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Human umbilical cord mesenchymal stem cells for psoriasis:a phase 1/2a,single-arm study

Signal Transduction and Targeted Therapy 2022年第9期7卷 3512-3522页

作者： Lamei Cheng Siqi Wang Cong Peng Xiao Zou Chao Yang Hua Mei Chuang Li Xian Su Na Xiao Qi Ouyang Mi Zhang Qiaolin Wang Yan Luo Minxue Shen Qun Qin Honglin Wang Wu Zhu Guangxiu Lu Ge Lin Yehong Kuang Xiang Chen Institute of Reproductive and Stem Cell Engineering School of Basic Medical ScienceCentral South UniversityChangsha 410031China National Engineering Research Center of Human Stem Cell Changsha 410205China The Department of Dermatology Xiangya HospitalCentral South UniversityChangsha 410008China Hunan Engineering Research Center of Skin Health and Disease Hunan Key Laboratory of Skin Cancer and PsoriasisNational Clinical Research Center for Geriatric Disorders(Xiangya Hospital)Changsha 410008China The Offce of Drug Clinical Trials Institution Xiangya HospitalCentral South UniversityChangsha 410031China precision Research Center for Refractory Diseases Shanghai General HospitalKey Laboratory of Cell Differentiation and Apoptosis of ChineseMinistry of EducationShanghai Jiao Tong University School of MedicineShanghai 200025China Reproductive and Genetic Hospital of CITIC-Xiangya Changsha 410221China

Psoriasis is a common,chronic immune-mediated systemic disease that had no effective and durable *** stem cells(MSCs)have immunomodulatory ***,we performed a phase 1/2a,single-arm clinical trial to evaluate the safety and efficacy of human umbilical cord-derived MSCs(UMSCs)in the treatment of psoriasis and to preliminarily explore the possible *** patients with psoriasis were enrolled and received UMsC *** events,laboratory parameters,PASl,and PGA were *** did not observe obvious side effects during the treatment and 6-month follow-up.A total of 47.1%(8/17)of the psoriasis patients had at least 40%improvement in the PASl score,and 17.6%(3/17)had no sign of disease or minimal disease based on the PGA *** the efficiency was 25%(2/8)for males and 66.7%(6/9)for *** UMSC transplantation(UMSCT),the frequencies of Tregs and CD4^(+)memory T cells were significantly increased,and the frequencies of T helper(Th)17 and CD4^(+)naive T cells were significantly decreased in peripheral blood(PB)of psoriasis *** all responders showed significant increases in Tregs and CD4^(+)memory T cells,and significant decreases in Th17 cells and serum IL-17 level after *** baseline level of Tregs in responders were significantly lower than those in *** conclusion,allogeneic UMSCT is safe and partially effective in psoriasis patients,and level of Tregs may be used as a potent biomarker to predict the clinical efficacy of *** registration Clinical Trials NCT03765957.

关键词： psoriasis infusion phase

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CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors

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cellular & Molecular Immunology 2024年第10期21卷 1089-1108页

作者： Lei Peng Giacomo Sferruzza Luojia Yang Liqun Zhou Sidi Chen Department of Genetics Yale University School of MedicineNew HavenCTUSA System Biology Institute Yale UniversityWest HavenCTUSA Combined Program in the Biological and Biomedical Sciences Yale UniversityNew HavenCTUSA Molecular Cell Biology Geneticsand Development ProgramYale UniversityNew HavenCTUSA Immunobiology Program Yale UniversityNew HavenCTUSA Yale Comprehensive Cancer Center Yale University School of MedicineNew HavenCTUSA Department of Neurosurgery Yale University School of MedicineNew HavenCTUSA Yale Stem Cell Center Yale University School of MedicineNew HavenCTUSA Yale Liver Center Yale University School of MedicineNew HavenCTUSA Yale Center for Biomedical Data Science Yale University School of MedicineNew HavenCTUSA Yale Center for RNA Science and Medicine Yale University School of MedicineNew HavenCTUSA

