{"title":"Targeting overexpressed antigens in glioblastoma via CAR T cells with computationally designed high-affinity protein binders","authors":"Zhen Xia, Qihan Jin, Zhilin Long, Yexuan He, Fuyi Liu, Chengfang Sun, Jinyang Liao, Chun Wang, Chentong Wang, Jian Zheng, Weixi Zhao, Tianxin Zhang, Jeremy N. Rich, Yongdeng Zhang, Longxing Cao, Qi Xie","doi":"10.1038/s41551-024-01258-8","DOIUrl":"https://doi.org/10.1038/s41551-024-01258-8","url":null,"abstract":"<p>Chimeric antigen receptor (CAR) T cells targeting receptors on tumour cells have had limited success in patients with glioblastoma. Here we report the development and therapeutic performance of CAR constructs leveraging protein binders computationally designed de novo to have high affinity for the epidermal growth factor receptor (EGFR) or the tumour-associated antigen CD276, which are overexpressed in glioblastoma. With respect to T cells with a CAR using an antibody-derived single-chain variable fragment as antigen-binding domain, the designed binders on CAR T cells promoted the proliferation of the cells, the secretion of cytotoxic cytokines and their resistance to cell exhaustion, and improved antitumour performance in vitro and in vivo. Moreover, CARs with the binders exhibited higher surface expression and greater resistance to degradation, as indicated by bulk and single-cell transcriptional profiling of the cells. The de novo design of binding domains for specific tumour antigens may potentiate the antitumour efficacy of CAR T cell therapies for other solid cancers.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440823","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}
Julia Garcia Mancebo, Kristen Sack, Jay Hartford, Saffron Dominguez, Michelle Balcarcel-Monzon, Elizabeth Chartier, Tien Nguyen, Alexis R. Cole, Francesca Sperotto, David M. Harrild, Brian D. Polizzotti, Allen D. Everett, Alan B. Packard, Jason Dearling, Arthur G. Nedder, Simon Warfield, Edward Yang, Hart G. W. Lidov, John N. Kheir, Yifeng Peng
{"title":"Systemically injected oxygen within rapidly dissolving microbubbles improves the outcomes of severe hypoxaemia in swine","authors":"Julia Garcia Mancebo, Kristen Sack, Jay Hartford, Saffron Dominguez, Michelle Balcarcel-Monzon, Elizabeth Chartier, Tien Nguyen, Alexis R. Cole, Francesca Sperotto, David M. Harrild, Brian D. Polizzotti, Allen D. Everett, Alan B. Packard, Jason Dearling, Arthur G. Nedder, Simon Warfield, Edward Yang, Hart G. W. Lidov, John N. Kheir, Yifeng Peng","doi":"10.1038/s41551-024-01266-8","DOIUrl":"https://doi.org/10.1038/s41551-024-01266-8","url":null,"abstract":"<p>Acute respiratory failure can cause profound hypoxaemia that leads to organ injury or death within minutes. When conventional interventions are ineffective, the intravenous administration of oxygen can rescue patients from severe hypoxaemia, but at the risk of microvascular obstruction and of toxicity of the carrier material. Here we describe polymeric microbubbles as carriers of high volumes of oxygen (350–500 ml of oxygen per litre of foam) that are stable in storage yet quickly dissolve following intravenous injection, reverting to their soluble and excretable molecular constituents. In swine with profound hypoxaemia owing to acute and temporary (12 min) upper-airway obstruction, the microbubble-mediated delivery of oxygen led to: the maintenance of critical oxygenation, lowered burdens of cardiac arrest, improved survival, and substantially improved neurologic and kidney function in surviving animals. Our findings underscore the importance of maintaining a critical threshold of oxygenation and the promise of injectable oxygen as a viable therapy in acute and temporary hypoxaemic crises.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440824","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}
