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Coexpression of CD163 and CD141 identifies human circulating IL-10-producing dendritic cells (DC-10)

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cellular & Molecular Immunology 2020年第1期17卷 95-107页

作者： Michela Comi Daniele Avancini Francesca Santoni de Sio Matteo Villa Molly Javier Uyeda Matteo Floris Daniela Tomasoni Alessandro Bulfone Maria Grazia Roncarolo Silvia Gregori San Raffaele Telethon Institute for Gene therapy(SR-TIGET) San Raffaele Scientific Institute(IRCCS)MilanItaly PhD program in Translational and Molecular Medicine(DIMET) University of Milan-BicoccaMilanItaly Division of stem cell transplantation and Regenerative Medicine Department of PediatricsISCBRMStanford School of MedicineStanfordCAUSA CRS4 Technology Park PolarisPulaItaly

Tolerogenic dendritic cells(DCs)are key players in maintaining immunological homeostasis,dampening immune responses,and promoting ***-10,a tolerogenic population of human IL-10-producing DCs characterized by the expression of HLA-G and ILT4,play a pivotal role in promoting tolerance via T regulatory type 1(Tr1)*** far,the absence of markers that uniquely identify DC-10 has limited in vivo *** in vitro gene expression profiling of differentiated human DCs,we identified CD141 and CD163 as surface markers for *** coexpression of CD141 and CD163 in combination with CD14 and CD16 enables the ex vivo isolation of DC-10 from the peripheral ***14+CD16+CD141+CD163+cells isolated from the peripheral blood of healthy subjects(ex vivo DC-10)produced spontaneously and upon activation of IL-10 and limited levels of ***,in vitro stimulation of allogeneic naive CD4+T cells with ex vivo DC-10 induced the differentiation of alloantigen-specific CD49b+LAG-3+Tr1 ***,ex vivo DC-10 and in vitro generated DC-10 exhibited a similar transcriptional profile,which are characterized by an anti-inflammatory and pro-tolerogenic *** results provide new insights into the phenotype and molecular signature of DC-10 and highlight the tolerogenic properties of circulating *** findings open the opportunity to track DC-10 in vivo and to define their role in physiological and pathological settings.

关键词： Dendritic cells IL-10 T regulatory type 1(Tr1)cells Tolerance

stem cells for liver tissue repair:Current knowledge and perspectives

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World Journal of Gastroenterology 2008年第6期14卷 864-875页

作者： Philippe A Lysy David Campard Fran oise Smets Mustapha Najimi Etienne M Sokal Université Catholique de Louvain & Cliniques Universitaires Saint Luc HPED Department Unit PEDI Laboratory of Pediatric Hepatology and Cell Therapy Brussels 1200 Belgium

stem cells from extra-or intrahepatic sources have been recently characterized and their usefulness for the generation of hepatocyte-like lineages has been demonstrated. Therefore, they are being increasingly considered for future applications in liver cell therapy. In that field, liver cell transplantation is currently regarded as a possible alternative to whole organ transplantation, while stem cells possess theoretical advantages on hepatocytes as they display higher in vitro culture performances and could be used in autologous transplant procedures. However, the current research on the hepatic fate of stem cells is still facing difficulties to demonstrate the acquisition of a full mature hepatocyte phenotype, both in vitro and in vivo. Furthermore, the lack of obvious demonstration of in vivo hepatocyte-like cell functionality remains associated to low repopulation rates obtained after current transplantation procedures. The present review focuses on the current knowledge of the stem cell potential for liver therapy. We discuss the characteristics of the principal cell candidates and the methods to demonstrate their hepatic potential in vitro and in vivo. We finally address the question of the future clinical applications of stem cells for liver tissue repair and the technical aspects that remain to be investigated.

关键词： stem cells Hepatocyte differentiation Liver regeneration cell therapy

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

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Signal Transduction and Targeted therapy 2021年第11期6卷 3230-3245页

作者： Xia Li Mi Shao Xiangjun Zeng Pengxu Qian He Huang Bone Marrow transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouPeople’s Republic of China Liangzhu Laboratory Zhejiang University Medical Center1369 West Wenyi RoadHangzhou311121People’s Republic of China Institute of Hematology Zhejiang UniversityHangzhouZhejiangPeople’s Republic of China Zhejiang Province Engineering Laboratory for stem cell and Immunity therapy HangzhouZhejiangPeople’s Republic of China Center of stem cell and Regenerative Medicine Zhejiang University School of MedicineHangzhouPeople’s Republic of China

