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Human umbilical cord-derived mesenchymal stem cell therapy in patients with COVID-19:a phase 1 clinical trial

Signal Transduction and Targeted Therapy 2020年第1期5卷 1010-1016页

作者： Fanping Meng Ruonan Xu Siyu Wang Zhe Xu Chao Zhang Yuanyuan Li Tao Yang Lei Shi Junliang Fu Tianjun Jiang Lei Huang Peng Zhao Xin Yuan Xing Fan Ji-Yuan Zhang Jinwen Song Dawei Zhang Yanmei Jiao Limin Liu Chunbao Zhou markus maeurer Alimuddin Zumla Ming Shi Fu-Sheng Wang Department of Infectious Diseases Fifth Medical Center of Chinese PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijingChina Immunotherapy Programme Champalimaud Centre for the UnknownLisbonPortugal I Med Clinic University of MainzMainzGermany Department of Infection Division of Infection and ImmunityUniversity College LondonLondonUK National Institute for Health Research Biomedical Research Centre University College London Hospitals NHS Foundation TrustLondonUK

No effective drug treatments are available for coronavirus disease 2019(COVID-19).Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage,death,or long-term functional disability in survivors require clinical *** performed a parallel assigned controlled,non-randomized,phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells(UC-MSCs)infusions in the treatment of patients with moderate and severe COVID-19 pulmonary *** study enrolled 18 hospitalized patients with COVID-19(n=9 for each group).The treatment group received three cycles of intravenous infusion of UC-MSCs(3×107 cells per infusion)on days 0,3,and *** groups received standard COVID-treatment *** events,duration of clinical symptoms,laboratory parameters,length of hospitalization,serial chest computed tomography(CT)images,the PaO2/FiO2 ratio,dynamics of cytokines,and IgG and IgM anti-SARS-CoV-2 antibodies were *** serious UC-MSCs infusion-associated adverse events were *** patients receiving UC-MSCs developed transient facial flushing and fever,and one patient developed transient hypoxia at 12 h post UC-MSCs *** ventilation was required in one patient in the treatment group compared with four in the control *** patients recovered and were *** data show that intravenous UC-MSCs infusion in patients with moderate and severe COVID-19 is safe and well *** 2/3 randomized,controlled,double-blinded trials with long-term follow-up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long-term treatment outcomes in patients with serious COVID-19.

关键词： patients infusion clinical

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Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients:a randomized,double-blind,placebo-controlled phase 2 trial

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Signal Transduction and Targeted Therapy 2021年第3期6卷 888-896页

作者： Lei Shi Hai Huang Xuechun Lu Xiaoyan Yan Xiaojing Jiang Ruonan Xu Siyu Wang Chao Zhang Xin Yuan Zhe Xu Lei Huang Jun-Liang Fu Yuanyuan Li Yu Zhang Wei-Qi Yao Tianyi Liu Jinwen Song Liangliang Sun Fan Yang Xin Zhang Bo Zhang Ming Shi Fanping Meng Yanning Song Yongpei Yu Jiqiu Wen Qi Li Qing Mao markus maeurer Alimuddin Zumla Chen Yao Wei-Fen Xie Fu-Sheng Wang Department of Infectious Diseases Fifth Medical Center of Chinese PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijingChina Wuhan Huoshenshan Hospital WuhanChina Department of Respiratory Changzheng HospitalSecond Military Medical UniversityShanghaiChina Optical Valley Branch of Maternal and Child Hospital of Hubei Province WuhanChina Department of Hematology Second Medical Center of Chinese PLA General HospitalBeijingChina Peking University Clinical Research Institute Peking University First HospitalBeijingChina Department of Infectious Disease General Hospital of Central Theater CommandWuhanChina VCANBIO Cell&Gene Engineering Corp. LtdTianjinChina National Industrial Base for Stem Cell Engineering Products TianjinChina Department of Hematology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Key Laboratory of Cancer Center Fifth Medical Center of Chinese PLA General HospitalBeijingChina Department of Endocrinology and Metabolism Changzheng HospitalSecond Military Medical UniversityShanghaiChina Department of Radiology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Nursing Department Fifth Medical Center of Chinese PLA General HospitalBeijingChina immunotherapy Programme Champalimaud Centre for the UnknownLisbonPortugal Med Clinic University of MainzMainzGermany Center for Clinical Microbiology Division of Infection and ImmunityUniversity College Londonand UCL Hospitals NIHR Biomedical Research CentreLondonUK Department of Gastroenterology Changzheng HospitalSecond Military Medical UniversityShanghaiChina

