In this editorial,we comment on the article published in the recent issue of the World Journal of Stem Cells.They focus on stem cell preconditioning to prevent ferroptosis by modulating the cystathionineγ-lyase/hydro...In this editorial,we comment on the article published in the recent issue of the World Journal of Stem Cells.They focus on stem cell preconditioning to prevent ferroptosis by modulating the cystathionineγ-lyase/hydrogen sulfide(H_(2)S)pathway as a novel approach to treat vascular disorders,particularly pulmonary hypertension.Preconditioned stem cells are gaining popularity in regenerative medicine due to their unique ability to survive by resisting the harsh,unfavorable microenvironment of the injured tissue.They also secrete various paracrine factors against apoptosis,necrosis,and ferroptosis to enhance cell survival.Ferroptosis,a regulated form of cell death characterized by iron accumulation and oxidative stress,has been implicated in various pathologies encompassing dege-nerative disorders to cancer.The lipid peroxidation cascade initiates and sustains ferroptosis,generating many reactive oxygen species that attack and damage multiple cellular structures.Understanding these intertwined mechanisms provi-des significant insights into developing therapeutic modalities for ferroptosis-related diseases.This editorial primarily discusses stem cell preconditioning in modulating ferroptosis,focusing on the cystathionase gamma/H_(2)S ferroptosis pathway.Ferroptosis presents a significant challenge in mesenchymal stem cell(MSC)-based therapies;hence,the emerging role of H_(2)S/cystathionase gamma/H_(2) S signaling in abrogating ferroptosis provides a novel option for therapeutic intervention.Further research into understanding the precise mechanisms of H_(2)S-mediated cytoprotection against ferroptosis is warranted to enhance the thera-peutic potential of MSCs in clinical settings,particularly vascular disorders.展开更多
The stem cell pre-treatment approaches at cellular and sub-cellular levels encompass physical manipulation of stem cells to growth factor treatment,genetic manipulation,and chemical and pharmacological treatment,each ...The stem cell pre-treatment approaches at cellular and sub-cellular levels encompass physical manipulation of stem cells to growth factor treatment,genetic manipulation,and chemical and pharmacological treatment,each strategy having advantages and limitations.Most of these pre-treatment protocols are non-combinative.This editorial is a continuum of Li et al’s published article and Wan et al’s editorial focusing on the significance of pre-treatment strategies to enhance their stemness,immunoregulatory,and immunosuppressive properties.They have elaborated on the intricacies of the combinative pre-treatment protocol using pro-inflammatory cytokines and hypoxia.Applying a well-defined multi-pronged combinatorial strategy of mesenchymal stem cells(MSCs),pre-treatment based on the mechanistic understanding is expected to develop“Super MSCs”,which will create a transformative shift in MSC-based therapies in clinical settings,potentially revolutionizing the field.Once optimized,the standardized protocols may be used with slight modifications to pre-treat different stem cells to develop“super stem cells”with augmented stemness,functionality,and reparability for diverse clinical applications with better outcomes.展开更多
BACKGROUND Mesenchymal stem cells(MSCs)as living biopharmaceuticals with unique properties,i.e.,stemness,viability,phenotypes,paracrine activity,etc.,need to be administered such that they reach the target site,mainta...BACKGROUND Mesenchymal stem cells(MSCs)as living biopharmaceuticals with unique properties,i.e.,stemness,viability,phenotypes,paracrine activity,etc.,need to be administered such that they reach the target site,maintaining these properties unchanged and are retained at the injury site to participate in the repair process.Route of delivery(RoD)remains one of the critical determinants of safety and efficacy.This study elucidates the safety and effectiveness of different RoDs of MSC treatment in heart failure(HF)based on phase II randomized clinical trials(RCTs).We hypothesize that the RoD modulates the safety and efficacy of MSCbased therapy and determines the outcome of the intervention.AIM To investigate the effect of RoD of MSCs on safety and efficacy in HF patients.METHODS RCTs were retrieved from six databases.Safety endpoints included mortality and serious adverse events(SAEs),while