{"title":"Interpretable discovery of patterns in tabular data via spatially semantic topographic maps","authors":"Rui Yan, Md Tauhidual Islam, Lei Xing","doi":"10.1038/s41551-024-01268-6","DOIUrl":"https://doi.org/10.1038/s41551-024-01268-6","url":null,"abstract":"<p>Tabular data—rows of samples and columns of sample features—are ubiquitously used across disciplines. Yet the tabular representation makes it difficult to discover underlying associations in the data and thus hinders their analysis and the discovery of useful patterns. Here we report a broadly applicable strategy for unravelling intertwined relationships in tabular data by reconfiguring each data sample into a spatially semantic 2D topographic map, which we refer to as TabMap. A TabMap preserves the original feature values as pixel intensities, with the relationships among the features spatially encoded in the map (the strength of two inter-related features correlates with their distance on the map). TabMap makes it possible to apply 2D convolutional neural networks to extract association patterns in the data to aid data analysis, and offers interpretability by ranking features according to importance. We show the superior predictive performance of TabMap by applying it to 12 datasets across a wide range of biomedical applications, including disease diagnosis, human activity recognition, microbial identification and the analysis of quantitative structure–activity relationships.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436341","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}
{"title":"Synthetic chest X-ray images from text prompts","authors":"Daniel Truhn, Jakob Nikolas Kather","doi":"10.1038/s41551-024-01261-z","DOIUrl":"https://doi.org/10.1038/s41551-024-01261-z","url":null,"abstract":"A latent diffusion model pre-trained on pairs of natural images and text descriptors can be adapted to generate realistic chest radiographs that are controlled by free-form medical text prompts.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383746","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}
Chima V. Maduka, Axel D. Schmitter-Sánchez, Ashley V. Makela, Evran Ural, Katlin B. Stivers, Hunter Pope, Maxwell M. Kuhnert, Oluwatosin M. Habeeb, Anthony Tundo, Mohammed Alhaj, Artem Kiselev, Shoue Chen, Alexis Donneys, Wade P. Winton, Jenelle Stauff, Peter J. H. Scott, Andrew J. Olive, Kurt D. Hankenson, Ramani Narayan, Sangbum Park, Jennifer H. Elisseeff, Christopher H. Contag
{"title":"Immunometabolic cues recompose and reprogram the microenvironment around implanted biomaterials","authors":"Chima V. Maduka, Axel D. Schmitter-Sánchez, Ashley V. Makela, Evran Ural, Katlin B. Stivers, Hunter Pope, Maxwell M. Kuhnert, Oluwatosin M. Habeeb, Anthony Tundo, Mohammed Alhaj, Artem Kiselev, Shoue Chen, Alexis Donneys, Wade P. Winton, Jenelle Stauff, Peter J. H. Scott, Andrew J. Olive, Kurt D. Hankenson, Ramani Narayan, Sangbum Park, Jennifer H. Elisseeff, Christopher H. Contag","doi":"10.1038/s41551-024-01260-0","DOIUrl":"10.1038/s41551-024-01260-0","url":null,"abstract":"Circulating monocytes infiltrate and coordinate immune responses in tissues surrounding implanted biomaterials and in other inflamed tissues. Here we show that immunometabolic cues in the biomaterial microenvironment govern the trafficking of immune cells, including neutrophils and monocytes, in a manner dependent on the chemokine receptor 2 (CCR2) and the C-X3-C motif chemokine receptor 1 (CX3CR1). This affects the composition and activation states of macrophage and dendritic cell populations, ultimately orchestrating the relative composition of pro-inflammatory, transitory and anti-inflammatory CCR2+, CX3CR1+ and CCR2+ CX3CR1+ immune cell populations. In amorphous polylactide implants, modifying immunometabolism by glycolytic inhibition drives a pro-regenerative microenvironment principally