Cytokine release syndrome(CRS)embodies a mixture of clinical manifestations,including elevated circulating cytokine levels,acute systemic inflammatory symptoms and secondary organ dysfunction,which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza,SARS-CoV and COVID-19,immunotherapy of tumor,after chimeric antigen receptor T(CAR-T)therapy,and in monogenic disorders and autoimmune ***,severe CRS is a very significant and life-threatening complication,which is clinically characterized by persistent high fever,hyperinflammation,and severe organ ***,CRS is a double-edged sword,which may be both helpful in controlling tumors/viruses/infections and harmful to the *** a high incidence and high levels of cytokines are features of CRS,the detailed kinetics and specific mechanisms of CRS in human diseases and intervention therapy remain *** the present review,we have summarized the most recent advances related to the clinical features and management of CRS as well as cutting-edge technologies to elucidate the mechanisms of *** that CRS is the major adverse event in human diseases and intervention therapy,our review delineates the characteristics,kinetics,signaling pathways,and potential mechanisms of CRS,which shows its clinical relevance for achieving both favorable efficacy and low toxicity.

关键词： cytokine release kinetics

Treatment of multiple sclerosis by transplantation of neural stem cells derived from induced pluripotent stem cells

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Science China(Life Sciences) 2016年第9期59卷 950-957页

作者： Chao Zhang Jiani Cao Xiaoyan Li Haoyu Xu Weixu Wang Libin Wang Xiaoyang Zhao Wei Li Jianwei Jiao Baoyang Hu Qi Zhou Tongbiao Zhao State Key Laboratory of stem cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China Graduate University of Chinese Academy of Sciences Beijing 100049 China

Multiple sclerosis(MS) is an autoimmune disease of the central nervous system(CNS), with focal T lymphocytic infiltration and damage of myelin and axons. The underlying mechanism of pathogenesis remains unclear and there are currently no effective treatments. The development of neural stem cell(NSC) transplantation provides a promising strategy to treat neurodegenerative disease. However, the limited availability of NSCs prevents their application in neural disease therapy. In this study, we generated NSCs from induced pluripotent stem cells(iPSCs) and transplanted these cells into mice with experimental autoimmune encephalomyelitis(EAE), a model of MS. The results showed that transplantation of iPSC-derived NSCs dramatically reduced T cell infiltration and ameliorated white matter damage in the treated EAE mice. Correspondingly, the disease symptom score was greatly decreased, and motor ability was dramatically rescued in the iPSC-NSC-treated EAE mice, indicating the effectiveness of using iPSC-NSCs to treat MS. Our study provides pre-clinical evidence to support the feasibility of treating MS by transplantation of iPSC-derived NSCs.

关键词： induced pluripotent stem cell multiple sclerosis neural stem cell regenerative medicine transplantation

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

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Neural Regeneration Research 2025年第2期20卷 343-353页

作者： Ana Milena Silva Olaya Fernanda Martins Almeida Ana Maria Blanco Martinez Suelen Adriani Marques PhD program in Pathological Anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Biomedical Science Institute Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate program in Pathological Anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate program in Pathological Anatomy(PPGAP/UFRJ) Department of Neurobiology/Institute of BiologyCampus do GragoatáNiteróiRio de JaneiroBrazil

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical ***,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord *** of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional *** the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in *** article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were ***,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

关键词： bioengineering biomaterials cell therapy humans non-human primates spinal cord injury stem cell therapy

Bilineage embryo-like structure from EPS cells can produce live mice with tetraploid trophectoderm

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Protein & cell 2023年第4期14卷 262-278页

作者： Kuisheng Liu Xiaocui Xu Dandan Bai Yanhe Li Yalin Zhang Yanping Jia Mingyue Guo Xiaoxiao Han Yingdong Liu Yifan Sheng Xiaochen Kou Yanhong Zhao jiqing Yin Sheng Liu jiayu Chen Hong Wang Yixuan Wang Wenqiang Liu Shaorong Gao Shanghai Key Laboratory of Matemal Fetal Medicine Clinical and Translational Research Center of Shanghai First Matemity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Translational Medical Center for stem cell therapy and Institute for Regenerative Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Shanghai Institute of Matermal-Fetal Medicine and Gynecologic Oncology Shanghai First Matermity and Infant HospitalTongji UniversityShanghai 200092China

Self-organized blastoids from extended pluripotent stem(EPs)cells possess enormous potential for investigating postimplantation embryo development and related ***,the limited ability of postimplantation development of Eps-blastoids hinders its further *** this study,single-cell transcriptomic analysis indicated that the“trophectoderm(TE)-like structure”of EPSblastoids was primarily composed of primitive endoderm(PrE)-related cells instead of TE-related *** further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like *** of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid ***,we demonstrated that blastocyst-like structures reconstituted by combining the EPs-derived bilineage embryo-like structure(BLEs)with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live *** summary,our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.

