Guidelines for Manufacturing and Application of Organoids: Liver DOI Open Access
Hye‐ran Moon, Seon Ju Mun, Tae Hun Kim

et al.

International Journal of Stem Cells, Journal Year: 2024, Volume and Issue: 17(2), P. 120 - 129

Published: May 22, 2024

Recent amendments to regulatory frameworks have placed a greater emphasis on the utilization of in vitro testing platforms for preclinical drug evaluations and toxicity assessments. This requires advanced tissue models capable accurately replicating liver functions efficacy predictions. Liver organoids, derived from human cell sources, offer promise as reliable platform evaluation. However, there is lack standardized quality evaluation methods, which hinders their acceptance. paper proposes comprehensive standards tailored addressing source validation, organoid generation, functional assessment. These guidelines aim enhance reproducibility accuracy testing, thereby accelerating adoption organoids alternative or complementary tool animal development. The include criteria size, cellular composition, gene expression, assays, thus ensuring robust hepatotoxicity platform.

Language: Английский

Patient-derived organoids in human cancer: a platform for fundamental research and precision medicine DOI Creative Commons
Shanqiang Qu, Rongyang Xu,

Guozhong Yi

et al.

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

Citations

19
Modelling metabolic diseases and drug response using stem cells and organoids DOI Open Access
Wenxiang Hu, Mitchell A. Lazar

Nature Reviews Endocrinology, Journal Year: 2022, Volume and Issue: 18(12), P. 744 - 759

Published: Sept. 7, 2022

Language: Английский

Citations

60
Advanced human developmental toxicity and teratogenicity assessment using human organoid models DOI Creative Commons
Minghui Li, Jing Gong, Lixiong Gao

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2022, Volume and Issue: 235, P. 113429 - 113429

Published: March 21, 2022

Tremendous progress has been made in the field of toxicology leading to advance developmental toxicity assessment. Conventional animal models and vitro two-dimensional cannot accurately describe toxic effects predict actual vivo responses due obvious inter-species differences between humans animals, as well lack a physiologically relevant tissue microenvironment. Human embryonic stem cell (hESC)- induced pluripotent (iPSC)-derived three-dimensional organoids are ideal complex multicellular organotypic models, which indispensable recapitulating morphogenesis, cellular interactions, molecular processes early human organ development. Recently, have used for drug discovery, chemical safety This review discusses recent advances use organoid (i.e., brain, retinal, cardiac, liver, kidney, lung, intestinal models) teratogenicity assessment distinct tissues/organs following exposure pharmaceutical compounds, heavy metals, persistent organic pollutants, nanomaterials, ambient air pollutants. Combining next-generation with innovative engineering technologies generates novel powerful tools assessment, rapid this is expected continue.

Language: Английский

Citations

52
Building consensus on the application of organoid-based drug sensitivity testing in cancer precision medicine and drug development DOI Creative Commons

Dongxi Xiang,

Aina He, Rong Zhou

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(8), P. 3300 - 3316

Published: Jan. 1, 2024

Patient-derived organoids (PDOs) have emerged as a promising platform for clinical and translational studies. A strong correlation exists between outcomes the use of PDOs to predict efficacy chemotherapy and/or radiotherapy. To standardize interpretation enhance scientific communication in field cancer precision medicine, we revisit concept PDO-based drug sensitivity testing (DST). We present an expert consensus-driven approach medication selection aimed at predicting patient responses. further DST, propose guidelines clarification characterization. Additionally, identify several major challenges prediction when utilizing PDOs.

Language: Английский

Citations

17
Spatial Transcriptomics: A Powerful Tool in Disease Understanding and Drug Discovery DOI Creative Commons
Junxian Cao, Caifeng Li,

Zhao Cui

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(7), P. 2946 - 2968

Published: Jan. 1, 2024

Recent advancements in modern science have provided robust tools for drug discovery. The rapid development of transcriptome sequencing technologies has given rise to single-cell transcriptomics and single-nucleus transcriptomics, increasing the accuracy accelerating discovery process. With evolution spatial (ST) technology emerged as a derivative approach. Spatial hot topic field omics research recent years; it not only provides information on gene expression levels but also offers expression. This shown tremendous potential disease understanding In this article, we introduce analytical strategies review its applications novel target mechanism unravelling. Moreover, discuss current challenges issues that need be addressed. conclusion, new perspective

Language: Английский

Citations

16
Acoustic levitation as a tool for cell‐driven self‐organization of human cell spheroids during long‐term 3D culture DOI Creative Commons
Lucile Rabiet, Lousineh Arakélian, Nathan Jeger‐Madiot

et al.

