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Advances in oral mesenchymal stem cell-derived extracellular vesicles in health and disease

Genes & Diseases 2024年第1期11卷 346-357页

作者： Huanyu Luo Anahid Ahmadi Birjandi Feilong Ren tianmeng sun Paul T.Sharpe Hongchen sun Zhengwen An Department of Oral Biology Jilin Provincial Key Laboratory of Tooth Development and Bone RemodelingSchool and Hospital of StomatologyJilin UniversityChangchunJilin 130021China Faculty of Dentistry Oral&Craniofacial SciencesCentre for Craniofacial and Regenerative BiologyKing's College LondonLondonSE19RTUK Department of Oral Pathology Jilin Provincial Key Laboratory of Tooth Development and Bone RemodelingSchool and Hospital of StomatologyJilin UniversityChangchunJilin 130021China

Extracellular vesicles(EVs)are nano-size vesicles secreted naturally by all cells into the extracellular space and have been recognized as important cell-cell mediators in multicel-lular *** contain nucleic acids,proteins,lipids,and other cellular components,regulating many basic biological processes and playing an important role in regenerative med-icine and *** can be traced to their cells of origin and exhibit a similar ***,EVs demonstrate low immunogenicity,good biocompatibility,and fewer side ef-fects,compared to their parent *** stem cells(MsCs)are one of the most important resource cells for EVs,with a great capacity for self-renewal and multipotent differ-entiation,and play an essential role in stem cell *** mechanism of MsC therapy was thought to be attributed to the differentiation of MsCs after targeted migration,as previously ***,emerging evidence shows the previously unknown role of MsC-derived para-crine factors in stem cell *** EVs derived from oral tissue MSCs(OMSC-EVs),show more advantages than those of all other MsCs in tissue repair and regeneration,due to their lower invasiveness and easier accessibility for sample ***,we systematically review the biogenesis and biological characteristics of OMSC-EVs,as well as the role of OMsC-EVs in intercellular ***,we discuss the potential therapeutic roles of OMSC-EVs in oral and systemic *** highlight the current challenges and future directions of OMSC-EVs to focus more attention on clinical *** aim to provide valuable insights for the explorative clinical application of OMSC-EVs.

关键词： Disease Extracellular vesicles Oral tissue MSC Therapeutic application Tissue regeneration

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Targeted nanostrategies eliminate pre-metastatic niche of cancer

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Nano Research 2024年第6期17卷 5358-5373页

作者： Juan Wang Ning Zhang Xiuping Ding Chengrui Fu Xiaodong Li Baosheng Li Jianxun Ding tianmeng sun Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education Institute of ImmunologyThe First HospitalJilin University1 Xinmin StreetChangchun 130061China Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of Sciences5625 Renmin StreetChangchun 130022China Department of Radiation Oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical Sciences440 Jiyan RoadJinan 250117China Department of orthopaedics The Second Hospital of Shandong UniversityShandong University247 Beiyuan StreetJinan 250033China State Key Laboratory of Molecular Engineering of Polymers Fudan University220 Handan RoadShanghai 200433China

Establishing a pre-metastatic niche(PMN)in secondary organs is a prerequisite for cancer *** advances in cancer therapy,the efficient inhibition of PMN formation remains a clinical *** advances in understanding the specific characteristics of PMN and advances in nanotechnology have provided hope for manipulating their microenvironments.A series of nanostrategies have been designed to eliminate the PMN,including the removal of pro-metastatic exosomes from the bloodstream for excretion via the intestines,the targeting and scavenging of myeloid-derived suppressor cells,fibroblasts,and critical extracellular matrix components,and the elimination of circulating tumor cells prior to colonization in distant *** review summarizes the underlying mechanisms of PMN formation,highlights the anti-PMN efficacy of currently reported nanostrategies,and underlines the unresolved questions.