by myeloid cells. In crystalline polylactide implants, together with arginase-1-expressing myeloid cells, T helper 2 cells and γδ+ T cells producing interleukin-4 substantially contribute to shaping the metabolically reprogrammed pro-regenerative microenvironment. Our findings inform the premise that local metabolic states regulate inflammatory processes in the biomaterial microenvironment. Immunometabolic cues surrounding implanted biomaterials govern the trafficking of subsets of neutrophils, monocytes and other immune cells, and determine the relative composition of pro-inflammatory and anti-inflammatory immune cell populations.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":26.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370071","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}
Namit Chaudhary, Lisa N. Kasiewicz, Alexandra N. Newby, Mariah L. Arral, Saigopalakrishna S. Yerneni, Jilian R. Melamed, Samuel T. LoPresti, Katherine C. Fein, Daria M. Strelkova Petersen, Sushant Kumar, Rahul Purwar, Kathryn A. Whitehead
{"title":"Amine headgroups in ionizable lipids drive immune responses to lipid nanoparticles by binding to the receptors TLR4 and CD1d","authors":"Namit Chaudhary, Lisa N. Kasiewicz, Alexandra N. Newby, Mariah L. Arral, Saigopalakrishna S. Yerneni, Jilian R. Melamed, Samuel T. LoPresti, Katherine C. Fein, Daria M. Strelkova Petersen, Sushant Kumar, Rahul Purwar, Kathryn A. Whitehead","doi":"10.1038/s41551-024-01256-w","DOIUrl":"https://doi.org/10.1038/s41551-024-01256-w","url":null,"abstract":"<p>Lipid nanoparticles (LNPs) are the most clinically advanced delivery vehicle for RNA therapeutics, partly because of established lipid structure–activity relationships focused on formulation potency. Yet such knowledge has not extended to LNP immunogenicity. Here we show that the innate and adaptive immune responses elicited by LNPs are linked to their ionizable lipid chemistry. Specifically, we show that the amine headgroups in ionizable lipids drive LNP immunogenicity by binding to Toll-like receptor 4 and CD1d and by promoting lipid-raft formation. Immunogenic LNPs favour a type-1 T-helper-cell-biased immune response marked by increases in the immunoglobulins IgG2c and IgG1 and in the pro-inflammatory cytokines tumour necrosis factor, interferon γ and the interleukins IL-6 and IL-2. Notably, the inflammatory signals originating from these receptors inhibit the production of anti-poly(ethylene glycol) IgM antibodies, preventing the often-observed loss of efficacy in the LNP-mediated delivery of siRNA and mRNA. Moreover, we identified computational methods for the prediction of the structure-dependent innate and adaptive responses of LNPs. Our findings may help accelerate the discovery of well-tolerated ionizable lipids suitable for repeated dosing.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368957","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}
Oren Avram, Berkin Durmus, Nadav Rakocz, Giulia Corradetti, Ulzee An, Muneeswar G. Nittala, Prerit Terway, Akos Rudas, Zeyuan Johnson Chen, Yu Wakatsuki, Kazutaka Hirabayashi, Swetha Velaga, Liran Tiosano, Federico Corvi, Aditya Verma, Ayesha Karamat, Sophiana Lindenberg, Deniz Oncel, Louay Almidani, Victoria Hull, Sohaib Fasih-Ahmad, Houri Esmaeilkhanian, Maxime Cannesson, Charles C. Wykoff, Elior Rahmani, Corey W. Arnold, Bolei Zhou, Noah Zaitlen, Ilan Gronau, Sriram Sankararaman, Jeffrey N. Chiang, Srinivas R. Sadda, Eran Halperin