efficacy outcomes encompassed changes in left ventricular ejection fraction(LVEF),6-minute walk distance(6MWD),and pro-B-type natriuretic peptide(pro-BNP).Subgroup analyses on RoD were performed for all study endpoints.RESULTS Twelve RCTs were included.Overall,MSC therapy demonstrated a significant decrease in mortality[relative risk(RR):0.55,95%confidence interval(95%CI):0.33-0.92,P=0.02]compared to control,while SAE outcomes showed no significant difference(RR:0.84,95%CI:0.66-1.05,P=0.11).RoD subgroup analysis revealed a significant difference in SAE among the transendocardial(TESI)injection subgroup(RR=0.71,95%CI:0.54-0.95,P=0.04).The pooled weighted mean difference(WMD)demonstrated an overall significant improvement of LVEF by 2.44%(WMD:2.44%,95%CI:0.80-4.29,P value≤0.001),with only intracoronary(IC)subgroup showing significant improvement(WMD:7.26%,95%CI:5.61-8.92,P≤0.001).Furthermore,the IC delivery route significantly improved 6MWD by 115 m(WMD=114.99 m,95%CI:91.48-138.50),respectively.In biochemical efficacy outcomes,only the IC subgroup showed a significant reduction in pro-BNP by-860.64 pg/mL(WMD:-860.64 pg/Ml,95%CI:-944.02 to-777.26,P=0.001).CONCLUSION Our study concluded that all delivery methods of MSC-based therapy are safe.Despite the overall benefits in efficacy,the TESI and IC routes provided better outcomes than other methods.Larger-scale trials are warranted before implementing MSC-based therapy in routine clinical practice.展开更多
BACKGROUND Mesenchymal stem cells(MSCs),as living biodrugs,have entered advanced phases of clinical assessment for cardiac function restoration in patients with myocardial infarction and heart failure.While MSCs are a...BACKGROUND Mesenchymal stem cells(MSCs),as living biodrugs,have entered advanced phases of clinical assessment for cardiac function restoration in patients with myocardial infarction and heart failure.While MSCs are available from diverse tissue sources,bone-marrow-derived MSCs(BM-MSCs)remain the most wellstudied cell type,besides umbilical-cord-derived MSCs(UC-MSCs).The latter offers advantages,including noninvasive availability without ethical considerations.AIM To compare the safety and efficacy of BM-MSCs and UC-MSCs in terms of left ventricular ejection fraction(LVEF),6-min walking distance(6MWD),and major adverse cardiac events(MACEs).METHODS Five databases were systematically searched to identify randomized controlled trials(RCTs).Thirteen RCTs(693 patients)were included using predefined eligibility criteria.Weighted mean differences and odds ratio(OR)for the changes in the estimated treatment effects.RESULTS UC-MSCs significantly improved LVEF vs controls by 5.08%[95%confidence interval(CI):2.20%-7.95%]at 6 mo and 2.78%(95%CI:0.86%-4.70%)at 12 mo.However,no significant effect was observed for BM-MSCs vs controls.No significant changes were observed in the 6MWD with either of the two cell types.Also,no differences were observed for MACEs,except rehospitalization rates,which were lower only with BM-MSCs(odds ratio 0.48,95%CI:0.24-0.97)vs controls.CONCLUSION UC-MSCs significantly improved LVEF compared with BM-MSCs.Their advant-Safwan M et al.Tissue-source and MSCs as living biodrugs ageous characteristics position them as a promising alternative to MSC-based therapy.展开更多
Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal regeneration.However,structural and functional recovery is a senile process involving mul...Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal regeneration.However,structural and functional recovery is a senile process involving multifaceted cellular and molecular processes.The contemporary treatment options are limited,with surgical intervention as the gold-standard method;however,each treatment option has its associated limitations,especially when the injury is severe with a large gap.Recent advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic PNI.The recent pilot study is a leap forward in the field,which is expected to pave the way for more enormous,systematic,and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach,in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.展开更多
