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Enhancing immunotherapy efficacy against MHC-I deficient triple-negative breast cancer using LCL161-loaded macrophage membranedecorated nanoparticles

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3218-3231页

作者： Wen Zhang Yihui Zhai Ying Cai Xiang Gong Yunxuan Jiang Rong Rong Chao Zheng Binyu Zhu Helen He Zhu Hao Wang Yaping Li Pengcheng Zhang China State institute of Pharmaceutical Industry Shanghai 201203China State Key Laboratory of Drug research&Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Biomedical Engineering&State Key Laboratory of Advanced Medical Materials and Devices ShanghaiTech UniversityShanghai 201210China School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China Yantai institute of Materia Medica Shandong 264000China State Key Laboratory of Oncogenes and Related Genes Renji-Med-X Stem Cell Research CenterDepartment of UrologyRen Ji HospitalSchool of Medicine and School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200127China University of Chinese Academy of Sciences Beijing 100049China

Current cytotoxic T lymphocyte(CTL)activating immunotherapy requires a major histocompatibility complex I(MHC-I)-mediated presentation of tumor-associated antigens,which malfunctions in around half of patients with triple-negative breast cancer(TNBC).Here,we create a LCL161-loaded macrophage membrane decorated nanoparticle(LMN)for immunotherapy of MHC-I-deficient *** on the macrophage membrane helps LMNs recognize CD47-expressing cancer cells for targeted delivery of LCL161,which induces the release of high mobility group protein 1 and proinflammatory cytokines from cancer *** released cytokines and high mobility group protein 1 activate antitumor immunity by increasing the intratumoral density of the phagocytic macrophage subtype by 15 times and elevating the intratumoral concentration of CTL lymphotoxin by 4.6 *** also block CD47-mediated phagocytosis *** inhibit the growth of MHC-I-deficient TNBC tumors,as well as those resistant to combined therapy of anti-PDL1 antibody and albumin-bound paclitaxel,and prolong the survival of animals,during which process CTLs also play important *** macrophage membrane-decorated nanoparticle presents a generalizable platform for increasing macrophagemediated antitumor immunity for effective immunotherapy of MHC-I-deficient cancers.

关键词： MHC-I deficiency Macrophage CD47 Immunotherapy Triple-negative breast cancer Phagocytosis Immune checkpoint Innate immunity

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Does astrocytic L-lactate enhance cognition through myelination?

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Neural Regeneration research 2024年第6期19卷 1167-1168页

作者： Mastura Akter Ying Li Department of Neuroscience City University of Hong Kong Department of Biomedical Sciences City Universit of Hong Kong Centre for regenerative medicine and Health Hong Kong Institute of Science & Innovation Chinese Academy of Sciences Centre for Biosystems Neuroscience and Nanotechnology City University of Hong Kong

Introduction: Astrocytes, the predominant glial cell in the brain, play a vital role in a plethora of central ner vous system functions. They are the major storage site of glycogen in the central nervous system. They produce L-lactate by glycogenolysis and glycolysis which is then transported to neurons(Magistreti and Allaman,

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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander J.P.Goldschmidt Damien D.Pearse W.Dalton Dietrich Allan D.Levi James D.Guest Miller School of medicine University of MiamiMiamiFLUSA stem cell institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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Mesenchymal stem cell-derived extracellular vesicles in skin wound healing:roles,opportunities and challenges

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Military Medical research 2024年第3期11卷 400-429页