{"title":"Accurate prediction of disease-risk factors from volumetric medical scans by a deep vision model pre-trained with 2D scans","authors":"Oren Avram, Berkin Durmus, Nadav Rakocz, Giulia Corradetti, Ulzee An, Muneeswar G. Nittala, Prerit Terway, Akos Rudas, Zeyuan Johnson Chen, Yu Wakatsuki, Kazutaka Hirabayashi, Swetha Velaga, Liran Tiosano, Federico Corvi, Aditya Verma, Ayesha Karamat, Sophiana Lindenberg, Deniz Oncel, Louay Almidani, Victoria Hull, Sohaib Fasih-Ahmad, Houri Esmaeilkhanian, Maxime Cannesson, Charles C. Wykoff, Elior Rahmani, Corey W. Arnold, Bolei Zhou, Noah Zaitlen, Ilan Gronau, Sriram Sankararaman, Jeffrey N. Chiang, Srinivas R. Sadda, Eran Halperin","doi":"10.1038/s41551-024-01257-9","DOIUrl":"https://doi.org/10.1038/s41551-024-01257-9","url":null,"abstract":"<p>The application of machine learning to tasks involving volumetric biomedical imaging is constrained by the limited availability of annotated datasets of three-dimensional (3D) scans for model training. Here we report a deep-learning model pre-trained on 2D scans (for which annotated data are relatively abundant) that accurately predicts disease-risk factors from 3D medical-scan modalities. The model, which we named SLIViT (for ‘slice integration by vision transformer’), preprocesses a given volumetric scan into 2D images, extracts their feature map and integrates it into a single prediction. We evaluated the model in eight different learning tasks, including classification and regression for six datasets involving four volumetric imaging modalities (computed tomography, magnetic resonance imaging, optical coherence tomography and ultrasound). SLIViT consistently outperformed domain-specific state-of-the-art models and was typically as accurate as clinical specialists who had spent considerable time manually annotating the analysed scans. Automating diagnosis tasks involving volumetric scans may save valuable clinician hours, reduce data acquisition costs and duration, and help expedite medical research and clinical applications.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330387","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}
N. T. Huynh, E. Zhang, O. Francies, F. Kuklis, T. Allen, J. Zhu, O. Abeyakoon, F. Lucka, M. Betcke, J. Jaros, S. Arridge, B. Cox, A. A. Plumb, P. Beard
{"title":"A fast all-optical 3D photoacoustic scanner for clinical vascular imaging","authors":"N. T. Huynh, E. Zhang, O. Francies, F. Kuklis, T. Allen, J. Zhu, O. Abeyakoon, F. Lucka, M. Betcke, J. Jaros, S. Arridge, B. Cox, A. A. Plumb, P. Beard","doi":"10.1038/s41551-024-01247-x","DOIUrl":"https://doi.org/10.1038/s41551-024-01247-x","url":null,"abstract":"<p>The clinical assessment of microvascular pathologies (in diabetes and in inflammatory skin diseases, for example) requires the visualization of superficial vascular anatomy. Photoacoustic tomography (PAT) scanners based on an all-optical Fabry–Perot ultrasound sensor can provide highly detailed 3D microvascular images, but minutes-long acquisition times have precluded their clinical use. Here we show that scan times can be reduced to a few seconds and even hundreds of milliseconds by parallelizing the optical architecture of the sensor readout, by using excitation lasers with high pulse-repetition frequencies and by exploiting compressed sensing. A PAT scanner with such fast acquisition minimizes motion-related artefacts and allows for the volumetric visualization of individual arterioles, venules, venous valves and millimetre-scale arteries and veins to depths approaching 15 mm, as well as for dynamic 3D images of time-varying tissue perfusion and other haemodynamic events. In exploratory case studies, we used the scanner to visualize and quantify microvascular changes associated with peripheral vascular disease, skin inflammation and rheumatoid arthritis. Fast all-optical PAT may prove useful in cardiovascular medicine, oncology, dermatology and rheumatology.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142329617","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}