关键词： nanoparticle controlled drug delivery pre-metastatic niche elimination metastasis suppression cancer therapy

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Surface-modulated and thermoresponsive polyphosphoester nanoparticles for enhanced intracellular drug delivery

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Science China Chemistry 2014年第4期57卷 579-585页

作者： LI Yang WANG Feng sun tianmeng DU JinZhi YANG XianZhu WANG Jun Department of Polymer Science and Engineering University of Science and Technology of China Hefei National Laboratory for Physical Sciences at Microscale School of Life Sciences University of Science and Technology of China School of Medical Engineering Hefei University of Technology High Magnetic Field Laboratory of CAS University of Science and Technology of China

The chemical structure of end groups influenced the phase transition temperature of thermoresponsive polymers. We demonstrated a strategy for the preparation of the pH/thermo-responsive polymeric nanoparticles via subtle modification of end groups of thermoresponsive polymer segments with a carboxyl group and revealed its potential application for enhanced intracellular drug delivery. By developing a polymeric nanoparticle composed of poly(aliphatic ester) as the inner core and thermoresponsive polyphosphoester as the outer shell, we showed that end groups of thermoresponsive polyphosphoester segments modified by carboxyl groups exhibited a pH/thermo-responsive behavior due to the hydrophilic to hydrophobic transitions of the end groups in response to the pH. Moreover, by encapsulating doxorubicin into the hydrophobic core of such pH/thermo-responsive polymer nanoparticles, their intracellular delivery and cytotoxicity to wild-type and drug-resistant tumor cells were significantly enhanced through the phase-transition-dependent drug release that was triggered by endosomal/lysosomal pH. This novel strategy and the multi-responsive polymer nanoparticles achieved by the subtle chain-terminal modification of thermoresponsive polymers provide a smart platform for biomedical applications.

关键词： thermoresponsive drug release polyphosphoester drug resistance

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单细胞组学揭示免疫补体系统抑制作为牙周炎与阿尔茨海默病的共同病理机制

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国际老年医学杂志 2024年第4期45卷 390-396页

作者：孙天萌孙泽文赵天元徐梦钰孙宏晨安政雯吉林大学白求恩口腔医学院长春130021

目的牙周炎和阿尔茨海默病(AD)作为老年人常见病,发病率随年龄增长而增高。为了探究两种疾病之间是否存在共同致病因素,从而为AD的早期诊断提供理论依据,本研究利用单细胞转录组数据和Bulk RNA-seq测序数据解析牙周炎与AD之间致病风险... 详细信息

目的牙周炎和阿尔茨海默病(AD)作为老年人常见病,发病率随年龄增长而增高。为了探究两种疾病之间是否存在共同致病因素,从而为AD的早期诊断提供理论依据,本研究利用单细胞转录组数据和Bulk RNA-seq测序数据解析牙周炎与AD之间致病风险的相关性。方法从基因表达数据集(GEO)数据库下载牙周炎(GSE164241)和AD(GSE157827)单细胞数据,包括3例患者样本与3例对照。对单细胞数据进行质控、数据整合、降维聚类、细胞类型注释及差异表达基因鉴定。比较两种疾病组间差异表达基因,获取共有的差异表达基因。随后对共有差异表达基因进行富集分析,并针对基因所编码蛋白构建蛋白质-蛋白质相互作用(PPI)网络以了解蛋白之间的相互作用关系。从GEO数据库下载牙周炎(GSE16134)与AD(GSE63060)的Bulk RNA-seq芯片测序表达矩阵与样本信息,验证单细胞数据中PPI的核心基因表达量,评估基因与疾病的相关性。结果通过对比牙周炎和AD的样本数据分析,发现牙周炎与AD中共有的免疫细胞为CD163+髓系细胞群,其中牙周炎来源的髓系细胞,疾病组/对照组发现1 934个下调的差异表达基因,AD来源的髓系细胞,疾病组/对照组发现232个下调的差异表达基因,两者取交集后得到49个共有的下调差异表达基因,对其进行富集分析,主要富集于髓系细胞和补体相关反应等。进一步分析表明补体通路中的STAB1基因表达与牙周炎和AD呈显著负相关(P<0.05)。结论髓系细胞是牙周炎和AD共有的免疫细胞,其中补体通路中STAB1基因是两种疾病发生过程中共同下调的免疫相关基因,并且与疾病的发生呈显著负相关,提示牙周炎患者中STAB1基因表达的检测可作为AD早期诊断和治疗的潜在靶点。

