Nature Biomedical Engineering最新文献_第2页

Molecular probes for in vivo optical imaging of immune cells 用于免疫细胞体内光学成像的分子探针

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-21 DOI: 10.1038/s41551-024-01275-7

Jing Liu, Penghui Cheng, Cheng Xu, Kanyi Pu

{"title":"Molecular probes for in vivo optical imaging of immune cells","authors":"Jing Liu, Penghui Cheng, Cheng Xu, Kanyi Pu","doi":"10.1038/s41551-024-01275-7","DOIUrl":"https://doi.org/10.1038/s41551-024-01275-7","url":null,"abstract":"Advancing the understanding of the various roles and components of the immune system requires sophisticated methods and technology for the detection of immune cells in their natural states. Recent advancements in the development of molecular probes for optical imaging have paved the way for non-invasive visualization and real-time monitoring of immune responses and functions. Here we discuss recent progress in the development of molecular probes for the selective imaging of specific immune cells. We emphasize the design principles of the probes and their comparative performance when using various optical modalities across disease contexts. We highlight molecular probes for imaging tumour-infiltrating immune cells, and their applications in drug screening and in the prediction of therapeutic outcomes of cancer immunotherapies. We also discuss the use of these probes in visualizing immune cells in atherosclerosis, lung inflammation, allograft rejection and other immune-related conditions, and the translational opportunities and challenges of using optical molecular probes for further understanding of the immune system and disease diagnosis and prognosis.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"2 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization of tumour heterogeneity through segmentation-free representation learning on multiplexed imaging data

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-20 DOI: 10.1038/s41551-025-01348-1

Jimin Tan, Hortense Le, Jiehui Deng, Yingzhuo Liu, Yuan Hao, Michelle Hollenberg, Wenke Liu, Joshua M. Wang, Bo Xia, Sitharam Ramaswami, Valeria Mezzano, Cynthia Loomis, Nina Murrell, Andre L. Moreira, Kyunghyun Cho, Harvey I. Pass, Kwok-Kin Wong, Yi Ban, Benjamin G. Neel, Aristotelis Tsirigos, David Fenyö

{"title":"Characterization of tumour heterogeneity through segmentation-free representation learning on multiplexed imaging data","authors":"Jimin Tan, Hortense Le, Jiehui Deng, Yingzhuo Liu, Yuan Hao, Michelle Hollenberg, Wenke Liu, Joshua M. Wang, Bo Xia, Sitharam Ramaswami, Valeria Mezzano, Cynthia Loomis, Nina Murrell, Andre L. Moreira, Kyunghyun Cho, Harvey I. Pass, Kwok-Kin Wong, Yi Ban, Benjamin G. Neel, Aristotelis Tsirigos, David Fenyö","doi":"10.1038/s41551-025-01348-1","DOIUrl":"10.1038/s41551-025-01348-1","url":null,"abstract":"High-dimensional multiplexed imaging can reveal the spatial organization of tumour tissues at the molecular level. However, owing to the scale and information complexity of the imaging data, it is challenging to discover and thoroughly characterize the heterogeneity of tumour microenvironments. Here we show that self-supervised representation learning on data from imaging mass cytometry can be leveraged to distinguish morphological differences in tumour microenvironments and to precisely characterize distinct microenvironment signatures. We used self-supervised masked image modelling to train a vision transformer that directly takes high-dimensional multiplexed mass-cytometry images. In contrast with traditional spatial analyses relying on cellular segmentation, the vision transformer is segmentation-free, uses pixel-level information, and retains information on the local morphology and biomarker distribution. By applying the vision transformer to a lung-tumour dataset, we identified and validated a monocytic signature that is associated with poor prognosis. Self-supervised representation learning on data from imaging mass cytometry can be used to distinguish morphological differences in tumour microenvironments and to precisely characterize distinct microenvironment signatures.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"9 3","pages":"405-419"},"PeriodicalIF":26.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Charting targeted courses for vaccination

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-17 DOI: 10.1038/s41551-025-01366-z

引用次数: 0

Microfluidic technologies for enhancing the potency, predictability and affordability of adoptive cell therapies

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-14 DOI: 10.1038/s41551-024-01315-2

Zongjie Wang, Shana O. Kelley

引用次数: 0

Nitroglycerin-responsive gene switch for the on-demand production of therapeutic proteins

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-14 DOI: 10.1038/s41551-025-01350-7

Mohamed Mahameed, Shuai Xue, Benjamin Danuser, Ghislaine Charpin-El Hamri, Mingqi Xie, Martin Fussenegger