High glucose(HG)culture conditions in vitro and persistent exposure to hyperglycemia in diabetes patients are detrimental to stem cells,analogous to any other cell type in our body.It interferes with diverse signaling...High glucose(HG)culture conditions in vitro and persistent exposure to hyperglycemia in diabetes patients are detrimental to stem cells,analogous to any other cell type in our body.It interferes with diverse signaling pathways,i.e.mammalian target of rapamycin(mTOR)-phosphoinositide 3-kinase(PI3K)-Akt signaling,to impact physiological cellular functions,leading to low cell survival and higher cell apoptosis rates.While elucidating the underlying mechanism responsible for the apoptosis of adipose tissue-derived mesenchymal stem cells(MSCs),a recent study has shown that HG culture conditions dysregulate mTORPI3K-Akt signaling in addition to mitochondrial malfunctioning due to defective mitochondrial membrane potential(MtMP)that lowers ATP production.This organelle-level dysfunction energy-starves the cells and increases oxidative stress and ultrastructural abnormalities.Disruption of the mitochondrial electron transport chain produces an altered mitochondrial NAD+/NADH redox state as evidenced by a low NAD+/NADH ratio that primarily contributes to the reduced cell survival in HG.Some previous studies have also reported altered mitochondrial membrane polarity(causing hyperpolarization)and reduced mitochondrial cell mass,leading to perturbed mitochondrial homeostasis.The hostile microenvironment created by HG exposure creates structural and functional changes in the mitochondria,altering their bioenergetics and reducing their capacity to produce ATP.These are significant data,as MSCs are extensively studied for tissue regeneration and restoring their normal functioning in cell-based therapy.Therefore,MSCs from hyperglycemic donors should be cautiously used in clinical settings for cell-based therapy due to concerns of their poor sur-vival rates and increased rates of post engraftment proliferation.As hypergly-cemia alters the bioenergetics of donor MSCs,rectifying the loss of MtMP may be an excellent target for future research to restore the normal functioning of MSCs in hyperglycemic patients.展开更多
Stem cell expansion in vitro and transplantation in the cytokine-rich proinflammatory milieu in the injured tissue generate immense oxidative stress that interferes with the cells’survival,stemness,and repairability....Stem cell expansion in vitro and transplantation in the cytokine-rich proinflammatory milieu in the injured tissue generate immense oxidative stress that interferes with the cells’survival,stemness,and repairability.Stem cell priming has gained popularity to overcome these issues.Given melatonin’s oxidative-scavenging properties,Gu et al have used periodontal ligament stem cells cultured under oxidative stress as an in vitro model to study the cytoprotective effects of melatonin.Our letter to the editor delves into melatonin-induced stem cell priming and the underlying molecular mechanism,focusing on the intriguing role of Yesassociated protein signaling in alleviating oxidative stress.We stress the importance of understanding the distinction between in vitro and in vivo oxidative stress conditions,a crucial aspect of stem cell research that invokes a sense of critical thinking in the readership.The study by Gu et al presents a novel approach to oxidative stress management,offering exciting possibilities for future research and applications.展开更多
2019-nCoV is the third consecutive coronavirus spread during the last 2 decades, but this time, unlike the previous two occasions, has achieved a pandemic proportion threatening widespread loss of human lives and a ma...2019-nCoV is the third consecutive coronavirus spread during the last 2 decades, but this time, unlike the previous two occasions, has achieved a pandemic proportion threatening widespread loss of human lives and a massive setback to the global economy. The situation warrants drastic measures in terms of preventing the spread of the virus and treating the virus-infected patients. The development of a new vaccine is a time-intensive option. Although efforts are underway to find possible pharmacological options, e.g., chloroquine, hydroxychloroquine, existing antiviral agents, etc., in the meanwhile we may work on the combinatorial interventional approach of combining drug therapy with passive immune therapy. It would be prudent to use a convalescent serum therapy approach with the serum from COVID-19 patients who have recovered from the infection.展开更多