关键词：牙周炎阿尔茨海默病免疫反应髓系细胞补体

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抗原改造联合纳米肿瘤疫苗用以克服肿瘤新抗原短缺及在多种肿瘤类型上激起强效抗肿瘤免疫反应

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Science Bulletin 2024年第7期69卷 922-932页

作者：陈宏宇黄子超李佳玄董思徐玉笛马胜赵佳雨刘丽萍孙天盟宋万通陈学思 School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei 230026China Key laboratory of Polymer Ecomaterials Changchun Institue of Applied ChemistryChinese Academy of SciencesChangchun 130022China Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education Institute of ImmunologyThe First HospitalJilin UniversityChangchun 130021China Jilin Biomedical Polymers Engineering Laboratory Changchun 130022China

Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer ***,identifying neoantigens for tumor types with low tumor mutation burdens continues to limit the effectiveness of neoantigen ***,we proposed a "hit-and-run" vaccine strategy which primes T cells to attack tumor cells decorated with exogenous "neo-antigens".This vaccine strategy utilizes a peptide nanovaccine to elicit antigen-specific T cell responses after tumor-specific decoration with a nanocarrier containing the same peptide *** demonstrated that a poly(2-oxazoline)s(POx) conjugated with OVA_(257-264) peptide through a matrix metalloprotease 2(MMP-2) sensitive linker could efficiently and selectively decorate tumor cells with OVA peptides in ***,a POx-based nanovaccine containing OVA_(257-264) peptides to elicit OVA-specific T cell responses was *** combination with this hit-and-run vaccine system,an effective vaccine therapy was demonstrated across tumor types even without OVA antigen *** approach provides a promising and uniform vaccine strategy against tumors with a low tumor mutation burden.

关键词： Cancer immunotherapy Cancer vaccine Neoantigen Nanocarrier Poly(2-oxazoline)s

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Multiresponsive Polymer Assemblies Achieved by a Subtle Chain Terminal Modification

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Chinese Journal of Chemistry 2014年第1期32卷 51-56页

作者： Weiwei Liu Yucai Wang Yang Li Feng Wang Xianzhu Yang tianmeng sun Jinzhi Du Jun Wang Nano Science and Technology Institute University of Science and Technology of China Suzhou Jiangsu 215123 China Department of Polymer Science and Engineering University of Science and Technology of China Hefei Anhui 230026 China CAS Key Laboratory of Brain Function and Disease and School of Life Sciences University of Science and Technology of China Hefei Anhui 230027 China School of Medical Engineering Hefei University of Technology Hefei Anhui 230009 China Email: Xianzhu Yang (yangxz@***) Jun Wang (jwang699@***)[*]CAS Key Laboratory of Brain Function and Disease and School of Life Sciences University of Science and Technology of China Hefei Anhui 230027 China Tel.: 0086-0551-63600335 Fax: 0086-0551-63600402

Inspired by the influence of chemical structure of end groups on the phase transition temperature of thermoresponsive polymers,we demonstrated a strategy to control the multi-responsiveness of polymer assemblies via subtle modification of end groups of thermoresponsive polymer segments and revealed its potential application for drug *** developing polymer assemblies composed of poly(aliphatic ester) as the inner core and thermoresponsive polyphosphoester as the outer shell,we showed that end groups of thermoresponsive polyphosphoester segments controlled the surface property of assemblies and further determined the stimuli-responsive *** phase-transition temperatures of the unmodified polymer assemblies are tightly controlled by their surface properties due to the hydrophilic to hydrophobic transitions of end groups in response to an environmental stimulus (*** or light irradiation).External control over these surface properties can by asserted by adjusting the chemical structure and composition of the terminal groups of the thermoresponsive polyphosphoesters.