{"title":"Nitroglycerin-responsive gene switch for the on-demand production of therapeutic proteins","authors":"Mohamed Mahameed, Shuai Xue, Benjamin Danuser, Ghislaine Charpin-El Hamri, Mingqi Xie, Martin Fussenegger","doi":"10.1038/s41551-025-01350-7","DOIUrl":"https://doi.org/10.1038/s41551-025-01350-7","url":null,"abstract":"Gene therapies and cell therapies require precise, reversible and patient-friendly control over the production of therapeutic proteins. Here we present a fully human nitric-oxide-responsive gene-regulation system for the on-demand and localized release of therapeutic proteins through clinically licensed nitroglycerin patches. Designed for simplicity and robust human compatibility, the system incorporates human mitochondrial aldehyde dehydrogenase for converting nitroglycerin into nitric oxide, which then activates soluble guanylate cyclase to produce cyclic guanosine monophosphate, followed by protein kinase G to amplify the signal and to trigger target gene expression. In a proof-of-concept study, human cells expressing the nitroglycerin-responsive system were encapsulated and implanted subcutaneously in obese mice with type 2 diabetes. Transdermal nitroglycerin patches applied over the implant enabled the controlled and reversible production of glucagon-like peptide-1 throughout the 35-day experimental period, effectively restoring blood glucose levels in these mice without affecting heart rate or blood pressure. The approach may facilitate the development of safe, convenient and responsive implantable devices for the sustained delivery of biopharmaceuticals for the management of chronic diseases.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"29 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting vaccines to dendritic cells by mimicking the processing and presentation of antigens in xenotransplant rejection

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-13 DOI: 10.1038/s41551-025-01343-6

Jinjin Wang, Yuxuan Zhang, Yaru Jia, Haonan Xing, Fengfei Xu, Bozhang Xia, Wenjia Lai, Yuan Yuan, Xianlei Li, Shaobo Shan, Junge Chen, Weisheng Guo, Jinchao Zhang, Aiping Zheng, Jinghong Li, Ningqiang Gong, Xing-Jie Liang

{"title":"Targeting vaccines to dendritic cells by mimicking the processing and presentation of antigens in xenotransplant rejection","authors":"Jinjin Wang, Yuxuan Zhang, Yaru Jia, Haonan Xing, Fengfei Xu, Bozhang Xia, Wenjia Lai, Yuan Yuan, Xianlei Li, Shaobo Shan, Junge Chen, Weisheng Guo, Jinchao Zhang, Aiping Zheng, Jinghong Li, Ningqiang Gong, Xing-Jie Liang","doi":"10.1038/s41551-025-01343-6","DOIUrl":"10.1038/s41551-025-01343-6","url":null,"abstract":"Targeting the delivery of vaccines to dendritic cells (DCs) is challenging. Here we show that, by mimicking the fast and strong antigen processing and presentation that occurs during the rejection of xenotransplanted tissue, xenogeneic cell membrane-derived vesicles exposing tissue-specific antibodies can be leveraged to deliver peptide antigens and mRNA-encoded antigens to DCs. In mice with murine melanoma and murine thymoma, xenogeneic vesicles encapsulating a tumour-derived antigenic peptide or coated on lipid nanoparticles encapsulating an mRNA coding for a tumour antigen elicited potent tumour-specific T-cell responses that inhibited tumour growth. Mice immunized with xenogeneic vesicle-coated lipid nanoparticles encapsulating an mRNA encoding for the spike protein of severe acute respiratory syndrome coronavirus 2 elicited titres of anti-spike receptor-binding domain immunoglobulin G and of neutralizing antibodies that were approximately 32-fold and 6-fold, respectively, those elicited by a commercialized mRNA–lipid nanoparticle vaccine. The advantages of mimicking the biological recognition between immunoglobulin G on xenogeneic vesicles and fragment crystallizable receptors on DCs may justify the assessment of the safety risks of using animal-derived biological products in humans. By mimicking antigen processing and presentation during the rejection of xenotransplanted tissue, xenogeneic cell membrane-derived vesicles encapsulating peptide antigens or mRNA-encoded antigens function as vaccines targeted to dendritic cells.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"9 2","pages":"201-214"},"PeriodicalIF":26.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High-throughput multiplexed serology via the mass-spectrometric analysis of isotopically barcoded beads

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-12 DOI: 10.1038/s41551-025-01349-0

