinatal period,with periventricular white matter injury(PWMI)serving as its primary pathological hallmark.PWMI is characterized by the loss of oligodendrocytes(OLs)and the disintegration of myelin sheaths,leading to impaired neural connectivity and motor dysfunction.Neural stem cells(NSCs)represent a promising regenerative source for replenishing lost OLs;however,conventional twodimensional(2D)in vitro culture systems lack the three-dimensional(3D)physiological microenvironment.Microfluidic chip technology has emerged as a powerful tool to overcome this limitation by enabling precise spatial and temporal control over 3D microenvironmental conditions,including the establishment of stable concentration gradients of bioactive molecules.Catalpol,an iridoid glycoside derived from traditional medicinal plants,exhibits dual antioxidant and anti-apoptotic properties.Despite its therapeutic potential,the capacity of catalpol to drive NSC differentiation toward OLs under biomimetic 3D conditions,as well as the underlying molecular mechanisms,remains poorly understood.This study aims to develop a microfluidic-based 3D biomimetic platform to systematically investigate the concentration-dependent effects of catalpol on promoting NSCs-to-OLs differentiation and to elucidate the role of the caveolin-1(Cav-1)signaling pathway in this process.Methods We developed a novel multiplexed microfluidic device featuring parallel microchannels with integrated gradient generators capable of establishing and maintaining precise linear concentration gradients(0-3 g/L catalpol)across 3D NSCs cultures.This platform facilitated the continuous perfusion culture of NSC-derived 3D spheroids,mimicking the dynamic in vivo microenvironment.Real-time cell viability was assessed using Calcein-AM/propidium iodide(PI)dual staining,with fluorescence imaging quantifying live/dead cell ratios.Oligodendrocyte differentiation was evaluated through quantitative reverse transcription polymerase chain reaction(qRT-PCR)for MBP and SOX10 gene expression,complemented by immunofluorescence staining to visualize corresponding protein changes.To dissect the molecular mechanism,the Cav-1-specific pharmacological inhibitor methyl‑β‑cyclodextrin(MCD)was employed to perturb the pathway,and its effects on differentiation markers were analyzed.Results Catalpol demonstrated excellent biocompatibility,with cell viability exceeding 96%across the entire tested concentration range(0-3 g/L),confirming its non-cytotoxic nature.At the optimal concentration of 0-3 g/L,catalpol significantly upregulated both MBP and SOX10 expression(P<0.05,P<0.01),indicating robust promotion of oligodendroglial differentiation.Intriguingly,Cav-1 mRNA expression was progressively downregulated during NSC differentiation into OLs.Further inhibition of Cav-1 with MCD further enhanced this effect,leading to a statistically significant increase in OL-specific gene expression(P<0.05,P<0.01),suggesting Cav-1 acts as a negative regulator of OLs differentiation.Conclusion This study established an integrated microfluidic gradient chip-3D NSC spheroid culture system,which combines the advantages of precise chemical gradient control with physiologically relevant 3D cell culture.The findings demonstrate that 3 g/L catalpol effectively suppresses Cav-1 signaling to drive NSC differentiation into functional OLs.This work not only provides novel insights into the Cav-1-dependent mechanisms of myelination but also delivers a scalable technological platform for future research on remyelination therapies,with potential applications in cerebral palsy and other white matter disorders.The platform’s modular design permits adaptation for screening other neurogenic compounds or investigating additional signaling pathways involved in OLs maturation.
基金funded by Basic Research Program of Shanghai,No.20JC1412200(to JW)the National Key Research and Development Program of China,No.2020YFA0113000(to RCZ)。
文摘Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.
基金Supported by the Henan Province Science and Technique Bureau R&D Project,No.222102310228.
文摘Mesenchymal stromal/stem cells(MSCs)are currently applied in regenerative medicine and tissue engineering.Numerous clinical studies have indicated that MSCs from different tissue sources can provide therapeutic benefits for patients.MSCs derived from either human adult or perinatal tissues have their own unique advantages in their medical practices.Usually,clinical studies are conducted by using of cultured MSCs after thawing or short-term cryopreserved-then-thawed MSCs prior to administration for the treatment of a wide range of diseases and medical disorders.Currently,cryogenically banking perinatal MSCs for potential personalized medicine for later use in lifetime has raised growing interest in China as well as in many other countries.Meanwhile,this has led to questions regarding the availability,stability,consistency,multipotency,and therapeutic efficiency of the potential perinatal MSC-derived therapeutic products after longterm cryostorage.This opinion review does not minimize any therapeutic benefit of perinatal MSCs in many diseases after short-term cryopreservation.This article mainly describes what is known about banking perinatal MSCs in China and,importantly,it is to recognize the limitation and uncertainty of the perinatal MSCs stored in cryobanks for stem cell medical treatments in whole life.This article also provides several recommendations for banking of perinatal MSCs for potentially future personalized medicine,albeit it is impossible to anticipate whether the donor will benefit from banked MSCs during her/his lifetime.
