Thrombosis-on-a-chip: Prospective impact of microphysiological models of vascular thrombosis
The most common pathology of the blood-vessel organ system is thrombosis or undesirable clotting of the blood. Thrombosis is life threatening as more than 25% of such cases lead to sudden death from stroke and myocardial infarction. Even though the process of thrombosis has been extensively investig...
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| Published in | Current opinion in biomedical engineering Vol. 5; pp. 29 - 34 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
Elsevier Inc
01.03.2018
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| Subjects | |
| Online Access | Get full text |
| ISSN | 2468-4511 2468-4511 |
| DOI | 10.1016/j.cobme.2017.12.001 |
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| Abstract | The most common pathology of the blood-vessel organ system is thrombosis or undesirable clotting of the blood. Thrombosis is life threatening as more than 25% of such cases lead to sudden death from stroke and myocardial infarction. Even though the process of thrombosis has been extensively investigated with animal models, its exact pathobiology in different blood vessels is not yet fully understood and drug assessment remains unpredictable. This is primarily because the cause for thrombus formation is multifactorial and depends on the interplay of flow patterns within the blood vessel, the vessel wall or endothelium, extracellular matrix, parenchymal tissue, and the cellular and plasma components of the blood. Current in vitro and animal models do not mimic or dissect this organ-level complexity faithfully. However, microfluidic technology has recently been deployed to effectively recapitulate blood-endothelial–epithelial interactions in the onset of thrombosis in blood vessels. This technology is promising because it permits inclusion of primary human cells and blood obtained from patients, which is currently lacking in other in vitro models of thrombosis. In this review, we summarize the current state-of-the-art and practices in microfluidics and expected improvements in this field that will impact basic understanding of thrombosis, drug discovery and personalized medicine.
•Thrombus functions as a living organ that constantly interacts with its environment.•Current models are inefficient in predicting thrombogenesis and for drug analysis.•3D co-culture microfluidic assays can assess organ-level thrombus regulation.•Study of patient-specific physiology possible with thrombosis-on-a-chip technology. |
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| AbstractList | The most common pathology of the blood-vessel organ system is thrombosis or undesirable clotting of the blood. Thrombosis is life threatening as more than 25% of such cases lead to sudden death from stroke and myocardial infarction. Even though the process of thrombosis has been extensively investigated with animal models, its exact pathobiology in different blood vessels is not yet fully understood and drug assessment remains unpredictable. This is primarily because the cause for thrombus formation is multifactorial and depends on the interplay of flow patterns within the blood vessel, the vessel wall or endothelium, extracellular matrix, parenchymal tissue, and the cellular and plasma components of the blood. Current in vitro and animal models do not mimic or dissect this organ-level complexity faithfully. However, microfluidic technology has recently been deployed to effectively recapitulate blood-endothelial-epithelial interactions in the onset of thrombosis in blood vessels. This technology is promising because it permits inclusion of primary human cells and blood obtained from patients, which is currently lacking in other in vitro models of thrombosis. In this review, we summarize the current state-of-the-art and practices in microfluidics and expected improvements in this field that will impact basic understanding of thrombosis, drug discovery and personalized medicine.The most common pathology of the blood-vessel organ system is thrombosis or undesirable clotting of the blood. Thrombosis is life threatening as more than 25% of such cases lead to sudden death from stroke and myocardial infarction. Even though the process of thrombosis has been extensively investigated with animal models, its exact pathobiology in different blood vessels is not yet fully understood and drug assessment remains unpredictable. This is primarily because the cause for thrombus formation is multifactorial and depends on the interplay of flow patterns within the blood vessel, the vessel wall or endothelium, extracellular matrix, parenchymal tissue, and the cellular and plasma components of the blood. Current in vitro and animal models do not mimic or dissect this organ-level complexity faithfully. However, microfluidic technology has recently been deployed to effectively recapitulate blood-endothelial-epithelial interactions in the onset of thrombosis in blood vessels. This technology is promising because it permits inclusion of primary human cells and blood obtained from patients, which is currently lacking in other in vitro models of thrombosis. In this review, we summarize the current state-of-the-art and practices in microfluidics and expected improvements in this field that will impact basic understanding of thrombosis, drug discovery and personalized medicine. The most common pathology of the blood-vessel organ system is thrombosis