Innovative Human Three-Dimensional Tissue-Engineered Models as an Alternative to Animal Testing

Bioengineering, Journal Year: 2020, Volume and Issue: 7(3), P. 115 - 115

Published: Sept. 17, 2020

Animal testing has long been used in science to study complex biological phenomena that cannot be investigated using two-dimensional cell cultures plastic dishes. With time, it appeared more differences could exist between animal models and even when translated human patients. Innovative became essential develop accurate knowledge. Tissue engineering provides some of those models, but mostly relies on the use prefabricated scaffolds which cells are seeded. The self-assembly protocol recently produced organ-specific human-derived three-dimensional without need for exogenous material. This strategy will help achieve 3R principles.

Language: Английский

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Opportunities and Challenges for Molecular Understanding of Ciliopathies–The 100,000 Genomes Project

Frontiers in Genetics, Journal Year: 2019, Volume and Issue: 10

Published: March 11, 2019

Cilia are highly specialized cellular organelles that serve multiple functions in human development and health. Their central importance the body is demonstrated by occurrence of a diverse range developmental disorders arise from defects cilia structure function, caused different inherited mutations found at least 150 genes. Genetic analysis has rapidly advanced our understanding cell biological basis ciliopathies over past two decades, with more recent technological advances genomics accelerating this progress. The 100,000 Genomes Project was launched 2012 UK to improve diagnosis future care for individuals affected rare diseases like ciliopathies, through whole genome sequencing (WGS). In review we discuss potential promise medical impact WGS report on current progress Project, reviewing medical, technical ethical challenges opportunities new, large scale initiatives such as can offer.

Language: Английский

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The regulatory roles of motile cilia in CSF circulation and hydrocephalus

Fluids and Barriers of the CNS, Journal Year: 2021, Volume and Issue: 18(1)

Published: July 7, 2021

Cerebrospinal fluid (CSF) is an ultra-filtrated colorless brain that circulates within spaces like the ventricular cavities, subarachnoid space, and spine. Its continuous flow serves many primary functions, including nourishment, protection, waste removal.The abnormal accumulation of CSF in cavities triggers severe hydrocephalus. Accumulating evidence had indicated synchronized beats motile cilia (cilia from multiciliated cells or ependymal lining ventricles) provide forceful pressure to generate restrain maintain overall circulation spaces. In humans, disorders caused by defective and/or are generally referred as ciliopathies. The key role development its functioning has not been fully elucidated.In this review, we briefly discuss underlying We have reviewed ciliated existing for regulatory functional brain. further findings obtained their potential involvement Furthermore, review will reinforce idea master regulators movements, development, neuronal diseases.

Language: Английский

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Animal Models of Human Disease

Published: April 17, 2024

The crucial role of animal models in biomedical research calls for philosophical investigation how and whether knowledge about human diseases can be gained by studying other species. This Element delves into the selection construction to serve as preclinical substitutes patients. It explores multifaceted roles fulfil translational boundaries between humans animals are negotiated this process. book also covers persistent challenges that have sparked debates across scientific, philosophical, public arenas regarding limitations future models. Among tensions standardization variation medicine, well strategies aiming reduce recapitulate biological complexity. Finally, examines prospects replacing with animal-free methods. demonstrates why modeling should interest philosophers, social scientists, scientists alike.

Language: Английский

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Xenbase: Facilitating the Use of Xenopus to Model Human Disease

Frontiers in Physiology, Journal Year: 2019, Volume and Issue: 10

Published: Feb. 26, 2019

At a fundamental level most genes, signaling pathways, biological functions and organ systems are highly conserved between man all vertebrate species. Leveraging this conservation, researchers increasingly using the experimental advantages of amphibian Xenopus to model human disease. The online resource, Xenbase, enables disease modeling by curating literature published in PubMed integrating these data with orthologous anatomy, more recently links Online Mendelian Inheritance Man resource (OMIM) Human Disease Ontology (DO). Here we review how Xenbase supports report on meta-analysis research providing an overview different types diseases being modeled variety approaches used. Text mining over 50,000 articles imported into from identified approximately 1,000 putative disease- articles. These were manually assessed annotated ontologies, which then used classify papers based type. We found that is study diverse array three main approaches: cell-free egg extracts aspects cellular molecular biology, oocytes ion transport channel physiology embryo experiments focused congenital diseases. integrated Pages allow easy navigation information external databases. Results analysis will equip suite available or dissect pathological process. Ideally clinicians basic use foster collaborations necessary interrogate development treatment