Since the first publication regarding the existence of stem cells in cancer[cancer stem cells(CSCs)]in 1994,many studies have been published providing in-depth information about their biology and function.This researc...Since the first publication regarding the existence of stem cells in cancer[cancer stem cells(CSCs)]in 1994,many studies have been published providing in-depth information about their biology and function.This research has paved the way in terms of appreciating the role of CSCs in tumour aggressiveness,progression,recurrence and resistance to cancer therapy.Targeting CSCs for cancer therapy has still not progressed to a sufficient degree,particularly in terms of exploring the mechanism of dynamic interconversion between CSCs and non-CSCs.Besides the CSC scenario,the problem of cancer dissemination has been analyzed indepth with the identification and isolation of microRNAs(miRs),which are now considered to be compelling molecular markers in the diagnosis and prognosis of tumours in general and specifically in patients with non-small cell lung cancer.Paracrine release of miRs via“exosomes”(small membrane vesicles(30-100 nm),the derivation of which lies in the luminal membranes of multi-vesicular bodies)released by fusion with the cell membrane is gaining popularity.Whether exosomes play a significant role in maintaining a dynamic equilibrium state between CSCs and non-CSCs and their mechanism of activity is as yet unknown.Future studies on CSC-related exosomes will provide new perspectives for precision-targeted treatment strategies.展开更多
BACKGROUND As living biodrugs,mesenchymal stem cells(MSCs)have progressed to phase 3 clinical trials for cardiovascular applications.However,their limited immediate availability hampers their routine clinical use.AIM ...BACKGROUND As living biodrugs,mesenchymal stem cells(MSCs)have progressed to phase 3 clinical trials for cardiovascular applications.However,their limited immediate availability hampers their routine clinical use.AIM To validate our hypothesis that cryopreserved MSCs(CryoMSCs)are as safe and effective as freshly cultured MSC counterparts but carry logistical advantages.METHODS Four databases were systematically reviewed for relevant randomized controlled trials(RCTs)evaluating the safety and efficacy of CryoMSCs from various tissue sources in treating patients with heart disease.A subgroup analysis was performed based on MSC source and post-thaw cell viability to determine treatment effects across different CryoMSCs sources and viability status.Weighted mean differences(WMDs)and odds ratios were calculated to measure changes in the estimated treatment effects.All statistical analyses were performed using RevMan version 5.4.1 software.RESULTS Seven RCTs(285 patients)met the eligibility criteria for inclusion in the metaanalysis.During short-term follow-up,^(Cryo)MSCs demonstrated a significant 2.11%improvement in left ventricular ejection fraction(LVEF)[WMD(95%CI)=2.11(0.66-3.56),P=0.004,I2=1%],with umbilical cord-derived MSCs being the most effective cell type.However,the significant effect on LVEF was not sustained over the 12 months of follow-up.Subgroup analysis demonstrated a substantial 3.44%improvement in LVEF[WMD(95%CI)=3.44(1.46-5.43),P=0.0007,I2=0%]when using MSCs with post-thaw viability exceeding 80%.There was no statistically significant difference in the frequency of major cardiac adverse events observed in rehospitalization or mortality in patients treated with ^(Cryo)MSCs vs the control group.CONCLUSION ^(Cryo)MSCs are a promising option for heart failure patients,particularly considering the current treatment options for cardiovascular diseases.Our data suggest that ^(Cryo)MSCs could be a viable alternative or complementary treatment to the current options,potentially improving patient outcomes.展开更多
BACKGROUND Iron overload cardiomyopathy is a significant cause of morbidity and mortality in transfusion-dependent thalassemia patients.Standard iron chelation therapy is less efficient in alleviating iron accumulatio...BACKGROUND Iron overload cardiomyopathy is a significant cause of morbidity and mortality in transfusion-dependent thalassemia patients.Standard iron chelation therapy is less efficient in alleviating iron accumulation in many organs,especially when iron enters the cells via specific calcium channels.AIM To validate our hypothesis that adding amlodipine to the iron chelation regimen is more efficient in alleviating myocardial iron overload.METHODS Five databases,including PubMed,Cochrane Library,Embase,ScienceDirect,and ClinicalTrials.gov,were systematically searched,and three randomized controlled trials involving 144 pediatric patients with transfusion-dependent thalassemia were included in our meta-analysis based on the