Human organs-on-chips for disease modelling, drug development and personalized medicine

Nature Reviews Genetics, Год журнала: 2022, Номер 23(8), С. 467 - 491

Опубликована: Март 25, 2022

The failure of animal models to predict therapeutic responses in humans is a major problem that also brings into question their use for basic research. Organ-on-a-chip (organ chip) microfluidic devices lined with living cells cultured under fluid flow can recapitulate organ-level physiology and pathophysiology high fidelity. Here, I review how single multiple human organ chip systems have been used model complex diseases rare genetic disorders, study host–microbiome interactions, whole-body inter-organ reproduce clinical drugs, radiation, toxins infectious pathogens. address the challenges must be overcome chips accepted by pharmaceutical industry regulatory agencies, as well discuss recent advances field. It evident instead drug development avatars personalized medicine ever closer realization. This Review discusses types organ-on-a-chip diverse applications disease modelling, medicine, reach full potential.

Язык: Английский

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Organs-on-chips: into the next decade

Nature Reviews Drug Discovery, Год журнала: 2020, Номер 20(5), С. 345 - 361

Опубликована: Сен. 10, 2020

Язык: Английский

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Organ-on-a-chip: recent breakthroughs and future prospects

BioMedical Engineering OnLine, Год журнала: 2020, Номер 19(1)

Опубликована: Фев. 12, 2020

Abstract The organ-on-a-chip (OOAC) is in the list of top 10 emerging technologies and refers to a physiological organ biomimetic system built on microfluidic chip. Through combination cell biology, engineering, biomaterial technology, microenvironment chip simulates that terms tissue interfaces mechanical stimulation. This reflects structural functional characteristics human can predict response an array stimuli including drug responses environmental effects. OOAC has broad applications precision medicine biological defense strategies. Here, we introduce concepts review its application construction models, development, toxicology from perspective different organs. We further discuss existing challenges provide future perspectives for application.

Язык: Английский

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Adhesion mechanisms mediated by probiotics and prebiotics and their potential impact on human health

Applied Microbiology and Biotechnology, Год журнала: 2019, Номер 103(16), С. 6463 - 6472

Опубликована: Июль 2, 2019

Adhesion ability to the host is a classical selection criterion for potential probiotic bacteria that could result in transient colonisation would help promote immunomodulatory effects, as well stimulate gut barrier and metabolic functions. In addition, have protective role against enteropathogens through different mechanisms including production of antimicrobial compounds, reduction pathogenic bacterial adhesion competition cell binding sites. The competitive exclusion by has beneficial effect not only on but also urogenital tract oral cavity. On other hand, prebiotics may act barriers pathogens toxins preventing their epithelial receptors. vitro studies with intestinal lines been widely used along last decades assess adherence pathogen antagonism. However, extrapolation these results vivo conditions still remains unclear, leading need optimisation more complex approaches include interaction resident microbiota address current limitations. aim this mini review provide comprehensive overview adhesive properties probiotics focusing most recent findings related antipathogenic human health.

Язык: Английский

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Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips

Nature Biomedical Engineering, Год журнала: 2020, Номер 4(4), С. 421 - 436

Опубликована: Янв. 27, 2020

Язык: Английский

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Robotic fluidic coupling and interrogation of multiple vascularized organ chips

Nature Biomedical Engineering, Год журнала: 2020, Номер 4(4), С. 407 - 420

Опубликована: Янв. 27, 2020

Язык: Английский

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Targeting the gut and tumor microbiota in cancer

Nature Medicine, Год журнала: 2022, Номер 28(4), С. 690 - 703

Опубликована: Апрель 1, 2022

Язык: Английский

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Host–microbiota maladaptation in colorectal cancer

Nature, Год журнала: 2020, Номер 585(7826), С. 509 - 517

Опубликована: Сен. 23, 2020

Язык: Английский

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Developing a new class of engineered live bacterial therapeutics to treat human diseases

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Апрель 8, 2020

Abstract A complex interplay of metabolic and immunological mechanisms underlies many diseases that represent a substantial unmet medical need. There is an increasing appreciation the role microbes play in human health disease, evidence accumulating new class live biotherapeutics comprised engineered could address specific disease. Using tools synthetic biology, nonpathogenic bacteria can be designed to sense respond environmental signals order consume harmful compounds deliver therapeutic effectors. In this perspective, we describe considerations for design development achieve regulatory patient acceptance.

Язык: Английский

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RapidAIM: a culture- and metaproteomics-based Rapid Assay of Individual Microbiome responses to drugs

Microbiome, Год журнала: 2020, Номер 8(1)

Опубликована: Март 11, 2020

Human-targeted drugs may exert off-target effects or can be repurposed to modulate the gut microbiota. However, our understanding of such is limited due a lack rapid and scalable assay comprehensively assess microbiome responses drugs. Drugs other compounds drastically change overall abundance, taxonomic composition, functions microbiome.Here, we developed an approach screen against individual microbiomes in vitro, using metaproteomics both measure absolute bacterial abundances functionally profile microbiome. Our was evaluated by testing 43 (including 4 antibiotics) 5 microbiomes. The method generated technically highly reproducible readouts, including changes functional pathways. Results show that besides antibiotics, berberine ibuprofen inhibited accumulation biomass during vitro growth By comparing genus species level-biomass contributions, selective antibacterial-like activities were found with 35 39 non-antibiotic compounds. Seven led global alteration metaproteome, apparent compound-specific patterns responses. distributions altered proteins varied among drugs, i.e., different affect members We also showed function shift response without abundance bacteria.Current drug-microbiome interaction studies largely focus on relative composition microbial drug metabolism. In contrast, workflow enables multiple insights into robust, reproducible, quantitative for personalized high-throughput screening applications.

Язык: Английский

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