关键词： multi-responsive thermoresponsive phase-transition polyphosphoester

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Poly(Ethylene Oxide) Mediated Synthesis of Sub-100-nm Aluminum Nanocrystals for Deep Ultraviolet Plasmonic Nanomaterials

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CCS Chemistry 2020年第4期2卷 516-526页

作者： Shuang Yang Shaoyong Lu Yang Li Hua Yu Linxia He tianmeng sun Bai Yang Kun Liu State Key Laboratory of Supramolecular Structure and Materials College of ChemistryJilin UniversityChangchun130012 The First Bethune Hospital and Institute of Immunology Jilin UniversityChangchun 130021 State Key Laboratory of Applied Optics Changchun Institute of OpticsFine Mechanics and PhysicsChinese Academy of SciencesChangchun 130012

Aluminum nanocrystals(Al NCs)are sustainable plasmonic nanomaterials with unique localized surface plasmonic resonance(LSPR)in the ultraviolet(UV)*** synthesis of sub-100-nm Al NCs remains a considerable challenge due to the lack of effective ligands to control their ***,we describe a precise size-controlled synthesis of small colloidal Al NCs(25–100 nm)with strong and tunable LSPR peak from 250 to 372 nmin the UV spectral region by the use of poly(ethylene oxide)(PEO)as a polydentate surface ligand.

关键词： aluminum nanocrystal UV plasmonics polymer ligands size-controlled synthesis poly (ethylene) oxide

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Gold Nanoparticle Enantiomers and Their Chiral-Morphology Dependence of Cellular Uptake

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CCS Chemistry 2022年第2期4卷 660-670页

作者： Ning-Ning Zhang Hao-Ran sun Shuhan Liu Yu-Chen Xing Jun Lu Fei Peng Cheng-Long Han Zhonglin Wei tianmeng sun Bai Yang Kun Liu State Key Laboratory of Supramolecular Structure and Materials College of ChemistryJilin UniversityChangchun 130012 Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education Institute of ImmunologyThe First HospitalJilin UniversityChangchun 130012 National-Local Joint Engineering Laboratory of Animal Models for Human Diseases Changchun 130012 Department of Chemical Engineering University of MichiganAnn ArborMI 48109 Department of Organic Chemistry College of ChemistryJilin UniversityChangchun 130012 International Center of Future Science Jilin UniversityChangchun 130012 Chiral Nanomaterial Research Center International Center of Future ScienceJilin UniversityChangchun 130012

Chiral molecules are widely prevalent in nature and biological systems,and artificial chiral nanoparticles have drawn enormous interest owing to their unique optical and physical ***,nanoparticles with chiral morphologies and their potential role in biology have been rarely ***,we report a seed-mediated synthesis of enantiomorphic Au nanooctopods(NOPs)and their chiralmorphology dependence of cellular *** a high yield(∼80%),the chiral NOPs possess eight uniform arms that bend fromtodirections,like a propeller *** chiral NOPs synthesized with L-or D-glutathione(GSH)have opposite handedness,resulting in opposite circular dichroism signals,which is consistent with finite-difference time-domain simulations.D-GSH NOPs demonstrate greater than 30%(ca.15%)enhanced cellular uptake in GL261 and bEnd.3 cells compared with L-GSH NOPs(racemic NOPs).Moreover,D-GSH NOPs modified with poly(ethylene glycol)or L-GSH are also preferred by the cells,proving the chiral-morphology dependence of cellular *** study develops the exploration of the chiral-specific interaction in biological systems,providing potential applications for drug delivery,biosensing,and tumor detection.

关键词： chirality branched nanoparticles chiral morphology selective cellular uptake surface plasmonic resonance

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Simultaneous Silencing CD40 Genes in Macrophages and Dendritic Cells Using a Novel siRNA Delivery System for Immunomodulation During Skin Transplantation

Simultaneous Silencing CD40 Genes in Macrophages and Dendrit...

