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Chinese Medical Journal 2024年第2期137卷 140-151页

作者： Minghao Lin Xiaosu Zhao Yingjun Chang Xiangyu Zhao Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China

Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell *** MRD detection methods include flow cytometry(FCM),polymerase chain reaction(PCR),and next-generation sequencing(NGS),and each method has advantages and *** has been well documented that MRD positivity predicts a poor prognosis and even disease ***,how to perform prognostic evaluations,stratify risk based on MRD status,and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical *** review assesses the common and novel MRD assessment *** addition,we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation(allo-HSCT),as well as other therapeutic strategies to improve treatment ***,this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.

关键词： Measurable/minimal residual disease Acute lymphoblastic leukemia Chimeric antigen receptor-modified T-cell therapy Allogeneic hematopoietic stem cell transplantation Relapse

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

One-step cell biomanufacturing platform:porous gelatin microcarrier beads promote human embryonic stem cell-derived midbrain dopaminergic progenitor cell differentiation in vitro and survival after transplantation in vivo

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Neural Regeneration Research 2024年第2期19卷 458-464页

作者： Lin Feng Da Li Yao Tian Chengshun Zhao Yun Sun Xiaolong Kou Jun Wu Liu Wang Qi Gu Wei Li Jie Hao Baoyang Hu Yukai Wang State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Institute for stem cell and Regenerative Medicine Chinese Academy of SciencesBeijingChina National stem cell Resource Center Chinese Academy of SciencesBeijingChina Savaid Medical School University of Chinese Academy of SciencesBeijingChina Beijing Institute for stem cell and Regenerative Medicine BeijingChina State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina

Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s *** of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s ***,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation ***,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor *** beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in ***,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell ***,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.

关键词： axonal integrity cell cryopreservation cellular environment cellular niche cell replacement therapy dopaminergic progenitors human pluripotent stem cell mechanical damage neuronal cell delivery Parkinson’s disease small-aperture gelatin microcarriers

Efficacy and safety of human umbilical cord-derived mesenchymal stem cells in the treatment of refractory immune thrombocytopenia:a prospective,single arm,phase I trial

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Signal Transduction and Targeted therapy 2024年第5期9卷 2250-2259页

作者： Yunfei Chen Yanmei Xu Ying Chi Ting Sun Yuchen Gao Xueqing Dou Zhibo Han Feng Xue Huiyuan Li Wei Liu Xiaofan Liu Huan Dong Rongfeng Fu Mankai Ju Xinyue Dai Wentian Wang Yueshen Ma Zhen Song Jundong Gu Wei Gong Renchi Yang Lei Zhang State Key Laboratory of Experimental Hematology National Clinical Research Centre for Blood DiseasesHaihe Laboratory of Cell EcosystemTianjin Key Laboratory of Gene Therapy for Blood DiseasesCAMS Key Laboratory of Gene Therapy for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China National Clinical Research Center for Hematologic Diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhou 215006China National Engineering Research Centre of cell Products Tianjin Key Laboratory of Engineering Technologies for Cell PharmaceuticalAmCellGene Engineering Co.LtdTianjin 300457China School of Population Medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical College100730 BeijingChina

Patients with refractory immune thrombocytopenia(ITP)frequently encounter substantial bleeding risks and demonstrate limited responsiveness to existing *** cord-derived mesenchymal stem cells(UC-MSCs)present a promising alternative,capitalizing on their low immunogenicity and potent immunomodulatory effects for treating diverse autoimmune *** prospective phase I trial enrolled eighteen eligible patients to explore the safety and efficacy of UC-MSCs in treating refractory *** research design included administering UC-MSCs at escalating doses of 0.5×10^(6)cells/kg,1.0×10^(6)cells/kg,and 2.0×10^(6)cells/kg weekly for four consecutive weeks across three cohorts during the dose-escalation phase,followed by a dose of 2.0×10^(6)cells/kg weekly for the dose-expansion *** events,platelet counts,and changes in peripheral blood immunity were monitored and recorded throughout the administration and follow-up ***,12(with an addition of three patients in the 2.0×10^(6)cells/kg group due to dose-limiting toxicity)and six patients were enrolled in the dose-escalation and dose-expansion phase,*** patients(13/18,72.2%)experienced one or more treatment emergent adverse *** adverse events occurred in four patients(4/18,22.2%),including gastrointestinal hemorrhage(2/4),profuse menstruation(1/4),and acute myocardial infarction(1/4).The response rates were 41.7%in the dose-escalation phase(5/12,two received 1.0×10^(6)cells/kg per week,and three received 2.0×10^(6)cells/kg per week)and 50.0%(3/6)in the dose-expansion *** overall response rate was 44.4%(8/18)among all enrolled *** sum up,UC-MSCs are effective and well tolerated in treating refractory ITP(*** ID:NCT04014166).

