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Summary: A multidisciplinary engineered strategy based on microfluidic technology is developed to generate human brain assembloids. Using microcapsules and a microfluidic chip, brain organoids can be assembled into desired structures. These brain assembloids exhibit active neural migration and interaction, demonstrating their potential in neurological and biomedical fields.
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ADVANCED MATERIALS
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Neurosciences
Madeline G. Andrews et al.
Summary: Organoids derived from human pluripotent stem cells are valuable tools for studying human brain development and neurological diseases. However, their utility is limited by the lack of high-fidelity cell types, limited maturation, atypical physiology, and lack of arealization.
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Young-Won Cho et al.
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Guocheng Fang et al.
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Bauer L. LeSavage et al.
Summary: The translation discusses how organotypic models of patient-specific tumors are changing our understanding of cancer heterogeneity and personalized medicine. These models can preserve genetic, proteomic, morphological, and pharmacotypic features of the parent tumor in vitro, and offer genomic and environmental manipulation. However, current cancer organoid culture techniques are uncontrolled and irreproducible, hindering the acceleration of insights into patient care.
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Sabina Kanton et al.
Summary: Deconstructing and reconstructing developmental processes ex vivo is essential for understanding organ assembly and disease physiology. Assembloids, self-organizing 3D cellular systems formed by integrating multiple organoids or combining organoids with missing cell types or primary tissue explants, have emerged as a powerful tool in studying development and disease. They provide a better representation of cellular interactions and emergent tissue properties during development.
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Sebastian Schuth et al.
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Moohyun Kim et al.
Summary: In this study, an unconventional method for multimodal characterization of three-dimensional cardiac organoids is presented. The method utilizes an active-matrix array of pressure-sensitive transistors to visualize the local pressure distributions of human-induced pluripotent stem-cell-derived cardiac organoids, and integrates it with three-dimensional electrodes formed by high-resolution printing of liquid metal for simultaneous electrophysiological recording and stimulation. This method enables electrical therapeutics of cardiac organoids without any interference between pressure signals and electrical pulses from pacing electrodes.
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Multidisciplinary Sciences
Omer Revah et al.
Summary: This study demonstrates the potential of transplanting self-organizing neural organoids derived from human stem cells into the somatosensory cortex of rats to develop mature cell types and integrate into sensory and motivation-related circuits. The transplanted cortical neurons exhibit more complex properties than their in vitro counterparts and can drive reward-seeking behavior when optogenetically activated. This approach has the potential to detect circuit-level phenotypes in patient-derived cells that cannot be uncovered using other methods.
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Neurosciences
Brett J. Kagan et al.
Summary: Integrating neurons into digital systems may enable performance infeasible with silicon alone. Here, the researchers developed a system called DishBrain that combines in vitro neural networks with in silico computing to harness the adaptive computation of neurons. By embedding the cultures in a simulated game-world, they observed apparent learning in the networks within five minutes of real-time gameplay, demonstrating the importance of closed-loop structured feedback in eliciting learning over time.
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Multidisciplinary Sciences
Gustavo de Medeiros et al.
Summary: This study presents an experimental and image processing framework to convert long-term light-sheet imaging of intestinal organoids into digital organoids, allowing for the visualization and understanding of multivariate and multiscale data. The researchers also identified cytokinesis failure of regenerative cells and discovered that these cells never reside in the intestinal crypt, suggesting tissue scale control on cellular fidelity.
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Chun-Chung Chen et al.
Summary: Malignant brain tumors pose a medical challenge, but patient-derived organoids (PDO) can serve as a drug-screening model and recapitulate the characteristics of primary tumors, showing potential for precision therapy.
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Ken Hiratsuka et al.
Summary: By integrating organoids with organ-on-a-chip technology, this study has demonstrated the potential of organoid-on-a-chip models in unraveling disease pathology and discovering therapeutic targets for autosomal recessive polycystic kidney disease.
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Chemistry, Analytical
Jooyoung Ro et al.