Alexandros P. Drainas, David R. McIlwain, Alec Dallas, Theresa Chu, Antonio Delgado-González, Maya Baron, Maria Angulo-Ibáñez, Angelica Trejo, Yunhao Bai, John W. Hickey, Guolan Lu, Scott Lu, Jesus Pineda-Ramirez, Khamal Anglin, Eugene T. Richardson, John C. Prostko, Edwin Frias, Venice Servellita, Noah Brazer, Charles Y. Chiu, Michael J. Peluso, Jeffrey N. Martin, Oliver F. Wirz, Tho D. Pham, Scott D. Boyd, J. Daniel Kelly, Julien Sage, Garry P. Nolan, Xavier Rovira-Clavé

{"title":"High-throughput multiplexed serology via the mass-spectrometric analysis of isotopically barcoded beads","authors":"Alexandros P. Drainas, David R. McIlwain, Alec Dallas, Theresa Chu, Antonio Delgado-González, Maya Baron, Maria Angulo-Ibáñez, Angelica Trejo, Yunhao Bai, John W. Hickey, Guolan Lu, Scott Lu, Jesus Pineda-Ramirez, Khamal Anglin, Eugene T. Richardson, John C. Prostko, Edwin Frias, Venice Servellita, Noah Brazer, Charles Y. Chiu, Michael J. Peluso, Jeffrey N. Martin, Oliver F. Wirz, Tho D. Pham, Scott D. Boyd, J. Daniel Kelly, Julien Sage, Garry P. Nolan, Xavier Rovira-Clavé","doi":"10.1038/s41551-025-01349-0","DOIUrl":"https://doi.org/10.1038/s41551-025-01349-0","url":null,"abstract":"In serology, each sample is typically tested individually, one antigen at a time. This is costly and time consuming. Serology techniques should ideally allow recurrent measurements in parallel in small sample volumes and be inexpensive and fast. Here we show that mass cytometry can be used to scale up multiplexed serology testing by leveraging polystyrene beads uniformly loaded with combinations of stable isotopes. We generated 18,480 unique isotopically barcoded beads to simultaneously detect, in a single tube with 924 serum samples, the levels of immunoglobulins G and M against 19 proteins from SARS-CoV-2 (a total of 36,960 tests in 400 nl of sample volume and 30 μl of reaction volume). As a rapid, high-throughput and cost-effective technique, serology by mass cytometry may contribute to the effective management of public health emergencies originating from infectious diseases.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"22 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A gut-on-a-chip incorporating human faecal samples and peristalsis predicts responses to immune checkpoint inhibitors for melanoma

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-12 DOI: 10.1038/s41551-024-01318-z

Mattia Ballerini, Serena Galiè, Punit Tyagi, Carlotta Catozzi, Hariam Raji, Amir Nabinejad, Angeli D. G. Macandog, Alessandro Cordiale, Bianca Ionela Slivinschi, Karol K. Kugiejko, Martina Freisa, Paola Occhetta, Jennifer A. Wargo, Pier F. Ferrucci, Emilia Cocorocchio, Nicola Segata, Andrea Vignati, Andrey Morgun, Michela Deleidi, Teresa Manzo, Marco Rasponi, Luigi Nezi

{"title":"A gut-on-a-chip incorporating human faecal samples and peristalsis predicts responses to immune checkpoint inhibitors for melanoma","authors":"Mattia Ballerini, Serena Galiè, Punit Tyagi, Carlotta Catozzi, Hariam Raji, Amir Nabinejad, Angeli D. G. Macandog, Alessandro Cordiale, Bianca Ionela Slivinschi, Karol K. Kugiejko, Martina Freisa, Paola Occhetta, Jennifer A. Wargo, Pier F. Ferrucci, Emilia Cocorocchio, Nicola Segata, Andrea Vignati, Andrey Morgun, Michela Deleidi, Teresa Manzo, Marco Rasponi, Luigi Nezi","doi":"10.1038/s41551-024-01318-z","DOIUrl":"https://doi.org/10.1038/s41551-024-01318-z","url":null,"abstract":"Patient responses to immune checkpoint inhibitors can be influenced by the gastrointestinal microbiome. Mouse models can be used to study microbiome–host crosstalk, yet their utility is constrained by substantial anatomical, functional, immunological and microbial differences between mice and humans. Here we show that a gut-on-a-chip system mimicking the architecture and functionality of the human intestine by including faecal microbiome and peristaltic-like movements recapitulates microbiome–host interactions and predicts responses to immune checkpoint inhibitors in patients with melanoma. The system is composed of a vascular channel seeded with human microvascular endothelial cells and an intestinal channel with intestinal organoids derived from human induced pluripotent stem cells, with the two channels separated by a collagen matrix. By incorporating faecal samples from patients with melanoma into the intestinal channel and by performing multiomic analyses, we uncovered epithelium-specific biomarkers and microbial factors that correlate with clinical outcomes in patients with melanoma and that the microbiome of non-responders has a reduced ability to buffer cellular stress and self-renew. The gut-on-a-chip model may help identify prognostic biomarkers and therapeutic targets.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"30 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synaptic connectivity mapping among thousands of neurons via parallelized intracellular recording with a microhole electrode array

