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

---

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

---

A guide to the organ-on-a-chip

Nature Reviews Methods Primers, Год журнала: 2022, Номер 2(1)

Опубликована: Май 12, 2022

Organs-on-chips (OoCs) are systems containing engineered or natural miniature tissues grown inside microfluidic chips. To better mimic human physiology, the chips designed to control cell microenvironments and maintain tissue-specific functions. Combining advances in tissue engineering microfabrication, OoCs have gained interest as a next-generation experimental platform investigate pathophysiology effect of therapeutics body. There many examples there applications, making it difficult for new researchers understand what makes one OoC more suited an application than another. This Primer is intended give introduction aspects that need be considered when developing application-specific OoC. The covers guiding principles considerations design, fabricate operate OoC, well subsequent assaying techniques extract biological information from devices. Alongside this discussion current future applications technology, inform design operational decisions during implementation systems. with aim mimicking physiology range biomedical therapeutic applications. Leung, de Haan et al. report practical tips organ-on-a-chip

Язык: Английский

---

Hypoxia-enhanced Blood-Brain Barrier Chip recapitulates human barrier function and shuttling of drugs and antibodies

Nature Communications, Год журнала: 2019, Номер 10(1)

Опубликована: Июнь 13, 2019

The high selectivity of the human blood-brain barrier (BBB) restricts delivery many pharmaceuticals and therapeutic antibodies to central nervous system. Here, we describe an in vitro microfluidic organ-on-a-chip BBB model lined by induced pluripotent stem cell-derived brain microvascular endothelium interfaced with primary astrocytes pericytes that recapitulates level function vivo for at least one week culture. expresses levels tight junction proteins functional efflux pumps, it displays selective transcytosis peptides previously observed vivo. Increased functionality was accomplished using a developmentally-inspired induction protocol includes period differentiation under hypoxic conditions. This enhanced Chip may therefore represent new tool development validation systems transport drugs across BBB.

Язык: Английский

---

Human iPSC-Derived Blood-Brain Barrier Chips Enable Disease Modeling and Personalized Medicine Applications

Cell stem cell, Год журнала: 2019, Номер 24(6), С. 995 - 1005.e6

Опубликована: Июнь 1, 2019

Язык: Английский

---

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

---

Multi-lineage Human iPSC-Derived Platforms for Disease Modeling and Drug Discovery

Cell stem cell, Год журнала: 2020, Номер 26(3), С. 309 - 329

Опубликована: Март 1, 2020

Язык: Английский

---

Is it Time for Reviewer 3 to Request Human Organ Chip Experiments Instead of Animal Validation Studies?

Advanced Science, Год журнала: 2020, Номер 7(22)

Опубликована: Окт. 12, 2020

For the past century, experimental data obtained from animal studies have been required by reviewers of scientific articles and grant applications to validate physiological relevance in vitro results. At same time, pharmaceutical researchers regulatory agencies recognize that results preclinical models frequently fail predict drug responses humans. This Progress Report reviews recent advances human organ-on-a-chip (Organ Chip) microfluidic culture technology, both with single Organ Chips fluidically coupled "Body-on-Chips" platforms, which demonstrate their ability recapitulate physiology disease states, as well patient clinically relevant pharmacokinetic exposures, higher fidelity than other or studies. These findings raise question whether continuing require testing for publication funding still makes ethical sense, if more physiologically Chip might better serve this purpose. issue is addressed article context history field, advantages disadvantages approaches versus are discussed should be considered wider research community.

Язык: Английский

---

Advances in Microfluidic Blood–Brain Barrier (BBB) Models

Trends in biotechnology, Год журнала: 2019, Номер 37(12), С. 1295 - 1314

Опубликована: Май 23, 2019

Язык: Английский

---

Molecular networks in Network Medicine: Development and applications

WIREs Systems Biology and Medicine, Год журнала: 2020, Номер 12(6)

Опубликована: Апрель 19, 2020

Abstract Network Medicine applies network science approaches to investigate disease pathogenesis. Many different analytical methods have been used infer relevant molecular networks, including protein–protein interaction correlation‐based gene regulatory and Bayesian networks. these integrated Omics Big Data (including genetics, epigenetics, transcriptomics, metabolomics, proteomics) using computational biology tools and, thereby, has the potential provide improvements in diagnosis, prognosis, treatment of complex diseases. We discuss briefly types data that are analyses, survey for inferring review efforts validate visualize Successful applications analysis reported pulmonary arterial hypertension, coronary heart disease, diabetes mellitus, chronic lung diseases, drug development. Important knowledge gaps include incompleteness interactome, challenges identifying key genes within genetic association regions, limited human This article is categorized under: Models Systems Properties Processes > Mechanistic Translational, Genomic, Translational Analytical Computational Methods

Язык: Английский

---