作者： Jia-Yi Ding Min-Jiang Chen Ling-Feng Wu Gao-Feng Shu Shi-Ji Fang Zhao-Yu Li Xu-Ran Chu Xiao-Kun Li Zhou-Guang Wang Jian-Song Ji Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention research Institute of Imaging Diagnosis and Minimally Invasive Intervention Researchthe Fifth Affiliated Hospital of Wenzhou Medical UniversityZhejiangLishui 323000China Oujiang Laboratory(Zhejiang Lab for regenerative medicine Vision and Brain Health)School of Pharmaceutical ScienceWenzhou Medical UniversityWenzhou 325035ZhejiangChina Clinical College of the Affiliated Central Hospital School of MedicineLishui UniversityLishui 323000ZhejiangChina Department of Overseas Education College Jimei UniversityXiamen 361021FujianChina Department of medicine Ⅱ Internal MedicineCardio-Pulmonary Institute(CPI)Universities of Giessen and Marburg Lung Center(UGMLC)Member of the German Center for Lung Research(DZL)Justus-Liebig University Giessen35392 GiessenGermany Pulmonary and Critical Care Department of Medicine VInternal MedicineInfectious Diseases and Infection ControlUniversities of Giessen and Marburg Lung Center(UGMLC)Member of the German Center for Lung Research(DZL)Justus-Liebig University Giessen35392 GiessenGermany

Skin wounds are characterized by injury to the skin due to trauma,tearing,cuts,or *** such injuries are common to all human groups,they may at times represent a serious socioeconomic ***,increasing numbers of studies have focused on the role of mesenchymal stem cell(MSC)-derived extracellular vesicles(EVs)in skin wound *** a cell-free therapy,MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell *** based on MSC-derived EVs can significantly promote the repair of damaged substructures,including the regeneration of vessels,nerves,and hair *** addition,MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization,wound angiogenesis,cell proliferation,and cell migration,and by inhibiting excessive extracellular matrix ***,these structures can serve as a scaffold for components used in wound repair,and they can be developed into bioengineered EVs to support trauma *** the formulation of standardized culture,isolation,purification,and drug delivery strategies,exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound *** conclusion,MSCderived EV-based therapies have important application prospects in wound *** we provide a comprehensive overview of their current status,application potential,and associated drawbacks.

关键词： Mesenchymal stem cell(MSC) Extracellular vesicles(EVs) Wound repair Engineered nanoparticles

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Epithelial stem cells and niches in lung alveolar regeneration and diseases

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Chinese Medical Journal Pulmonary and Critical Care medicine 2024年第1期2卷 17-26页

作者： Jilei Zhang Yuru Liu Department of Pharmacology and regenerative medicine University of Illinois College of MedicineChicagoIL 60612USA University of Illinois Cancer Center ChicagoIL 60612USA

Alveoli serve as the functional units of the lungs,responsible for the critical task of blood-gas ***-prising type I(AT1)and type II(AT2)cells,the alveolar epithelium is continuously subject to external aggressors like pathogens and airborne *** such,preserving lung function requires both the homeostatic renewal and reparative regeneration of this epithelial *** in these processes contribute to various lung *** research has pinpointed specific cell subgroups that act as potential stem or progenitor cells for the alveolar epithelium during both homeostasis and ***,endothelial cells,fibroblasts,and immune cells synergistically establish a nurturing microenvironment-or“niche”-that modulates these ep-ithelial stem *** review aims to consolidate the latest findings on the identities of these stem cells and the components of their niche,as well as the molecular mechanisms that govern ***,this article highlights diseases that arise due to perturbations in stem cell-niche *** also discuss recent technical innovations that have catalyzed these ***,this review underscores the heterogeneity,plastic-ity,and dynamic regulation of these stem cell-niche *** is our aspiration that a deeper understanding of the fundamental cellular and molecular mechanisms underlying alveolar homeostasis and regeneration will open avenues for identifying novel therapeutic targets for conditions such as chronic obstructive pulmonary disease(COPD),fibrosis,coronavirus disease 2019(COVID-19),and lung cancer.