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第十一届全国免疫学学术大会

作者： Wang Jialiang sun tianmeng Yang Yongguang The First Hospital and Institute of Immunology Jilin University Department of Medicine Columbia Center for Translational ImmunologyColumbia University College of Physicians and Surgeons

Objects: Develop a novel siRNA delivery system to down-regulate the expression of CD40 in macrophages and DCs in vivo and prolong the survival of allogeneic skin ***: In our study, PLGA/si CD40 nanoparticles were prepared by a double emulsion-solvent evaporation technique. An aqueous solution of siRNA(0.2 mg) in 25 μL RNase free water was emulsified by sonication for 30 s over an ice bath in 0.5 ml of chloroform containing 1.0 mg DOTAP and 25 mg m PEG5k-PLGA10 k. This primary emulsion was further emulsified in 5 m L dd H2 O by sonication for 1 min to form a water-in-oil-in-water emulsion. Then, the emulsion was moved into round-bottomed flasks to evaporate the chloroform. The PLGA/FAM-siRNA NPs were added into the medium of DC1.2 and RAW264.7 cells and the cells were collected after 48 h for flow cytometry(FCM) and confocal imaging. Furthermore, DC1.2 and RAW264.7 cells were collected for analysis of CD40 expression by quantitative PCR(qP CR) after co-cultured with PLGA/si CD40 NPs for 48 h. The C57BL/6 mice were sacrificed and PBMCs, splenocytes and bone marrow cells were collected for FCM 16 h after PLGA/Cy5-siRNA NPs i.v. injection. We evaluated the biological effects of PLGA/si CD40 NPs in vivo in PLGA NPs i.v. injection Balb/c to C57BL/6 skin graft ***: PEG-PLGA nanoparticles could deliver siRNAinto macrophages and DCs in vitro, which was demonstrated by both FCM results and confocal imaging. Also, we evaluated the efficiency of down regulation of CD40 expression by PLGA/si CD40 NPs both in vitro and in vivo. In the transient parabiosis skin transplantation model, PLGA/si CD40 NPs could prolong the survival of transplanted skin ***: PEG-PLGA nanoparticles was a proper siRNA delivery system for macrophages and DCs, which can effectively down-regulate the expression of CD40 both in vitro and in vivo, and prolonged the survival of allogeneic skin graft.

关键词： CD40 RNAi nanoparticles immunomodulation

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The role of GITR-GITRL interaction in transplantation

The role of GITR-GITRL interaction in transplantation

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第十届全国免疫学学术大会

作者： Xue Wan tianmeng sun Yongguang Yang First Hospital Academy of Translational Medicine of Jilin University Institute of Immunology of Jilin University

The immunomodulatory molecules expressed on the membranes of immune cells can co-stimulate or co-inhibit cell ***-induced TNF receptor(GITR),also known as TNFRSF18,is a type I transmembrane protein with high homology to other members of the TNFR *** is preferentially expressed by regulatory T cells(Tregs).GITRL,the ligand of GITR,is expressed on endothelial cells,B cells,macrophages,and bone-marrow-derived *** GITR–GITRL interaction plays a significant role in cancer,autoimmunity,infection,and *** in vivo models of transplant tolerance have been found to depend on the induction of *** is upregulated on dendritic cells(DCs)in the draining lymph node(LN)after allotransplantation,and thought to regulate Tregs via interaction with *** a soluble GITR fusion protein(GITR-Fc)that binds to GITRL,it has been shown that disruption of the interaction between GITR and GITRL can improve Treg function,offering an important strategy for prolonging allograft *** contrast to in vitro studies with human Retinal pigment epithelium(RPE)cells,corneal allografts appear to depend on GITRL for Treg expansion and the protection from immune rejection perhaps because of the unique immune environment of the *** the setting of graft-versus-host disease(GVHD)following MHC-mismatched allogeneic bone marrow transplantation,GITR stimulation in vivo led to increased alloreactive CD8 T cell proliferation,but decreased CD4 T cell alloresponses due to the enhanced Fas L-dependent activation-induced cell death(AICD).In summary,GITR signaling represents a potential therapeutic target for acute inflammatory responses following *** further consideration,blockade of GITR–GITRL interaction is a potential strategy for inducing transplant tolerance.

关键词： GITR GITRL transplantation Treg tolerance

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