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-11 DOI: 10.1038/s41551-025-01352-5

Jun Wang, Woo-Bin Jung, Rona S. Gertner, Hongkun Park, Donhee Ham

{"title":"Synaptic connectivity mapping among thousands of neurons via parallelized intracellular recording with a microhole electrode array","authors":"Jun Wang, Woo-Bin Jung, Rona S. Gertner, Hongkun Park, Donhee Ham","doi":"10.1038/s41551-025-01352-5","DOIUrl":"https://doi.org/10.1038/s41551-025-01352-5","url":null,"abstract":"The massive parallelization of neuronal intracellular recording, which enables the measurement of synaptic signals across a neuronal network, and thus the mapping and characterization of synaptic connections, is an open challenge, with the state of the art being limited to the mapping of about 300 synaptic connections. Here we report a 4,096 platinum/platinum-black microhole electrode array fabricated on a complementary metal-oxide semiconductor chip for parallel intracellular recording and thus for synaptic-connectivity mapping. The microhole–neuron interface, together with current-clamp electronics in the underlying semiconductor chip, allowed a 90% average intracellular coupling rate in rat neuronal cultures, generating network-wide intracellular-recording data with abundant synaptic signals. From these data, we extracted more than 70,000 plausible synaptic connections among more than 2,000 neurons and catalogued them into electrical synaptic connections and into inhibitory, weak/uneventful excitatory and strong/eventful excitatory chemical synaptic connections, with an estimated overall error rate of about 5%. This scale of synaptic-connectivity mapping and the ability to characterize synaptic connections is a step towards the functional connectivity mapping of large-scale neuronal networks.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"21 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Small circular RNAs as vaccines for cancer immunotherapy

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2025-02-07 DOI: 10.1038/s41551-025-01344-5

Yu Zhang, Xiang Liu, Tingting Shen, Qiyan Wang, Shurong Zhou, Suling Yang, Shimiao Liao, Ting Su, Lei Mei, Bei Zhang, Khoa Huynh, Linying Xie, Youzhong Guo, Chunqing Guo, Katarzyna M. Tyc, Xufeng Qu, Xiang-Yang Wang, Jinze Liu, Guizhi Zhu

{"title":"Small circular RNAs as vaccines for cancer immunotherapy","authors":"Yu Zhang, Xiang Liu, Tingting Shen, Qiyan Wang, Shurong Zhou, Suling Yang, Shimiao Liao, Ting Su, Lei Mei, Bei Zhang, Khoa Huynh, Linying Xie, Youzhong Guo, Chunqing Guo, Katarzyna M. Tyc, Xufeng Qu, Xiang-Yang Wang, Jinze Liu, Guizhi Zhu","doi":"10.1038/s41551-025-01344-5","DOIUrl":"10.1038/s41551-025-01344-5","url":null,"abstract":"Messenger RNA vaccines have shown strong prophylactic efficacy against viral infections. Here we show that antigen-encoding small circular RNAs (circRNAs) loaded in lipid nanoparticles elicit potent and durable T cell responses for robust tumour immunotherapy after subcutaneous injection in mice, particularly when combined with immune checkpoint inhibition. The small circRNA vaccines are highly stable and show low levels of activation of protein kinase R as well as low cytotoxicity, enabling long-lasting antigen translation (longer than 1 week in cells). Relative to large protein-encoding unmodified or modified mRNAs and circRNAs, small circRNA vaccines elicited up to 10-fold antigen-specific T cells in mice and accounted for 30–75% of the total peripheral CD8+ T cells over 6 months. Small circRNA vaccines encoding tumour-associated antigens, neoantigens and oncoviral or viral antigens elicited substantial CD8+ and CD4+ T cell responses in young adult mice and in immunosenescent aged mice. Combined with immune checkpoint inhibition, monovalent and multivalent circRNA vaccines reduced tumour-induced immunosuppression and inhibited poorly immunogenic mouse tumours, including melanoma resistant to immune checkpoint blockade. Small circular RNAs encoding one or more antigens and enclosed in subcutaneously injected lipid nanoparticles can elicit potent and durable antitumour T cell responses for robust tumour immunotherapy, particularly in combination with immune checkpoint inhibition, as shown in multiple mouse models of tumours.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"9 2","pages":"249-267"},"PeriodicalIF":26.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0