or undesirable clotting of the blood. Thrombosis is life threatening as more than 25% of such cases lead to sudden death from stroke and myocardial infarction. Even though the process of thrombosis has been extensively investigated with animal models, its exact pathobiology in different blood vessels is not yet fully understood and drug assessment remains unpredictable. This is primarily because the cause for thrombus formation is multifactorial and depends on the interplay of flow patterns within the blood vessel, the vessel wall or endothelium, extracellular matrix, parenchymal tissue, and the cellular and plasma components of the blood. Current in vitro and animal models do not mimic or dissect this organ-level complexity faithfully. However, microfluidic technology has recently been deployed to effectively recapitulate blood-endothelial–epithelial interactions in the onset of thrombosis in blood vessels. This technology is promising because it permits inclusion of primary human cells and blood obtained from patients, which is currently lacking in other in vitro models of thrombosis. In this review, we summarize the current state-of-the-art and practices in microfluidics and expected improvements in this field that will impact basic understanding of thrombosis, drug discovery and personalized medicine. The most common pathology of the blood-vessel organ system is thrombosis or undesirable clotting of the blood. Thrombosis is life threatening as more than 25% of such cases lead to sudden death from stroke and myocardial infarction. Even though the process of thrombosis has been extensively investigated with animal models, its exact pathobiology in different blood vessels is not yet fully understood and drug assessment remains unpredictable. This is primarily because the cause for thrombus formation is multifactorial and depends on the interplay of flow patterns within the blood vessel, the vessel wall or endothelium, extracellular matrix, parenchymal tissue, and the cellular and plasma components of the blood. Current in vitro and animal models do not mimic or dissect this organ-level complexity faithfully. However, microfluidic technology has recently been deployed to effectively recapitulate blood-endothelial–epithelial interactions in the onset of thrombosis in blood vessels. This technology is promising because it permits inclusion of primary human cells and blood obtained from patients, which is currently lacking in other in vitro models of thrombosis. In this review, we summarize the current state-of-the-art and practices in microfluidics and expected improvements in this field that will impact basic understanding of thrombosis, drug discovery and personalized medicine. •Thrombus functions as a living organ that constantly interacts with its environment.•Current models are inefficient in predicting thrombogenesis and for drug analysis.•3D co-culture microfluidic assays can assess organ-level thrombus regulation.•Study of patient-specific physiology possible with thrombosis-on-a-chip technology. |
| Author | Jain, Abhishek Mannino, Robert G. Pandian, Navaneeth K.R. Lam, Wilbur A. |
| AuthorAffiliation | 5 Children’s Healthcare of Atlanta, Aflac Cancer & Blood Disorders Center, USA 6 Institute of Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA, USA 3 The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA 2 The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, GA, USA 4 Emory University School of Medicine, Department of Pediatrics, Division of Pediatric Hematology/Oncology, Atlanta, GA, USA 1 Department of Biomedical Engineering, College of Engineering, Texas A&M University, USA |
| AuthorAffiliation_xml | – name: 1 Department of Biomedical Engineering, College of Engineering, Texas A&M University, USA – name: 3 The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA – name: 6 Institute of Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA, USA – name: 4 Emory University School of Medicine, Department of Pediatrics, Division of Pediatric Hematology/Oncology, Atlanta, GA, USA – name: 5 Children’s Healthcare of Atlanta, Aflac Cancer & Blood Disorders Center, USA – name: 2 The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, GA, USA |
| Author_xml | – sequence: 1 givenname: Navaneeth K.R. surname: Pandian fullname: Pandian, Navaneeth K.R. organization: Department of Biomedical Engineering, College of Engineering, Texas A&M University, USA – sequence: 2 givenname: Robert G. surname: Mannino fullname: Mannino, Robert G. organization: The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, GA, USA – sequence: 3 givenname: Wilbur A. surname: Lam fullname: Lam, Wilbur A. organization: The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, GA, USA – sequence: 4 givenname: Abhishek surname: Jain fullname: Jain, Abhishek email: a.jain@tamu.edu organization: Department of Biomedical Engineering, College of Engineering, Texas A&M University, USA |
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| Snippet | The most common pathology of the blood-vessel organ system is thrombosis or undesirable clotting of the blood. Thrombosis is life threatening as more than 25%... |
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| SubjectTerms | Disease model Endothelium Hemostasis Microphysiological systems Organ-on-a-chip Thrombosis |
| Title | Thrombosis-on-a-chip: Prospective impact of microphysiological models of vascular thrombosis |
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