BACKGROUND Osteoarthritis(OA),a chronic age-related disease characterized by the slowly progressive destruction of articular cartilage,is one of the leading causes of disability.As a new strategy for treatment of OA,m...BACKGROUND Osteoarthritis(OA),a chronic age-related disease characterized by the slowly progressive destruction of articular cartilage,is one of the leading causes of disability.As a new strategy for treatment of OA,mesenchymal stem cells(MSCs)have the potential for articular cartilage regeneration.Meanwhile,thrombospondin 2(TSP2)promotes the chondrogenic differentiation of MSCs.AIM To investigate whether TSP2 induces chondrogenic differentiation of human adipose-derived MSCs(hADMSCs)and potentiates the therapeutic effects of hADMSCs in OA rabbits.METHODS We investigated the chondrogenic potential of TSP2 in hADMSCs by analyzing the expression of chondrogenic markers as well as NOTCH signaling genes in normal and TSP2 small interfering RNA(siRNA)-treated stem cells.Anterior cruciate ligament transection surgery was performed in male New Zealand white rabbits,and 8 wk later,hADMSCs(1.7×10^6 or 1.7×10^7 cells)were injected into the injured knees alone or in combination with intra-articular injection of TSP2(100 ng/knee)at 2-d intervals.OA progression was monitored by gross,radiological,and histological examinations.RESULTS In hADMSC culture,treatment with TSP2 increased the expression of chondrogenic markers(SOX9 and collagen Ⅱ)as well as NOTCH signaling genes(JAGGED1 and NOTCH3),which were inhibited by TSP2 siRNA treatment.In vivo,OA rabbits treated with hADMSCs or TSP2 alone exhibited lower degree of cartilage degeneration,osteophyte formation,and extracellular matrix loss 8 wk after cell transplantation.Notably,such cartilage damage was further alleviated by the combination of hADMSCs and TSP2.In addition,synovial inflammatory cytokines,especially tumor-necrosis factor-α,markedly decreased following the combination treatment.CONCLUSION The results indicate that TSP2 enhances chondrogenic differentiation of hADMSCs via JAGGED1/NOTCH3 signaling,and that combination therapy with hADMSCs and TSP2 exerts synergistic effects in the cartilage regeneration of OA joints.展开更多
Mesenchymal stem cells(MSCs)derived from human embryonic stem cells(hESCs)have significant potential for cell-mediated bone regeneration.Our recent study revealed that inhibiting the epigenetic regulator EZH2 plays a ...Mesenchymal stem cells(MSCs)derived from human embryonic stem cells(hESCs)have significant potential for cell-mediated bone regeneration.Our recent study revealed that inhibiting the epigenetic regulator EZH2 plays a key role in promoting the mesodermal differentiation of hESCs.In this study,an epigenome-wide analysis of hESCs and MSCs revealed that growth differentiation factor 6(GDF6),which is involved in bone formation,was the most upregulated gene associated with MSCs compared to hESCs.Furthermore,we identified GDF6 as a repressive target of EZH2 and found that ectopic GDF6 selectively promoted hESC differentiation towards the mesodermal lineage and enriched the MSC population.Our results provide molecular insights governing the mesenchymal commitment of hESCs and identify an inducing factor that offers strong promise for the future of regenerative medicine.展开更多
The ongoing outbreak of coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2 has become a sudden public emergency of international concern and seriously threatens milli...The ongoing outbreak of coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2 has become a sudden public emergency of international concern and seriously threatens millions of people’s life health.Two current studies have indicated a favorable role for mesenchymal stem/stromal cells(MSCs)in clinical remission of COVID-19 associated pulmonary diseases,yet the systematical elaboration of the therapeutics and underlying mechanism is far from satisfaction.In the present review,we summarize the therapeutic potential of MSCs in COVID-19 associated pulmonary diseases such as pneumonia induced acute lung injury,acute respiratory distress syndrome,and pulmonary fibrosis.Furthermore,we review the underlying mechanism of MSCs including direct-and trans-differentiation,autocrine and paracrine anti-inflammatory effects,homing,and neovascularization,as well as constitutive microenvironment.Finally,we discuss the prospects and supervision of MSC-based cytotherapy for COVID-19 management before large-scale application in clinical practice.Collectively,this review supplies overwhelming new references for understanding the landscapes of MSCs in the remission of COVID-19 associated pulmonary diseases.展开更多