In the past decade,chimeric antigen receptor(CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers,demonstrating remarkable efficacy in relapsed/refractory hematological malignancies in both pediatric and adult ***-natural killer(CAR-NK)cell complements CAR-T cell therapy by offering several distinct ***-NK cells do not require HLA compatibility and exhibit low safety ***,CAR-NK cells are conducive to“off-the-shelf”therapeutics,providing significant logistic advantages over CAR-T *** CAR-T and CAR-NK cells have shown consistent and promising results in hematological ***,their efficacy against solid tumors remains limited due to various obstacles including limited tumor trafficking and infiltration,as well as an immuno-suppressive tumor *** this review,we discuss the recent advances and current challenges of CAR-T and CAR-NK cell immunotherapies,with a specific focus on the obstacles to their application in solid *** also analyze in depth the advantages and drawbacks of CAR-NK cells compared to CAR-T cells and highlight CAR-NK CAR ***,we explore future perspectives of these adoptive immunotherapies,highlighting the increasing contribution of cutting-edge biotechnological tools in shaping the next generation of cellular immunotherapy.

关键词： CAR-T CAR-NK cell therapy Cancer immunotherapy Solid tumor

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Application of metabolomics in urolithiasis:the discovery and usage of succinate

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Signal Transduction and Targeted Therapy 2023年第2期8卷 771-783页

作者： Xiu-zhen Zhang Xiong-xin Lei Yan-lin Jiang Long-mei Zhao Chen-yu Zou Yun-jin Bai Ya-xing Li Rui Wang Qian-jin Li Qiu-zhu Chen Ming-hui Fan Yu-ting Song Wen-qian Zhang Yi Zhang Jesse Li-Ling Hui-qi Xie Laboratory of Stem Cell and Tissue Engineering Orthopedic Research InstituteDepartment of OrthopedicsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan 610041China Department of Urology Institute of UrologyWest China HospitalSichuan UniversityChengduSichuan 610041China Research Core Facility of West China Hospital Sichuan UniversityChengduSichuan 610041China Department of Medical Genetics West China Second University HospitalChengduSichuan 610041China

Urinary stone is conceptualized as a chronic metabolic disorder punctuated by symptomatic stone *** has been shown that the occurrence of calcium oxalate monohydrate(COM)during stone formation is regulated by crystal growth *** crystallization inhibitors have been recognized as a therapeutic modality for decades,limited progress has been made in the discovery of effective modifiers to intervene with stone *** this study,we have used metabolomics technologies,a powerful approach to identify biomarkers by screening the urine components of the dynamic progression in a bladder stone *** in-depth mining and analysis of metabolomics data,we have screened five differential *** density functional theory studies and bulk crystallization,we found that three of them(salicyluric,gentisic acid and succinate)could effectively inhibit nucleation in *** thereby assessed the impact of the inhibitors with an EG-induced rat model for kidney ***,succinate,a key player in the tricarboxylic acid cycle,could decrease kidney calcium deposition and injury in the *** analysis further showed that the protective effect of succinate was mainly through anti-inflammation,inhibition of cell adhesion and osteogenic *** findings indicated that succinate may provide a new therapeutic option for urinary stones.

关键词： crystallization thereby protective

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Neuron-fibrous scaffold interfaces in the peripheral nervous system: a perspective on the structural requirements

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Neural Regeneration Research 2022年第9期17卷 1893-1897页

作者： Sanaz Behtaj James A.St John Jenny A.K.Ekberg Maksym Rybachuk Clem Jones Centre for Neurobiology and Stem Cell Research Griffith UniversityQueenslandAustralia Menzies Health Institute Queensland Griffith UniversitySouthportAustralia Griffith Institute for Drug Discovery NathanAustralia School of Engineering and Built Environment Griffith UniversityNathanAustralia Centre for Quantum Dynamics and Australian Attosecond Science Facility Griffith UniversityNathanAustralia

The nerves of the peripheral nervous system are not able to effectively regenerate in cases of severe neural *** can result in debilitating consequences,including morbidity and lifelong impairments affecting the quality of the patient’s *** findings in neural tissue engineering have opened promising avenues to apply fibrous tissue-engineered scaffolds to promote tissue regeneration and functional *** scaffolds,known as neural scaffolds,are able to improve neural regeneration by playing two major roles,namely,by being a carrier for transplanted peripheral nervous system cells or biological cues and by providing structural support to direct growing nerve fibers towards the target ***,successful implementation of scaffold-based therapeutic approaches calls for an appropriate design of the neural scaffold structure that is capable of up-and down-regulation of neuron-scaffold interactions in the extracellular matrix *** review discusses the main challenges that need to be addressed to develop and apply fibrous tissue-engineered scaffolds in clinical *** describes some promising solutions that,so far,have shown to promote neural cell adhesion and growth and a potential to repair peripheral nervous system injuries.

