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Safety and efficiency of Wharton’s Jelly-derived mesenchymal stem cell administration in patients with traumatic brain injury:First results of a phase I study

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World Journal of stem cells 2024年第6期16卷 641-655页

作者： Serdar Kabatas ErdinçCivelek Osman Boyalı Gülseli Berivan Sezen Omer Ozdemir Yeliz Bahar-Ozdemir Necati Kaplan Eyüp Can Savrunlu Erdal Karaöz Department of neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalIstanbul 34360Türkiye Center for stem cell&Gene Therapy research and Practice University of Health Sciences TurkeyIstanbul 34255Türkiye Department of neurosurgery University of Health SciencesGaziosmanpaşa Training and Research HospitalIstanbul 34255Türkiye Department of Physical Medicine and Rehabilitation Health Sciences University Sultan Abdulhamid Han Training and Research HospitalIstanbul 34668Türkiye Department of neurosurgery Istanbul Rumeli UniversityÇorlu Reyap HospitalTekirdağ59860Türkiye Department of neurosurgery Nevşehir State HospitalNevşehir 50300Türkiye Center for Regenerative Medicine and stem cell research&Manufacturing(LivMedcell) Liv HospitalIstanbul 34340Türkiye Department of Histology and Embryology Istinye UniversityFaculty of MedicineIstanbul 34010Türkiye Center for stem cell and Tissue Engineering research and Practice Istinye UniversityIstanbul 34340Türkiye

BACKGROUND Traumatic brain injury(TBI)is characterized by a disruption in the normal function of the brain due to an injury following a trauma,which can potentially cause severe physical,cognitive,and emotional *** cell transplantation has evolved as a novel treatment modality in the management of TBI,as it has the potential to arrest the degeneration and promote regeneration of new cells in the ***’s Jelly-derived mesenchymal stem cells(WJ-MSCs)have recently shown beneficial effects in the functional recovery of neurological *** To evaluate the safety and efficiency of MSC therapy in *** We present 6 patients,4 male and 2 female aged between 21 and 27 years who suffered a *** 6 patients underwent 6 doses of intrathecal,intramuscular(i.m.)and intravenous transplantation of WJ-MSCs at a target dose of 1×106/kg for each application *** was assessed using the Modified Ashworth scale(MAS),motor function according to the Medical research Council Muscle Strength Scale,quality of life was assessed by the Functional Independence Measure(FIM)scale and Karnofsky Performance Status *** Our patients showed only early,transient complications,such as subfebrile fever,mild headache,and muscle pain due to ***,which resolved within 24 *** the one year follow-up,no other safety issues or adverse events were *** 6 patients showed improvements in their cognitive abilities,muscle spasticity,muscle strength,performance scores and fine motor skills when compared before and after the *** values,which we used to assess spasticity,were observed to statistically significantly decrease for both left and right sides(P<0.001).The FIM scale includes both motor scores(P<0.05)and cognitive scores(P<0.001)and showed a significant increase in pretest posttest *** difference observed in the participants’Karnofsky Performance Scale values pre and post the intervention was statistically si

关键词： Traumatic brain injury Wharton Jelly stem cell therapy Transplantation Mesenchymal stem cell

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Role of cancer stem cell ecosystem on breast cancer metastasis and related mouse models

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Zoological research 2024年第3期45卷 506-517页

作者： Xilei Peng Haonan Dong Lixing Zhang Suling Liu Fudan University Shanghai Cancer Center&Institutes of Biomedical Sciences/State Key laboratory of Genetic Engineering/Cancer Institutes/Department of oncology/Key laboratory of Breast Cancer in Shanghai/Shanghai Key laboratory of Medical Epigenetics/Shanghai Key laboratory of Radiation oncology/International Co-laboratory of Medical Epigenetics and Metabolism Ministry of Science and Technology/Shanghai Medical College/Fudan UniversityShanghai 200032China

Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and *** cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and *** have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast *** tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ***,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer *** this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory ***,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during ***,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.