关键词： Alveoli Epithelium Type II cell(AT2) stem cell Niche

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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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RBM25 depletion suppresses the growth of colon cancer cells through regulating alternative splicing of MNK2

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Science China Life Sciences 2024年

作者： Lili Zhi Chaoqun Chen Ge Zhang Tian Huang Wenxia He Jinrui Zhang Dan Chen Jiayi Liu Jinyao Zhao Yangfan Qi Guiying Wang Wenjing Zhang Yang Wang Sino-US research Center for Cancer Translational medicine of the Second Affiliated Hospital of Dalian Medical University&institute of Cancer stem cell Dalian Medical University Department of Immunology College of Basic Medical SciencesDalian Medical University institute of Cancer stem cell Dalian Medical University Department of Pathology the First Affiliated Hospital of Dalian Medical UniversityDalian Medical University Department of General Surgery the Second Hospital of Hebei Medical University The Second Department of General Surgery the Fourth Hospital of Hebei Medical University Hebei Key Laboratory of Etiology Tracing and Individualized Diagnosis and Treatment for Digestive System Carcinoma

Increasing evidence suggests that deregulated RNA splicing factors play critical roles in tumorigenesis;however,their specific involvement in colon cancer remains largely *** we report that the splicing factor RBM25 is overexpressed in colon cancer,and this increased expression correlates with a poor prognosis of patients with colon ***,RBM25 ablation suppresses the growth of colon cancer cells both in vitro and in ***,our transcriptome-wide analysis of splicing events revealed that RBM25regulates a large number of cancer-related alternative splicing events across the human genome in colon ***,RBM25regulates the splicing of MNK2 by interacting with the poly G rich region in exon 14a,thereby inhibiting the selection of the proximal 3′splice site (ss),resulting in the production of the oncogenic short isoform,*** of RBM25 leads to an increase in the MNK2a isoform and a decrease in the MNK2b ***,re-expression of MNK2b or blocking the 3′ss of the alternative exon 14a with ASO partially reverses the RBM25 knockdown mediated tumor ***,MNK2b levels were significantly increased in colon cancer tissues,which is positively correlated with the expression level of ***,our findings uncover the critical role of RBM25 as a key splicing factor in colon cancer,suggesting its potential as a prognostic marker and therapeutic target.

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Expression levels of K_(ATP)channel subunits and morphological changes in the mouse liver after exposure to radiation

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World Journal of Experimental medicine 2024年第2期14卷 103-113页

作者： Ming Zhou Tao-Sheng Li Hiroshi Abe Hideo Akashi Ryoji Suzuki Yoshio Bando Department of Anatomy Akita University Graduate School of MedicineAkita 010-8543Japan Department of stem cell Biology Atomic Bomb Disease InstituteNagasaki UniversityNagasaki 852-8523Japan Sendai Old Age Refresh Station A Long-term Care Health FacilitySendai 981-1105Japan

BACKGROUND ATP sensitive K+(K_(ATP))channels are ubiquitously distributed in various of cells and tissues,including the *** play a role in the pathogenesis of myocardial and liver *** To evaluate the radiation-induced changes in the expression of K_(ATP)channel subunits in the mouse liver to understand the potential role of K_(ATP)channels in radiation *** Adult C57BL/6 mice were randomly exposed toγ-rays at 0 Gy(control,n=2),0.2 Gy(n=6),1 Gy(n=6),or 5 Gy(n=6).The livers were removed 3 and 24 h after radiation *** and eosin staining was used for morphological observation;immunohistochemical staining was applied to determine the expression of K_(ATP)channel subunits in the liver *** Compared with the control group,the livers exposed to 0.2 Gyγ-ray showed an initial increase in the expression of Kir6.1 at 3 h,followed by recovery at 24 h after *** to a high dose of 5.0 Gy resulted in decreased expression of Kir6.1 and increased expression of SUR2B at 24 ***,the expression of Kir6.2,SUR1,or SUR2A had no remarkable changes at 3 and 24 h after exposure to any of these *** The expression levels of Kir6.1 and SUR2B in mouse liver changed differently in response to different radiation doses,suggesting a potential role for them in radiation-induced liver injury.