Summary: Three-dimensional multicellular spheroid models can accurately recapitulate the tumor microenvironment and microfluidic platforms are extensively used to study spheroids and understand cellular interactions and discover cancer therapeutics.
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Idris Salmon et al.
Summary: The generation of tissue and organs requires close interaction with vasculature. This study presents a 3D printing-based platform that allows pluripotent stem cells to interact with vascular cells in a spatially determined manner, resulting in the formation of organized vascular networks. This method provides a means to vascularize organoids and opens new avenues for understanding and manipulating the co-development of tissue-specific organoids with vasculature.
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Biotechnology & Applied Microbiology
Lucie A. Low et al.
Summary: OoCs, also known as microphysiological systems or 'tissue chips', have the potential to be informative at multiple stages of drug discovery and development, providing insights into normal human organ function and disease pathophysiology, as well as predicting the safety and efficacy of investigational drugs in humans. The field of OoCs has seen significant advances in recent years, but there are still challenges and opportunities that need to be addressed to fully realize their potential for translational research.
NATURE REVIEWS DRUG DISCOVERY
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Chemistry, Multidisciplinary
Sang Ah Yi et al.
Summary: Recent advances in 3D cell culture technology have enabled scientists to generate stem cell derived organoids that mimic the structural and functional characteristics of native organs. Current technologies are striving to identify essential factors for controlling organoid development processes, while there is a growing demand for engineering dynamic environments to generate reproducible and reliable organoids. Innovative biomaterial-based and advanced engineering-based approaches have been incorporated into conventional organoid culture methods to facilitate research development.
ADVANCED MATERIALS
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Xiaobei Luo et al.
Summary: This study developed a comprehensive three-dimensional model by establishing in vitro conditions for co-culturing colorectal cancer PDO and patient-derived CAFs, which helps to maintain the characteristics of tumor cells. Ultimately, this model is suitable for evaluating standard-of-care drugs and potentially useful for personalized cancer medicine.
ACTA BIOMATERIALIA
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Molong Qu et al.
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Biochemical Research Methods
Yue Wu et al.
Summary: Chemotherapy is an effective cancer treatment, but the process of bringing new drugs from the lab to patients is time-consuming and costly. Microfluidic tumor chips, with their ability to construct in vitro tumor models and utilize machine learning for accurate data acquisition and analysis, offer a promising platform for efficient drug screening and evaluation.
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Engineering, Environmental
Yujuan Zhu et al.
Summary: Our multidisciplinary strategy involves engineering vascularized human induced pluripotent stem cells (hiPSCs)-derived brain organoids system with biomimetic features using microfluidic hydrogel microcapsules. The precise fluids control of microfluidic electrospray technology enables the efficient encapsulation of hiPSCs-derived neural cells and formation of uniform human brain organoids. The resulting vascularized brain organoids exhibit structured organization, reasonable tissue size, in vivo-like neural identity, brain region, layered cortex, and complex vascular networks.
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Biochemical Research Methods
Yoonseok Park et al.
Summary: Recent advances in bio-interface technologies have provided a wide range of options for probing and modulating the behaviors of smallscale three dimensional biological constructs. Some effective design strategies in this emerging field of bioelectronics include thin deformable sheets, filamentary penetrating pins, open mesh structures and 3D interconnected networks. Multimodal interfaces, such as tissue-embedding scaffolds and tissue-surrounding frameworks, are highlighted in this review.
CURRENT OPINION IN BIOTECHNOLOGY
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Gastroenterology & Hepatology
Martina Poletti et al.
Summary: The gut microbiota plays a central role in health and is altered in inflammatory bowel disease. Host-microbiota interactions in IBD, especially at the intestinal epithelial cell level, are not fully understood. Organoid microfluidics technology is facilitating the study of these interactions, with potential for personalized medicine.
JOURNAL OF CROHNS & COLITIS
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Biochemistry & Molecular Biology
Ilya Lukonin et al.
