Human and rat renal proximal tubule in vitro models for ADME applications

Archives of Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Abstract The kidney is a major organ dictating excretion rates of chemicals and their metabolites from the body thus renal clearance frequently component pharmaco-(toxico)-kinetic profiles. Within nephron, proximal tubule site for xenobiotic reabsorption glomerular filtrate secretion blood into lumen via expression multiple inward (lumen to interstitium) outward transport systems (interstitium lumen). While there exist several human tubular cell culture options that could be utilized modelling clearance, they do not necessarily represent full complement processes in vivo counterparts. Here, we review available rat vitro models, including subcellular fractions, immortalized lines, primary cultures, induced pluripotent stem (iPSC)-derived models also consider more organotypic environments such as microporous growth supports, organoids microfluidic systems. This focuses on levels function transporters phase I II metabolizing enzymes these order critically assess usefulness identify potential solutions overcome identified limitations.

Language: Английский

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Revolutionizing biomedical research: The imperative need for heart–kidney-connected organoids

APL Bioengineering, Journal Year: 2024, Volume and Issue: 8(1)

Published: Feb. 27, 2024

Organoids significantly advanced our comprehension of organ development, function, and disease modeling. This Perspective underscores the potential heart–kidney-connected organoids in understanding intricate relationship between these vital organs, notably cardiorenal syndrome, where dysfunction one can negatively impact other. Conventional models fall short replicating this complexity, necessitating an integrated approach. By co-culturing heart kidney organoids, combined with microfluidic 3D bioprinting technologies, a more accurate representation vivo conditions be achieved. Such interconnected systems could revolutionize grasp multi-organ diseases, drive drug discovery by evaluating therapeutic agents on both organs simultaneously, reduce need for animal models. In essence, present promising avenue to delve deeper into pathophysiology underlying disorders, bridging existing knowledge gaps, advancing biomedical research.

Language: Английский

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Application of Artificial Intelligence at All Stages of Bone Tissue Engineering

Biomedicines, Journal Year: 2023, Volume and Issue: 12(1), P. 76 - 76

Published: Dec. 28, 2023

The development of artificial intelligence (AI) has revolutionized medical care in recent years and plays a vital role number areas, such as diagnostics forecasting. In this review, we discuss the most promising areas AI application to field bone tissue engineering prosthetics, which can drastically benefit from AI-assisted optimization patient personalization implants scaffolds ways ranging visualization real-time monitoring implantation cases prediction, thereby leveraging compromise between specific architecture decisions, material choice, synthesis procedure. With emphasized crucial accuracy robustness developed algorithms, especially engineering, it was shown that rigorous validation testing, demanding large datasets extensive clinical trials, are essential, how through developing multidisciplinary cooperation among biology, chemistry with materials science, AI, these challenges be addressed.

Language: Английский

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Essential Guidelines for Manufacturing and Application of Organoids

International Journal of Stem Cells, Journal Year: 2024, Volume and Issue: 17(2), P. 102 - 112

Published: May 20, 2024

An organoid is a self-organized three-dimensional structure derived from stem cells that mimics the structure, cell composition, and functional characteristics of specific organs tissues used for evaluating safety effectiveness drugs toxicity industrial chemicals. Organoid technology new methodology could replace testing on animals accelerate development precision regenerative medicine. However, large variations in production can occur between laboratories with low reproducibility process no internationally agreed standards quality evaluation factors at endpoints. To overcome these barriers hinder regulatory acceptance commercialization organoids, Korea established Standards Initiative September 2023 various stakeholders, including industry, academia, agencies, standard experts, through public private partnerships. This developed general guidelines manufacturing organoid-specific liver, intestines, heart extensive evidence analysis consensus among experts. report based common guideline v1.0, which to promote practical use organoids. does not focus organoids or contexts but provides guidance makers users materials, procedures, essential assessment methods end points are applicable current level.

Language: Английский

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Advancements in Research on Genetic Kidney Diseases Using Human-Induced Pluripotent Stem Cell-Derived Kidney Organoids

Cells, Journal Year: 2024, Volume and Issue: 13(14), P. 1190 - 1190

Published: July 13, 2024

Genetic or hereditary kidney disease stands as a pivotal cause of chronic (CKD). The proliferation and widespread utilization DNA testing in clinical settings have notably eased the diagnosis genetic diseases, which were once elusive but are now increasingly identified cases previously deemed CKD unknown etiology. However, despite these diagnostic strides, research into pathogenesis novel drug development faces significant hurdles, chiefly due to dearth appropriate animal models challenges posed by limited patient cohorts studies. Conversely, advent human-induced pluripotent stem cells (hiPSCs) offer promising avenue for research. Particularly, hiPSC-derived organoid systems presents platform investigating various forms diseases. Moreover, integration CRISPR/Cas9 technique this system holds immense potential efficient on This review aims explore applications vitro organoids generated from hiPSCs study diverse Additionally, it will delve limitations outline future perspectives advancing crucial area.