关键词： Radiation exposure ATP-sensitive K^(+)channel Mouse Liver

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XELOX(capecitabine plus oxaliplatin)plus bevacizumab(anti-VEGF-A antibody)with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer:a multicenter,open-label,randomized,controlled,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2104-2113页

作者： Qiu-Zhong Pan Jing-Jing Zhao Liang Liu Dong-Sheng Zhang Li-Ping Wang Wen-Wei Hu De-Sheng Weng Xiang Xu Yi-Zhuo Li Yan Tang Wei-Hong Zhang Jie-Yao Li Xiao Zheng Qi-Jing Wang Yong-Qiang Li Tong Xiang Li Zhou Shuang-Ning Yang Chen Wu Rong-Xing Huang Jia He Wei-Jiao Du Lu-Jun Chen Yue-Na Wu Bin Xu Qiong Shen Yi Zhang Jing-Ting Jiang Xiu-Bao Ren Jian-Chuan Xia State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerCollaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Department of Biotherapy Sun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Tianjin Medical University Cancer institute and Hospital National Clinical Research Center for CancerTianjin 300060PR China Key Laboratory of Cancer Immunology and Biotherapy Tianjin 300060PR China Department of Biotherapy/Immunology Tianjin Medical University Cancer Institute and HospitalTianjin 300060PR China Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060PR China Department of Oncology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052PR China Department of Tumor Biological Treatment the Third Affiliated Hospital of Soochow UniversityChangzhouJiangsu 213003PR China Jiangsu Engineering research Center for Tumor Immunotherapy ChangzhouJiangsu 213003PR China institute for cell Therapy of Soochow University ChangzhouJiangsu 213003PR China Department of stem cell&regenerative medicine State Key Laboratory of TraumaBurn and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042PR China Imaging Diagnosis and Interventional Center Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060PR China

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer(mCRC),but the prognosis remains *** phase 3 trial(***:NCT03950154)assessed the efficacy and adverse events(AEs)of the combination of PD-1 blockade-activated DC-CIK(PD1-T)cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC.A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab(the control group,n=102)or the same regimen plus autologous PD1-T cell immunotherapy(the immunotherapy group,n=100)every 21 days for up to 6 cycles,followed by maintenance treatment with capecitabine and *** main endpoint of the trial was progression-free survival(PFS).The median follow-up was 19.5 *** PFS was 14.8 months(95%CI,11.6-18.0)for the immunotherapy group compared with 9.9 months(8.0-11.8)for the control group(hazard ratio[HR],0.60[95%CI,0.40-0.88];p=0.009).Median overall survival(OS)was not reached for the immunotherapy group and 25.6 months(95%CI,18.3-32.8)for the control group(HR,0.57[95%CI,0.33-0.98];p=0.043).Grade 3 or higher AEs occurred in 20.0%of patients in the immunotherapy group and 23.5%in the control groups,with no toxicity-associated deaths *** addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

关键词： PD1 immunotherapy bevacizumab

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Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

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Bio-Design and Manufacturing 2024年第2期7卷 121-136页

作者： Yang-Hee Kim Janos M.Kanczler Stuart Lanham Andrew Rawlings Marta Roldo Gianluca Tozzi Jonathan I.Dawson Gianluca Cidonio Richard O.C.Oreffo Faculty of medicine Bone and Joint Research GroupCentre for Human DevelopmentStem Cells and RegenerationInstitute of Developmental SciencesUniversity of SouthamptonSouthampton SO166YDUK School of Pharmacy and Biomedical Science University of PortsmouthPortsmouth PO12DTUK School of Engineering Faculty of Engineering and ScienceUniversity of GreenwichGreenwich ME44TBUK Center for Life Nano-and Neuro-Science(CLN2S) Italian Institute of Technology00161 RomeItaly

Autograft or metal implants are routinely used in skeletal ***,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering *** use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor ***,human bone extracellular matrix(bone-ECM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBMSCs)to proliferate and differentiate along the osteogenic *** this study,we engineered a novel material ink(LAB)by blending human bone-ECM(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based *** inclusion of the nanoﬁller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBMSCs viability upon *** composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAM)*** inclusion of bone morphogenetic protein-2(BMP-2)with the HBMSCs further enhanced vascularization and mineralization after only seven *** study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

关键词： Extracellular matrix Nanoclay Bone 3D bioprinting

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