This study reports an increase in power generation of a MFC （microbial fuel cell） by the addition of Korean ginseng （Panax ginseng）. It was noted that the use of ginseng enhances the microbial anaerobic degradatio...This study reports an increase in power generation of a MFC （microbial fuel cell） by the addition of Korean ginseng （Panax ginseng）. It was noted that the use of ginseng enhances the microbial anaerobic degradation of cellobiose, a disaccharide that was used as a substrate in the anode chamber of the MFC. The power output of the MFC where ginseng was added showed noticeable enhancement compared to the control MFC. The increase slowly ramped at the initial days and became appreciably higher after the 11th day of incubation in an experiment set up for 16 days duration. It is attributed that the ginseng increases the CO2 production by accelerating the fermentation process. Decrease in CH4/CO2 ratio was observed also due to decrease in methane production per digested cellobiose, the proton donor in the current study. Four ring steroid-like structural moiety Ginsenoside of Panax ginseng seemed to play a beneficial role in the electron transfer from ceilobiose to the anode, perhaps by rendering easier electron transfer due to favorable energy level alignments.展开更多
Oxidative stress is a hallmark of secondary injury associated with spinal cord injury.Identifying stable and specific oxidative biomarkers is of important significance for studying spinal cord injury-associated second...Oxidative stress is a hallmark of secondary injury associated with spinal cord injury.Identifying stable and specific oxidative biomarkers is of important significance for studying spinal cord injury-associated secondary injury.Mature erythrocytes do not contain nuclei and mitochondria and cannot be transcribed and translated.Therefore, mature erythrocytes are highly sensitive to oxidative stress and may become a valuable biomarker.In the present study, we revealed the proteome dynamics of protein expression in erythrocytes of beagle dogs in the acute and subacute phases of spinal cord injury using mass spectrometry-based approaches.We found 26 proteins that were differentially expressed in the acute(0–3 days) and subacute(7–21 days) phases of spinal cord injury.Bioinformatics analysis revealed that these differentially expressed proteins were involved in glutathione metabolism, lipid metabolism, and pentose phosphate and other oxidative stress pathways.Western blot assays validated the differential expression of glutathione synthetase, transaldolase, and myeloperoxidase.This result was consistent with mass spectrometry results, suggesting that erythrocytes can be used as a novel sample source of biological markers of oxidative stress in spinal cord injury.Glutathione synthetase, transaldolase, and myeloperoxidase sourced from erythrocytes are potential biomarkers of oxidative stress after spinal cord injury.This study was approved by the Experimental Animal Centre of Ningxia Medical University, China(approval No.2017-073) on February 13, 2017.展开更多
Aging is a degenerative process that leads to tissue dysfunction and death.Embryonic stem cells(ESCs)have great therapeutic potential for age-related diseases due to their capacity for self-renewal and plasticity.Howe...Aging is a degenerative process that leads to tissue dysfunction and death.Embryonic stem cells(ESCs)have great therapeutic potential for age-related diseases due to their capacity for self-renewal and plasticity.However,the use of ESCs in clinical treatment is limited by immune rejection,tumourigenicity and ethical issues.ESC-derived extracellular vesicles(EVs)may provide therapeutic effects that are comparable to those of ESCs while avoiding unwanted effects.Here,we fully evaluate the role of ESC-EVs in rejuvenation in vitro and in vivo.Using RNA sequencing(RNA-Seq)and microRNA sequencing(miRNA-Seq)screening,we found that miR-15b-5p and miR-290a-5p were highly enriched in ESC-EVs,and induced rejuvenation by silencing the Ccn2-mediated AKT/mTOR pathway.These results demonstrate that miR-15b-5p and miR-290a-5p function as potent activators of rejuvenation mediated by ESC-EVs.The rejuvenating effect of ESC-EVs was further investigated in vivo by injection into aged mice.The results showed that ESC-EVs successfully ameliorated the pathological age-related phenotypes and rescued the transcriptome profile of aged mice.Our findings demonstrate that ESC-EVs treatment can rejuvenate senescence both in vitro and in vivo and suggest the therapeutic potential of ESC-EVs as a novel cell-free alternative to ESCs for age-related diseases.展开更多
基金Supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT to Y.B.K.,No.2017R1A2A2A05069417