predefined eligibility criteria.The quality of the included studies was assessed based on the Cochrane collab-oration tool for bias assessment.The primary outcome assessed was myocardial-T2 and myocardial iron concentration,while the secondary results showed serum ferritin level,liver iron concentration,and treatment adverse outcomes.Weighted mean difference and odds ratio were calculated to measure the changes in the estimated treatment effects.RESULTS During the follow-up period,Amlodipine treatment significantly improved cardiac T2 by 2.79 ms compared to the control group[95%confidence interval(CI):0.34-5.24,P=0.03,I2=0%].Additionally,a significant reduction of 0.31 in myocardial iron concentration was observed with amlodipine treatment compared to the control group[95%CI:-0.38-(-0.25),P<0.00001,I2=0%].Liver iron concentration was slightly lower in the amlodipine group by-0.04 mg/g,but this difference was not statistically significant(95%CI:-0.33-0.24,P=0.77,I2=0%).Amlodipine also showed a non-significant trend toward a reduction in serum ferritin levels(-328.86 ng/mL,95%CI:-1212.34-554.62,P=0.47,I2=90%).Regarding safety,there were no significant differences between the groups in the incidence of gastrointestinal upset,hypotension,or lower limb edema.CONCLUSION Amlodipine with iron chelation therapy significantly improved cardiac parameters,including cardiac-T2 and myocardial iron,in patients with transfusion-dependent thalassemia without causing significant adverse events but enhancing the efficacy of iron chelation therapy.展开更多
文摘In this editorial,we comment on the article published in the recent issue of the World Journal of Stem Cells.They focus on stem cell preconditioning to prevent ferroptosis by modulating the cystathionineγ-lyase/hydrogen sulfide(H_(2)S)pathway as a novel approach to treat vascular disorders,particularly pulmonary hypertension.Preconditioned stem cells are gaining popularity in regenerative medicine due to their unique ability to survive by resisting the harsh,unfavorable microenvironment of the injured tissue.They also secrete various paracrine factors against apoptosis,necrosis,and ferroptosis to enhance cell survival.Ferroptosis,a regulated form of cell death characterized by iron accumulation and oxidative stress,has been implicated in various pathologies encompassing dege-nerative disorders to cancer.The lipid peroxidation cascade initiates and sustains ferroptosis,generating many reactive oxygen species that attack and damage multiple cellular structures.Understanding these intertwined mechanisms provi-des significant insights into developing therapeutic modalities for ferroptosis-related diseases.This editorial primarily discusses stem cell preconditioning in modulating ferroptosis,focusing on the cystathionase gamma/H_(2)S ferroptosis pathway.Ferroptosis presents a significant challenge in mesenchymal stem cell(MSC)-based therapies;hence,the emerging role of H_(2)S/cystathionase gamma/H_(2) S signaling in abrogating ferroptosis provides a novel option for therapeutic intervention.Further research into understanding the precise mechanisms of H_(2)S-mediated cytoprotection against ferroptosis is warranted to enhance the thera-peutic potential of MSCs in clinical settings,particularly vascular disorders.
文摘The stem cell pre-treatment approaches at cellular and sub-cellular levels encompass physical manipulation of stem cells to growth factor treatment,genetic manipulation,and chemical and pharmacological treatment,each strategy having advantages and limitations.Most of these pre-treatment protocols are non-combinative.This editorial is a continuum of Li et al’s published article and Wan et al’s editorial focusing on the significance of pre-treatment strategies to enhance their stemness,immunoregulatory,and immunosuppressive properties.They have elaborated on the intricacies of the combinative pre-treatment protocol using pro-inflammatory cytokines and hypoxia.Applying a well-defined multi-pronged combinatorial strategy of mesenchymal stem cells(MSCs),pre-treatment based on the mechanistic understanding is expected to develop“Super MSCs”,which will create a transformative shift in MSC-based therapies in clinical settings,potentially revolutionizing the field.Once optimized,the standardized protocols may be used with slight modifications to pre-treat different stem cells to develop“super stem cells”with augmented stemness,functionality,and reparability for diverse clinical applications with better outcomes.
