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Bio-Design and Manufacturing 2023年第3期6卷 319-339页

作者： Xuan Du Zaozao Chen Qiwei Li Sheng Yang Lincao Jiang Yi Yang Yanhui Li Zhongze Gu State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China State Key Laboratory for Novel Software Technology Nanjing UniversityNanjing 210008China Key Laboratory of Environmental Medicine Engineering Ministry of EducationSchool of Public HealthSoutheast UniversityNanjing 210009China

In modern terminology,“organoids”refer to cells that grow in a specific three-dimensional(3D)environment in vitro,sharing similar structures with their source organs or *** themorphology or growth characteristics of organoids through a microscope is a commonly used method of organoid ***,it is difficult,time-consuming,and inaccurate to screen and analyze organoids only manually,a problem which cannot be easily solved with traditional *** intelligence(AI)technology has proven to be effective in many biological and medical research fields,especially in the analysis of single-cell or hematoxylin/eosin stained tissue *** used to analyze organoids,AI should also provide more efficient,quantitative,accurate,and fast *** this review,we will first briefly outline the application areas of organoids and then discuss the shortcomings of traditional organoid measurement and analysis ***,we will summarize the development from machine learning to deep learning and the advantages of the latter,and then describe how to utilize a convolutional neural network to solve the challenges in organoid observation and ***,we will discuss the limitations of current AI used in organoid research,as well as opportunities and future research directions.

关键词： Artificial intelligence organoids Morphology Growth characteristics Deep learning Convolutional neural network

organoids of liver diseases: From bench to bedside

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World Journal of Gastroenterology 2019年第16期25卷 1913-1927页

作者： Li-Jun Wu Zi-Yan Chen Yi Wang Jun-Gang Zhao Xiao-Zai Xie Gang Chen Department of Hepatobiliary Surgery The First Affiliated Hospital Wenzhou Medical University Research Center of Evidence-Based Medicine and Clinical Epidemiology School of Public Health and Management Wenzhou Medical University

Understanding the occurrence, development, and treatment of liver diseases is the main goal of hepatopathology research. Liver diseases are not only diverse but also highly heterogeneous among individuals. At present, research on liver diseases is conducted mainly through cell culture, animal models, pathological specimens, etc. However, these methods cannot fully reveal the pathogenic mechanism and therapeutic characteristics of individualized liver *** advances in three-dimensional cell culture technology(organoid culture techniques) include pluripotent stem cells and adult stem cells that are cultured in vitro to form self-organizing properties, making it possible to achieve individualized liver disease research. This review provides a comprehensive overview of the development of liver organoids, the existing and potential applications of liver regenerative medicine, the pathogenesis of liver disease heterogeneity, and drug screening.

关键词： organoids Liver diseases Individualized research Liver cancer Threedimensional cell culture Liver organoids

organoids in concert:engineering in vitro models toward enhanced fidelity

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Aggregate 2024年第2期5卷 99-111页

作者： Zhengkun Chen Ryohichi Sugimura Yu Shrike Zhang Changshun Ruan Chunyi Wen Department of Chemistry University of TorontoTorontoOntarioCanada Centre for Translational Stem Cell Biology Hong Kong SARChina Li Ka Shing Faculty of Medicine University of Hong KongHong Kong SARChina Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolCambridgeMassachusettsUSA Research Center for Human Tissue and Organs Degeneration Institute of Biomedicine and BiotechnologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenChina Department of Biomedical Engineering Faculty of EngineeringThe Hong Kong Polytechnic UniversityHong Kong SARChina Research Institute of Smart Ageing The Hong Kong Polytechnic UniversityHong Kong SARChina

organoids have emerged as a powerful platform for studying complex biological processes and diseases in ***,most studies have focused on individual organoids,overlooking the inter-organ interactions in vivo and limiting the physiological relevance of the *** address this limitation,the development of a multi-organoid system has gained considerable *** system aims to recapitulate inter-organ communication and enable the study of complex physiological *** review provides a comprehensive overview of the recent advancements in organoid engineering and the emerging strategies for constructing a multi-organoid ***,we highlight the critical mechanical,structural,and biochemical factors involved in designing suitable materials for the growth of different ***,we discuss the incorporation of dynamic culture environments to enhance organoid culture and enable inter-organoid ***,we explore techniques for manipulating organoid morphogenesis and spatial positioning of organoids to establish effective inter-organoid communication *** summarize the achievements in utilizing organoids to recapitulate inter-organ communication in vitro,including assembloids and microfluidic multiorganoid ***,we discuss the existing challenges and opportunities in developing a multi-organoid system from its technical bottlenecks in scalability to its applications toward complex human diseases.

