Organoids Pub Date : 2025-12-03 DOI: 10.3390/organoids4040030

Elisa Heinzelmann, Francesco Piraino

{"title":"AI-Enhanced Patient-Derived Cancer Organoids: Integrating Machine Learning for Precision Oncology","authors":"Elisa Heinzelmann, Francesco Piraino","doi":"10.3390/organoids4040030","DOIUrl":"https://doi.org/10.3390/organoids4040030","url":null,"abstract":"Cancer remains a leading cause of mortality worldwide. Patient-derived organoids (PDOs) are three-dimensional (3D) cultures that recapitulate tumor histology, genetics, and cellular heterogeneity, providing physiologically relevant preclinical models. Integrating PDOs with artificial intelligence (AI) and machine learning (ML) enables scalable analysis of high-dimensional datasets, including imaging, transcriptomics, proteomics, and pharmacological readouts. These approaches support prediction of drug sensitivity, biomarker discovery, and patient stratification. Recent advances—such as deep learning (DL), transfer learning, federated learning, and self-supervised learning—enhance phenotypic profiling, cross-institutional model training, and translational prediction. In this review, we summarize the current state of AI-driven PDO research, highlighting methodological approaches, preclinical and clinical applications, challenges, and emerging trends. We also propose strategies for standardization, validation, and multi-modal integration to accelerate patient-specific therapeutic strategies.","PeriodicalId":489221,"journal":{"name":"Organoids","volume":"4 4","pages":"30-30"},"PeriodicalIF":0.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.mdpi.com/2674-1172/4/4/30/pdf?version=1764755918","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147907087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Three-Dimensional Morphological Characterisation of Human Cortical Organoids Using a Customised Image Analysis Workflow 使用自定义图像分析工作流的人类皮质类器官三维形态表征

Organoids Pub Date : 2025-01-17 DOI: 10.3390/organoids4010001

Sarah Handcock, Kay Richards, T. J. Karle, Pamela Kairath, Alita Soch, Carolina Chavez, Steven Petrou, Snezana Maljevic

{"title":"Three-Dimensional Morphological Characterisation of Human Cortical Organoids Using a Customised Image Analysis Workflow","authors":"Sarah Handcock, Kay Richards, T. J. Karle, Pamela Kairath, Alita Soch, Carolina Chavez, Steven Petrou, Snezana Maljevic","doi":"10.3390/organoids4010001","DOIUrl":"https://doi.org/10.3390/organoids4010001","url":null,"abstract":"Summary Statement: A tailored image analysis workflow was applied to quantify cortical organoid health, development, morphology and cellular composition over time. The assessment of cellular composition and viability of stem cell-derived organoid models is a complex but essential approach to understanding the mechanisms of human development and disease. Aim: Our study was motivated by the need for an image-analysis workflow, including high-cell content, high-throughput methods, to measure the architectural features of developing organoids. We assessed stem cell-derived cortical organoids at 4 and 6 months post-induction using immunohistochemistry-labelled sections as the analysis testbed. The workflow leveraged fluorescence imaging tailored to classify cells as viable and dying or non-viable and assign neuronal and astrocytic perinuclear markers to count cells. Results/Outcomes: Image acquisition was accelerated by capturing the organoid slice in 3D using widefield-fluorescence microscopy. This method used computational clearing to resolve nuclear and perinuclear markers and retain their spatial information within the organoid’s heterogeneous structure. The customised workflow analysed over 1.5 million cells using DAPI-stained nuclei, filtering and quantifying viable and non-viable cells and the necrotic-core regions. Temporal analyses of neuronal cell number derived from perinuclear labelling were consistent with organoid maturation from 4 to 6 months of in vitro differentiation. Overall: We have provided a comprehensive and enhanced image analysis workflow for organoid structural evaluation, creating the ability to gather cellular-level statistics in control and disease models.","PeriodicalId":489221,"journal":{"name":"Organoids","volume":"4 1","pages":"1-1"},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.mdpi.com/2674-1172/4/1/1/pdf?version=1737111616","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147921844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Organoids, Biocybersecurity, and Cyberbiosecurity—A Light Exploration 有机体、生物网络安全和网络生物安全--浅探