Language: Английский

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Organoids in skin wound healing

Burns & Trauma, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 1, 2025

Abstract Stem cells (SCs) can self-replicate and differentiate into multiple lineages. Organoids, 3D cultures derived from SCs, replicate the spatial structure physiological characteristics of organs in vitro. Skin organoids effectively simulate function skin tissue, reliably restoring natural ecology various vitro environments. have been employed extensively development pathology research, offering valuable insights for drug screening. Moreover, they play crucial roles regeneration tissue repair. This in-depth review explores construction applications wound healing, with a focus on their process, including appendage integration, significant advancements wound-healing research.

Language: Английский

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Advances in cardiac organoid research: implications for cardiovascular disease treatment

Cardiovascular Diabetology, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 18, 2025

Globally, cardiovascular diseases remain among the leading causes of mortality, highlighting urgent need for innovative research models. Consequently, development accurate models that simulate cardiac function holds significant scientific and clinical value both disease therapeutic interventions. Cardiac organoids, which are three-dimensional structures derived from induced differentiation stem cells, particularly promising. These organoids not only replicate autonomous beating essential electrophysiological properties heart but also widely employed in studies related to diseases, drug efficacy testing, regenerative medicine. This review comprehensively surveys various fabrication techniques used create their diverse applications modeling a range diseases. We emphasize role advanced technologies enhancing maturation functionality ensuring these closely resemble native tissue. Furthermore, we discuss monitoring evaluation parameters critical assessing performance considering complex interactions within multi-organ systems. approach is vital precision efficiency development, allowing more effective strategies. Ultimately, this aims provide thorough perspective on fundamental treatment offering insights could pave way future advancements understanding addressing prevalent health challenges.

Language: Английский

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Cardiac‐Focused Multi‐Organ Chips: Advanced Disease Modeling, Drug Testing, and Inter‐Organ Communication

Advanced Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

Heart disease remains a leading cause of mortality worldwide, posing significant challenge to global healthcare systems. Traditional animal models and cell culture techniques are instrumental in advancing the understanding cardiac pathophysiology. However, these methods limited their ability fully replicate heart's intricate functions. This underscores need for deeper investigation into fundamental mechanisms heart disease. Notably, pathology is often influenced by systemic factors, with conditions other organs contributing onset progression. Cardiac-focused multi-organ chip technology has emerged better elucidate complex inter-organ communications address limitations current vitro models. offers novel approach recreating microenvironment integrating it organ systems, thereby enabling more precise modeling drug toxicity assessment. review provides comprehensive overview structure function, explores advancements development, highlights applications cardiac-focused chips medical research. Finally, future potential this enhancing therapeutic evaluation discussed.

Language: Английский

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Organoid Models to Study Human Infectious Diseases

Cell Proliferation, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

ABSTRACT Infectious diseases have become significant events that threaten global public health and economic development. Since the 20th century, multiple outbreaks of infectious gradually deepened humanity's understanding viral infections, prevention treatment. Organoids possess a high degree similarity to human physiological states strong self‐organising capabilities. Research on based organoids offers advantages in terms availability, editability diversity. In this perspective, we briefly introduce development organoids, focusing historically caused fatal harm health, such as HIV, ZIKV, SARS‐CoV‐2 MPXV. We further summarise relevant research pathogenic mechanisms these viruses organoid models, host reactivity, therapeutic strategies. Finally, list latest techniques combined with discuss challenges faced look forward future prospects vaccine drug

Language: Английский

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Advances in humanoid organoid-based research on inter-organ communications during cardiac organogenesis and cardiovascular diseases

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 28, 2025

The intimate correlation between cardiovascular diseases and other organ pathologies, such as metabolic kidney diseases, underscores the intricate interactions among these organs. Understanding inter-organ communications is crucial for developing more precise drugs effective treatments systemic diseases. While animal models have traditionally been pivotal in studying interactions, human-induced pluripotent stem cells (hiPSCs) offer distinct advantages when constructing vitro models. Beyond conventional two-dimensional co-culture model, hiPSC-derived humanoid organoids emerged a substantial advancement, capable of replicating essential structural functional attributes internal organs vitro. This breakthrough has spurred development multilineage organoids, assembloids, organoids-on-a-chip technologies, which allow enhanced physiological relevance. These technologies shown great potential mimicking coordinated organogenesis, exploring disease pathogenesis, facilitating drug discovery. As central system, heart serves focal point an extensively studied network interactions. review focuses on advancements challenges organs, presenting comprehensive exploration this cutting-edge approach research.

Language: Английский

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