关键词： doses immunity treatment

Lipid droplets in the nervous system:involvement in cell metabolic homeostasis

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Neural Regeneration Research 2025年第3期20卷 740-750页

作者： Yuchen Zhang Yiqing Chen Cheng Zhuang Jingxuan Qi Robert Chunhua Zhao Jiao Wang School of Life Sciences Shanghai UniversityShanghaiChina School of Medicine Shanghai UniversityShanghaiChina Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic MedicinePeking Union Medical CollegeBeijingChina Center of Excellence in Tissue Engineering Chinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory of New Drug Development and Clinical Trial of stem cell therapy BeijingChina

Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous *** droplet formation begins with the synthesis of neutral lipids in the endoplasmic ***,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous *** addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress ***,lipid droplets exhibit specific functions in neurons and glial *** of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system *** review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and ***,it will explore the association between lipid droplets and neurodegenerative *** the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

关键词： Alzheimer's disease lipid droplet biogenesis lipid droplets lipid metabolism nervous system neurodegenerative disorders oxidative stress Parkinson's disease

Three-dimensional cell-based strategies for liver regeneration

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BIOcell 2024年第7期48卷 1023-1036页

作者： DAN GUO XI XIA JIAN YANG Liver transplant Center Transplant CenterWest China HospitalSichuan UniversityChengdu610041China Frontiers Medical Center Tianfu Jincheng LaboratoryChengdu610212China

Liver regeneration and the development of effective therapies for liver failure remain formidable challenges in modern *** recent years,the utilization of 3D cell-based strategies has emerged as a promising approach for addressing these urgent clinical *** review provides a thorough analysis of the application of 3D cell-based approaches to liver regeneration and their potential impact on patients with end-stage liver ***,we discuss various 3D culture models that incorporate hepatocytes and stem cells to restore liver function and ameliorate the consequences of liver ***,we explored the challenges in transitioning these innovative strategies from preclinical studies to clinical *** collective insights presented herein highlight the signiﬁcance of 3D cell-based strategies as a transformative paradigm for liver regeneration and improved patient care.

关键词： Three-Dimensional Liver regeneration Organoids stem cells cell therapy

Treatment of postherpetic neuralgia by bone marrow aspirate injection:A case report

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World Journal of Clinical Cases 2023年第15期11卷 3619-3624页

作者： Takahiro Honda Pazili Regenerative Medicine Department of cell therapy Japan Tokyo Stem Cell Transplant Research InstituteTokyo 104-0061Japan

BACKGROUND Postherpetic neuralgia(PHN)is the most frequent and a difficult-to-treat complication of herpes zoster(HZ).Its symptoms include allodynia,hyperalgesia,burning,and an electric shock-like sensation stemming from the hyperexcitability of damaged neurons and varicella-zoster virus-mediated inflammatory tissue ***-related PHN has an incidence of 5%–30%,and in some patients,the pain is intolerable and can lead to insomnia or *** many cases,the pain is resistant to pain-relieving drugs,necessitating radical *** SUMMARY We present the case of a patient with PHN whose pain was not cured by conventional treatments,such as analgesics,block injections,or Chinese medicines,but by bone marrow aspirate concentrate(BMAC)injection containing bone marrow mesenchymal stem *** has already been used for joint ***,this is the first report on its use for PHN *** This report reveals that bone marrow extract can be a radical therapy for PHN.

关键词： Bone marrow aspirate concentrate Postherpetic neuralgia Herpes zoster Bone marrow mesenchymal stem cells Pain syndrome Case report

Outcomes of haploidentical bone marrow transplantation in patients with severe aplastic anemia-II that progressed from non-severe acquired aplastic anemia

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Frontiers of Medicine 2021年第5期15卷 718-727页

作者： Hongchen Liu Xiaoli Zheng Chengtao Zhang Jiajun Xie Beibei Gao Jing Shao Yan Yang Hengxiang Wang Jinsong Yan Department of Hematology Liaoning Medical Center for Hematopoietic Stem Cell TransplantationDalian Key Laboratory of HematologyLiaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational MedicineDiamond Bay Institute of Hematologythe Second Hospital of Dalian Medical UniversityDalian 116027China Department of Hematology Air Force Medical CenterPLABeijing 100142China Department of Environmental Health and Toxicology Liaoning Medical Center for Hematopoietic Stem Cell TransplantationLiaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational MedicineSchool of Public HealthDalian Medical UniversityDalian 116044China