关键词： electrospun scaffold extracellular matrix nerve conduit neural tissue engineering physical lumen filler scaffold topography structural support surface interaction

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Organoids in concert:engineering in vitro models toward enhanced fidelity

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Aggregate 2024年第2期5卷 99-111页

作者： Zhengkun Chen Ryohichi Sugimura Yu Shrike Zhang Changshun Ruan Chunyi Wen Department of Chemistry University of TorontoTorontoOntarioCanada Centre for Translational Stem Cell Biology Hong Kong SARChina Li Ka Shing Faculty of Medicine University of Hong KongHong Kong SARChina Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolCambridgeMassachusettsUSA Research Center for Human Tissue and Organs Degeneration Institute of Biomedicine and BiotechnologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenChina Department of Biomedical Engineering Faculty of EngineeringThe Hong Kong Polytechnic UniversityHong Kong SARChina Research Institute of Smart Ageing The Hong Kong Polytechnic UniversityHong Kong SARChina

Organoids have emerged as a powerful platform for studying complex biological processes and diseases in ***,most studies have focused on individual organoids,overlooking the inter-organ interactions in vivo and limiting the physiological relevance of the *** address this limitation,the development of a multi-organoid system has gained considerable *** system aims to recapitulate inter-organ communication and enable the study of complex physiological *** review provides a comprehensive overview of the recent advancements in organoid engineering and the emerging strategies for constructing a multi-organoid ***,we highlight the critical mechanical,structural,and biochemical factors involved in designing suitable materials for the growth of different ***,we discuss the incorporation of dynamic culture environments to enhance organoid culture and enable inter-organoid ***,we explore techniques for manipulating organoid morphogenesis and spatial positioning of organoids to establish effective inter-organoid communication *** summarize the achievements in utilizing organoids to recapitulate inter-organ communication in vitro,including assembloids and microfluidic multiorganoid ***,we discuss the existing challenges and opportunities in developing a multi-organoid system from its technical bottlenecks in scalability to its applications toward complex human diseases.

关键词： assembloids biomaterials in vitro models microfluidics organoids

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A self-fused hydrogel for the treatment of glottic insufficiency through outstanding durability,extracellular matrix-inducing bioactivity and function preservation

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Bioactive Materials 2023年第6期24卷 54-68页

作者： Chen-Yu Zou Juan-Juan Hu Dan Lu Qian-Jin Li Yan-Lin Jiang Rui Wang Hai-Yang Wang Xiong-Xin Lei Jesse Li-Ling Hui Yang Hui-Qi Xie Laboratory of Stem Cell and Tissue Engineering Orthopedic Research InstituteMed-X Center for MaterialsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041PR China Department of Otolaryngology Head and Neck SurgeryWest China HospitalSichuan UniversityChengduSichuan610041PR China Department of Medical Genetics West China Second HospitalSichuan UniversityChengduSichuan610041PR China

Injection laryngoplasty with biomaterials is an effective technique to treat glottic ***,the inadequate durability,deficient pro-secretion of extracellular matrix(ECM)and poor functional preservation of current biomaterials have yielded an unsatisfactory therapeutic ***,a self-fusing bioactive hydrogel comprising modified carboxymethyl chitosan and sodium alginate is developed through a dual-crosslinking mechanism(photo-triggered and dynamic covalent bonds).Owing to its characteristic networks,the synergistic effect of the hydrogel for vocal folds(VFs)vibration and phonation is adequately ***,owing to its inherent bioactivity of polysaccharides,the hydrogel could significantly enhance the secretion of major components(type I/III collagen and elastin)in the lamina propria of the VFs both in vivo and in *** a rabbit model for glottic insufficiency,the optimized hydrogel(C1A1)has demonstrated a durability far superior to that of the commercially made hyaluronic acid(HA)*** importantly,owing to the ECM-inducing bioactivity,the physiological functions of the VFs treated with the C1A1 hydrogel also outperformed that of the HA Gel,and were similar to those of the normal *** together,through a simple-yet-effective strategy,the novel hydrogel has demonstrated outstanding durability,ECM-inducing bioactivity and physiological function preservation,therefore has an appealing clinical value for treating glottic insufficiency.