关键词： EPS cells blastoid primitive endoderm(PrE) trophectoderm(TE) Gata6

Advances in medical decision support systems for diagnosis of acute graft-versus-host disease: molecular and computational intelligence joint approaches

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Frontiers in Biology 2011年第4期6卷 263-273页

作者： Maurizio FIASCHÉ Maria CUZZOLA Giuseppe IRRERA Pasquale IACOPINO Francesco Carlo MORABITO DIMET University“Mediterranea”of Reggio CalabriaItaly transplant Regional Center of stem cells and cellular therapy “A.Neri”Reggio CalabriaItaly School of Hematology University of MessinaItaly

Acute graft-versus-host disease (aGVHD) is a serious systemic complication of allogeneic hematopoietic stemcell transplantation (HSCT) causing considerable morbidity and mortality. Acute GVHD occurs when alloreactivedonor-derived T cells recognize host-recipient antigens as foreign. These trigger a complex multiphase process thatultimately results in apoptotic injury in target organs. The early events leading to GVHD seem to occur very soon,presumably within hours from the graft infusion. Therefore, when the first signs of aGVHD clinically manifest, thedisease has been ongoing for several days at the cellular level, and the inflammatory cytokine cascade is fully ***, it comes as no surprise that progress in treatment based on clinical diagnosis of aGVHD has been limited in the past30 years. It is likely that a pre-emptive strategy using systemic high-dose corticosteroids as early as possible couldimprove the outcome of aGVHD. Due to the deleterious effects of such treatment particularly in terms of infection riskposed by systemic steroid administration in a population that is already immune-suppressed, it is critical to identifybiomarker signatures for approaching this very complex task. Some research groups have begun addressing this issuethrough molecular and proteomic analyses, combining these approaches with computational intelligence techniques,with the specific aim of facilitating the identification of diagnostic biomarkers in aGVHD. In this review, we focus on theaGVHD scenario and on the more recent *** also attempt to give an overview of the classical and noveltechniques proposed as medical decision support system for the diagnosis of GVHD.

关键词： computational intelligence gene selection GVHD machine learning personalized modelling wrapper

Neuroregeneration and functional recovery after stroke: advancing neural stem cell therapy toward clinical application

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Neural Regeneration Research 2021年第1期16卷 80-92页

作者： Yang Jiao Yu-Wan Liu Wei-Gong Chen Jing Liu stem cell Clinical Research Center National Joint Engineering LaboratoryRegenerative Medicine CenterThe First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina Dalian Innovation Institute of stem cells and Precision Medicine DalianLiaoning ProvinceChina

Stroke is a main cause of death and disability *** ability of the brain to selfrepair in the acute and chronic phases after stroke is minimal;however,promising stem cell-based interventions are emerging that may give substantial and possibly complete recovery of brain function after *** animal models and clinical trials have demonstrated that neural stem cells(NSCs)in the central nervous system can orchestrate neurological repair through nerve regeneration,neuron polarization,axon pruning,neurite outgrowth,repair of myelin,and remodeling of the microenvironment and brain *** with other types of stem cells,NSCs have unique advantages in cell replacement,paracrine action,inflammatory regulation and *** review summarizes NSC origins,characteristics,therapeutic mechanisms and repair processes,then highlights current research findings and clinical evidence for NSC *** results may be helpful to inform the direction of future stroke research and to guide clinical decision-making.

关键词： brain central nervous system cognitive impairment neurological function plasticity recovery regeneration stem cells stroke

Techniques for increasing the yield of stem cell-derived exosomes:what factors may be involved?

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Science China(Life Sciences) 2022年第7期65卷 1325-1341页

作者： Zi-Yuan Feng Qing-Yi Zhang Jie Tan Hui-Qi Xie Laboratory of stem cell and Tissue Engineering Orthopedic Research InstituteMed-X Center for MaterialsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Exosomes are nano-scale extracellular vesicles secreted by cells and constitute an important part in the cell-cell *** main contents of the exosomes include proteins,micro RNAs,and *** mechanism and safety of stem cell-derived exosomes have rendered them a promising therapeutic strategy for regenerative ***,limited yield has restrained full explication of their functions and clinical *** address this,various attempts have been made to explore the up-and down-stream manipulations in a bid to increase the production of *** review has recapitulated factors which may influence the yield of stem cell-derived exosomes,including selection and culture of stem cells,isolation and preservation of the exosomes,and development of artificial exosomes.

关键词： exosome stem cell yield therapy