Nature Biomedical Engineering最新文献

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Bioengineered immunocompetent preclinical trial-on-chip tool enables screening of CAR T cell therapy for leukaemia 生物工程免疫能力的临床前芯片试验工具能够筛选CAR - T细胞治疗白血病
IF 28.1 1区 医学
Nature Biomedical Engineering Pub Date : 2025-07-01 DOI: 10.1038/s41551-025-01428-2
Chao Ma, Huishu Wang, Lunan Liu, Ruiqi Chen, Nandana Mukherjee, Jie Tong, Shadab Kazmi, Xiangyi Fang, Matthew T. Witkowski, Iannis Aifantis, Saba Ghassemi, Weiqiang Chen
{"title":"Bioengineered immunocompetent preclinical trial-on-chip tool enables screening of CAR T cell therapy for leukaemia","authors":"Chao Ma, Huishu Wang, Lunan Liu, Ruiqi Chen, Nandana Mukherjee, Jie Tong, Shadab Kazmi, Xiangyi Fang, Matthew T. Witkowski, Iannis Aifantis, Saba Ghassemi, Weiqiang Chen","doi":"10.1038/s41551-025-01428-2","DOIUrl":"https://doi.org/10.1038/s41551-025-01428-2","url":null,"abstract":"<p>Chimeric antigen receptor (CAR) T cell immunotherapy is promising for treatment of blood cancers; however, clinical benefits remain unpredictable, necessitating development of optimal CAR T cell products. Unfortunately, current preclinical evaluation platforms are inadequate owing to their limited physiological relevance to humans. Here we engineer an organotypic immunocompetent chip that recapitulates microarchitectural and pathophysiological characteristics of human leukaemia bone marrow stromal and immune niches for CAR T cell therapy modelling. This leukaemia chip empowers real-time spatiotemporal monitoring of CAR T cell functionality, including T cell extravasation, recognition of leukaemia, immune activation, cytotoxicity and killing. We use our chip to model clinically observed heterogeneous responses such as remission, resistance and relapse under CAR T cell therapy and map factors that drive therapeutic success or failure. Finally, we demarcate functional performance of CAR T cells produced from different healthy donors and patients with cancer, with various CAR designs and protocols, systematically and multidimensionally. Together, our chip introduces an enabling ‘(pre-)clinical-trial-on-chip’ tool for CAR T cell development, which may translate to personalized therapies and improved clinical decision-making.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"19 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520438","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
Self-powered rapid antigen-specific T-cell response assay for Mycobacterium tuberculosis infections 自供电快速抗原特异性t细胞反应测定结核分枝杆菌感染
IF 28.1 1区 医学
Nature Biomedical Engineering Pub Date : 2025-06-27 DOI: 10.1038/s41551-025-01441-5
Bo Ning, Sutapa Chandra, Yongchun Pan, Riti Sharan, Ngan Ha, Sanjay Singh, Alexandra Portillo Varela, Lin Li, Qingli Wu, Alexander Kay, Gugu P. Maphalala, Clement Adu-Gyamfi, Santiago Carrero Longlax, Anna M. Mandalakas, Smriti Mehra, Christopher J. Lyon, Edward A. Graviss, Andrew R. DiNardo, Tony Hu
{"title":"Self-powered rapid antigen-specific T-cell response assay for Mycobacterium tuberculosis infections","authors":"Bo Ning, Sutapa Chandra, Yongchun Pan, Riti Sharan, Ngan Ha, Sanjay Singh, Alexandra Portillo Varela, Lin Li, Qingli Wu, Alexander Kay, Gugu P. Maphalala, Clement Adu-Gyamfi, Santiago Carrero Longlax, Anna M. Mandalakas, Smriti Mehra, Christopher J. Lyon, Edward A. Graviss, Andrew R. DiNardo, Tony Hu","doi":"10.1038/s41551-025-01441-5","DOIUrl":"https://doi.org/10.1038/s41551-025-01441-5","url":null,"abstract":"<p>Interferon-gamma release assays (IGRAs) that evaluate an individual’s T-cell activation response to <i>Mycobacterium tuberculosis</i> (<i>M.tb</i>)-specific peptides serve an important role in diagnosing tuberculosis (TB). However, there are substantial challenges to the use of IGRAs in resource-limited settings. Further, IGRA