Summary: Image-based phenotypic screening using organoids offers great potential but also unique challenges, requiring careful experimental design and process optimization. Advances in high-throughput microscopy and three-dimensional image analysis algorithms are crucial for robust chemical screening of organoids.
EXPERIMENTAL AND MOLECULAR MEDICINE
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Chemistry, Physical
Elena Garreta et al.
Summary: Significant progress has been made in the differentiation of human pluripotent stem cells and the development of organoids. The convergence of stem cell biology and bioengineering allows for controlled stimuli to be provided to the system. Engineering solutions are emphasized to control the self-organization and functionality of stem cell-derived organoids.
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Biochemical Research Methods
Lei Tang
Summary: The assembloids, which are generated by spatially organizing multiple cell types, will provide deeper insights into tissue function.
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Biochemical Research Methods
Hiroyuki Koike et al.
Summary: This study introduces a method for continuous patterning of hepatic, biliary and pancreatic structures from human pluripotent stem cells (PSCs) in 3D culture. By fusing anterior and posterior gut spheroids together in one well, the self-patterning of multi-organ (HBP) domains occurs within the boundary region of the two spheroids. Long-term culture of these structures leads to the differentiation of segregated organs with developmentally relevant features.
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Biochemistry & Molecular Biology
Emilie Darrigues et al.
Summary: This study screened potential GBM therapeutic drugs using patient-derived 3D models, finding that tubulin inhibitor had the best efficacy in U-251 MG cells but showed highly variable results in patient organoids. The efficacy of compounds was found to be closely related to patient tumor heterogeneity, suggesting that such models can be used to evaluate individualized cancer treatment strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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Review
Biochemistry & Molecular Biology
Derek C. Liberti et al.
Summary: Organoids derived from various lung cell types offer a reproducible model for understanding complex signals driving cell fate decisions in a regenerative context. Integrating organoid assays with in vivo modeling helps explore responses of different niches and compartments in the respiratory system to acute and chronic lung diseases. Strategic implementation and improvement of organoid techniques provide exciting opportunities to identify new therapeutic approaches for lung disease states.
TRENDS IN MOLECULAR MEDICINE
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Multidisciplinary Sciences
Yuan Guan et al.
Summary: In this study, human hepatic organoids engineered to express the ARPKD mutation developed key features of ARPKD liver pathology in just 21 days, including abnormal bile ducts and fibrosis. The mutation increased collagen abundance and thick collagen fiber production, which activated the TGF beta pathway and stimulated myofibroblasts to form collagen fibers. Moreover, the transcriptome of the organoids resembled that of liver fibrosis, indicating their potential use in anti-fibrotic therapy testing.
NATURE COMMUNICATIONS
(2021)
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Nanoscience & Nanotechnology
Moritz Hofer et al.
Summary: This review discusses the application of engineering approaches to enhance the reproducibility and physiological relevance of organoids, including cellular engineering, designer matrices, and microfluidics.
NATURE REVIEWS MATERIALS
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Biochemical Research Methods
Ikram Khan et al.
Summary: Organoids are biological systems grown in vitro that self-organize into 3D cellular tissues of specific organs, with brain organoids being valuable models for studying human brain development. Researchers are developing improved tools, such as microfluidic chips and bioreactors, to track and image brain organoids in real-time on a chip, enabling long-term live-imaging of the growing organoids with high resolution.
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Cell Biology
Megan R. Reed et al.
Summary: Li Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome caused by germline mutations in TP53. The study utilized comparative transcriptomics to identify uniquely overexpressed genes in an LFS GBM patient, leading to the discovery of STAT1 and STAT2 as significantly overexpressed genes, suggesting ruxolitinib as a potential therapy. Adherent and organoid cell cultures confirmed the sensitivity of LFS patient cells to ruxolitinib, supporting personalized therapeutic targets for malignant brain tumors.
Review
Oncology
Zilong Zhou et al.
Summary: Organoids are three-dimensional cellular structures that resemble organs, can be generated from healthy or pathological tissues, and retain cellular composition and drug features. Patient-derived organoids are used in clinical trials to predict responses to treatment and potentially improve outcomes.