文摘BACKGROUND Osteoarthritis(OA),a chronic age-related disease characterized by the slowly progressive destruction of articular cartilage,is one of the leading causes of disability.As a new strategy for treatment of OA,mesenchymal stem cells(MSCs)have the potential for articular cartilage regeneration.Meanwhile,thrombospondin 2(TSP2)promotes the chondrogenic differentiation of MSCs.AIM To investigate whether TSP2 induces chondrogenic differentiation of human adipose-derived MSCs(hADMSCs)and potentiates the therapeutic effects of hADMSCs in OA rabbits.METHODS We investigated the chondrogenic potential of TSP2 in hADMSCs by analyzing the expression of chondrogenic markers as well as NOTCH signaling genes in normal and TSP2 small interfering RNA(siRNA)-treated stem cells.Anterior cruciate ligament transection surgery was performed in male New Zealand white rabbits,and 8 wk later,hADMSCs(1.7×10^6 or 1.7×10^7 cells)were injected into the injured knees alone or in combination with intra-articular injection of TSP2(100 ng/knee)at 2-d intervals.OA progression was monitored by gross,radiological,and histological examinations.RESULTS In hADMSC culture,treatment with TSP2 increased the expression of chondrogenic markers(SOX9 and collagen Ⅱ)as well as NOTCH signaling genes(JAGGED1 and NOTCH3),which were inhibited by TSP2 siRNA treatment.In vivo,OA rabbits treated with hADMSCs or TSP2 alone exhibited lower degree of cartilage degeneration,osteophyte formation,and extracellular matrix loss 8 wk after cell transplantation.Notably,such cartilage damage was further alleviated by the combination of hADMSCs and TSP2.In addition,synovial inflammatory cytokines,especially tumor-necrosis factor-α,markedly decreased following the combination treatment.CONCLUSION The results indicate that TSP2 enhances chondrogenic differentiation of hADMSCs via JAGGED1/NOTCH3 signaling,and that combination therapy with hADMSCs and TSP2 exerts synergistic effects in the cartilage regeneration of OA joints.
基金the NIH/NIDCR grant R01DE16513(C.Y.W.),NIH/NIDCR K08DE024603(C.H.)the Shapiro family Charitable Funds.The Flow cytometry was performed in the UCLA Flow Cytometry Core Facility that is supported by NIH awards P30CA016042 and 5P30AI028697.
文摘Mesenchymal stem cells(MSCs)derived from human embryonic stem cells(hESCs)have significant potential for cell-mediated bone regeneration.Our recent study revealed that inhibiting the epigenetic regulator EZH2 plays a key role in promoting the mesodermal differentiation of hESCs.In this study,an epigenome-wide analysis of hESCs and MSCs revealed that growth differentiation factor 6(GDF6),which is involved in bone formation,was the most upregulated gene associated with MSCs compared to hESCs.Furthermore,we identified GDF6 as a repressive target of EZH2 and found that ectopic GDF6 selectively promoted hESC differentiation towards the mesodermal lineage and enriched the MSC population.Our results provide molecular insights governing the mesenchymal commitment of hESCs and identify an inducing factor that offers strong promise for the future of regenerative medicine.
基金Supported by Shandong Provincial Natural Science Foundation,No.ZR2020QC097China Postdoctoral Science Foundation,No.2019M661033+7 种基金Jiangxi Key New Product Incubation Program Funded by Technical Innovation Guidance Program of Shangrao city,No.2020G002Tianjin Science and Technology Project for Overseas Students,No.JH-20180070802Natural Science Foundation of Tianjin,No.19JCQNJC12500Major Project of Fundamental Research Funds of the Central Public Welfare Scientific Research Institutes of the Chinese Academy of Medical Sciences,No.2018PT31048Major Project of Fundamental Research Funds of the Central Public Welfare Scientific Research Institutes of the Chinese Academy of Medical Sciences,No.2019PT310013National Science and Technology Major Projects of China for“Major New Drugs Innovation and Development”,No.2014ZX09508002-003National Natural Science Foundation of China,No.81330015and Science and Technology Project of Tianjin,No.17ZXSCSY00030.
文摘The ongoing outbreak of coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2 has become a sudden public emergency of international concern and seriously threatens millions of people’s life health.Two current studies have indicated a favorable role for mesenchymal stem/stromal cells(MSCs)in clinical remission of COVID-19 associated pulmonary diseases,yet the systematical elaboration of the therapeutics and underlying mechanism is far from satisfaction.In the present review,we summarize the therapeutic potential of MSCs in COVID-19 associated pulmonary diseases such as pneumonia induced acute lung injury,acute respiratory distress syndrome,and pulmonary fibrosis.Furthermore,we review the underlying mechanism of MSCs including direct-and trans-differentiation,autocrine and paracrine anti-inflammatory effects,homing,and neovascularization,as well as constitutive microenvironment.Finally,we discuss the prospects and supervision of MSC-based cytotherapy for COVID-19 management before large-scale application in clinical practice.Collectively,this review supplies overwhelming new references for understanding the landscapes of MSCs in the remission of COVID-19 associated pulmonary diseases.