diagnostic performance can also be compromised in anergic individuals. Here we describe a microfluidic chip-based antigen-specific T-cell response assay (ASTRA) that automates the detection of <i>M.tb</i>-specific T-cell activation responses to facilitate screening for latent <i>M.tb</i> infection and TB. We observe that ASTRA demonstrates high specificity for <i>M.tb</i> infection in independent patient cohorts. Compared with IGRA, ASTRA shows greater diagnostic sensitivity in individuals with HIV-1 co-infections (93.8% versus 67%), comparable diagnostic sensitivity in HIV-negative individuals (92.8%) and faster detection (4 h versus 24–48 h). We also find that a self-powered ASTRA chip that analysed microsample (~25 μl) whole-blood samples produced comparable results. ASTRA holds the potential to facilitate efforts to control the global TB epidemic and serve as a versatile platform for analysing T-cell responses across various infectious diseases and immunotherapeutic interventions.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"57 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500406","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
Extension of replicative lifespan by synthetic engineered telomerase RNA in patient induced pluripotent stem cells 利用合成工程化端粒酶RNA延长患者诱导的多能干细胞的复制寿命
IF 28.1 1区 医学
Nature Biomedical Engineering Pub Date : 2025-06-27 DOI: 10.1038/s41551-025-01429-1
Neha Nagpal, Suneet Agarwal
{"title":"Extension of replicative lifespan by synthetic engineered telomerase RNA in patient induced pluripotent stem cells","authors":"Neha Nagpal, Suneet Agarwal","doi":"10.1038/s41551-025-01429-1","DOIUrl":"https://doi.org/10.1038/s41551-025-01429-1","url":null,"abstract":"<p>RNA engineering has yielded a new class of medicines but faces limitations depending on RNA size and function. Here we demonstrate the synthesis and enzymatic stabilization of telomerase RNA component (TERC), a therapeutically relevant long non-coding RNA (lncRNA) that extends telomere length and replicative lifespan in human stem cells. Compared with therapeutic mRNAs, engineered TERC RNA (eTERC) depends on avoiding nucleoside base modifications and incorporates a distinct trimethylguanosine 5′ cap during in vitro transcription. We show that the non-canonical polymerase TENT4B can be repurposed to enzymatically stabilize synthetic RNAs of any size by catalysing self-limited 2′-<i>O</i>-methyladenosine tailing, which is critical for optimal eTERC function in cells. A single transient exposure to eTERC forestalls telomere-induced senescence in telomerase-deficient human cell lines and lengthens telomeres in induced pluripotent stem cells from nine patients carrying different mutations in telomere-maintenance genes, as well as primary CD34<sup>+</sup> blood stem/progenitor cells. Our results provide methods and proof of functional reconstitution for a stabilized, synthetic human lncRNA. eTERC may have therapeutic potential to safely extend replicative capacity in human stem cells.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"16 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500441","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
Peripheral neural interfaces for reading high-frequency brain signals 读取高频脑信号的外周神经接口
IF 28.1 1区 医学
Nature Biomedical Engineering Pub Date : 2025-06-27 DOI: 10.1038/s41551-025-01445-1
Jaime Ibáñez, Blanka Zicher, Etienne Burdet, Stuart N. Baker, Carsten Mehring, Dario Farina
