Journey of organ on a chip technology and its role in future healthcare scenario DOI Creative Commons
Deepanmol Singh, Ashish Mathur, Smriti Arora

et al.

Applied Surface Science Advances, Journal Year: 2022, Volume and Issue: 9, P. 100246 - 100246

Published: April 11, 2022

Organ on a chip refers to microengineered biomimetic system which reflects structural and functional characteristics of human tissue. It involves biomaterial technology, cell biology engineering combined together in miniaturized platform. Several models using different organs such as lungs chip, liver kidney heart intestine skin have been successfully developed. Food Drug administration (FDA) has also shown confidence this technology partnered with industries/institutes are working technology. In review, the concepts applications model scientific domains including disease development, drug screening, toxicology, pathogenesis study, efficacy testing virology is discussed. envisaged that amalgamation various modules into unified body device utmost importance for diagnosis treatment, especially considering complications due ongoing COVID-19 pandemic. expected market demand developing organ devices skyrocket near future.

Language: Английский

Pluripotent stem cell-derived epithelium misidentified as brain microvascular endothelium requires ETS factors to acquire vascular fate DOI Creative Commons
Tyler M. Lu, Sean Houghton,

Tarig Magdeldin

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(8)

Published: Feb. 4, 2021

Significance Human PSC-derived iBMECs have been generated to study disease mechanisms and drug development for neurological disorders. However, their full transcriptomic characterization is unclear, which could result in inaccurate physiological studies of treatments with ineffective clinical outcomes. Utilizing a comprehensive metaanalysis validated by studies, we find that many current protocols used generate produce homogenous epithelial cell population. Overexpression ETS transcription factors reprogram these cells into phenotypic endothelial (rECs) recapitulate certain vascular functions, albeit lacking expression some organotypic transporter genes high electrical resistance vitro. Nevertheless, they represent crucial step toward the generation an vitro model suitable pharmaceutical blood–brain barrier.

Language: Английский

Citations

171
Modeling alpha-synuclein pathology in a human brain-chip to assess blood-brain barrier disruption DOI Creative Commons
Iosif Pediaditakis, Konstantia Kodella, Dimitris V. Manatakis

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Oct. 8, 2021

Abstract Parkinson’s disease and related synucleinopathies are characterized by the abnormal accumulation of alpha-synuclein aggregates, loss dopaminergic neurons, gliosis substantia nigra. Although clinical evidence in vitro studies indicate disruption Blood-Brain Barrier disease, mechanisms mediating endothelial dysfunction is not well understood. Here we leveraged Organs-on-Chips technology to develop a human Brain-Chip representative nigra area brain containing astrocytes, microglia, pericytes, microvascular cells, cultured under fluid flow. Our αSyn fibril-induced model was capable reproducing several key aspects including phosphorylated (pSer129-αSyn), mitochondrial impairment, neuroinflammation, compromised barrier function. This may enable research into dynamics cell-cell interactions serve as testing platform for target identification validation novel therapeutics.

Language: Английский

Citations

164
Microfluidic high-throughput 3D cell culture DOI
Jihoon Ko, Dohyun Park,

Jungseub Lee

et al.

Nature Reviews Bioengineering, Journal Year: 2024, Volume and Issue: 2(6), P. 453 - 469

Published: April 4, 2024

Language: Английский

Citations

22
Recent advances in human iPSC-derived models of the blood–brain barrier DOI Creative Commons
Michael J. Workman,

Clive N. Svendsen

Fluids and Barriers of the CNS, Journal Year: 2020, Volume and Issue: 17(1)

Published: April 22, 2020

The blood-brain barrier (BBB) is a critical component of the central nervous system that protects neurons and other cells brain parenchyma from potentially harmful substances found in peripheral circulation. Gaining thorough understanding development function human BBB has been hindered by lack relevant models given significant species differences limited access to vivo tissue. However, advances induced pluripotent stem cell (iPSC) organ-chip technologies now allow us improve our knowledge both health disease. This review focuses on recent progress modeling vitro using iPSCs.

Language: Английский

Citations

108
Human Organs-on-Chips for Virology DOI Creative Commons
Huaqi Tang, Yasmine Abouleila, Longlong Si

et al.