文摘This study reports an increase in power generation of a MFC （microbial fuel cell） by the addition of Korean ginseng （Panax ginseng）. It was noted that the use of ginseng enhances the microbial anaerobic degradation of cellobiose, a disaccharide that was used as a substrate in the anode chamber of the MFC. The power output of the MFC where ginseng was added showed noticeable enhancement compared to the control MFC. The increase slowly ramped at the initial days and became appreciably higher after the 11th day of incubation in an experiment set up for 16 days duration. It is attributed that the ginseng increases the CO2 production by accelerating the fermentation process. Decrease in CH4/CO2 ratio was observed also due to decrease in methane production per digested cellobiose, the proton donor in the current study. Four ring steroid-like structural moiety Ginsenoside of Panax ginseng seemed to play a beneficial role in the electron transfer from ceilobiose to the anode, perhaps by rendering easier electron transfer due to favorable energy level alignments.
基金supported by the Key Research Projects of the Ningxia Hui Autonomous Region of China, No.2018 BCG01002(to HCX)the Plan of Postgraduate Education Innovation, Discipline Construction Project of Ningxia, China(2017), No.YXW2017014(to LJZ)。
文摘Oxidative stress is a hallmark of secondary injury associated with spinal cord injury.Identifying stable and specific oxidative biomarkers is of important significance for studying spinal cord injury-associated secondary injury.Mature erythrocytes do not contain nuclei and mitochondria and cannot be transcribed and translated.Therefore, mature erythrocytes are highly sensitive to oxidative stress and may become a valuable biomarker.In the present study, we revealed the proteome dynamics of protein expression in erythrocytes of beagle dogs in the acute and subacute phases of spinal cord injury using mass spectrometry-based approaches.We found 26 proteins that were differentially expressed in the acute(0–3 days) and subacute(7–21 days) phases of spinal cord injury.Bioinformatics analysis revealed that these differentially expressed proteins were involved in glutathione metabolism, lipid metabolism, and pentose phosphate and other oxidative stress pathways.Western blot assays validated the differential expression of glutathione synthetase, transaldolase, and myeloperoxidase.This result was consistent with mass spectrometry results, suggesting that erythrocytes can be used as a novel sample source of biological markers of oxidative stress in spinal cord injury.Glutathione synthetase, transaldolase, and myeloperoxidase sourced from erythrocytes are potential biomarkers of oxidative stress after spinal cord injury.This study was approved by the Experimental Animal Centre of Ningxia Medical University, China(approval No.2017-073) on February 13, 2017.
基金the National Natural Science Foundation of China(32070860)Tianjin Natural Science Foundation(22JCYBJC01220)National Key R&D Plan(2021YFA1101002).
文摘Aging is a degenerative process that leads to tissue dysfunction and death.Embryonic stem cells(ESCs)have great therapeutic potential for age-related diseases due to their capacity for self-renewal and plasticity.However,the use of ESCs in clinical treatment is limited by immune rejection,tumourigenicity and ethical issues.ESC-derived extracellular vesicles(EVs)may provide therapeutic effects that are comparable to those of ESCs while avoiding unwanted effects.Here,we fully evaluate the role of ESC-EVs in rejuvenation in vitro and in vivo.Using RNA sequencing(RNA-Seq)and microRNA sequencing(miRNA-Seq)screening,we found that miR-15b-5p and miR-290a-5p were highly enriched in ESC-EVs,and induced rejuvenation by silencing the Ccn2-mediated AKT/mTOR pathway.These results demonstrate that miR-15b-5p and miR-290a-5p function as potent activators of rejuvenation mediated by ESC-EVs.The rejuvenating effect of ESC-EVs was further investigated in vivo by injection into aged mice.The results showed that ESC-EVs successfully ameliorated the pathological age-related phenotypes and rescued the transcriptome profile of aged mice.Our findings demonstrate that ESC-EVs treatment can rejuvenate senescence both in vitro and in vivo and suggest the therapeutic potential of ESC-EVs as a novel cell-free alternative to ESCs for age-related diseases.