{"title":"Peripheral neural interfaces for reading high-frequency brain signals","authors":"Jaime Ibáñez, Blanka Zicher, Etienne Burdet, Stuart N. Baker, Carsten Mehring, Dario Farina","doi":"10.1038/s41551-025-01445-1","DOIUrl":"https://doi.org/10.1038/s41551-025-01445-1","url":null,"abstract":"<p>Accurate and robust recording and decoding from the central nervous system (CNS) is essential for advances in human–machine interfacing. Technologies for direct measurements of CNS activity are limited by their resolution, sensitivity to interference and invasiveness. Motor neurons (MNs) represent the motor output layer of the CNS, receiving and sampling signals from different regions in the nervous system and generating the neural commands that control muscles. Muscle recordings and deep learning decode the spiking activity of spinal MNs in real time and with high accuracy. The input signals to MNs can be estimated from MN outputs. Here we argue that peripheral neural interfaces using muscle sensors represent a promising, non-invasive approach to estimate some of the neural activity from the CNS that reaches the MNs but does not directly modulate force production. We discuss the evidence supporting this concept and the advances needed to consolidate and test MN-based CNS interfaces in controlled and real-world settings.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"630 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500400","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
Movement-responsive deep brain stimulation for Parkinson’s disease using a remotely optimized neural decoder 使用远程优化的神经解码器对帕金森病进行运动反应性脑深部刺激
IF 28.1 1区 医学
Nature Biomedical Engineering Pub Date : 2025-06-27 DOI: 10.1038/s41551-025-01438-0
Tanner C. Dixon, Gabrielle Strandquist, Alicia Zeng, Tomasz Frączek, Raphael Bechtold, Daryl Lawrence, Shravanan Ravi, Philip A. Starr, Jack L. Gallant, Jeffrey A. Herron, Simon J. Little
{"title":"Movement-responsive deep brain stimulation for Parkinson’s disease using a remotely optimized neural decoder","authors":"Tanner C. Dixon, Gabrielle Strandquist, Alicia Zeng, Tomasz Frączek, Raphael Bechtold, Daryl Lawrence, Shravanan Ravi, Philip A. Starr, Jack L. Gallant, Jeffrey A. Herron, Simon J. Little","doi":"10.1038/s41551-025-01438-0","DOIUrl":"https://doi.org/10.1038/s41551-025-01438-0","url":null,"abstract":"<p>Deep brain stimulation (DBS) has garnered widespread use as an effective treatment for advanced Parkinson’s disease. Conventional DBS (cDBS) provides electrical stimulation to the basal ganglia at fixed amplitude and frequency, yet patients’ therapeutic needs are often dynamic with residual symptom fluctuations or side effects. Adaptive DBS (aDBS) is an emerging technology that modulates stimulation with respect to real-time clinical, physiological or behavioural states, enabling therapy to dynamically align with patient-specific symptoms. Here we report an aDBS algorithm intended to mitigate movement slowness by delivering targeted stimulation increases during movement using decoded motor signals from the brain. Our approach demonstrated improvements in dominant hand movement speeds and study participant-reported therapeutic efficacy compared with an inverted control, as well as increased typing speed and reduced dyskinesia compared with cDBS. Furthermore, we demonstrate proof of principle of a machine learning pipeline capable of remotely optimizing aDBS parameters in a home setting. This work illustrates the potential of movement-responsive aDBS as a promising therapeutic approach and highlights how machine learning-assisted programming can simplify complex optimization to facilitate translational scalability.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"46 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500399","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
Scalable production of human cortical organoids using a biocompatible polymer 利用生物相容性聚合物大规模生产人类皮质类器官
IF 28.1 1区 医学
Nature Biomedical Engineering Pub Date : 2025-06-27 DOI: 10.1038/s41551-025-01427-3
Genta Narazaki, Yuki Miura, Sergey D. Pavlov, Mayuri Vijay Thete, Julien G. Roth, Merve Avar, Sungchul Shin, Ji-il Kim, Zuzana Hudacova, Sarah C. Heilshorn, Sergiu P. Pașca
