Tumor heterogeneity: preclinical models, emerging technologies, and future applications

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: April 28, 2023

Heterogeneity describes the differences among cancer cells within and between tumors. It refers to describing variations in morphology, transcriptional profiles, metabolism, metastatic potential. More recently, field has included characterization of tumor immune microenvironment depiction dynamics underlying cellular interactions promoting ecosystem evolution. been found most tumors representing one challenging behaviors ecosystems. As critical factors impairing long-term efficacy solid therapy, heterogeneity leads resistance, more aggressive metastasizing, recurrence. We review role main models emerging single-cell spatial genomic technologies our understanding heterogeneity, its contribution lethal outcomes, physiological challenges consider designing therapies. highlight how dynamically evolve because leverage this unleash recognition through immunotherapy. A multidisciplinary approach grounded novel bioinformatic computational tools will allow reaching integrated, multilayered knowledge required implement personalized, efficient therapies urgently for patients.

Language: Английский

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Organoids and organoids-on-a-chip as the new testing strategies for environmental toxicology-applications & advantages

Environment International, Journal Year: 2024, Volume and Issue: 184, P. 108415 - 108415

Published: Jan. 8, 2024

An increasing number of harmful environmental factors are causing serious impacts on human health, and there is an urgent need to accurately identify the toxic effects mechanisms these factors. However, traditional toxicity test methods (e.g., animal models cell lines) often fail provide accurate results. Fortunately, organoids differentiated from stem cells can more accurately, sensitively specifically reflect body. They also suitable for specific studies frequently used in toxicology nowadays. As a combination organ-on-a-chip technology, organoids-on-a-chip has great potential toxicology. It controllable physicochemical microenvironment not easy be contaminated. higher homogeneity size shape organoids. In addition, it achieve vascularization exchange nutrients metabolic wastes time. Multi-organoids-chip simulate interactions different organs. These advantages facilitate better function maturity organoids, which make up shortcomings common certain extent. This review firstly discussed limitations testing platforms, leading introduction new platforms: organoids-on-a-chip. Next, applications were summarized prospected. Since platforms have been sufficiently considered previous literature, we particularly emphasized them. Finally, this opportunities challenges faced by organoids-on-a-chip, with expectation that readers will gain deeper understanding their value field

Language: Английский

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Patient-derived organoids in human cancer: a platform for fundamental research and precision medicine

Molecular Biomedicine, Journal Year: 2024, Volume and Issue: 5(1)

Published: Feb. 12, 2024

Abstract Cancer is associated with a high degree of heterogeneity, encompassing both inter- and intra-tumor along considerable variability in clinical response to common treatments across patients. Conventional models for tumor research, such as vitro cell cultures vivo animal models, demonstrate significant limitations that fall short satisfying the research requisites. Patient-derived organoids, which recapitulate structures, specific functions, molecular characteristics, genomics alterations expression profiles primary tumors. They have been efficaciously implemented illness portrayal, mechanism exploration, high-throughput drug screening assessment, discovery innovative therapeutic targets potential compounds, customized treatment regimen cancer In contrast conventional organoids offer an intuitive, dependable, efficient model by conserving phenotypic, genetic diversity, mutational attributes originating tumor. Nevertheless, organoid technology also confronts bottlenecks challenges, how comprehensively reflect microenvironment, angiogenesis, reduce costs, establish standardized construction processes while retaining reliability. This review extensively examines use techniques fundamental precision medicine. It emphasizes importance patient-derived biobanks development, screening, safety evaluation, personalized Additionally, it evaluates application experimental better understand mechanisms The intent this explicate significance present new avenues future research.

Language: Английский

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Beyond hype: unveiling the Real challenges in clinical translation of 3D printed bone scaffolds and the fresh prospects of bioprinted organoids

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 21, 2024

Bone defects pose significant challenges in healthcare, with over 2 million bone repair surgeries performed globally each year. As a burgeoning force the field of tissue engineering, 3D printing offers novel solutions to traditional transplantation procedures. However, current 3D-printed scaffolds still face three critical material selection, methods, cellular self-organization and co-culture, significantly impeding their clinical application. In this comprehensive review, we delve into performance criteria that ideal should possess, particular focus on core faced by technology during translation. We summarize latest advancements non-traditional materials advanced techniques, emphasizing importance integrating organ-like technologies bioprinting. This combined approach enables more precise simulation natural structure function. Our aim writing review is propose effective strategies address these promote translation for defect treatment.