Biotechnology and Bioengineering, Journal Year: 2024, Volume and Issue: 121(4), P. 1421 - 1433

Published: Jan. 15, 2024

Abstract Acoustic levitation, which allows contactless manipulation of micro‐objects with ultrasounds, is a promising technique for spheroids formation and culture. This acoustofluidic favors cell–cell interactions, away from the walls chip, leads to spontaneous self‐organization cells. Using this approach, we generated mesenchymal stromal cells, hepatic endothelial showed that long‐term culture cells in acoustic levitation feasible. We also demonstrated its dynamics depended weakly on parameters but were strongly dependent levitated cell type. Moreover, spheroid organization was modified by actin cytoskeleton inhibitors or calcium‐mediated interaction inhibitors. Our results confirmed rising fundamental research biotechnological industrial application rapidly growing field microphysiological systems. It allowed easily obtaining specific predictable shape size, could be cultivated over several days, without requiring hydrogels extracellular matrix.

Language: Английский

Citations

9
Protocol to generate human liver spheroids to study liver fibrosis induced by metabolic stress DOI Creative Commons
Hyun Young Kim,

Wonseok Lee,

Xiao Liu

et al.

STAR Protocols, Journal Year: 2024, Volume and Issue: 5(2), P. 103111 - 103111

Published: June 1, 2024

Currently, there is no effective treatment for obesity and alcohol-associated liver diseases, partially due to the lack of translational human models. Here, we present a protocol generate 3D spheroids that contain all cell types mimic "livers in dish." We describe strategies induce metabolic hepatic steatosis, inflammation, fibrosis. outline potential applications, including using experimental research drug screening identify anti-fibrotic therapies.

Language: Английский

Citations

9
Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method DOI Creative Commons
Qiushi Feng, Xiaofeng Shan, Vicky Yau

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 62 - 62

Published: Jan. 8, 2025

Background: Tumors, as intricate ecosystems, comprise oncocytes and the highly dynamic tumor stroma. Tumor stroma, representing non-cancerous non-cellular composition of microenvironment (TME), plays a crucial role in oncogenesis progression, through its interactions with biological, chemical, mechanical signals. This review aims to analyze challenges stroma mimicry models, highlight advanced personalized co-culture approaches for recapitulating using patient-derived organoids (PDTOs). Methods: synthesizes findings from recent studies on composition, stromal remodeling, spatiotemporal heterogeneities TME. It explores popular stroma-related systems integrating PDTOs elements, techniques improve mimicry. Results: Stroma driven by cells, highlights dynamism heterogeneity PDTOs, derived tissues or cancer-specific stem accurately mimic tissue-specific genetic features primary tumors, making them valuable drug screening. Co-culture models combining elements effectively recreate TME, showing promise anti-cancer therapy. Advanced flexible combinations enhance precision tumor-stroma recapitulation. Conclusions: PDTO-based offer promising platform therapy development. underscores importance refining these advance medicine therapeutic outcomes.

Language: Английский

Citations

1
Ecological and Health Risk Mediated by Micro(nano)plastics Aging Process: Perspectives and Challenges DOI
Kyuseok Song, Shu-Hong Gao,

Yu-Sheng Pan

et al.

Environmental Science & Technology, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Aged micro(nano)plastics (MNPs) are normally the ultimate state of plastics in environment after aging. The changes physical and chemical characteristics aged MNPs significantly influence their environmental behavior by releasing additives, forming byproducts, adsorbing contaminants. However, a systematic review is lacking on effects ecological human health regarding increasing but scattered studies results. This Review first summarizes unique methods for quantifying aging degree. Then we focused potential impacts organisms, ecosystems, health, including "Trojan horse" under real conditions. Through combining meta-analysis analytic hierarchy process (AHP) model, demonstrated that, compared to virgin MNPs, would result biomass decrease oxidative stress increase organisms lead total N/P greenhouse gas emissions ecosystems while causing cell apoptosis, antioxidant system reaction, inflammation health. Within framework risk assessment, used quotient (RQ) physiologically based pharmacokinetic (PBK) models as examples illustrate importance considering degree data acquisition, model building, formula evaluation. Given risks our urgent call more understand hazards real-world environments.

Language: Английский

Citations

1
3D tumor cultures for drug resistance and screening development in clinical applications DOI Creative Commons
Zheng Peng,

Xiaolan Lv,

Hao Sun

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 21, 2025

Tumor drug resistance presents a growing challenge in medical practice, particularly during anti-cancer therapies, where the emergence of drug-resistant cancer cells significantly complicates clinical treatment. In recent years, three-dimensional (3D) tumor culture technology, which more effectively simulates vivo physiological environment, has gained increasing attention research and applications. By mimicking cellular microenvironment, 3D technology not only recapitulates cell-cell interactions but also faithfully reproduces biological effects therapeutic agents. Consequently, is emerging as crucial tool biomedical research. We summarize benefits models organoid explore their application realm resistance, screening, personalized therapy, discuss potential prospects challenges transformation, with aim providing insights for optimizing treatment strategies advancing precision therapy.

Language: Английский

Citations

1