{"title":"Scalable production of human cortical organoids using a biocompatible polymer","authors":"Genta Narazaki, Yuki Miura, Sergey D. Pavlov, Mayuri Vijay Thete, Julien G. Roth, Merve Avar, Sungchul Shin, Ji-il Kim, Zuzana Hudacova, Sarah C. Heilshorn, Sergiu P. Pașca","doi":"10.1038/s41551-025-01427-3","DOIUrl":"https://doi.org/10.1038/s41551-025-01427-3","url":null,"abstract":"<p>The generation of neural organoids from human pluripotent stem cells holds great promise in modelling disease and screening drugs, but current approaches are difficult to scale due to undesired organoid fusion. Here we develop a scalable cerebral cortical organoid platform by screening biocompatible polymers that prevent the fusion of organoids cultured in suspension. We identify a cost-effective polysaccharide that increases the viscosity of the culture medium, significantly enhancing the yield of cortical organoids while preserving key features such as regional patterning, neuronal morphology and functional activity. We further demonstrate that this platform enables straightforward screening of 298 FDA-approved drugs and teratogens for growth defects using over 2,400 cortical organoids, uncovering agents that disrupt organoid growth and development. We anticipate this approach to provide a robust and scalable system for modelling human cortical development, and facilitate efficient compound screening for neuropsychiatric disorders-associated phenotypes.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"246 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500403","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
Engineering multi-specific nano-antibodies for cancer immunotherapy 工程多特异性纳米抗体用于癌症免疫治疗
IF 28.1 1区 医学
Nature Biomedical Engineering Pub Date : 2025-06-26 DOI: 10.1038/s41551-025-01425-5
Ya-Nan Fan, Long Zhu, Yu-Xin Qing, Si-Yi Ye, Qian-Ni Ye, Xiao-Yi Huang, Dong-Kun Zhao, Tai-Yu Tian, Fang-Chao Li, Guan-Rong Yan, Xian-Zhu Yang, Song Shen, Jun Wang
{"title":"Engineering multi-specific nano-antibodies for cancer immunotherapy","authors":"Ya-Nan Fan, Long Zhu, Yu-Xin Qing, Si-Yi Ye, Qian-Ni Ye, Xiao-Yi Huang, Dong-Kun Zhao, Tai-Yu Tian, Fang-Chao Li, Guan-Rong Yan, Xian-Zhu Yang, Song Shen, Jun Wang","doi":"10.1038/s41551-025-01425-5","DOIUrl":"https://doi.org/10.1038/s41551-025-01425-5","url":null,"abstract":"<p>Immobilizing multiple types of monoclonal antibody (mAb) on nanoparticle surfaces is a promising approach for creating nanomedicines that emulate the functionality of multi-specific antibodies. However, the clinical translation of these multi-specific nano-antibodies (multi-NanoAbs) has been hindered by intricate fabrication procedures, inevitable attenuation in mAb affinity and insufficient carrier biosecurity. Here we develop a versatile nano-adaptor for immobilizing mAbs and construct multi-NanoAbs using a recombinant fusion protein that consists of Fc gamma receptor 1 and serum albumin, along with the biomedical polymer poly(<span>l</span>-lactide). Our findings demonstrate that fusion protein/polymer-based nano-adaptor is facilitated by FcγR1 on its surface to bind mAbs through receptor–ligand interactions rather than complex chemical conjugation and enables convenient and controlled construction of diverse multi-NanoAbs with efficacious therapeutic effects. We achieved large-scale production of humanized fusion protein/polymer-based nano-adaptor and confirmed the antitumour effectiveness of multi-NanoAb in humanized immune system mouse models, highlighting their prospects for clinical translation.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"21 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488378","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