关键词： assembloids biomaterials in vitro models microfluidics organoids

AI-enabled organoids:Construction,analysis,and application

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Bioactive Materials 2024年第1期31卷 525-548页

作者： Long Bai Yan Wu Guangfeng Li Wencai Zhang Hao Zhang Jiacan Su Department of Orthopedics Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200092China Organoid Research Center Institute of Translational MedicineShanghai UniversityShanghai200444China National Center for Translational Medicine(Shanghai)SHU Branch Shanghai UniversityShanghai200444China Department of Orthopedics First Affiliated HospitalJinan UniversityGuangzhou510632China Department of Orthopedics Shanghai Zhongye HospitalShanghai201941China Wenzhou Institute of Shanghai University Wenzhou325000China

organoids,miniature and simplified in vitro model systems that mimic the structure and function of organs,have attracted considerable interest due to their promising applications in disease modeling,drug screening,personalized medicine,and tissue *** the substantial success in cultivating physiologically relevant organoids,challenges remain concerning the complexities of their assembly and the difficulties associated with data *** advent of AI-Enabled organoids,which interfaces with artificial intelligence(AI),holds the potential to revolutionize the field by offering novel insights and methodologies that can expedite the development and clinical application of *** review succinctly delineates the fundamental concepts and mechanisms underlying AI-Enabled organoids,summarizing the prospective applications on rapid screening of construction strategies,cost-effective extraction of multiscale image features,streamlined analysis of multi-omics data,and precise preclinical evaluation and *** also explore the challenges and limitations of interfacing organoids with AI,and discuss the future direction of the *** together,the AI-Enabled organoids hold significant promise for advancing our understanding of organ development and disease progression,ultimately laying the groundwork for clinical application.

关键词： organoids Artificial intelligence Construction strategy Data analysis Preclinical evaluation and application

Ultrasound-guided fine-needle aspiration/biopsy-based pancreatic organoids establishment:an alternative model for basic and preclinical research

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Gastroenterology Report 2023年第1期11卷 88-94页

作者： Sheng Chen Min Wang Lei Liu Guodong Wang Lei Wang Changqing Zhong Chao Gao Wei Wu Lianyong Li Department of Gastroenterology PLA Strategic Support Force Medical CenterBeijingP.R.China State Environmental Protection Key Laboratory of Environmental Sense Organ Stress and Health PLA Strategic Support Force Medical CenterBeijingP.R.China Department of Medical Psychology PLA Strategic Support Force Medical CenterBeijingP.R.China Department of Otorhinolaryngology Head and Neck Surgery PLA Strategic Support Force Medical CenterBeijingP.R.China

Pancreatic ductal adenocarcinoma(PDAC),as one of the malignant cancers with the worst prognosis,is becoming the most urgent clinical *** to the lack of early diagnosis and curable therapeutic methods,it is critical to exploit proper models that can capture the overall attributes of the primary ***,organoid technology has emerged and flourished as a powerful tool to enable long-termculture of pancreatic tissues,including *** accumulating studies suggest,organoids can retain morphological,genetic,and behavioral traits,and have tremendous value in predicting the therapeutic response to conventional chemotherapy drugs or newfangled ***,this review comprehensively summarizes the tissue source including human fetal and adult pancreatic tissue to generate a pancreatic organoid as well as current organoids cultivate *** PDAC organoids can be established from a small number of samples derived from endoscopic ultrasound-guided fine-needle aspiration/biopsy(EUS-FNA/FNB),we also review the literature to date on EUS-FNA/FNBbased organoid constitution and its implementation in inquiring tumor behavior and evaluating therapeutic *** enabling the alignment of basic and clinical research platforms,the application of organoids would open up new avenues for drug discovery and maximally benefit translational medicine in the near future.