基金Shenzhen Science and Technology Program,No.JCYJ20240813162036046.
文摘This article comments on the study by Fang,which demonstrates that reduced nuclear factor erythroid-derived 2(NRF2)activity promotes endoplasmic reticulum stress and senescence in adipose-derived mesenchymal stem cells from hypertrophic obese mice,primarily through downregulation of mitofusin-2(MFN2).Robust methodologies,including knockdown/rescue experiments,chromatin immunoprecipitation quantitative polymerase chain reaction,coimmunoprecipitation,and transplantation assays,substantiate that NRF2 or MFN2 disruption impairs the therapeutic potential of these cells in insulin resistance.However,the proposed MFN2-binding immunoglobulin protein interaction remains indirectly supported and requires biochemical validation(e.g.,glutathione S-transferase pull-down/Forster resonance energy transfer/crosslinking mass spectrometry).Moreover,NRF2 may influence endoplasmic reticulum stress and senescence through additional unexplored targets.Future studies should clarify the structural and functional nature of the MFN2-binding immunoglobulin protein relationship and its implications for mitochondrial dynamics,endoplasmic reticulum-mitochondria tethering,and calcium signaling.
基金Deanship of Scientific Research,King Khalid University through Large Research Group Project,No.G.R.P 2/27/40.
文摘BACKGROUND The proteomic signature or profile best describes the functional component of a cell during its routine metabolic and survival activities.Additional complexity in differentiation and maturation is observed in stem/progenitor cells.The role of functional proteins at the cellular level has long been attributed to anatomical niches,and stem cells do not deflect from this attribution.Human dental stem cells(hDSCs),on the whole,are a combination of mesenchymal and epithelial coordinates observed throughout craniofacial bones to pulp.AIM To specify the proteomic profile and compare each type of hDSC with other mesenchymal stem cells(MSCs)of various niches.Furthermore,we analyzed the characteristics of the microenvironment and preconditioning changes associated with the proteomic profile of hDSCs and their influence on committed lineage differentiation.METHODS Literature searches were performed in PubMed,EMBASE,Scopus,and Web of Science databases,from January 1990 to December 2018.An extra inquiry of the grey literature was completed on Google Scholar,ProQuest,and OpenGrey.Relevant MeSH terms(PubMed)and keywords related to dental stem cells were used independently and in combination.RESULTS The initial search resulted in 134 articles.Of the 134 full-texts assessed,96 articles were excluded and 38 articles that met the eligibility criteria were reviewed.The overall assessment of hDSCs and other MSCs suggests that differences in the proteomic profile can be due to stem cellular complexity acquired from varied tissue sources during embryonic development.However,our comparison of the proteomic profile suffered inconsistencies due to the heterogeneity of various hDSCs.We believe that the existence of a heterogeneous population of stem cells at a given niche determines the modalities of regeneration or tissue repair.Added prominences to the differences present between various hDSCs have been reasoned out.CONCLUSION Systematic review on proteomic studies of various hDSCs are promising as an eye-opener for revisiting the proteomic profile and in-depth analysis to elucidate more refined mechanisms of hDSC functionalities.
基金Supported by the National Natural Science Foundation of China,No.32000511Medical Science and Technology Joint Construction Program of Henan Province,No.LHGJ20230053.
文摘BACKGROUND Hypertrophy obesity is closely associated with obesity-related metabolic diseases.The senescence of adipose-derived mesenchymal stem cells(ASCs)is believed to play a significant role in the development of hypertrophy obesity.AIM To investigate the relationship between ASC senescence,endoplasmic reticulum(ER)stress,and nuclear factor erythroid-derived 2(NRF2)activity in a mouse model of hypertrophy obesity.Additionally,we explored the mechanism through which NRF2 affects ASC senescence via mitofusin-2(MFN2).METHODS We observed the senescent phenotype and ER stress(ERS)in ASCs from hypertrophic obese mouse models,and determined NRF2 activity.Chromatin immunoprecipitation-quantitative polymerase chain reaction(qPCR)was used to analyze the transcriptional activity of NRF2 on Mfn2.Additionally,co-immunoprecipitation experiments were conducted to investigate the interaction between MFN2 and binding immunoglobulin protein.The impact of NRF2 and MFN2 on the therapeutic effect of ASC transplantation against insulin resistance was explored through ASC transplantation.RESULTS The study found significant increases in senescence and ERS,accompanied by decreased NRF2 activity in ASCs from hypertrophic obese mouse models.Simultaneously,chromatin immunoprecipitation-qPCR analysis revealed a reduction in NRF2 transcriptional activity on Mfn2.The downregulation of NRF2 activity and Mfn2 expression promoted senescence and ERS in ASCs,subsequently impacting the anti-insulin resistance effect of ASC transplantation.Furthermore,there exists a direct or indirect binding between MFN2 and binding immunoglobulin protein.CONCLUSION The research outcomes suggest that NRF2 may regulate ERS and senescence in subcutaneous ASCs of hypertrophic obese mice by modulating Mfn2.These discoveries offer new insights into understanding metabolic diseases associated with hypertrophic obesity and potentially provide a foundation for intervention strategies.