Discovery of high-affinity ligands for prostatic acid phosphatase via DNA-encoded library screening enables targeted cancer therapy 通过dna编码文库筛选发现前列腺酸性磷酸酶的高亲和力配体,使靶向癌症治疗成为可能
IF 28.1 1区 医学
Nature Biomedical Engineering Pub Date : 2025-06-26 DOI: 10.1038/s41551-025-01432-6
Tony Georgiev, Francesca Migliorini, Andrea Ciamarone, Marco Mueller, Ilaria Biancofiore, Pinuccia Faviana, Francesco Bartoli, Young Seo Park Kim, Lucrezia Principi, Ettore Gilardoni, Gabriele Bassi, Nicholas Favalli, Emanuele Puca, Dario Neri, Sebastian Oehler, Samuele Cazzamalli
{"title":"Discovery of high-affinity ligands for prostatic acid phosphatase via DNA-encoded library screening enables targeted cancer therapy","authors":"Tony Georgiev, Francesca Migliorini, Andrea Ciamarone, Marco Mueller, Ilaria Biancofiore, Pinuccia Faviana, Francesco Bartoli, Young Seo Park Kim, Lucrezia Principi, Ettore Gilardoni, Gabriele Bassi, Nicholas Favalli, Emanuele Puca, Dario Neri, Sebastian Oehler, Samuele Cazzamalli","doi":"10.1038/s41551-025-01432-6","DOIUrl":"https://doi.org/10.1038/s41551-025-01432-6","url":null,"abstract":"<p>Improving the specificity of prostate cancer treatment requires ligands that bind selectively and with ultra-high affinity to tumour-associated targets absent from healthy tissues. Prostatic acid phosphatase has emerged as an alternative target to prostate-specific membrane antigen, as it is expressed in a broader subset of prostate cancers and is not detected in healthy organs such as the salivary glands and kidneys. Here, to discover selective binders to prostatic acid phosphatase, we constructed two DNA-encoded chemical libraries comprising over 6.7 million small molecules based on proline and phenylalanine scaffolds. Screening against the purified human prostatic acid phosphatase yielded OncoACP3, a small organic ligand with picomolar binding affinity. When radiolabelled with lutetium-177, OncoACP3 selectively accumulated in enzyme-expressing tumours with a long residence time (biological half-life greater than 72 h) and a high tumour-to-blood ratio (&gt;148 at 2 h after administration). Lutetium-177-labelled OncoACP3 cured tumours in mice at low, well-tolerated doses. Its conjugation to the cytotoxic agent monomethyl auristatin E facilitated tumour-selective payload deposition, resulting in potent anti-tumour activity. The modular structure of OncoACP3 supports flexible payload delivery for the targeted treatment of metastatic prostate cancer.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"102 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488425","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
Self-organization of sinusoidal vessels in pluripotent stem cell-derived human liver bud organoids 多能干细胞衍生的人肝芽类器官中正弦血管的自组织
IF 28.1 1区 医学
Nature Biomedical Engineering Pub Date : 2025-06-25 DOI: 10.1038/s41551-025-01416-6
Norikazu Saiki, Yasunori Nio, Yosuke Yoneyama, Shuntaro Kawamura, Kentaro Iwasawa, Eri Kawakami, Kohei Araki, Junko Fukumura, Tsuyoshi Sakairi, Tamaki Kono, Rio Ohmura, Masaru Koido, Masaaki Funata, Wendy L. Thompson, Pamela Cruz-Encarnacion, Ya-Wen Chen, Takanori Takebe
{"title":"Self-organization of sinusoidal vessels in pluripotent stem cell-derived human liver bud organoids","authors":"Norikazu Saiki, Yasunori Nio, Yosuke Yoneyama, Shuntaro Kawamura, Kentaro Iwasawa, Eri Kawakami, Kohei Araki, Junko Fukumura, Tsuyoshi Sakairi, Tamaki Kono, Rio Ohmura, Masaru Koido, Masaaki Funata, Wendy L. Thompson, Pamela Cruz-Encarnacion, Ya-Wen Chen, Takanori Takebe","doi":"10.1038/s41551-025-01416-6","DOIUrl":"https://doi.org/10.1038/s41551-025-01416-6","url":null,"abstract":"<p>The induction of tissue-specific vessels in in vitro living tissue systems remains challenging. Here, we directly differentiated human pluripotent stem cells into CD32b<sup>+</sup> putative liver sinusoidal progenitors by dictating