关键词： organoids pancreatic ductal adenocarcinoma ultrasound-guided fine-needle aspiration/biopsy review

A quick and reliable image-based AI algorithm for evaluating cellular senescence of gastric organoids

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Cancer Biology & Medicine 2023年第7期20卷 519-536页

作者： Ruixin Yang Yutong Du Wingyan Kwan Ranlin Yan Qimeng Shi Lu Zang Zhenggang Zhu Jianming Zhang Chen Li Yingyan Yu Department of General Surgery of Ruijin Hospital Shanghai Institute of Digestive SurgeryShanghai Key Laboratory for Gastric NeoplasmsShanghai Jiaotong University School of MedicineShanghai 200025China Institute of Translational Medicine Zhangjiang Institute for Advanced StudyShanghai Jiao Tong UniversityShanghai 201210China

Objective:organoids are a powerful tool with broad application prospects in ***,they provide alternatives to animal models for testing potential drugs before clinical ***,the number of passages for which organoids maintain cellular vitality ex vivo remains ***:Herein,we constructed 55 gastric organoids from 35 individuals,serially passaged the organoids,and captured microscopic images for phenotypic ***-associatedβ-galactosidase(SA-β-Gal),cell diameter in suspension,and gene expression reflecting cell cycle regulation were *** YOLOv3 object detection algorithm integrated with a convolutional block attention module(CBAM)was used to evaluate organoid ***:SA-β-Gal staining intensity;single-cell diameter;and expression of p15,p16,p21,CCNA2,CCNE2,and LMNB1 reflected the progression of aging in organoids during *** CBAM-YOLOv3 algorithm precisely evaluated aging organoids on the basis of organoid average diameter,organoid number,and number×diameter,and the findings positively correlated with SA-β-Gal staining and single-cell *** derived from normal gastric mucosa had limited passaging ability(passages 1–5),before aging,whereas tumor organoids showed unlimited passaging potential for more than 45 passages(511 days)without showing clear ***:Given the lack of indicators for evaluating organoid growth status,we established a reliable approach for integrated analysis of phenotypic parameters that uses an artificial intelligence algorithm to indicate organoid *** method enables precise evaluation of organoid status in biomedical studies and monitoring of living biobanks.

关键词： Gastric cancer organoids cellular senescence senescence-associatedβ-galactosidase artificial intelligence

Loss of SHROOM3 affects neuroepithelial cell shape through regulating cytoskeleton proteins in cynomolgus monkey organoids

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Zoological Research 2024年第2期45卷 233-241页

作者： Peng Li Ting Zhang Ruo Wu Jun-Yu Zhang Yan Zhuo Shan-Gang Li Jiao-Jian Wang Wen-Ting Guo Zheng-Bo Wang Yong-Chang Chen State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingYunnan 650500China Yunnan Key Laboratory of Primate Biomedical Research KunmingYunnan 650500China

Neural tube defects(NTDs)are severe congenital neurodevelopmental disorders arising from incomplete neural tube *** folate supplementation has been shown to mitigate the incidence of NTDs,some cases,often attributable to genetic factors,remain *** SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation;at present,however,the underlying mechanism remains *** tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural *** determine the role of SHROOM3 in early developmental morphogenesis,we established a neuroepithelial organoid culture system derived from cynomolgus monkeys to closely mimic the in vivo neural plate *** of SHROOM3 resulted in shorter neuroepithelial cells and smaller *** morphological changes were attributed to the insufficient recruitment of cytoskeletal proteins,namely fibrous actin(F-actin),myosin II,and phospho-myosin light chain(PMLC),to the apical side of the neuroepithelial ***,these defects were not rescued by folate *** sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ *** summary,we established an authentic in vitro system to study NTDs and identified a novel mechanism for NTDs that are unresponsive to folate supplementation.

关键词： Neural tube defects SHROOM3 Neuroepithelial organoids Cynomolgus monkey

Development of glioblastoma organoids and their applications in personalized therapy

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Cancer Biology & Medicine 2023年第5期20卷 353-368页

作者： Can Xu Xiaoye Yuan Pengyu Hou Ziru Li Changsheng Wang Chuan Fang Yanli Tan School of Clinical Medicine Hebei UniversityDepartment of NeurosurgeryAffiliated Hospital of Hebei UniversityBaoding 07100China School of Basic Medical Sciences Hebei UniversityBaoding 07100China Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma Baoding 071000China Department of Pathology Affiliated Hospital of Hebei UniversityBaoding 07100China