Severe aplastic anemia II(SAA-II)progresses from non-severe aplastic anemia(NSAA).The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation(haplo-BMT)in patients lacking a human leukocyte antigen(HLA)-matched *** study aimed to investigate the efficacy of haplo-BMT for patients with ***-two patients were included and followed up,and FLU/BU/CY/ATG was used as conditioning *** these patients,21 were successfully engrafted,19 of whom survived after *** patients experienced grade II–IV aGvHD,including two with grade III–IV *** patients experienced chronic GvHD,among whom four were mild and two were *** patients experienced infections during *** was diagnosed with post-transplant lymphoproliferative disorder and one with probable EBV disease,and both recovered after rituximab ***-BMT achieved 3-year overall survival and disease-free survival rate of 86.4%±0.73%after a median follow-up of 42 months,indicating its effectiveness as a salvage *** promising outcomes may support haplo-BMT as an alternative treatment strategy for patients with SAA-II lacking HLA-matched donors.

关键词： severe aplastic anemia non-severe acquired aplastic anemia haploidentical bone marrow transplantation outcomes

Interferon α: the salvage therapy for patients with unsatisfactory response to minimal residual disease-directed modified donor lymphocyte infusion

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中华医学杂志(英文版) 2014年第14期127卷 2583-2587页

作者： Mo Xiaodong Zhao Xiangyu Xu Lanping Liu Daihong Zhang Xiaohui Chen Huan Wang Yu Huang Xiaojun Beijing Key Laboratory of hematopoietic stem cell transplantation Institute of HematologyPeople’s HospitalPeking University

Background Minimal residual disease(MRD)-directedmodified donor lymphocyte infusion(mDLI) is used to treat relapse after hematopoietic stem cell transplantation(HSCT). For patients who experience an unsatisfactory response tomDLI, relapse is usually inevitable. Therefore, we sought to evaluate the efficacy ofinterferon α therapy in these *** Regular MRD monitoring was carried out after the HSCT. The patients who were MRD-positive underwent mDLI. Patients with an unsatisfactory response to mDLI received interferon α therapy(3 million units, twice weekly) with regular monitoring of MRD. To ensure the immunomodulatory effects of interferon α, immunosuppressant treatment would be stopped before interferon α *** Five patients with an unsatisfactory response to mDLI treatment received interferon α(3 had t(8;21) chromosomal translocation acute myeloid leukemia, and 2 had common acute leukemia). They had significantly reduced or resolved MRD. Four patients developed chronic graft-versus-host disease. Two of the 5 patients reported transient fevers, and no significant bone marrow suppression was observed. All of them were in continuous complete remission after interferon α treatment. The median survival time was 469 days(range 368–948 days). Conclusions In patients with an unsatisfactory response to MRD-directed mDLI, interferon α may directly or indirectly induce the graft-versus-leukemia effect to improve mDLI efficacy and clear MRD.

关键词： interferon α hematopoietic stem cell transplantation donor lymphocyte infusion

Skeletal stem cells in bone development,homeostasis,and disease

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Protein & cell 2024年第8期15卷 559-574页

作者： Guixin Yuan Xixi Lin Ying Liu Matthew B.Greenblatt Ren Xu The First Affliated Hospital of Xiamen University-ICMRS Collaborating Center for Skeletal stem cell State Key Laboratory of Cellular Stress BiologySchool of MedicineFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361005China Xiamen Key Laboratory of Regeneration Medicine Fujian Provincial Key Laboratory of Organ and Tissue RegenerationOrgan Transplantation InstituteSchool of MedicineXiamen UniversityXiamen 361102China Department of Pathology and Laboratory Medicine Weill Cormell Medical CollegeNew YorkNY 10065USA Research Division Hospital for Special SurgeryNew YorkNY10065USA

Tissue-resident stem cells are essential for development and repair,and in the skeleton,this function is fulfilled by recently identified skeletal stem cells(SSCs).However,recent work has identified that SSCs are not monolithic,with long bones,craniofacial sites,and the spine being formed by distinct stem *** studies have utilized techniques such as fluorescence-activated cell sorting,lineage tracing,and single-cell sequencing to investigate the involvement of ssCs in bone development,homeostasis,and *** investigations have allowed researchers to map the lineage commitment trajectory of ssCs in different parts of the body and at different time ***,recent studies have shed light on the characteristics of ssCs in both physiological and pathological *** review focuses on discussing the spatiotemporal distribution of ssCs and enhancing our understanding of the diversity and plasticity of ssCs by summarizing recent discoveries.

关键词： skeletal stem cells bone development endochondral ossification intramembranous ossification lineage tracing