Mesenchymal stem cells(MSCs)experience substantial viability issues in the stroke infarct region,limiting their therapeutic efficacy and clinical translation.High levels of deadly reactive oxygen radicals(ROS)and proi...Mesenchymal stem cells(MSCs)experience substantial viability issues in the stroke infarct region,limiting their therapeutic efficacy and clinical translation.High levels of deadly reactive oxygen radicals(ROS)and proinflammatory cytokines(PC)in the infarct milieu kill transplanted MSCs,whereas low levels of beneficial ROS and PC stimulate and improve engrafted MSCs’viability.Based on the intrinsic hormesis effects in cellular biology,we built a microglia-inspired MSC bioengineering system to transform detrimental high-level ROS and PC into vitality enhancers for strengthening MSC therapy.This system is achieved by bioorthogonally arming metabolic glycoengineered MSCs with microglial membrane-coated nanoparticles and an antioxidative extracellular protective layer.In this system,extracellular ROSscavenging and PC-absorbing layers effectively buffer the deleterious effects and establish a microlivable niche at the level of a single MSC for transplantation.Meanwhile,the infarct’s inanimate milieu is transformed at the tissue level into a new living niche to facilitate healing.The engineered MSCs achieved viability five times higher than natural MSCs at seven days after transplantation and exhibited a superior therapeutic effect for stroke recovery up to 28 days.This vitality-augmented system demonstrates the potential to accelerate the clinical translation of MSC treatment and boost stroke recovery.展开更多
Ligusticum sinense cv.Chuanxiong(L.Chuanxiong),one of the widely used traditional Chinese medicines(TCM),is currently facing the problem of excessive cadmium(Cd)content.This problem has significantly affected the qual...Ligusticum sinense cv.Chuanxiong(L.Chuanxiong),one of the widely used traditional Chinese medicines(TCM),is currently facing the problem of excessive cadmium(Cd)content.This problem has significantly affected the quality and safety of L.Chuanxiong and become a vital factor restricting its clinical application and international trade development.Currently,to solve the problem of excessive Cd,it is essential to research the response mechanisms of L.Chuanxiong to Cd stress.However,there are few reports on its physiological and biochemical responses under Cd stress.In this study,we conducted the hydroponic experiment under 25μM Cd stress,based on the Cd content of the genuine producing areas soil.The results showed that 25μM Cd stress not only had no significant inhibitory effect on the growth of L.Chuanxiong seedlings but also significantly increased the chlorophyll a content(11.79%)and root activity(51.82%)compared with that of the control,which might be a hormesis effect.Further results showed that the absorption and assimilation of NH_(4)^(+)increased in seedlings under 25μM Cd stress,which was associated with high photosynthetic pigments.Here,we initially hypothesized and confirmed that Cd exceedance in the root system of L.Chuanxiong was due to the thickening of the root cell wall,changes in the content of the cell wall components,and chelation of Cd by GSH.There was an increase in cell wall thickness(57.64%)and a significant increase in cellulose(25.48%)content of roots under 25μM Cd stress.In addition,L.Chuanxiong reduced oxidative stress caused by 25μM Cd stress mainly through the GSH/GSSG cycle.Among them,GSH-Px(48.26%)and GR(42.64%)activities were significantly increased,thereby maintaining a high GSH/GSSG ratio.This study preliminarily reveals the response of L.Chuanxiong to Cd stress and the mechanism of Cd enrichment.It provides a theoretical basis for solving the problem of Cd excessive in L.Chuanxiong.展开更多
基金supported by National Natural Science Foundation of China(Nos.92068110,81973272 and 92068111)Shanghai Science and Technology Committee(Nos.20JC1411800,and 23S41900100,China)+4 种基金Programs of Shanghai Academic/Technology Research Leader(Nos.21XD1400200 and 21XD1422200,China)Innovation Program of Shanghai Municipal Education Commission(2023ZKZD21,China)the fund of Research Grant for Health Science and Technology of Shanghai Municipal Commission of Health Committee(No.20214Y0268,China)Science and Technology Development Fund of Shanghai Pudong New Area(No.PKJ2020-Y49,China)the Project of Key Medical Specialty and Treatment Center of Pudong Hospital of Fudan University(No.Zdzk2020-15,China)。
文摘Mesenchymal stem cells(MSCs)experience substantial viability issues in the stroke infarct region,limiting their therapeutic efficacy and clinical translation.High levels of deadly reactive oxygen radicals(ROS)and proinflammatory cytokines(PC)in the infarct milieu kill transplanted MSCs,whereas low levels of beneficial ROS and PC stimulate and improve engrafted MSCs’viability.Based on the intrinsic hormesis effects in cellular biology,we built a microglia-inspired MSC bioengineering system to transform detrimental high-level ROS and PC into vitality enhancers for strengthening MSC therapy.This system is achieved by bioorthogonally arming metabolic glycoengineered MSCs with microglial membrane-coated nanoparticles and an antioxidative extracellular protective layer.In this system,extracellular ROSscavenging and PC-absorbing layers effectively buffer the deleterious effects and establish a microlivable niche at the level of a single MSC for transplantation.Meanwhile,the infarct’s inanimate milieu is transformed at the tissue level into a new living niche to facilitate healing.The engineered MSCs achieved viability five times higher than natural MSCs at seven days after transplantation and exhibited a superior therapeutic effect for stroke recovery up to 28 days.This vitality-augmented system demonstrates the potential to accelerate the clinical translation of MSC treatment and boost stroke recovery.
基金supported by Natural Science Foundation of Sichuan Province(2024NSFSC1832)The National Natural Science Foundation of China(grant numbers 82404796,82373986)+2 种基金China Postdoctoral Science Foundation(grant number 2023M730381)Key R&D Projects of Sichuan Provincial Department of Science and Technology(grant numbers 22ZDYF1861)Natural Science Foundation of Sichuan Province(2024NSFSC1831).
文摘Ligusticum sinense cv.Chuanxiong(L.Chuanxiong),one of the widely used traditional Chinese medicines(TCM),is currently facing the problem of excessive cadmium(Cd)content.This problem has significantly affected the quality and safety of L.Chuanxiong and become a vital factor restricting its clinical application and international trade development.Currently,to solve the problem of excessive Cd,it is essential to research the response mechanisms of L.Chuanxiong to Cd stress.However,there are few reports on its physiological and biochemical responses under Cd stress.In this study,we conducted the hydroponic experiment under 25μM Cd stress,based on the Cd content of the genuine producing areas soil.The results showed that 25μM Cd stress not only had no significant inhibitory effect on the growth of L.Chuanxiong seedlings but also significantly increased the chlorophyll a content(11.79%)and root activity(51.82%)compared with that of the control,which might be a hormesis effect.Further results showed that the absorption and assimilation of NH_(4)^(+)increased in seedlings under 25μM Cd stress,which was associated with high photosynthetic pigments.Here,we initially hypothesized and confirmed that Cd exceedance in the root system of L.Chuanxiong was due to the thickening of the root cell wall,changes in the content of the cell wall components,and chelation of Cd by GSH.There was an increase in cell wall thickness(57.64%)and a significant increase in cellulose(25.48%)content of roots under 25μM Cd stress.In addition,L.Chuanxiong reduced oxidative stress caused by 25μM Cd stress mainly through the GSH/GSSG cycle.Among them,GSH-Px(48.26%)and GR(42.64%)activities were significantly increased,thereby maintaining a high GSH/GSSG ratio.This study preliminarily reveals the response of L.Chuanxiong to Cd stress and the mechanism of Cd enrichment.It provides a theoretical basis for solving the problem of Cd excessive in L.Chuanxiong.