Trends in Microbiology, Journal Year: 2020, Volume and Issue: 28(11), P. 934 - 946

Published: July 13, 2020

Language: Английский

Citations

106
Brain-on-a-chip: A history of development and future perspective DOI Open Access
Seokyoung Bang, Sohyeon Jeong, Nakwon Choi

et al.

Biomicrofluidics, Journal Year: 2019, Volume and Issue: 13(5)

Published: Sept. 1, 2019

Since the advent of organ-on-a-chip, many researchers have tried to mimic physiology human tissue on an engineered platform. In case brain tissue, structural connections and cell-cell interactions are important factors for function. The recent development brain-on-a-chip is effort those functional aspects within a miniaturized From this perspective, we provide overview trace development, especially in terms complexity high-content/high-throughput screening capabilities, future perspectives more vivo-like development.

Language: Английский

Citations

105
Mechanical Stimulation: A Crucial Element of Organ-on-Chip Models DOI Creative Commons

Clare L. Thompson,

Su Fu,

Hannah K. Heywood

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2020, Volume and Issue: 8

Published: Dec. 10, 2020

Organ-on-chip (OOC) systems recapitulate key biological processes and responses in vitro exhibited by cells, tissues, organs vivo. Accordingly, these models of both health disease hold great promise for improving fundamental research, drug development, personalized medicine, testing pharmaceuticals, food substances, pollutants etc. Cells within the body are exposed to biomechanical stimuli, nature which is tissue specific may change with or injury. These stimuli regulate cell behavior can amplify, annul, even reverse response a given biochemical cue candidate. As such, application an appropriate physiological pathological environment essential successful recapitulation vivo OOC models. Here we review current range commercially available platforms incorporate active stimulation. We highlight recent findings demonstrating importance including mechanical used development outline emerging factors cellular environment. explore incorporation different organ identify areas where further research required. Challenges associated integration mechanics alongside other requirements scaling increase throughput diagnostic imaging discussed. In summary, compelling evidence demonstrates that microphysiological fully replicating physiology disease.

Language: Английский

Citations

103
Developmentally inspired human ‘organs on chips’ DOI Open Access
Donald E. Ingber

Development, Journal Year: 2018, Volume and Issue: 145(16)

Published: May 18, 2018

ABSTRACT Although initially developed to replace animal testing in drug development, human ‘organ on a chip’ (organ chip) microfluidic culture technology offers new tool for studying tissue development and pathophysiology, which has brought us one step closer carrying out experimentation vitro. In this Spotlight article, I discuss the central role that developmental biology played early stages of organ-chip technology, how these models have led insights into physiology disease mechanisms. Advantages disadvantages approach relative organoids other cell cultures are also discussed.

Language: Английский

Citations

98
A neurovascular-unit-on-a-chip for the evaluation of the restorative potential of stem cell therapies for ischaemic stroke DOI
Zhonglin Lyu, Jon Park, Kwangmin Kim

et al.

Nature Biomedical Engineering, Journal Year: 2021, Volume and Issue: 5(8), P. 847 - 863

Published: Aug. 12, 2021

Language: Английский

Citations

93
Human Huntington’s Disease iPSC-Derived Cortical Neurons Display Altered Transcriptomics, Morphology, and Maturation DOI Creative Commons

Shagun Mehta,

Colton M. Tom,

Yizhou Wang

et al.

Cell Reports, Journal Year: 2018, Volume and Issue: 25(4), P. 1081 - 1096.e6

Published: Oct. 1, 2018

Highlights•Differentiated HD and non-diseased iPSCs into functional cortical neurons•HD iPSC-derived neurons display altered transcriptomics•HD morphology•HD phenotypesSummaryHuntington's disease (HD) is a neurodegenerative caused by an expanded CAG repeat in the Huntingtin (HTT) gene. Induced pluripotent stem cell (iPSC) models of provide opportunity to study mechanisms underlying pathology disease-relevant patient tissues. Murine studies have demonstrated that HTT intricately involved corticogenesis. However, effect mutant Hungtintin (mtHTT) human corticogenesis has not yet been thoroughly explored. This examination critical, due inherent differences development timing between humans mice. We therefore differentiated neurons. While can successfully differentiate toward fate culture, resulting transcriptomics, morphological phenotypes indicative HD.Graphical abstract

Language: Английский

Citations

92