Language: Английский

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Precision Medicine in the Management of Dilated Cardiomyopathy

Journal of the American College of Cardiology, Journal Year: 2019, Volume and Issue: 74(23), P. 2921 - 2938

Published: Dec. 1, 2019

Language: Английский

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Xenopus leads the way: Frogs as a pioneering model to understand the human brain

genesis, Journal Year: 2020, Volume and Issue: 59(1-2)

Published: Dec. 27, 2020

From its long history in the field of embryology to recent advances genetics, Xenopus has been an indispensable model for understanding human brain. Foundational studies that gave us our first insights into major embryonic patterning events serve as a crucial backdrop newer avenues investigation organogenesis and organ function. The vast array tools available laevis tropicalis allows interrogation developmental phenomena at all levels, from molecular behavioral, application CRISPR technology enabled disorder risk genes higher-throughput manner. As only tetrapod which stages are easily manipulated observed, frogs provide unique opportunity study development earliest stages. All these features make premier studying brain, notoriously complex process demands fertilization beyond. Importantly, core processes brain conserved between human, underlining advantages this model. This review begins by summarizing discoveries made amphibians form cornerstones vertebrate neurodevelopmental biology goes on discuss have catapulted relation disease. we engage new era patient-driven gene discovery, offers exceptional potential uncover underlying disorders move towards rational drug design.

Language: Английский

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A nanobody-based fluorescent reporter reveals human α-synuclein in the cell cytosol

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: June 1, 2020

Abstract Aggregation and spreading of α-Synuclein (αSyn) are hallmarks several neurodegenerative diseases, thus monitoring human αSyn (hαSyn) in animal models or cell cultures is vital for the field. However, detection native hαSyn such systems challenging. We show that nanobody NbSyn87, previously-described to bind hαSyn, also shows cross-reactivity proteasomal subunit Rpn10. As such, when NbSyn87 expressed absence it continuously degraded by proteasome, while stabilized binds hαSyn. Here, we exploit this feature design a new Fluorescent Reporter (FluoReSyn) fusing fluorescent proteins, which results fluorescence signal fluctuations depending on presence amounts intracellular characterize biosensor cells tissues finally reveal transmittable cerebrospinal fluid, demonstrating potential FluoReSyn clinical research diagnostics.

Language: Английский

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A frog with three sex chromosomes that co-mingle together in nature: Xenopus tropicalis has a degenerate W and a Y that evolved from a Z chromosome

PLoS Genetics, Journal Year: 2020, Volume and Issue: 16(11), P. e1009121 - e1009121

Published: Nov. 9, 2020

In many species, sexual differentiation is a vital prelude to reproduction, and disruption of this process can have severe fitness effects, including sterility. It thus interesting that genetic systems governing vary among—and even within—species. To understand these more, we investigated rare example frog with three sex chromosomes: the Western clawed frog, Xenopus tropicalis . We demonstrate natural populations from western eastern edges Ghana young Y chromosome, male-determining factor on chromosome in very similar genomic location as previously known female-determining W chromosome. Nucleotide polymorphism expressed transcripts suggests degeneration emergence new an ancestral Z co-mingling W, Z, chromosomes same population. Compared rest genome, small sex-associated portion has 50-fold enrichment male-biased expression during early gonadal differentiation. Additionally, X. sex-differences rates locations recombination events gametogenesis are at least two other which differences genus-wide. These findings consistent theoretical expectations associated suppression chromosomes, several characteristics old established (e.g., nucleotide divergence, biased expression) arise well before become cytogenetically distinguished, show how lingering consequences carried forward through turnovers.

Language: Английский

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A convergent molecular network underlying autism and congenital heart disease

Cell Systems, Journal Year: 2021, Volume and Issue: 12(11), P. 1094 - 1107.e6

Published: Aug. 18, 2021

Language: Английский

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