基金Supported by the Natural Science Foundation of Shanghai,No.24ZR1459300(to Xiao-Ting Liang)and the Pyramid Talent Project,No.YQ677(to Yue Ding).
文摘This article discusses the study by Xiao et al,which investigated the therapeutic efficacy of serum-free cultured human umbilical cord mesenchymal stem cells(NhUCMSCs)in a mouse model of knee osteoarthritis.The results showed that NhUCMSCs alleviated osteoarthritis-related cartilage damage and inflammation comparably to both serum-cultured hUCMSCs and hyaluronic acid.While these findings broaden the potential clinical utility of N-hUCMSCs by circumventing certain drawbacks of serum-based cultures,the equivalence in efficacy raises important questions.First,how do N-hUCMSCs differ phenotypically from serum-cultured hUCMSCs,particularly in terms of proliferation rate,replicative capacity,and senescence profile?Second,what advantages might N-hUCMSCs offer over hyaluronic acid-a well-established therapy-beyond avoiding xenogeneic components and ethical concerns?Future research should focus on longterm phenotypic stability,sustained functional benefits,safety profiles,and mechanistic insights to ascertain whether N-hUCMSCs can surpass current standards of care.
基金Supported by the Major Science and Technology Project of Gansu Province-Social Development Field,No.25ZDFA007Health Industry Research Funding Project of Gansu Province,No.GSWSKY2024-54+3 种基金Youth Science and Technology Fund Program of Gansu Province,No.21JR11RA014National Natural Science Foundation of China,No.81273568Health Industry Research Funding Project of Gansu Province,No.GSWSKY2022-03Logistics Scientific Research Independent Project of the PLA.
文摘BACKGROUND While acute exposure to high-altitude hypoxic environments can lead to increased thrombosis risk,preventive measures are currently limited.Recently,human umbilical cord mesenchymal stem cell(hUC-MSC)transplantation has been found effective in preventing and treating various clinical conditions,including thro-mbotic diseases.Platelets are crucial for thrombus formation,and theirα-granules are key determinants of platelet function.However,little is known about the influence of hUC-MSCs on plateletα-granules.METHODS Rats were assigned to three groups,namely,low-altitude,high-altitude,and hUC-MSC-treated groups.The low-altitude group was pretreated with normal saline and housed at an altitude of 1500 m.Rats in the high-altitude group received similar pretreatment and were housed in a simulated hypobaric hypoxia chamber with an altitude of 6500 m and oxygen partial pressure of 7.7 kPa.hUC-MSC-treated rats were pretreated with hUC-MSCs and exposed to hypoxic conditions.Aortic blood was collected after three days to assess platelet counts and mor-phology andα-granule release.RESULTS Compared to the low-altitude group,the high-altitude group exhibited significantly higher platelet counts,plasma levels of von Willebrand factor,platelet factor 4,beta-thromboglobulin,as well as surface P-selectin(CD62p)and p-protein kinase B,p-mitogen-activated protein kinase,and p-extracellular-signal regulated kinase expression in platelets.Platelet morphology in the high-altitude group was irregular,with extended pseudopodia and increasedα-granule densities.However,these changes were not apparent in the hUC-MSC-treated group.CONCLUSION Acute exposure to high-altitude hypoxia increased platelet counts,altered platelet morphology,and increasedα-granule density and release.These effects were mitigated by hUC-MSC treatment,mediated by the protein kinase B/mitogen-activated protein kinase/extracellular-signal regulated kinase pathway.The results indicate that hUC-MSCs may represent a promising and effective approach for the prevention and treatment of acute high-altitude-associated thrombosis,providing an experimental foundation for the development of clinical applications.
文摘MicroRNAs(miRNAs)are small non-coding RNAs of 20-22 nucleotides in length.They have been identified as major regulators in the secretome of mesenchymal stem cells(MSCs)including adipose tissue,bone marrow,Wharton’s jelly,and dental pulp.These MSCs and their secretome with specific miRNAs are known modulators of the immune response,angiogenesis,inflammation,and apoptosis.In this review,the application of MSC-derived miRNAs in treating several ocular conditions including dry eye,glaucoma,and retinal degenerative diseases has been compiled.In addition,the emerging role of MSC-derived extracellular vesicles carrying miRNAs as a major cargo,regulating the target cells in the human eye has been reviewed.Finally,the bioengineering of nanovesicles with specific MSC-derived miRNAs as novel drug therapy has been discussed.
