iPSC-Derived Liver Organoids: A Journey from Drug Screening, to Disease Modeling, Arriving to Regenerative Medicine DOI Open Access
Cristina Olgasi, Alessia Cucci, Antonia Follenzi

и другие.

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(17), С. 6215 - 6215

Опубликована: Авг. 27, 2020

Liver transplantation is the most common treatment for patients suffering from liver failure that caused by congenital diseases, infectious agents, and environmental factors. Despite a high rate of patient survival following transplantation, organ availability remains key limiting factor. As such, research has focused on different cell types are capable repopulating restoring function. The best cellular mix engrafting proliferating over long-term, as well optimal immunosuppression regimens, remain to be clearly well-defined. Hence, alternative strategies in field regenerative medicine have been explored. Since discovery induced pluripotent stem cells (iPSC) potential differentiating into broad spectrum types, many studies reported achievement iPSCs differentiation cells, such hepatocytes, cholangiocytes, endothelial Kupffer cells. In parallel, an increasing interest study self-assemble or matrix-guided three-dimensional (3D) organoids paved way functional bioartificial livers. this review, we will focus recent breakthroughs development iPSCs-based major drawbacks challenges need overcome future applications.

Язык: 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

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2021, Номер 118(8)

Опубликована: Фев. 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.

Язык: Английский

Процитировано

172

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

и другие.

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Окт. 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.

Язык: Английский

Процитировано

165

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

и другие.

Nature Reviews Bioengineering, Год журнала: 2024, Номер 2(6), С. 453 - 469

Опубликована: Апрель 4, 2024

Язык: Английский

Процитировано

26

Systemic HER3 ligand-mimicking nanobioparticles enter the brain and reduce intracranial tumour growth DOI Creative Commons
Felix Alonso-Valenteen,

Simoun Mikhael,

Hongqiang Wang

и другие.

Nature Nanotechnology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 21, 2025

Язык: Английский

Процитировано

2

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, Год журнала: 2020, Номер 17(1)

Опубликована: Апрель 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.

Язык: Английский

Процитировано

108

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

и другие.

Trends in Microbiology, Год журнала: 2020, Номер 28(11), С. 934 - 946

Опубликована: Июль 13, 2020

Язык: Английский

Процитировано

107

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

и другие.

Biomicrofluidics, Год журнала: 2019, Номер 13(5)

Опубликована: Сен. 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.

Язык: Английский

Процитировано

105

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

Clare L. Thompson,

Su Fu,

Hannah K. Heywood

и другие.

Frontiers in Bioengineering and Biotechnology, Год журнала: 2020, Номер 8

Опубликована: Дек. 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.

Язык: Английский

Процитировано

103

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

Development, Год журнала: 2018, Номер 145(16)

Опубликована: Май 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.

Язык: Английский

Процитировано

98

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

Shagun Mehta,

Colton M. Tom,

Yizhou Wang

и другие.

Cell Reports, Год журнала: 2018, Номер 25(4), С. 1081 - 1096.e6

Опубликована: Окт. 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

Язык: Английский

Процитировано

94