文摘BACKGROUND Mesenchymal stem cells(MSCs)as living biopharmaceuticals with unique properties,i.e.,stemness,viability,phenotypes,paracrine activity,etc.,need to be administered such that they reach the target site,maintaining these properties unchanged and are retained at the injury site to participate in the repair process.Route of delivery(RoD)remains one of the critical determinants of safety and efficacy.This study elucidates the safety and effectiveness of different RoDs of MSC treatment in heart failure(HF)based on phase II randomized clinical trials(RCTs).We hypothesize that the RoD modulates the safety and efficacy of MSCbased therapy and determines the outcome of the intervention.AIM To investigate the effect of RoD of MSCs on safety and efficacy in HF patients.METHODS RCTs were retrieved from six databases.Safety endpoints included mortality and serious adverse events(SAEs),while efficacy outcomes encompassed changes in left ventricular ejection fraction(LVEF),6-minute walk distance(6MWD),and pro-B-type natriuretic peptide(pro-BNP).Subgroup analyses on RoD were performed for all study endpoints.RESULTS Twelve RCTs were included.Overall,MSC therapy demonstrated a significant decrease in mortality[relative risk(RR):0.55,95%confidence interval(95%CI):0.33-0.92,P=0.02]compared to control,while SAE outcomes showed no significant difference(RR:0.84,95%CI:0.66-1.05,P=0.11).RoD subgroup analysis revealed a significant difference in SAE among the transendocardial(TESI)injection subgroup(RR=0.71,95%CI:0.54-0.95,P=0.04).The pooled weighted mean difference(WMD)demonstrated an overall significant improvement of LVEF by 2.44%(WMD:2.44%,95%CI:0.80-4.29,P value≤0.001),with only intracoronary(IC)subgroup showing significant improvement(WMD:7.26%,95%CI:5.61-8.92,P≤0.001).Furthermore,the IC delivery route significantly improved 6MWD by 115 m(WMD=114.99 m,95%CI:91.48-138.50),respectively.In biochemical efficacy outcomes,only the IC subgroup showed a significant reduction in pro-BNP by-860.64 pg/mL(WMD:-860.64 pg/Ml,95%CI:-944.02 to-777.26,P=0.001).CONCLUSION Our study concluded that all delivery methods of MSC-based therapy are safe.Despite the overall benefits in efficacy,the TESI and IC routes provided better outcomes than other methods.Larger-scale trials are warranted before implementing MSC-based therapy in routine clinical practice.
文摘BACKGROUND Mesenchymal stem cells(MSCs),as living biodrugs,have entered advanced phases of clinical assessment for cardiac function restoration in patients with myocardial infarction and heart failure.While MSCs are available from diverse tissue sources,bone-marrow-derived MSCs(BM-MSCs)remain the most wellstudied cell type,besides umbilical-cord-derived MSCs(UC-MSCs).The latter offers advantages,including noninvasive availability without ethical considerations.AIM To compare the safety and efficacy of BM-MSCs and UC-MSCs in terms of left ventricular ejection fraction(LVEF),6-min walking distance(6MWD),and major adverse cardiac events(MACEs).METHODS Five databases were systematically searched to identify randomized controlled trials(RCTs).Thirteen RCTs(693 patients)were included using predefined eligibility criteria.Weighted mean differences and odds ratio(OR)for the changes in the estimated treatment effects.RESULTS UC-MSCs significantly improved LVEF vs controls by 5.08%[95%confidence interval(CI):2.20%-7.95%]at 6 mo and 2.78%(95%CI:0.86%-4.70%)at 12 mo.However,no significant effect was observed for BM-MSCs vs controls.No significant changes were observed in the 6MWD with either of the two cell types.Also,no differences were observed for MACEs,except rehospitalization rates,which were lower only with BM-MSCs(odds ratio 0.48,95%CI:0.24-0.97)vs controls.CONCLUSION UC-MSCs significantly improved LVEF compared with BM-MSCs.Their advant-Safwan M et al.Tissue-source and MSCs as living biodrugs ageous characteristics position them as a promising alternative to MSC-based therapy.
文摘Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal regeneration.However,structural and functional recovery is a senile process involving multifaceted cellular and molecular processes.The contemporary treatment options are limited,with surgical intervention as the gold-standard method;however,each treatment option has its associated limitations,especially when the injury is severe with a large gap.Recent advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic PNI.The recent pilot study is a leap forward in the field,which is expected to pave the way for more enormous,systematic,and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach,in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.