关键词： Glottic insufficiency Self-fusion Hydrogel Extracellular matrix Physiological function

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Heterogeneity of neutrophils in cancer:one size does not fit all

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Cancer Biology & Medicine 2022年第12期19卷 1629-1648页

作者： Song Chen Qingyu Zhang Lisha Lu Chunhui Xu Jiajia Li Jiali Zha Fengxia Ma Hongbo R.Luo Alan Y.Hsu State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Department of Pathology Harvard Medical SchoolBostonMA 02115USA Department of Laboratory Medicine The Stem Cell ProgramBoston Children's HospitalBostonMA 02115USA Dana-Farber/Harvard CancerCenter BostonMA02115USA

Neutrophils play an essential role in the defense against bacterial infections and orchestrate both the innate and adaptive immune *** their abundant numbers,diverse function and short life span,these cells are at the forefront of immune responses,and have gained attention in recent years because of their presence in tumor *** involvement pertains to tumor cells'ability to construct a suitable tumor microenvironment(TME)that accelerates their own growth and malignancy,by facilitating their interaction with surrounding cells through the circulatory and lymphatic systems,thereby influencing tumor development and *** have indicated both pro-and anti-tumor properties of infiltrating *** TME can exploit neutrophil function,recruitment,and even production,thus resulting in pro-tumor properties of neutrophils,including promotion of genetic instability,tumor cell proliferation,angiogenesis and suppression of anti-tumor or inflammatory *** contrast,neutrophils can mediate anti-tumor resistance by direct cytotoxicity to the tumor cells or by facilitating anti-tumor functions via crosstalk with T ***,we summarize current knowledge regarding the effects of neutrophil heterogeneity under homeostatic and tumor conditions,including neutrophil phenotype and function,in cancer biology.

关键词： Neutrophils in cancer tumor microenvironment TAN neutrophil heterogeneity neutrophils

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Effect of astragaloside Ⅳ on the immunoregulatory function of adipose-derived mesenchymal stem cells from patients with psoriasis vulgaris

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Journal of Traditional Chinese Medicine 2022年第4期42卷 513-519页

作者： YIN Xiuping ZHANG Xiaotong ZHU Rongjia SONG Ping Department of Dermatology Guang'anmen HospitalChina Academy of Chinese Medical SciencesBeijing 100053China Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy(BZ0381)/Center of Excellence in Tissue Engineering Institute of Basic Medical Sciences CAMSSchool of Basic Medicine PUMCBeijing 100005China

OBJECTⅣE:To compare the phenotype and adipogenic and osteogenic differentiation capacities of adiposederived mesenchymal stem cells(AMSCs)isolated from patients with psoriasis vulgaris and healthy donors,and to explore the effects of astragalosideⅣ,a Traditional Chinese Medicine,on the immunoregulatory function of ***:AMSCs were isolated from human adipose tissue and cultured for three generations in *** phenotype and cell cycle analysis were performed by flow *** and osteogenic differentiation of AMSCs was examined by lipid(oil red O)and alkaline phosphatase staining,*** of inflammatory mediators was examined by real-time quantitative polymerase chain reaction analysis,and proliferation was quantified using the cell counting kit-8 ***:Expression of CD29,CD44,and CD73 was higher in AMSCs from healthy donors than psoriasis patients,while the reverse was true for expression of CD45,CD31,and *** from psoriasis patients had a greater ability to undergo adipogenic differentiation than cells from healthy donors,whereas there was no significant difference in osteogenic differentiation between AMSCs from the two *** with AMSCs from healthy donors,psoriasis patient-derived AMSCs expressed lower levels of the anti-inflammatory cytokines interleukin-10 and transforming growth factor-β(TGF-β)and the immune checkpoint ligand programmed cell death 1 ligand 1(PDL1)(P<0.05)and higher levels of the pro-inflammatory cytokines tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ).Incubation of AMSCs from psoriasis patients with astragalosideⅣhad no significant effect on proliferation but increased the expression of TGF-βand PDL1 and decreased the expression of IFN-γand TNF-α.CONCLUSION:AMSCs from patients with psoriasis vulgaris display abnormal proliferation and adipogenesis and an enhanced pro-inflammatory *** defects were normalized by treatment with astragalosideⅣ,suggesting that this

