Broad spectrum immunomodulation using biomimetic blood cell margination for sepsis therapy

Sepsis represents a systemic inflammatory response caused by microbial infection in blood. Herein, we present a novel comprehensive approach to mitigate inflammatory responses through broad spectrum removal of pathogens, leukocytes and cytokines based on biomimetic cell margination. Using a murine m...

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Main Authors: Hou, Han Wei, Wu, Lidan, Amador-Munoz, Diana P., Vera, Miguel Pinilla, Coronata, Anna, Englert, Joshua A., Levy, Bruce D., Baron, Rebecca M., Han, Jongyoon
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:en_US
Published: Royal Society of Chemistry, The 2017
Online Access:http://hdl.handle.net/1721.1/110938
https://orcid.org/0000-0003-3150-6170
https://orcid.org/0000-0001-7215-1439
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author Hou, Han Wei
Wu, Lidan
Amador-Munoz, Diana P.
Vera, Miguel Pinilla
Coronata, Anna
Englert, Joshua A.
Levy, Bruce D.
Baron, Rebecca M.
Han, Jongyoon
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Hou, Han Wei
Wu, Lidan
Amador-Munoz, Diana P.
Vera, Miguel Pinilla
Coronata, Anna
Englert, Joshua A.
Levy, Bruce D.
Baron, Rebecca M.
Han, Jongyoon
author_sort Hou, Han Wei
collection MIT
description Sepsis represents a systemic inflammatory response caused by microbial infection in blood. Herein, we present a novel comprehensive approach to mitigate inflammatory responses through broad spectrum removal of pathogens, leukocytes and cytokines based on biomimetic cell margination. Using a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP), we performed extracorporeal blood filtration with the developed microfluidic blood margination (μBM) device. Circulating bacteremia, leukocytes and cytokines in blood decreased post-filtration and significant attenuation of immune cell and cytokine responses were observed 3–5 days after intervention, indicating successful long-term immunomodulation. A dose-dependent effect on long-term immune cell count was also achieved by varying filtration time. As proof of concept for human therapy, the μBM device was scaled up to achieve ∼100-fold higher throughput (∼150 mL h⁻¹). With further multiplexing, the μBM technique could be applied in clinical settings as an adjunctive treatment for sepsis and other inflammatory diseases.
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spelling mit-1721.1/1109382022-10-01T19:03:27Z Broad spectrum immunomodulation using biomimetic blood cell margination for sepsis therapy Hou, Han Wei Wu, Lidan Amador-Munoz, Diana P. Vera, Miguel Pinilla Coronata, Anna Englert, Joshua A. Levy, Bruce D. Baron, Rebecca M. Han, Jongyoon Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology. Research Laboratory of Electronics Hou, Han Wei Wu, Lidan Han, Jongyoon Sepsis represents a systemic inflammatory response caused by microbial infection in blood. Herein, we present a novel comprehensive approach to mitigate inflammatory responses through broad spectrum removal of pathogens, leukocytes and cytokines based on biomimetic cell margination. Using a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP), we performed extracorporeal blood filtration with the developed microfluidic blood margination (μBM) device. Circulating bacteremia, leukocytes and cytokines in blood decreased post-filtration and significant attenuation of immune cell and cytokine responses were observed 3–5 days after intervention, indicating successful long-term immunomodulation. A dose-dependent effect on long-term immune cell count was also achieved by varying filtration time. As proof of concept for human therapy, the μBM device was scaled up to achieve ∼100-fold higher throughput (∼150 mL h⁻¹). With further multiplexing, the μBM technique could be applied in clinical settings as an adjunctive treatment for sepsis and other inflammatory diseases. United States. Defense Advanced Research Projects Agency (N66001-11-1-4182) 2017-08-14T14:34:14Z 2017-08-14T14:34:14Z 2016-01 2015-09 Article http://purl.org/eprint/type/JournalArticle 1473-0197 1473-0189 http://hdl.handle.net/1721.1/110938 Hou, Han Wei, et al. “Broad Spectrum Immunomodulation Using Biomimetic Blood Cell Margination for Sepsis Therapy.” Lab on a Chip 16, 4 (2016): 688–699 © 2016 The Royal Society of Chemistry https://orcid.org/0000-0003-3150-6170 https://orcid.org/0000-0001-7215-1439 en_US http://dx.doi.org/10.1039/c5lc01110h Lab on a Chip Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Royal Society of Chemistry, The PMC
spellingShingle Hou, Han Wei
Wu, Lidan
Amador-Munoz, Diana P.
Vera, Miguel Pinilla
Coronata, Anna
Englert, Joshua A.
Levy, Bruce D.
Baron, Rebecca M.
Han, Jongyoon
Broad spectrum immunomodulation using biomimetic blood cell margination for sepsis therapy
title Broad spectrum immunomodulation using biomimetic blood cell margination for sepsis therapy
title_full Broad spectrum immunomodulation using biomimetic blood cell margination for sepsis therapy
title_fullStr Broad spectrum immunomodulation using biomimetic blood cell margination for sepsis therapy
title_full_unstemmed Broad spectrum immunomodulation using biomimetic blood cell margination for sepsis therapy
title_short Broad spectrum immunomodulation using biomimetic blood cell margination for sepsis therapy
title_sort broad spectrum immunomodulation using biomimetic blood cell margination for sepsis therapy
url http://hdl.handle.net/1721.1/110938
https://orcid.org/0000-0003-3150-6170
https://orcid.org/0000-0001-7215-1439
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