Organoids Pub Date : 2024-05-13 DOI: 10.3390/organoids3020007

Xavier Palmer, Cyril Akafia, Eleasa Woodson, Amanda Woodson, Lucas Potter

{"title":"Organoids, Biocybersecurity, and Cyberbiosecurity—A Light Exploration","authors":"Xavier Palmer, Cyril Akafia, Eleasa Woodson, Amanda Woodson, Lucas Potter","doi":"10.3390/organoids3020007","DOIUrl":"https://doi.org/10.3390/organoids3020007","url":null,"abstract":"Organoids present immense promise for studying organ systems and their functionality. Recently, they have become the subject of exploration outside of purely biomedical uses in multiple directions. We will explore the rapidly evolving landscape of organoid research over the 21st century, discussing significant advancements in organoid research and highlighting breakthroughs, methodologies, and their transformative impact on our understanding of physiology and modeling. In addition, we will explore their potential use for biocomputing and harnessing organoid intelligence, investigate how these miniaturized organ-like structures promise to create novel computational models and processing platforms allowing for innovative approaches in drug discovery, personalized medicine, and disease prediction. Lastly, we will address the ethical dilemmas surrounding organoid research by dissecting the intricate ethical considerations related to the creation, use, and potential implications of these in vitro models. Through this work, the goal of this paper is to provide introductory perspectives and bridges that will connect organoids to cybersecurity applications and the imperative ethical discourse accompanying its advancements with commentary on future uses.","PeriodicalId":489221,"journal":{"name":"Organoids","volume":"104 30","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140986035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analysis of Osteosarcoma Cell Lines and Patient Tissue Using a 3D In Vivo Tumor Model—Possible Effects of Punicalagin 利用三维体内肿瘤模型对骨肉瘤细胞系和患者组织进行分析-- Punicalagin 的可能作用

Organoids Pub Date : 2024-03-04 DOI: 10.3390/organoids3010004

Anna Rebecca Dorn, Sara Neff, Sophia Hupp, Melissa Engelhardt, Eric Pion, Ulrich Lenze, Carolin Knebel, Anna Duprée, Simone Schewe, Markus Weber, Christian Wulbrand, Axel Hillmann, Florian Weber, Phillip Clarke, Philipp Kainz, Thiha Aung, Silke Haerteis

{"title":"Analysis of Osteosarcoma Cell Lines and Patient Tissue Using a 3D In Vivo Tumor Model—Possible Effects of Punicalagin","authors":"Anna Rebecca Dorn, Sara Neff, Sophia Hupp, Melissa Engelhardt, Eric Pion, Ulrich Lenze, Carolin Knebel, Anna Duprée, Simone Schewe, Markus Weber, Christian Wulbrand, Axel Hillmann, Florian Weber, Phillip Clarke, Philipp Kainz, Thiha Aung, Silke Haerteis","doi":"10.3390/organoids3010004","DOIUrl":"https://doi.org/10.3390/organoids3010004","url":null,"abstract":"Osteosarcomas are the most common primary malignant bone tumors and mostly affect children, adolescents, and young adults. Despite current treatment options such as surgery and polychemotherapy, the survival of patients with metastatic disease remains poor. In recent studies, punicalagin has reduced the cell viability, angiogenesis, and invasion in cell culture trials. The aim of this study was to examine the effects of punicalagin on osteosarcomas in a 3D in vivo tumor model. Human osteosarcoma biopsies and SaOs-2 and MG-63 cells, were grown in a 3D in vivo chorioallantoic membrane (CAM) model. After a cultivation period of up to 72 h, the tumors received daily treatment with punicalagin for 4 days. Weight measurements of the CAM tumors were performed, and laser speckle contrast imaging (LSCI) and a deep learning-based image analysis software (CAM Assay Application v.3.1.0) were used to measure angiogenesis. HE, Ki-67, and Caspase-3 staining was performed after explantation. The osteosarcoma cell lines SaOs-2 and MG-63 and osteosarcoma patient tissue displayed satisfactory growth patterns on the CAM. Treatment with punicalagin decreased tumor weight, proliferation, and tumor-induced angiogenesis, and the tumor tissue showed pro-apoptotic characteristics. These results provide a robust foundation for the implementation of further studies and show that punicalagin offers a promising supplementary treatment option for osteosarcoma patients. The 3D in vivo tumor model represents a beneficial model for the testing of anti-cancer therapies.","PeriodicalId":489221,"journal":{"name":"Organoids","volume":"75 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140265733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Next Generation of Organoids Will Be More Complex and Even Closer to Resembling Real Organs: An Interview with Prof. Dr. Hans Clevers 下一代有机体将更加复杂，甚至更接近真实器官：汉斯-克莱沃斯博士教授访谈录

Organoids Pub Date : 2024-02-20 DOI: 10.3390/organoids3010003

Süleyman Ergün

引用次数: 0

Human Nasal Epithelium Organoids for Assessing Neutralizing Antibodies to a Protective SARS-CoV-2 Virus-like Particle Vaccine 用于评估保护性 SARS-CoV-2 病毒样颗粒疫苗中和抗体的人鼻上皮细胞器官组织