文摘High glucose(HG)culture conditions in vitro and persistent exposure to hyperglycemia in diabetes patients are detrimental to stem cells,analogous to any other cell type in our body.It interferes with diverse signaling pathways,i.e.mammalian target of rapamycin(mTOR)-phosphoinositide 3-kinase(PI3K)-Akt signaling,to impact physiological cellular functions,leading to low cell survival and higher cell apoptosis rates.While elucidating the underlying mechanism responsible for the apoptosis of adipose tissue-derived mesenchymal stem cells(MSCs),a recent study has shown that HG culture conditions dysregulate mTORPI3K-Akt signaling in addition to mitochondrial malfunctioning due to defective mitochondrial membrane potential(MtMP)that lowers ATP production.This organelle-level dysfunction energy-starves the cells and increases oxidative stress and ultrastructural abnormalities.Disruption of the mitochondrial electron transport chain produces an altered mitochondrial NAD+/NADH redox state as evidenced by a low NAD+/NADH ratio that primarily contributes to the reduced cell survival in HG.Some previous studies have also reported altered mitochondrial membrane polarity(causing hyperpolarization)and reduced mitochondrial cell mass,leading to perturbed mitochondrial homeostasis.The hostile microenvironment created by HG exposure creates structural and functional changes in the mitochondria,altering their bioenergetics and reducing their capacity to produce ATP.These are significant data,as MSCs are extensively studied for tissue regeneration and restoring their normal functioning in cell-based therapy.Therefore,MSCs from hyperglycemic donors should be cautiously used in clinical settings for cell-based therapy due to concerns of their poor sur-vival rates and increased rates of post engraftment proliferation.As hypergly-cemia alters the bioenergetics of donor MSCs,rectifying the loss of MtMP may be an excellent target for future research to restore the normal functioning of MSCs in hyperglycemic patients.
文摘Stem cell expansion in vitro and transplantation in the cytokine-rich proinflammatory milieu in the injured tissue generate immense oxidative stress that interferes with the cells’survival,stemness,and repairability.Stem cell priming has gained popularity to overcome these issues.Given melatonin’s oxidative-scavenging properties,Gu et al have used periodontal ligament stem cells cultured under oxidative stress as an in vitro model to study the cytoprotective effects of melatonin.Our letter to the editor delves into melatonin-induced stem cell priming and the underlying molecular mechanism,focusing on the intriguing role of Yesassociated protein signaling in alleviating oxidative stress.We stress the importance of understanding the distinction between in vitro and in vivo oxidative stress conditions,a crucial aspect of stem cell research that invokes a sense of critical thinking in the readership.The study by Gu et al presents a novel approach to oxidative stress management,offering exciting possibilities for future research and applications.
文摘2019-nCoV is the third consecutive coronavirus spread during the last 2 decades, but this time, unlike the previous two occasions, has achieved a pandemic proportion threatening widespread loss of human lives and a massive setback to the global economy. The situation warrants drastic measures in terms of preventing the spread of the virus and treating the virus-infected patients. The development of a new vaccine is a time-intensive option. Although efforts are underway to find possible pharmacological options, e.g., chloroquine, hydroxychloroquine, existing antiviral agents, etc., in the meanwhile we may work on the combinatorial interventional approach of combining drug therapy with passive immune therapy. It would be prudent to use a convalescent serum therapy approach with the serum from COVID-19 patients who have recovered from the infection.
文摘Since the first publication regarding the existence of stem cells in cancer[cancer stem cells(CSCs)]in 1994,many studies have been published providing in-depth information about their biology and function.This research has paved the way in terms of appreciating the role of CSCs in tumour aggressiveness,progression,recurrence and resistance to cancer therapy.Targeting CSCs for cancer therapy has still not progressed to a sufficient degree,particularly in terms of exploring the mechanism of dynamic interconversion between CSCs and non-CSCs.Besides the CSC scenario,the problem of cancer dissemination has been analyzed indepth with the identification and isolation of microRNAs(miRs),which are now considered to be compelling molecular markers in the diagnosis and prognosis of tumours in general and specifically in patients with non-small cell lung cancer.Paracrine release of miRs via“exosomes”(small membrane vesicles(30-100 nm),the derivation of which lies in the luminal membranes of multi-vesicular bodies)released by fusion with the cell membrane is gaining popularity.Whether exosomes play a significant role in maintaining a dynamic equilibrium state between CSCs and non-CSCs and their mechanism of activity is as yet unknown.Future studies on CSC-related exosomes will provide new perspectives for precision-targeted treatment strategies.