FRONTIERS IN ONCOLOGY
(2021)
Review
Microbiology
Samuel Flashner et al.
Summary: The microbiome plays a crucial role in the development of esophageal cancer, but research on its specific contributions to esophageal squamous cell carcinoma and esophageal adenocarcinoma is lacking. By utilizing 3D organoid models, advancements have been made in understanding these cancers and potentially improving prevention and treatment strategies for patients.
Article
Biochemical Research Methods
Benjamin Fook Lun Lai et al.
Summary: The study presents an alternative method for cultivating millimeter-scale functional vascularized tissues on a biofabricated platform, facilitating the easy integration of organoid technology. By utilizing 3D stamping with a synthetic polymeric elastomer, a scaffold called 'AngioTube' is generated to support a perfusable vascular system and the self-assembly of various parenchymal tissues. The platform allows easy connection of two or more tissue compartments through a common vasculature, with built-in micropores for studying cell invasion.
Review
Polymer Science
Amit M. E. Arefin et al.
Summary: Polymer 3D printing shows great potential in medical applications, with ongoing research focusing on improving materials, processes, and design strategies to meet the needs of medical devices and tissue engineering.
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Multidisciplinary Sciences
Yoonseok Park et al.
Summary: Scientists are developing microfabricated 3D frameworks as neural interfaces for studying complex brain features in biological systems. These neural interfaces can achieve multiple functions, providing various opportunities for basic neuroscience research.
Review
Gastroenterology & Hepatology
Xiao Han et al.
Summary: Intestinal organoids play a crucial role in gastrointestinal research, particularly in studying nontransformed intestinal epithelial cells and their involvement in diseases like inflammatory bowel disease and colon cancer. Research on the advantages of using organoids derived from adult stem cells, as well as the impact of biopsy location and patient age on organoids and their interactions with microbes, has made significant progress. Various methods of introducing bacteria in a relevant manner and assessing key outputs using these models have also been addressed.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Gordana Vunjak-Novakovic et al.
Summary: Bioengineered human tissues exhibit enough complexity to mimic native tissues, and organs-on-a-chip are better at displaying specific organ functions compared to organoids. The key to this emerging technology lies in establishing, validating, and fully utilizing the fidelity of these models.
Review
Microbiology
Jens Puschhof et al.
Summary: In vitro co-culture models are important tools for studying interactions between microbiota and intestinal tissues. These models can replicate specific processes of microbe-epithelia interactions. By using different models of bacterial, viral, and parasitic infections, the advantages of each culture model can be highlighted.
CELL HOST & MICROBE
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Clinical Neurology
Henrik Renner et al.
Summary: Researchers have developed a new, fully scalable workflow for generating, maintaining, and analyzing three-dimensional microtissues mimicking key characteristics of the human midbrain. These automated midbrain organoids lay a reproducible, scalable foundation for creating next-generation 3D models of human neural disease and phenotypic drug discovery.
MOVEMENT DISORDERS
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Biochemistry & Molecular Biology
Lu Wang et al.
Summary: Research findings suggest that pericytes may serve as important portals for SARS-CoV-2 infection in the nervous system. Introducing pericyte-like cells (PLCs) into cortical organoids can provide an experimental model that supports virus entry and replication.
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Biochemical Research Methods
Jens Puschhof et al.
Summary: This protocol outlines methods for co-culturing human small intestinal and colon organoids with microbes, including microinjection and exposure to bacteria. It provides detailed protocols for assessing cell viability and growth kinetics, as well as spatial relationships using microscopy techniques. Considerations for evaluating the impact of bacteria on gene expression and mutations through sequencing are also discussed.
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Biology
Thomas M. Rawlings et al.
Summary: The study suggests that decidual senescence controls endometrial fate decisions at implantation and the presence of senescent decidual cells creates a dynamic implantation environment, enabling embryo expansion and attachment but leading to gradual disintegration of assembloids. Pharmacological inhibition of stress responses in pre-decidual cells accelerated decidualization and eliminated the emergence of senescent decidual cells, resulting in a strong, static decidual matrix. The research highlights how endometrial assembloids may facilitate the discovery of new treatments to prevent reproductive failure.
