A novel in vitro ischemia/reperfusion injury model

Lee, Won Hee; Kang, Sungkwon; Vlachos, Pavlos P.; Lee, Yong Woo

doi:10.1007/s12272-009-1316-9

Cited by 11 publications

(6 citation statements)

References 44 publications

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“…While our results aligned with previous animal and in vitro studies [36][37][38], studies using rodent as animal model for IRI also showed an increase in the levels of ICAM-1 on EC membrane [37] and in leukocyte adhesion to EC after IRI [36]. Hence, we were able to recapitulate certain feature of IRI as seen in in vivo studies.…”

Section: Discussionsupporting

confidence: 90%

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Endothelial Cell Activation in an Embolic Ischemia-Reperfusion Injury Microfluidic Model

2019

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Ischemia, lack of blood supply, is associated with a variety of life-threatening cardiovascular diseases, including acute ischemic stroke and myocardial infraction. While blood flow restoration is critical to prevent further damage, paradoxically, rapid reperfusion can increase tissue damage. A variety of animal models have been developed to investigate ischemia/reperfusion injury (IRI), however they do not fully recapitulate human physiology of IRI. Here, we present a microfluidic IRI model utilizing a vascular compartment comprising human endothelial cells, which can be obstructed via a human blood clot and then re-perfused via thrombolytic treatment. Using our model, a significant increase in the expression of the endothelial cell inflammatory surface receptors E-selectin and I-CAM1 was observed in response to embolic occlusion. Following the demonstration of clot lysis and reperfusion via treatment using a thrombolytic agent, a significant decrease in the number of adherent endothelial cells and an increase in I-CAM1 levels compared to embolic occluded models, where reperfusion was not established, was observed. Altogether, the presented model can be applied to allow better understanding of human embolic based IRI and potentially serve as a platform for the development of improved and new therapeutic approaches.

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Section: Discussionsupporting

confidence: 90%

“…Hence, we were able to recapitulate certain feature of IRI as seen in in vivo studies. Other in vitro model of IRI also exhibited higher levels of ICAM-1 after reperfusion [38]. However, this study induced ischemia in artificial manner.…”

Section: Discussionmentioning

confidence: 60%

Endothelial Cell Activation in an Embolic Ischemia-Reperfusion Injury Microfluidic Model

2019

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“…Dynamic test results further showed that rapid (<130 seconds) and reversible (<0.3% O 2 deviation) hypoxic conditions (from 12.6% to 1.2% oxygen tension) can be induced by changing the distance between the cells and biomaterials from 200 μm to 1200 μm. The results highlighted the potential of the developed hypoxia insert to be used for in vitro hypoxia / reoxygenation model of ischemia-reperfusion injury [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

A New Approach for On-Demand Generation of Various Oxygen Tensions for In Vitro Hypoxia Models

Chaung

Mozayan

et al. 2016

PLoS ONE

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The development of in vitro disease models closely mimicking the functions of human disease has captured increasing attention in recent years. Oxygen tensions and gradients play essential roles in modulating biological systems in both physiologic and pathologic events. Thus, controlling oxygen tension is critical for mimicking physiologically relevant in vivo environments for cell, tissue and organ research. We present a new approach for on-demand generation of various oxygen tensions for in vitro hypoxia models. Proof-of-concept prototypes have been developed for conventional cell culture microplate by immobilizing a novel oxygen-consuming biomaterial on the 3D-printed insert. For the first time, rapid (~3.8 minutes to reach 0.5% O2 from 20.9% O2) and precisely controlled oxygen tensions/gradients (2.68 mmHg per 50 μm distance) were generated by exposing the biocompatible biomaterial to the different depth of cell culture media. In addition, changing the position of 3D-printed inserts with immobilized biomaterials relative to the cultured cells resulted in controllable and rapid changes in oxygen tensions (<130 seconds). Compared to the current technologies, our approach allows enhanced spatiotemporal resolution and accuracy of the oxygen tensions. Additionally, it does not interfere with the testing environment while maintaining ease of use. The elegance of oxygen tension manipulation introduced by our new approach will drastically improve control and lower the technological barrier of entry for hypoxia studies. Since the biomaterials can be immobilized in any devices, including microfluidic devices and 3D-printed tissues or organs, it will serve as the basis for a new generation of experimental models previously impossible or very difficult to implement.

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“…Conventional in vitro models for tissues generate an ischemic environment in 2D cultures by using a hypoxia chamber and a nutrient‐poor culture medium to define the amount of nutrients available to cells . These systems have provided a plethora of information about the responses of cells to ischemia (i.e., viability, changes in metabolism, release of free radicals), including the elucidation of many ischemia‐related pathways . The culture conditions in these 2D models, however, provide information about the effects of global ischemia but not those resulting from the physiological gradients formed in a tissue.…”

Section: Introductionmentioning

confidence: 99%

Three‐Dimensional Paper‐Based Model for Cardiac Ischemia

Mosadegh

Dabiri

Lockett

et al. 2014

Adv Healthcare Materials

126

121

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In vitro models of ischemia have not historically recapitulated the cellular interactions and gradients of molecules that occur in a 3D tissue. This work demonstrates a paper-based 3D culture system that mimics some of the interactions that occur among populations of cells in the heart during ischemia. Multiple layers of paper containing cells, suspended in hydrogels, are stacked to form a layered 3D model of a tissue. Mass transport of oxygen and glucose into this 3D system can be modulated to induce an ischemic environment in the bottom layers of the stack. This ischemic stress induces cardiomyocytes at the bottom of the stack to secrete chemokines that subsequently trigger fibroblasts residing in adjacent layers to migrate toward the ischemic region. This work demonstrates the usefulness of patterned, stacked paper for performing in vitro mechanistic studies of cellular motility and viability within a model of the laminar ventricle tissue of the heart.

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A novel in vitro ischemia/reperfusion injury model

Cited by 11 publications

References 44 publications

Endothelial Cell Activation in an Embolic Ischemia-Reperfusion Injury Microfluidic Model

Endothelial Cell Activation in an Embolic Ischemia-Reperfusion Injury Microfluidic Model

A New Approach for On-Demand Generation of Various Oxygen Tensions for In Vitro Hypoxia Models

Three‐Dimensional Paper‐Based Model for Cardiac Ischemia

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