关键词： Breast cancer Metastasis Cancer stem cell Ecosystem Tumor microenvironment Mouse model

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Deer antler stem cell niche: An interesting perspective

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World Journal of stem cells 2024年第5期16卷 479-485页

作者： Claudia Cavallini Elena Olivi Riccardo Tassinari Chiara Zannini Gregorio Ragazzini Martina Marcuzzi Valentina Taglioli Carlo Ventura National laboratory of Molecular Biology and stem cell Engineering National Institute of Biostructures and Biosystems-Eldor LabBologna 40128Italy Eldor Lab Bologna 40128Italy Department of Medical and Surgical Sciences(DIMEC) University of BolognaBologna 40138Italy

In recent years,there has been considerable exploration into methods aimed at enhancing the regenerative capacity of transplanted and/or tissue-resident ***,in particular,have garnered significant interest for their potential to serve as natural scaffolds for *** this editorial,we provide commentary on the study by Wang et al,in a recently published issue of World J stem cells,which investigates the use of a decellularized xenogeneic extracellular matrix(ECM)derived from antler stem cells for repairing osteochondral defects in rat knee *** focus lies specifically on the crucial role of biological scaffolds as a strategy for augmenting stem cell potential and regenerative capabilities,thanks to the establishment of a favorable microenvironment(niche).stem cell differen-tiation heavily depends on exposure to intrinsic properties of the ECM,including its chemical and protein composition,as well as the mechanical forces it can ***,these physicochemical cues contribute to a bio-instructive signaling environment that offers tissue-specific guidance for achieving effective repair and *** interest in mechanobiology,often conceptualized as a form of“structural memory”,is steadily gaining more validation and momen-tum,especially in light of findings such as these.

关键词： Extracellular matrix Antler stem cells stem cell niche Regenerative medicine Decellularized scaffolds cell memory

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Cadherin-18 loss in prospermatogonia and spermatogonial stem cells enhances cell adhesion through a compensatory mechanism

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Zoological research 2024年第5期45卷 1048-1060页

作者： Xiao-Xiao Li Dan-Chen Zhang Yan Wang Jian Wen Xing-Ju Wang Yu-Lu Cao Ru Jiang Jia-Rui Li Yi-Nuo Li He-He Liu Wen-Hai Xie Zheng-Feng Xu Ping Hu Kang Zou Germline stem cells and Microenvironment Lab College of Animal Science and TechnologyNanjing Agricultural UniversityNanjingJiangsu 210095China stem cell research and Translation Center Nanjing Agricultural UniversityNanjingJiangsu 210095China School of Life Sciences and Medicine Shandong University of TechnologyZiboShandong 255000China Department of Prenatal Diagnosis Women’s Hospital of Nanjing Medical UniversityNanjing Maternity and Child Health Care HospitalNanjingJiangsu 210004China

Extracellular membrane proteins are crucial for mediating cell attachment,recognition,and signal transduction in the testicular microenvironment,particularly germline stem *** 18(CDH18),a type II classical cadherin,is primarily expressed in the nervous and reproductive ***,we investigated the expression of CDH18 in neonatal porcine prospermatogonia(ProSGs)and murine spermatogonial stem cells(SSCs).Disruption of CDH18 expression did not adversely affect cell morphology,proliferation,self-renewal,or differentiation in cultured porcine ProSGs,but enhanced cell adhesion and prolonged cell *** analysis indicated that the down-regulation of CDH18 in ProSGs significantly up-regulated genes and signaling pathways associated with cell *** further elucidate the function of CDH18 in germ cells,Cdh18 knockout mice were generated,which exhibited normal testicular morphology,histology,and *** analysis showed increased expression of genes associated with adhesion,consistent with the observations in porcine *** interaction of CDH18 withβ-catenin and JAK2 in both porcine ProSGs and murine SSCs suggested an inhibitory effect on the canonical Wnt and JAK-STAT signaling pathways during CDH18 ***,these findings highlight the crucial role of CDH18 in regulating cell adhesion in porcine ProSGs and mouse *** this regulatory mechanism provides significant insights into the testicular niche.