developmental pathways. By devising an inverted multilayered air–liquid interface culture, hepatic endoderm, septum mesenchyme, arterial and sinusoidal quadruple progenitors self-organize to generate and sustain hepatocyte-like cells neighboured by divergent endothelial subsets composed of CD32b<sup>low</sup>CD31<sup>high</sup>, LYVE1<sup>+</sup>STAB1<sup>+</sup>CD32b<sup>high</sup>CD31<sup>low</sup>THBD<sup>−</sup>vWF<sup>−</sup> and LYVE1<sup>−</sup>THBD<sup>+</sup>vWF<sup>+</sup> cells. WNT2 mediates sinusoidal-to-hepatic intercellular crosstalk potentiating hepatocyte differentiation and branched endothelial network formation. Intravital imaging reveals the iPS-cell-derived putative liver sinusoidal endothelial progenitor develops fully perfused human vessels with functional sinusoid-like features. Organoid-derived hepatocyte- and sinusoid-derived coagulation factors enable correction of in vitro clotting time with Factor V-, VIII-, IX- and XI-deficient plasma, and rescues the severe bleeding phenotype in haemophilia A mice on transplantation. Advanced organoid vascularization technology allows for interrogating key insights governing organ-specific vessel development, paving the way for coagulation disorder therapeutics.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"45 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478988","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
Panoramic photoacoustic computed tomography with learning-based classification enhances breast lesion characterization 全景光声计算机断层扫描与基于学习的分类增强乳房病变特征
IF 28.1 1区 医学
Nature Biomedical Engineering Pub Date : 2025-06-24 DOI: 10.1038/s41551-025-01435-3
Xin Tong, Cindy Z. Liu, Yilin Luo, Li Lin, Jessica Dzubnar, Marta Invernizzi, Stephanie Delos Santos, Yide Zhang, Rui Cao, Peng Hu, Junfu Zheng, Jaclene Torres, Armine Kasabyan, Lily L. Lai, Lisa D. Yee, Lihong V. Wang
{"title":"Panoramic photoacoustic computed tomography with learning-based classification enhances breast lesion characterization","authors":"Xin Tong, Cindy Z. Liu, Yilin Luo, Li Lin, Jessica Dzubnar, Marta Invernizzi, Stephanie Delos Santos, Yide Zhang, Rui Cao, Peng Hu, Junfu Zheng, Jaclene Torres, Armine Kasabyan, Lily L. Lai, Lisa D. Yee, Lihong V. Wang","doi":"10.1038/s41551-025-01435-3","DOIUrl":"https://doi.org/10.1038/s41551-025-01435-3","url":null,"abstract":"<p>Breast cancer diagnosis is crucial due to the high prevalence and mortality rate associated with the disease. However, mammography involves ionizing radiation and has compromised sensitivity in radiographically dense breasts, ultrasonography lacks specificity and has operator-dependent image quality, and magnetic resonance imaging faces high cost and patient exclusion. Photoacoustic computed tomography (PACT) offers a promising solution by combining light and ultrasound for high-resolution imaging that detects tumour-related vasculature changes. Here we introduce a workflow using panoramic PACT for breast lesion characterization, offering detailed visualization of vasculature irrespective of breast density. Analysing PACT features of 78 breasts in 39 patients, we develop learning-based classifiers to distinguish between normal and suspicious tissue, achieving a maximum area under the receiver operating characteristic curve of 0.89, which is comparable with that of conventional imaging standards. We further differentiate malignant and benign lesions using 13 features. Finally, we developed a learning-based model to segment breast lesions. Our study identifies PACT as a non-invasive and sensitive imaging tool for breast lesion evaluation.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"39 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144371138","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
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