Language: Английский

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Bioreactor Technologies for Enhanced Organoid Culture

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11427 - 11427

Published: July 13, 2023

An organoid is a 3D organization of cells that can recapitulate some the structure and function native tissue. Recent work has seen organoids gain prominence as valuable model for studying tissue development, drug discovery, potential clinical applications. The requirements successful culture in vitro differ significantly from those traditional monolayer cell cultures. generation maturation high-fidelity entails developing optimizing environmental conditions to provide optimal cues growth maturation, such oxygenation, mechanical fluidic activation, nutrition gradients, etc. To this end, we discuss four main categories bioreactors used culture: stirred (SBR), microfluidic (MFB), rotating wall vessels (RWV), electrically stimulating (ES) bioreactors. We aim lay out state-of-the-art both commercial in-house developed bioreactor systems, their benefits derived various tissues, limitations technology, including sterilization, accessibility, suitability ease use long-term culture. Finally, future directions improvements existing technology how they may be enhance specific

Language: Английский

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Brain organoids are new tool for drug screening of neurological diseases

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 0(0), P. 0 - 0

Published: Jan. 1, 2023

At the level of in vitro drug screening, development a phenotypic analysis system with high-content screening at core provides strong platform to support high-throughput screening. There are few systematic reports on brain organoids, as new three-dimensional model, terms model stability, key fingerprint, and schemes, particularly regarding strategies for massive numbers traditional Chinese medicine monomers. This paper reviews organoids advantages over induced neurons or cells simulated diseases. The also highlights prospects from induction criteria schemes based characteristics application system.

Language: Английский

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Application of Human Brain Organoids—Opportunities and Challenges in Modeling Human Brain Development and Neurodevelopmental Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12528 - 12528

Published: Aug. 7, 2023

Brain organoids are three-dimensional (3D) structures derived from human pluripotent stem cells (hPSCs) that reflect early brain organization. These contain different cell types, including neurons and glia, similar to those found in the brain. Human provide unique opportunities model features of development not well-reflected animal models. Compared with traditional cultures models, offer a more accurate representation function, rendering them suitable models for neurodevelopmental diseases. In particular, patients’ have enabled researchers study diseases at stages gain better understanding disease mechanisms. Multi-brain regional assembloids allow investigation interactions between distinct regions while achieving higher level consistency molecular functional characterization. Although possess promising features, their usefulness is limited by several unresolved constraints, cellular stress, hypoxia, necrosis, lack high-fidelity maturation, circuit formation. this review, we discuss studies overcome natural limitations organoids, emphasizing importance combinations all neural such as glia (astrocyte, oligodendrocytes, microglia) vascular cells. Additionally, considering similarity developing brain, regionally patterned organoid-derived (NSCs) could serve scalable source replacement therapy. We highlight potential application therapy within field.

Language: Английский

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Bone Organoids: Recent Advances and Future Challenges

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 13(5)

Published: Dec. 12, 2023

Bone defects stemming from tumorous growths, traumatic events, and diverse conditions present a profound conundrum in clinical practice research. While bone has the inherent ability to regenerate, substantial anomalies require regeneration techniques. organoids represent new concept this field, involving 3D self-assembly of bone-associated stem cells guided vitro with or without extracellular matrix material, resulting tissue that mimics structural, functional, genetic properties native tissue. Within scientific panorama, ascend an esteemed status, securing significant experimental endorsement. Through synthesis current literature pioneering studies, review offers comprehensive survey organoid paradigm, delves into quintessential architecture ontogeny bone, highlights latest progress fabrication. Further, existing challenges prospective directions for future research are identified, advocating interdisciplinary collaboration fully harness potential burgeoning domain. Conclusively, as technology continues mature, its implications both landscapes poised be profound.

Language: Английский

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3D Bioprinting for Vascularization

Bioengineering, Journal Year: 2023, Volume and Issue: 10(5), P. 606 - 606

Published: May 18, 2023

In the world of clinic treatments, 3D-printed tissue constructs have emerged as a less invasive treatment method for various ailments. Printing processes, scaffold and free materials, cells used, imaging analysis are all factors that must be observed in order to develop successful 3D clinical applications. However, current research bioprinting model development lacks diverse methods vascularization result issues with scaling, size, variations printing method. This study analyzes printing, bioinks techniques vascularization. These discussed evaluated determine most optimal strategies Integrating stem endothelial prints, selecting type bioink according its physical properties, choosing properties desired printed steps will aid bioprinted

Language: Английский

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Recreating the extracellular matrix: novel 3D cell culture platforms in cancer research

FEBS Journal, Journal Year: 2023, Volume and Issue: 290(22), P. 5238 - 5247

Published: March 17, 2023

Cancer initiation and progression heavily rely on microenvironmental cues derived from various components of the niche including extracellular matrix (ECM). ECM is a complex macromolecular network that governs cell functionality. Although two-dimensional (2D) culture systems provide useful information at molecular level preclinical testing, they could not accurately represent in vivo architecture. Hence, it no surprise researchers last decade have focussed their efforts establishing novel advanced vitro models mimic tumour tissue-specific niches interactions. These numerous three-dimensional (3D) are now widely available, as well those still under development, grant with new, improved tools to study cancer explore innovative therapeutic options. Herein, we report emerging methods cutting-edge technologies 3D platforms discuss potential use unveiling cues, drug screening personalized treatment.

Language: Английский

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