关键词： Extracellular signal Fertility Quiescency Wnt signaling pathway

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Establishment of a humanized mouse model using steady-state peripheral blood-derived hematopoietic stem and progenitor cells facilitates screening of cancer-targeted T-cell repertoires

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Cancer Innovation 2024年第3期3卷 1-21页

作者： Yulin Xu Wei Shan Qian Luo Meng Zhang Dawei Huo Yijin Chen Honghu Li Yishan Ye Xiaohong Yu Yi Luo He Huang Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina Liangzhu laboratory Zhejiang UniversityHangzhouChina Institute of Hematology Zhejiang UniversityHangzhouChina Zhejiang Province Engineering research Center for stem cell and Immunity Therapy HangzhouChina School of Medicine Zhejiang UniversityHangzhouChina

Background:Cancer-targeted T-cell receptor T(TCR-T)cells hold promise in treating cancers such as hematological malignancies and breast ***,approaches to obtain cancer-reactive TCR-T cells have been ***:Here,we developed a novel strategy to screen for cancer-targeted TCR-T cells using a special humanized mouse model with person-specific immune *** steady-state circulating hematopoietic stem and progenitor cells were expanded via three-dimensional culture of steady-state peripheral blood mononuclear cells,and then the expanded cells were applied to establish humanized *** human immune system was evaluated according to the kinetics of dendritic cells,monocytes,T-cell subsets,and *** fully stimulate the immune response and to obtain B-cell precursor NAML-6-and triple-negative breast cancer MDA-MB-231-targeted TCR-T cells,we used the inactivated cells above to treat humanized mice twice a day every 7 ***,human T cells were processed for TCRβ-chain(TRB)sequencing *** the repertoires had been constructed,features such as the fraction,diversity,and immune signature were ***:The results demonstrated an increase in diversity and clonality of T cells after *** preferential usage and features of TRBV,TRBJ,and the V–J combination were also *** stress also induced highly clonal Science and Technology,Grant/Award Number:2021C03010;Zhejiang Provincial Natural Science Foundation of China,Grant/Award Numbers:LTGY24H080003,LY21H080004 *** burden and survival analysis demonstrated that stress induction could significantly inhibit the growth of subsequently transfused live tumor cells and prolong the survival of the humanized ***:We constructed a personalized humanized mouse model to screen cancer-targeted TCR-T *** platform provides an effective source of cancer-targeted TCR-T cells and allows for the design of patient-specific engineered T cells.

关键词： cancer-targeted T-cell receptor T(TCR-T)cells circulating hematopoietic stem and progenitor cells(HSPCs) humanized mouse model steady-state peripheral blood T-cell receptorβ-chain(TRB) three-dimensional culture

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Advancements in personalized stem cell models for aging-related neurodegenerative disorders

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Neural Regeneration research 2024年第11期19卷 2333-2334页

作者： Mingxi Weng Ralf Jauch School of Biomedical Sciences Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Center for Translational stem cell Biology Hong Kong Special Administrative RegionChina

neurodegenerative diseases(NDDs)are a class of disorders characterized by the gradual loss or malfunction of specific cell populations in the nervous system,which can be triggered by genetic or environmental *** a result,patients often experience a decline in mobility,sensation,memory,and cognition,which can ultimately lead to a fatal *** global incidence of NDDs,including Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,amyotrophic lateral sclerosis(ALS),and multiple sclerosis,is increasing.

关键词： degenerative Huntington sensation

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Comparison of clinical features of nephrotic syndrome after haploidentical and matched donor hematopoietic stem cell transplantation

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Chinese Medical Journal 2024年第4期137卷 478-480页

作者： Wei Sun Yuanyuan Zhang Yuhong Chen Yuqian Sun Yifei Cheng Fengrong Wang Huan Chen Yao Chen Chenhua Yan Xiaodong Mo Wei Han Lanping Xu Yu Wang Xiaohui Zhang Kaiyan Liu Xiaojun Huang Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationPeking UniversityBeijing 10004China

To the Editor:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is one of the most effective options for hematological ***,allo-HSCT treatment can cause serious ***-transplant kidney damage is an important *** this study,we retrospectively analyzed the frequency of nephrotic syndrome(NS)after allo-HSCT and compared the frequency and clinical characteristics of NS between haploidentical donor(HID)and matched donor(MD)HSCT(including matched sibling donors[MSD]and unrelated donors[URD]).