Glioblastomas(GBMs)are the brain tumors with the highest malignancy and poorest *** is characterized by high heterogeneity and resistance to drug *** are 3-dimensional cultures that are constructed in vitro and comprise cell types highly similar to those in organs or tissues in vivo,thus simulating specific structures and physiological functions of *** have been technically developed into an advanced ex vivo disease model used in basic and preclinical research on *** organoids,which simulate the brain microenvironment while preserving tumor heterogeneity,have been used to predict patients’therapeutic responses to antitumor drugs,thus enabling a breakthrough in glioma *** organoids provide an effective supplementary model that reflects human tumors’biological characteristics and functions in vitro more directly and accurately than traditional experimental ***,GBM organoids are widely applicable in disease mechanism research,drug development and screening,and glioma precision *** review focuses on the development of various GBM organoid models and their applications in identifying new individualized therapies against drug-resistant GBM.

关键词： Glioblastoma organoids glioma stem cell drug screening

Drug repurposing screening and mechanism analysis based on human colorectal cancer organoids

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Protein & Cell 2024年第4期15卷 285-304页

作者： Yunuo Mao Wei Wang Jingwei Yang Xin Zhou Yongqu Lu Junpeng Gao Xiao Wang Lu Wen Wei Fu Fuchou Tang School of Life Sciences Biomedical Pioneering Innovation CenterDepartment of General SurgeryThird HospitalPeking UniversityBeijing 100871China Beijing Advanced Innovation Center for Genomics(ICG) Ministry of Education Key Laboratory of Cell Proliferation and DifferentiationBeijing 100871China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing 100871China Peking University Third Hospital Cancer Center Beijing 100871China The Research Center of Stem Cell and Regenerative Medicine School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China

Colorectal cancer(CRC)is a highly heterogeneous cancer and exploring novel therapeutic options is a pressing issue that needs to be ***,we established human CRC tumor-derived organoids that well represent both morphological and molecular heterogeneities of original *** efficiently identify repurposed drugs for CRC,we developed a robust organoid-based drug screening *** combining the repurposed drug library and computation-based drug prediction,335 drugs were tested and 34 drugs with anti-CRC effects were *** importantly,we conducted a detailed transcriptome analysis of drug responses and divided the drug response signatures into five representative patterns:differentiation induction,growth inhibition,metabolism inhibition,immune response promotion,and cell cycle *** anticancer activities of drug candidates were further validated in the established patient-derived organoids-based xenograft(PDOX)system in *** found that fedratinib,trametinib,and bortezomib exhibited effective anticancer ***,the concordance and discordance of drug response signatures between organoids in vitro and pairwise PDOX in vivo were *** study offers an innovative approach for drug discovery,and the representative transcriptome features of drug responses provide valuable resources for developing novel clinical treatments for CRC.

关键词： colorectal cancer organoids drug repurposing patient-derived organoids-based xenograft mechanism of action

Cancer organoids:A platform in basic and translational research

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Genes & Diseases 2024年第2期11卷 614-632页

作者： Xin Ma Qin Wang Guozheng Li Hui Li Shouping Xu Da Pang Department of Breast Surgery Harbin Medical University Cancer HospitalHarbinHeilongjiang 150081China Sino-Russian Medical Research Center Harbin Medical University Cancer HospitalHarbinHeilongjiang 150081China Heilongjiang Academy of Medical Sciences HarbinHeilongjiang 150086China Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China) College of Pharmacy of Harbin Medical UniversityHarbinHeilongjiang 150086China

An accumulation of previous work has established organoids as good preclinical models of human tumors,facilitating translation from basic research to clinical *** are changing the paradigm of preclinical cancer research because they can recapitulate the heterogeneity and pathophysiology of human cancers and more closely approximate the complex tissue environment and structure found in clinical tumors than in vitro cell lines and animal ***,the potential applications of cancer organoids remain to be comprehensively *** the review,we firstly describe what is currently known about cancer organoid culture and then discuss in depth the basic mechanisms,including tumorigenesis and tumor metastasis,and describe recent advances in patient-derived tumor organoids(PDOs)for drug screening and immunological ***,the present challenges faced by organoid technology in clinical practice and its prospects are *** review highlights that organoids may offer a novel therapeutic strategy for cancer research.

关键词： Drug assays Immunotherapy Mechanism research organoids Precision medicine