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Cell & Tissue Engineering
Ranjie Xu et al.
Summary: By coculturing human pluripotent stem cell (hPSC)-derived microglia and primitive macrophage progenitors, a new brain region-specific organoid model containing microglia has been established. This model allows control of the number of human microglia, which exhibit phagocytic activity and synaptic pruning function. Additionally, human microglia in the organoids respond to Zika virus infection, providing a novel platform to study human microglial function in various neurological disorders.
Review
Biochemical Research Methods
Alexandra Louey et al.
Summary: Organoids, three-dimensional functional structures that mimic in vivo organs, offer new opportunities for modeling cancer and infectious diseases. Automation in organoid culture and analysis is becoming increasingly important, with a rising demand for automated organoid platforms anticipated in the future.
Review
Nanoscience & Nanotechnology
Shawn Kang et al.
Summary: The field of nanoengineering and nanomedicine has experienced explosive growth in the last two decades, with engineered nanoparticles garnering great attention. Researchers are focusing on developing new technologies to simulate and analyze the efficacy and safety of nanotherapeutics in human physiological systems in vitro. Organ-on-a-chip technology represents the latest advance in addressing the limitations of conventional preclinical models.
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Emergency Medicine
Yijie Zhang et al.
Summary: An in vitro model of skin constructs with sweat glands (SGs) and hair follicles (HFs) was established to explore the interaction between these two appendages in regeneration. The results showed that HF spheroids promoted differentiation of both SGs and HFs in SG scaffolds, while SG scaffolds mainly promoted SG differentiation and had little effect on HF potency in HF spheroids. The study provides insights into the molecular mechanisms of SG and HF regeneration.
Review
Engineering, Biomedical
Zahra Heydari et al.
Summary: The limitations of monolayer culture have prompted scientists to explore new models that can accurately replicate the architecture and function of human organs. Recent advancements in protocol improvement have led to the development of three-dimensional organ-like structures known as 'organoids', which can mimic the characteristics of real organs. These organoid-based 3D models offer novel opportunities for drug screening, toxicology research, and molecular pathophysiology studies.
BIO-DESIGN AND MANUFACTURING
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Engineering, Biomedical
Ya Ren et al.
Summary: Organoids developed from pluripotent stem cells or adult stem cells are three-dimensional cell cultures that mimic certain biological developmental processes of organs, with promising applications in drug screening, disease modeling, and regenerative repair. The challenges facing organoid construction include breakthroughs in scale size, vascularization, reproducibility, and precise architecture. Bioprinting techniques, with the application of bioinks, have accelerated the process of organoid construction, and a multidisciplinary combination of developmental biology, disease pathology, cell biology, and materials science will help overcome obstacles to further develop real organs.
INTERNATIONAL JOURNAL OF BIOPRINTING
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Cell & Tissue Engineering
Jin Yu
Summary: The 2019-novel coronavirus pneumonia epidemic presents a significant public health challenge, and the use of organoid models can provide a more accurate simulation of viral activity, facilitating the development of antiviral drugs.
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Biochemical Research Methods
Zheng Ao et al.
Summary: Researchers developed a controllable acoustofluidic method to improve the standardization of fused organoid models by effectively modeling the development of human mesocortical pathways. They successfully manipulated neuroepithelial bud alignment in acoustically fused human forebrain and midbrain organoids, demonstrating regulation of neuronal projection and progenitor cell division. This approach offers a label-free, contact-free, and highly biocompatible tool for assembling organoids and enhancing disease modeling and tissue engineering.
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Biochemical Research Methods
Fangchao Yin et al.
Summary: The study developed a multi-organoids-on-a-chip system derived from human induced pluripotent stem cells to assess drug safety, showing the hepatic metabolism-dependent cardiotoxicity induced by an antidepressant drug through co-culturing liver and heart organoids.
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