关键词： psoriasis mesenchymal stem cells cell proliferation astragalosideⅣ adipogenesis osteogenesis immune regulation

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Ocular safety of intravitreal ethylene diamine tetra acetic acid (EDTA): An experimental feasibility study

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Toxicology Reports 2023年 10卷 463-468页

作者： Zand, Amin Falavarjani, Khalil Ghasemi Kanavi, Mozhgan Rezaei Habibi, Abbas Anvari, Pasha Alemzadeh, Sayyed Amirpooya Eye Research Center The Five Senses Health Institute Rassoul Akram Hospital Iran University of Medical Sciences Tehran Iran Ocular Tissue Engineering Research Center Shahid Beheshti University of Medical Sciences Tehran Iran Stem Cell and Regenerative Medicine Research Center Iran University of Medical Sciences Tehran Iran

Ethylene diamine tetra acetic acid (EDTA) is a chelating component that is able to diminish oxidative reactivity and can be a potential neuroprotective drug in various ocular diseases. For assessing the safety of intravitreal EDTA, 10 rabbits were allocated and divided into 5 groups. Right eyes of the animals received intravitreal EDTA (112.5, 225, 450, 900 and 1800 µg /0.1 ml). Fellow eyes were considered as controls. Clinical examinations and electroretinography (ERG) were performed at the baseline and on day 28. The enucleated eyes were subjected to hematoxylin and eosin (H&E) staining, immunohistochemistry for glial fibrillary acidic protein (GFAP) and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. Clinical examinations, H&E staining and TUNEL assay were unremarkable. The ERG test did not exhibit any significant alteration compared to the baseline values, except for a significant decrease in just one measurement of the eyes injected with 225 µg EDTA. The mean scores of GFAP immune reactivity in the eyes injected with 112.5 and 225 µg EDTA indicated a non-significant reaction. The scores in higher doses were significant. We suggest intravitreal EDTA with a dose threshold of < 450 µg should be studied for ratification of the safe dose. © 2023 The Authors

关键词： Electroretinography Ethylene diamine tetra acetic acid Glial fibrillary acidic protein Intravitreal injection Rabbit Retina toxicity

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A bioinformatics approach to study the role of calcium phosphate properties in bone regeneration

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European Journal of Materials 2022年第1期2卷 499-530页

作者： Galván-Chacón, Víctor P. Vasilevich, Aliaksei Yuan, Huipin Groen, Nathalie de Boer, Jan Habibović, Pamela Vermeulen, Steven Department of Instructive Biomaterials Engineering MERLN Institute for Technology-Inspired Regenerative Medicine Maastricht University Netherlands Biointerface Science Group Department of Biomedical Engineering Eindhoven University of Technology Netherlands Kuros Biosciences BV Bilthoven Netherlands Department of Developmental Biology and Stem Cell Research Hubrecht Institute Utrecht Netherlands

Calcium phosphates (CaPs) are extensively used as biomaterials for bone repair and regeneration and are considered an interesting synthetic alternative for natural bone grafts. However, the bone regenerative potential of many CaP bone graft substitutes requires further improvements. The bioactivity of CaPs is regulated by a variety of properties, including their chemical composition and (surface) structural properties. In this study, we performed a comprehensive characterization of six CaP ceramics that had been previously tested in several in vitro and in vivo studies, allowing us to in silico distinguish osteoinductive and non-osteoinductive CaP ceramics. The numerical parameters obtained from this characterization were further correlated with osteogenesis-associated gene expression and pathways of osteoblastic MG63 cells cultured on these six CaP ceramics. The results showed, among others, the influence of both chemical and structural parameters on cytoskeleton- and extracellular matrix-related gene expression and osteogenesis-associated pathways such as MAPK and BMP. The bioinformatics approach presented here allows exploring the transcriptional landscape induced by CaP ceramics and gaining fundamental knowledge about cell-biomaterial interactions. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

关键词： Calcium phosphate Cluster analysis Correlation analysis Material characterization MG63 Regenerative medicine Transcriptomics

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