文摘BACKGROUND As living biodrugs,mesenchymal stem cells(MSCs)have progressed to phase 3 clinical trials for cardiovascular applications.However,their limited immediate availability hampers their routine clinical use.AIM To validate our hypothesis that cryopreserved MSCs(CryoMSCs)are as safe and effective as freshly cultured MSC counterparts but carry logistical advantages.METHODS Four databases were systematically reviewed for relevant randomized controlled trials(RCTs)evaluating the safety and efficacy of CryoMSCs from various tissue sources in treating patients with heart disease.A subgroup analysis was performed based on MSC source and post-thaw cell viability to determine treatment effects across different CryoMSCs sources and viability status.Weighted mean differences(WMDs)and odds ratios were calculated to measure changes in the estimated treatment effects.All statistical analyses were performed using RevMan version 5.4.1 software.RESULTS Seven RCTs(285 patients)met the eligibility criteria for inclusion in the metaanalysis.During short-term follow-up,^(Cryo)MSCs demonstrated a significant 2.11%improvement in left ventricular ejection fraction(LVEF)[WMD(95%CI)=2.11(0.66-3.56),P=0.004,I2=1%],with umbilical cord-derived MSCs being the most effective cell type.However,the significant effect on LVEF was not sustained over the 12 months of follow-up.Subgroup analysis demonstrated a substantial 3.44%improvement in LVEF[WMD(95%CI)=3.44(1.46-5.43),P=0.0007,I2=0%]when using MSCs with post-thaw viability exceeding 80%.There was no statistically significant difference in the frequency of major cardiac adverse events observed in rehospitalization or mortality in patients treated with ^(Cryo)MSCs vs the control group.CONCLUSION ^(Cryo)MSCs are a promising option for heart failure patients,particularly considering the current treatment options for cardiovascular diseases.Our data suggest that ^(Cryo)MSCs could be a viable alternative or complementary treatment to the current options,potentially improving patient outcomes.
文摘BACKGROUND Iron overload cardiomyopathy is a significant cause of morbidity and mortality in transfusion-dependent thalassemia patients.Standard iron chelation therapy is less efficient in alleviating iron accumulation in many organs,especially when iron enters the cells via specific calcium channels.AIM To validate our hypothesis that adding amlodipine to the iron chelation regimen is more efficient in alleviating myocardial iron overload.METHODS Five databases,including PubMed,Cochrane Library,Embase,ScienceDirect,and ClinicalTrials.gov,were systematically searched,and three randomized controlled trials involving 144 pediatric patients with transfusion-dependent thalassemia were included in our meta-analysis based on the predefined eligibility criteria.The quality of the included studies was assessed based on the Cochrane collab-oration tool for bias assessment.The primary outcome assessed was myocardial-T2 and myocardial iron concentration,while the secondary results showed serum ferritin level,liver iron concentration,and treatment adverse outcomes.Weighted mean difference and odds ratio were calculated to measure the changes in the estimated treatment effects.RESULTS During the follow-up period,Amlodipine treatment significantly improved cardiac T2 by 2.79 ms compared to the control group[95%confidence interval(CI):0.34-5.24,P=0.03,I2=0%].Additionally,a significant reduction of 0.31 in myocardial iron concentration was observed with amlodipine treatment compared to the control group[95%CI:-0.38-(-0.25),P<0.00001,I2=0%].Liver iron concentration was slightly lower in the amlodipine group by-0.04 mg/g,but this difference was not statistically significant(95%CI:-0.33-0.24,P=0.77,I2=0%).Amlodipine also showed a non-significant trend toward a reduction in serum ferritin levels(-328.86 ng/mL,95%CI:-1212.34-554.62,P=0.47,I2=90%).Regarding safety,there were no significant differences between the groups in the incidence of gastrointestinal upset,hypotension,or lower limb edema.CONCLUSION Amlodipine with iron chelation therapy significantly improved cardiac parameters,including cardiac-T2 and myocardial iron,in patients with transfusion-dependent thalassemia without causing significant adverse events but enhancing the efficacy of iron chelation therapy.