Treatment of severe Coronavirus Disease 2019(COVID-19)is *** performed a phase 2 trial to assess the efficacy andsafety of human umbilical cord-mesenchymal stem cells(UC-MScs)to treat severe coViD-19 patients with lung damage,based onour phase 1 *** this randomized,double-blind,and placebo-controlled trial,we recruited 101 severe coVID-19 patients withlung *** were randomly assigned at a 2:1 ratio to receive either UC-MSCs(4×10^(7)cells per infusion)or placebo on day 0,3,and *** primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day *** imagingoutcomes,6-minute walk test(6-MWT),maximum vital capacity,diffusing capacity,and adverse events were recorded and *** all,100 COVID-19 patients were finally received either UC-MSCs in=65)or placebo(n=35).UC-MSCs administrationexerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo(the mediandifference was-13.31%,95%Cl-29.14%,2.13%,P=0.08).UC-MSCs significanty reduced the proportions of solid componentlesion volume compared with the placebo(median difference:-15.45%;95%CI-30.82%,-0.39%;P=0.043).The 6-MWT showedan increased distance in patients treated with UC-MSCs(difference:27.00 m;95%CI 0.00,57.00;P=0.057).The incidence of adverseevents was similar in the two *** results suggest that UC-MSCs treatment is a safe and potentially effective therapeuticapproach for COVID-19 patients with lung damage.A phase 3 trial is required to evaluate effects on reducing mortality andpreventing long-term pulmonary disability.

关键词： damage patients double

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Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： Carina Hromada Patrick Heimel markus Kerbl LászlóGál Sylvia Nürnberger Barbara Schaedl James Ferguson Nicole Swiadek Xavier Monforte Johannes C.Heinzel Antal Nógrádi Andreas H.Teuschl-Woller David Hercher Department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria Ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria Department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria Department of Hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

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Extending harmonized national forest inventory herb layer vegetation cover observations to derive comprehensive biomass estimates

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Forest Ecosystems 2020年第2期7卷 201-214页

作者： markus Didion Forest Resources and Management Swiss Federal Research Institute WSLZürcherstrasse 1118903 BirmensdorfSwitzerland

Background:National forest inventories(NFI)have a long history providing data to obtain nationally representative and accurate estimates of growing ***,in most NFIs additional data are collected to provide information on a range of forest ecosystem functions such as biodiversity,habitat,nutrient and carbon *** important driver of nutrient and C cycling is decomposing biomass produced by forest *** studies have demonstrated that understory vegetation,particularly annual plant litter of the herb layer can contribute significantly to nutrient and C cycling in forests.A methodology to obtain comprehensive,consistent and nationally representative estimates of herb layer biomass on NFI plots could provide added value to NFIs by complementing the existing strong basis of biomass estimates of the tree and tall shrub *** study was based on data from the Swiss NFI since it covers a large environmental gradient,which extends its applicability to other ***:Based on data from 405 measurements in nine forest strata,a parsimonious model formulation was identified to predict total and non-ligneous herb layer *** herb layer cover,elevation was the main statistically significant explanatory variable for *** regression models accurately predicted biomass based on absolute percentage cover(for total biomass:R2=0.65,p=0;for non-ligneous biomass:R2=0.76;p=0)as well as on cover classes(R2=0.83;p=0;and R2=0.79,p=0),which are typically used in *** good performance was supported by the verification with data from repeated *** the 2 nd,3 rd,and 4 th Swiss NFI estimates of non-ligneous above-ground herb layer biomass 586.6±7.7,575.2±7.6,and 586.7±7.9 kg·ha-1,***:The study presents a methodology to obtain herb layer biomass estimates based on a harmonized and standardized attribute available in many *** result of this study was a parsimonious model requiring only elevation data of sample plo

关键词： Model ENFIN Switzerland Ground layer Herbs Ferns Grasses Shrubs Carbon Litter

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Robustness evaluation of cutting tool maintenance planning for soft ground tunneling projects

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Underground Space 2018年第1期3卷 72-85页

作者： Alena Conrads markus Scheffer markus Konig markus Thewes Inastitute of Tunneling cand Construction Management Ruhr-Universitat BochunGermany Chair of Computing in Engineering Ruhr-Universitit BochunGermany