Organoids Pub Date : 2024-02-01 DOI: 10.3390/organoids3010002

Julio Carrera Montoya, S. Collett, Daniel Fernandez Ruiz, Linda Earnest, M. A. Edeling, A. Yap, C. Y. Wong, James P. Cooney, Kathryn C. Davidson, Jason Roberts, Steven Rockman, B. Tran, Julie L. McAuley, Georgia Deliyannis, S. Grimley, Damian F. J. Purcell, S. Waters, Dale I. Godfrey, Dhiraj Hans, Marc Pellegrini, Jason M. Mackenzie, E. Vincan, William R. Heath, Joseph Torresi

{"title":"Human Nasal Epithelium Organoids for Assessing Neutralizing Antibodies to a Protective SARS-CoV-2 Virus-like Particle Vaccine","authors":"Julio Carrera Montoya, S. Collett, Daniel Fernandez Ruiz, Linda Earnest, M. A. Edeling, A. Yap, C. Y. Wong, James P. Cooney, Kathryn C. Davidson, Jason Roberts, Steven Rockman, B. Tran, Julie L. McAuley, Georgia Deliyannis, S. Grimley, Damian F. J. Purcell, S. Waters, Dale I. Godfrey, Dhiraj Hans, Marc Pellegrini, Jason M. Mackenzie, E. Vincan, William R. Heath, Joseph Torresi","doi":"10.3390/organoids3010002","DOIUrl":"https://doi.org/10.3390/organoids3010002","url":null,"abstract":"Existing mRNA COVID-19 vaccines have shown efficacy in reducing severe cases and fatalities. However, their effectiveness against infection caused by emerging SARS-CoV-2 variants has waned considerably, necessitating the development of variant vaccines. Ideally, next-generation vaccines will be capable of eliciting broader and more sustained immune responses to effectively counteract new variants. Additionally, in vitro assays that more closely represent virus neutralization in humans would greatly assist in the analysis of protective vaccine-induced antibody responses. Here, we present findings from a SARS-CoV-2 VLP vaccine encompassing three key structural proteins: Spike (S), Envelope (E), and Membrane (M). The VLP vaccine effectively produced neutralizing antibodies as determined by surrogate virus neutralization test, and induced virus-specific T-cell responses: predominantly CD4+, although CD8+ T cell responses were detected. T cell responses were more prominent with vaccine delivered with AddaVax compared to vaccine alone. The adjuvanted vaccine was completely protective against live virus challenge in mice. Furthermore, we utilized air–liquid-interface (ALI)-differentiated human nasal epithelium (HNE) as an in vitro system, which authentically models human SARS-CoV-2 infection and neutralization. We show that immune sera from VLP-vaccinated mice completely neutralized SARS-CoV-2 virus infection, demonstrating the potential of ALI-HNE to assess vaccine induced Nab.","PeriodicalId":489221,"journal":{"name":"Organoids","volume":"33 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139685710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vascularizing Organoids to Promote Long-Term Organogenesis on a Chip 血管化器官组织，促进芯片上的长期器官生成

Organoids Pub Date : 2023-12-07 DOI: 10.3390/organoids2040019

Xinhui Wang, Brent M. Bijonowski, N. A. Kurniawan

{"title":"Vascularizing Organoids to Promote Long-Term Organogenesis on a Chip","authors":"Xinhui Wang, Brent M. Bijonowski, N. A. Kurniawan","doi":"10.3390/organoids2040019","DOIUrl":"https://doi.org/10.3390/organoids2040019","url":null,"abstract":"Organoids have emerged as a powerful tool for studying organ development, disease modeling, and drug discovery due to their ability to mimic the in vivo structure and function of organs in a three-dimensional in vitro model. During in vivo organ maturation, the process of vascularization is crucial for the provision of nutrients and oxygen to cells and the removal of waste products as the organ increases in size. Similarly, organoids can grow to sizes greater than the millimeter scale, yet transport of oxygen and nutrients to the center becomes increasingly difficult, often resulting in the formation of a necrotic core. Herein, we provide a concise summary of the recent development of methods to initiate and maintain vascularization of organoids. Broadly, vascularization of organoids has been achieved primarily by two means: generating organoids that contain endothelial cells or employing the secretion of vascular growth factors to promote vascularization. Growth factors play a fundamental role in regulating blood vessel formation through chemical signals that cause changes in the cell–cell adhesions and ultimately the migration of endothelial cells. Furthermore, models with perfusable systems demonstrate that through the application of growth factors and cells, the vascular network in vascularization-based organoids can administer biological substances to the interior of the organoid, opening up new possibilities for long-term organoid culture in vitro. This goal is being realized through the development of bioengineering tools, such as vascularized organoids on a chip, which are currently tested for various organ systems, including the lung, brain, kidney, and tumors, with applications in cancer angiogenesis and metastasis research. Taken together, our review underlines the vast potential of vascularized organoids to improve the understanding of organ development, while also proposing exciting avenues of organoid-on-a-chip and disease modeling.","PeriodicalId":489221,"journal":{"name":"Organoids","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138592632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stem Cell-Derived Organoids, Embryoids, and Embryos: Advances in Organismic Development In Vitro Force Us to Re-Focus on Ethical and Legal Aspects of Model Choice 干细胞衍生的器官组织、胚胎和胚胎：体外器官发育的进展迫使我们重新关注模型选择的伦理和法律问题