Edo Kapetanovic, Cédric R. Weber, Marine Bruand, Daniel Pöschl, Jakub Kucharczyk, Elisabeth Hirth, Claudius Dietsche, Riyaz Khan, Bastian Wagner, Olivier Belli, Rodrigo Vazquez-Lombardi, Rocío Castellanos- Rueda, Raphael B. Di Roberto, Kevin Kalinka, Luca Raess, Kevin Ly, Shivam Rai, Petra S. Dittrich, Randall J. Platt, Elisa Oricchio, Sai T. Reddy
{"title":"Engineered allogeneic T cells decoupling T-cell-receptor and CD3 signalling enhance the antitumour activity of bispecific antibodies","authors":"Edo Kapetanovic, Cédric R. Weber, Marine Bruand, Daniel Pöschl, Jakub Kucharczyk, Elisabeth Hirth, Claudius Dietsche, Riyaz Khan, Bastian Wagner, Olivier Belli, Rodrigo Vazquez-Lombardi, Rocío Castellanos- Rueda, Raphael B. Di Roberto, Kevin Kalinka, Luca Raess, Kevin Ly, Shivam Rai, Petra S. Dittrich, Randall J. Platt, Elisa Oricchio, Sai T. Reddy","doi":"10.1038/s41551-024-01255-x","DOIUrl":"https://doi.org/10.1038/s41551-024-01255-x","url":null,"abstract":"<p>Bispecific antibodies (biAbs) used in cancer immunotherapies rely on functional autologous T cells, which are often damaged and depleted in patients with haematological malignancies and in other immunocompromised patients. The adoptive transfer of allogeneic T cells from healthy donors can enhance the efficacy of biAbs, but donor T cells binding to host-cell antigens cause an unwanted alloreactive response. Here we show that allogeneic T cells engineered with a T-cell receptor that does not convert antigen binding into cluster of differentiation 3 (CD3) signalling decouples antigen-mediated T-cell activation from T-cell cytotoxicity while preserving the surface expression of the T-cell-receptor–CD3 signalling complex as well as biAb-mediated CD3 signalling and T-cell activation. In mice with CD19<sup>+</sup> tumour xenografts, treatment with the engineered human cells in combination with blinatumomab (a clinically approved biAb) led to the recognition and clearance of tumour cells in the absence of detectable alloreactivity. Our findings support the development of immunotherapies combining biAbs and ‘off-the-shelf’ allogeneic T cells.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317022","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}
James G Shamul,Zhiyuan Wang,Hyeyeon Gong,Wenquan Ou,Alisa M White,Diogo P Moniz-Garcia,Shuo Gu,Alisa Morss Clyne,Alfredo Quiñones-Hinojosa,Xiaoming He
{"title":"Meta-analysis of the make-up and properties of in vitro models of the healthy and diseased blood-brain barrier.","authors":"James G Shamul,Zhiyuan Wang,Hyeyeon Gong,Wenquan Ou,Alisa M White,Diogo P Moniz-Garcia,Shuo Gu,Alisa Morss Clyne,Alfredo Quiñones-Hinojosa,Xiaoming He","doi":"10.1038/s41551-024-01250-2","DOIUrl":"https://doi.org/10.1038/s41551-024-01250-2","url":null,"abstract":"In vitro models of the human blood-brain barrier (BBB) are increasingly used to develop therapeutics that can cross the BBB for treating diseases of the central nervous system. Here we report a meta-analysis of the make-up and properties of transwell and microfluidic models of the healthy BBB and of BBBs in glioblastoma, Alzheimer's disease, Parkinson's disease and inflammatory diseases. We found that the type of model, the culture method (static or dynamic), the cell types and cell ratios, and the biomaterials employed as extracellular matrix are all crucial to recapitulate the low permeability and high expression of tight-junction proteins of the BBB, and to obtain high trans-endothelial electrical resistance. Specifically, for models of the healthy BBB, the inclusion of endothelial cells and pericytes as well as physiological shear stresses (~10-20 dyne cm-2) are necessary, and when astrocytes are added, astrocytes or pericytes should outnumber endothelial cells. We expect this meta-analysis to facilitate the design of increasingly physiological models of the BBB.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275158","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}
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