关键词： hematopoietic clinical matched

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Programmable synthetic receptors:the next-generation of cell and gene therapies

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Signal Transduction and Targeted Therapy 2024年第2期9卷 376-400页

作者： Fei Teng Tongtong Cui Li Zhou Qingqin Gao Qi Zhou Wei Li University of Chinese Academy of Sciences Beijing 101408China State Key laboratory of stem cell and Regenerative Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for stem cell and Regenerative Medicine Beijing 100101China

cell and gene therapies hold tremendous promise for treating a range of difficult-to-treat ***,concerns over the safety and efficacy require to be further addressed in order to realize their full *** receptors,a synthetic biology tool that can precisely control the function of therapeutic cells and genetic modules,have been rapidly developed and applied as a powerful *** designed and engineered,they can be applied to finetune the therapeutic activities,i.e.,to regulate production of dosed,bioactive payloads by sensing and processing user-defined signals or *** review provides an overview of diverse synthetic receptor systems being used to reprogram therapeutic cells and their wide applications in biomedical *** a special focus on four synthetic receptor systems at the forefront,including chimeric antigen receptors(CARs)and synthetic Notch(synNotch)receptors,we address the generalized strategies to design,construct and improve synthetic ***,we also highlight the expanding landscape of therapeutic applications of the synthetic receptor systems as well as current challenges in their clinical translation.

关键词： synthetic landscape payload

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Genome-edited rabbits:Unleashing the potential of a promising experimental animal model across diverse diseases

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Zoological research 2024年第2期45卷 253-262页

作者： Yang Han Jiale Zhou Renquan Zhang Yuru Liang Liangxue Lai Zhanjun Li Key laboratory of Zoonosis research Ministry of EducationCollege of Animal ScienceJilin UniversityChangchunJilin 130062China CAS Key laboratory of Regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineSouth China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China Guangzhou Regenerative Medicine and Health Guang Dong laboratory(GRMH-GDL) GuangzhouGuangdong 510005China Institute for stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene *** field of genome modification in rabbits has progressed ***,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic *** models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to *** review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.

关键词： Genome editing Animal model Rabbit CRISPR/Cas9 Genetic diseases

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TAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance

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Zoological research 2024年第4期45卷 937-950页

作者： Yi-Fu Zhu Rong-Hua Yu Shuai Zhou Pei-Pei Tang Rui Zhang Yu-Xin Wu Ran Xu Jia-Ming Wei Ying-Ying Wang Jia-Li Zhang Meng-Ke Li Xiao-Jing Shi Yu-Wei Zhang Guang-Zhi Liu Rick FThorne Xu Dong Zhang Mian Wu Song Chen School of Life Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China Translational research Institute of Henan Provincial People’s Hospital and People'’s Hospital of Zhengzhou University Tianjian Laboratory of Advanced Biomedical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan 450053China Institute of Medicinal Biotechnology Jiangsu College of NursingHuai’anJiangsu 223300China laboratory Animal Center Academy of Medical ScienceZhengzhou UniversityZhengzhouHenan 450052China Henan Key laboratory of stem cell Differentiation and Modification Henan Provincial People’s HospitalHenan UniversityZhengzhouHenan 450053China School of Biomedical Sciences and Pharmacy The University of NewcastleNSW 2308Australia

Autophagy plays a pivotal role in diverse biological processes,including the maintenance and differentiation of neural stem cells(NSCs).Interestingly,while complete deletion of Fip200 severely impairs NSC maintenance and differentiation,inhibiting canonical autophagy via deletion of core genes,such as Atg5,Atg16l1,and Atg7,or blockade of canonical interactions between FIP200 and ATG13(designated as FIP200-4A mutant or FIP200 KI)does not produce comparable detrimental *** highlights the likely critical involvement of the non-canonical functions of FIP200,the mechanisms of which have remained ***,utilizing genetic mouse models,we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1,primarily via TAX1BP1 in *** deletion of Tax1bp1 in fip200hGFAP conditional knock-in(cKI)mice led to NSC deficiency,resembling the fip200hGFAP conditional knockout(cKO)mouse ***,reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200hGFAP cKI mice but also led to a marked reduction in p62 aggregate ***,a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this ***,conditional deletion of Tax1bp1 in fip200hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200hGFAP cKO ***,these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function,presenting novel therapeutic targets for neurodegenerative diseases.

关键词： Non-canonical autophagy TAX1BP1 FIP200 p62 Aggregates Neural stem cell

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