Organoids Pub Date : 2023-12-05 DOI: 10.3390/organoids2040018

Hans-Werner Denker

引用次数: 0

Modelling Meningioma Using Organoids: A Review of Methodologies and Applications 使用有机体模拟脑膜瘤：方法与应用综述

Organoids Pub Date : 2023-12-04 DOI: 10.3390/organoids2040017

Clara Elena López Vásquez, Clint Gray, Claire Henry, Matthew J. Munro

{"title":"Modelling Meningioma Using Organoids: A Review of Methodologies and Applications","authors":"Clara Elena López Vásquez, Clint Gray, Claire Henry, Matthew J. Munro","doi":"10.3390/organoids2040017","DOIUrl":"https://doi.org/10.3390/organoids2040017","url":null,"abstract":"Meningiomas are the most common tumours of the central nervous system. According to the World Health Organization (WHO), this disease is classified into three different grades: 80% of meningioma patients present with benign grade I tumours, while less than 2% present with malignant grade III meningiomas. Despite affecting thousands of people worldwide, much remains unknown about this disease, and the development of systemic treatments is still far behind in comparison to other types of tumours. Therefore, forming 3D structures (spheroids and organoids) could facilitate research on the mechanisms of formation, proliferation, migration, and invasion of these, for the most part, benign tumours, while also helping in the process of drug development. To date, there are three published methods for the formation of meningioma organoids primarily derived from patient tissue samples. Organoids offer many advantages in the development of treatments because they recapitulate the cellular complexity within tumours. These new methodological advances could open a substantial number of possibilities for the further characterisation and treatment of meningiomas. This review includes an overview of the disease and a description and comparison of established protocols for meningioma organoid formation.","PeriodicalId":489221,"journal":{"name":"Organoids","volume":"5 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138602986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SMAD1 Is Dispensable for CDX2 Induction but Required for the Repression of Ectopic Small-Intestinal Gene Expression in Human-Pluripotent-Stem-Cell-Derived Colonic Organoids SMAD1在CDX2诱导中是不可缺少的，但在人类多能干细胞衍生的结肠类器官中，SMAD1是抑制小肠异位基因表达所必需的

Organoids Pub Date : 2023-11-14 DOI: 10.3390/organoids2040015

Na Qu, Abdelkader Daoud, Braxton Jeffcoat, Jorge O. Múnera

{"title":"SMAD1 Is Dispensable for CDX2 Induction but Required for the Repression of Ectopic Small-Intestinal Gene Expression in Human-Pluripotent-Stem-Cell-Derived Colonic Organoids","authors":"Na Qu, Abdelkader Daoud, Braxton Jeffcoat, Jorge O. Múnera","doi":"10.3390/organoids2040015","DOIUrl":"https://doi.org/10.3390/organoids2040015","url":null,"abstract":"The generation of gastrointestinal tissues from human pluripotent stem cells has provided unprecedented insight into the molecular mechanisms that drive the patterning of the primitive gut tube. Previous work has identified bone-morphogenetic-protein (BMP) signaling as an important mediator of mid/hindgut versus foregut and hindgut versus midgut cell fate choice. Inhibition of BMP signaling during gut tube morphogenesis inhibits the expression of the pan-intestinal transcription factor CDX2. Treatment of CDX2+ mid/hindgut cultures with BMP patterns them into hindgut, which gives rise to colonic organoids (HCOs). While the role for BMP signaling is clear, the molecular mechanisms through which BMP signaling patterns the mid/hindgut and colon remain unclear. BMPs bind to BMP receptors, activating a signaling cascade that results in the activation of SMADs, which function as transcription factors. We hypothesized that one of these factors, SMAD1, would be necessary for establishing the CDX2 domain and the colon domain. Unexpectedly, endoderm derived from SMAD1-deficient induced pluripotent stem cells was capable of inducing CDX2 in response to WNT and FGF signaling. In addition, CDX2+ gut tube cultures could activate posterior HOX genes in response to BMP. However, examination of HCOs following cytodifferentiation revealed that SMAD1-deficient HCOs ectopically expressed small-intestinal markers despite expressing posterior HOX genes. These results indicate that there is redundancy of SMADs during early hindgut patterning but that SMAD1 is required for the inhibition of small-intestinal gene expression in HCOs.","PeriodicalId":489221,"journal":{"name":"Organoids","volume":"69 12","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134900751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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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