Tunnel boring machines require extensive maintenance and inspection effort to provide a high *** cutting tools of the cutting wheel must be changed timely upon reaching a critical *** one possible maintenance strategy is to change tools only when it is absolutely necessary,tools can also be changed preventively to avoid further *** different maintenance strategies inﬂuence the maintenance duration and the overall project ***,determine downtime related to a particular mainte-nance strategy is still a challenging *** paper shows an analysis of the robustness to achieve the planned project performance of a maintenance strategy considering uncertainties of wear behavior of the cutting tools.A simulation based analysis is presented,imple-menting an empirical wear prediction *** strategies of maintenance planning are compared by performing a parameter vari-ation study including Monte-Carlo *** maintenance costs are calculated and evaluated with respect to their ***,an improved and robust maintenance strategy has been determined.

关键词： Mechanized tunneling,Maintenance Wear of cutting tools Process simulation Robustness Uncertainty modeling

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Nacre replication: down to the bottom

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Science Bulletin 2016年第21期61卷 1662-1664页

作者： markus Antonietti Max Planck Institute for Colloids and Interfaces Potsdam-Golm Science ParkAm Muhlenberg 1144776 PotsdamGermany

Organisms always have limited options when constructing their hard tissues. Therefore, they appeal to the combination of soft and hard materials with structural designs at multiscale , creating a performance well beyond the ones of the single components. Nacre, the inner shell of some mollusks, is famous for its extraordinary mechanical and optical property through optimized hierarchical structural design with thin aragonite platelets （- 95 wt%） glued together by organic components （- 5 wt% of chitin and proteins）.

关键词： down to the bottomNacre replication

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Polymer coated nanowire network promises self-healing and superstretchable conductors

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Science China Chemistry 2019年第2期62卷 151-152页

作者： markus Antonietti Max Planck Institute for Colloids and Interfaces Potsdam-Golm Science Park

The generation of stretchable conductors is a mandatory precondition for the next-generation electronic devices ineluding flexible,wearable electronics,smart skins and bioinspired devices [1-4].This new class of electronic materials takes up external mechanical deformations and maintains structural integrity and electronic performance throughout bending,folding and stretching *** intense efforts have been devoted to the construction of stretchable conductors,large stretchability is still difficult to achieve.

关键词： generation Polymer stretchable

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A 'hot' oil sorbent for fast cleanup of viscous crude-oil spills

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National Science Review 2018年第4期5卷 445-446页

作者： markus Antonietti Max Planck Institute for Colloids and Interfaces

In 2010,the Gulf of Mexico oil spill created the largest environmental ocean accident in *** estimated number of 4.9 million barrels of crude oil were released into the ocean and brought severe damage to the marine ecosystems and fishing,and threatened the health of *** oil cleanup technologies,including skimmers,dispersants and controlled burning,were used to treat the

关键词： hot oil sorbent for fast cleanup of viscous crude-oil spills

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The Effect of Grain Properties for Artificial Bedload Supply

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四川大学学报（工程科学版） 2005年第S1期37卷 30-33页

作者： markus PROMNY Inst.of Hydrosciences Gennan Armed Forces Univ.Munich85577 NeubibergGermany

The German Armed Forces University in Munich has conducted experiments in a laboratory flume to determine the influence of roundness on bed load *** investigations were assigned by the German Federal Institute of Hydrology (BIG),with a focus on incipient motion,transport velocity and the depth of mixing into the riverbed. The results of the experiments show that the transport velocity of angular graim is lower and the critical shear stress for incipient motion is slightly higher than of well-ro...

关键词： bed load supply bed load transport grain properties roundness tracer experiments incipient motion transport velocity

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Supercompressible conductive hydrogels in harsh environments

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Science China Materials 2023年第1期66卷 419-420页

作者： markus Antonietti Department of Colloid Chemistry Max Planck Institute for Colloids and Interfaces14476 PotsdamGermany

Conductive hydrogels are key materials for the further development of flexible and wearable electronics,bioelectronics and soft robotics,due to their soft conformability to the curved surfaces and intelligent response to mechanical stimuli[1-6].The mechanical properties of currently used hydrogels,especially in harsh environments,are far inferior to those of natural tissues,which creates a mechanical contrast and causes the related mechanical failures shortening the lifetime.

关键词： hydrogel compressible curved

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