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Microparticles as biomarkers of lung disease : enumeration in biological fluids using lipid bilayer microspheres

McVey, Mark J; Spring, Christopher M; Semple, John W LU ; Maishan, Mazharul and Kuebler, Wolfgang M (2016) In American Journal of Physiology - Lung Cellular and Molecular Physiology 310(9). p.14-802
Abstract

Extracellular vesicles, specifically microparticles (MPs), are rapidly gaining attention for their capacity to act as biomarkers for diagnosis, prognosis, or responsiveness to therapy in lung disease, in keeping with the concept of precision medicine. However, MP analysis by high-sensitivity flow cytometry (FCM) is complicated by a lack of accurate means for MP enumeration. To address this gap, we report here an enhanced FCM MP gating and enumeration technique based on the use of novel engineered lipid bilayer microspheres (LBMs). By comparison of LBM-based MP enumeration with conventional bead- or fluorescent-based FCM enumeration techniques and a gravimetric consumption gold standard, we found LBMs to be superior to commercial bead... (More)

Extracellular vesicles, specifically microparticles (MPs), are rapidly gaining attention for their capacity to act as biomarkers for diagnosis, prognosis, or responsiveness to therapy in lung disease, in keeping with the concept of precision medicine. However, MP analysis by high-sensitivity flow cytometry (FCM) is complicated by a lack of accurate means for MP enumeration. To address this gap, we report here an enhanced FCM MP gating and enumeration technique based on the use of novel engineered lipid bilayer microspheres (LBMs). By comparison of LBM-based MP enumeration with conventional bead- or fluorescent-based FCM enumeration techniques and a gravimetric consumption gold standard, we found LBMs to be superior to commercial bead preparations, showing the smallest fixed bias and limits of agreement in Bland Altman analyses. LBMs had simultaneous capacity to aid FCM enumeration of MPs in plasma, BAL, and cell culture supernatants. LBM enumeration detected differences in MP counts in mice exposed to intraperitoneal lipopolysaccharide or saline. LBMs provided for 1) higher sensitivity for gating MPs populations, 2) reduced background within MP gates, 3) more appropriate size, and 4) an inexpensive alternative amenable to different fluorescent tags. LBM-based MP enumeration was useful for a series of different FCM systems assessed, whereas LBM gating benefited high- but not low-sensitivity FCM systems compared with fluorescence gating. By offering exclusive advantages over current means of gating and enumerating MPs, LBMs are uniquely suited to realizing the potential of MPs as biomarkers in biological lung fluids and facilitating precision medicine in lung disease.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Journal Article
in
American Journal of Physiology - Lung Cellular and Molecular Physiology
volume
310
issue
9
pages
14 - 802
publisher
American Physiological Society
external identifiers
  • Scopus:84983741932
ISSN
1522-1504
DOI
10.1152/ajplung.00369.2015
language
English
LU publication?
no
id
2a6b59c2-af10-448b-86c1-834bf6923546
date added to LUP
2016-09-23 11:56:14
date last changed
2017-01-15 04:41:38
@article{2a6b59c2-af10-448b-86c1-834bf6923546,
  abstract     = {<p>Extracellular vesicles, specifically microparticles (MPs), are rapidly gaining attention for their capacity to act as biomarkers for diagnosis, prognosis, or responsiveness to therapy in lung disease, in keeping with the concept of precision medicine. However, MP analysis by high-sensitivity flow cytometry (FCM) is complicated by a lack of accurate means for MP enumeration. To address this gap, we report here an enhanced FCM MP gating and enumeration technique based on the use of novel engineered lipid bilayer microspheres (LBMs). By comparison of LBM-based MP enumeration with conventional bead- or fluorescent-based FCM enumeration techniques and a gravimetric consumption gold standard, we found LBMs to be superior to commercial bead preparations, showing the smallest fixed bias and limits of agreement in Bland Altman analyses. LBMs had simultaneous capacity to aid FCM enumeration of MPs in plasma, BAL, and cell culture supernatants. LBM enumeration detected differences in MP counts in mice exposed to intraperitoneal lipopolysaccharide or saline. LBMs provided for 1) higher sensitivity for gating MPs populations, 2) reduced background within MP gates, 3) more appropriate size, and 4) an inexpensive alternative amenable to different fluorescent tags. LBM-based MP enumeration was useful for a series of different FCM systems assessed, whereas LBM gating benefited high- but not low-sensitivity FCM systems compared with fluorescence gating. By offering exclusive advantages over current means of gating and enumerating MPs, LBMs are uniquely suited to realizing the potential of MPs as biomarkers in biological lung fluids and facilitating precision medicine in lung disease.</p>},
  author       = {McVey, Mark J and Spring, Christopher M and Semple, John W and Maishan, Mazharul and Kuebler, Wolfgang M},
  issn         = {1522-1504},
  keyword      = {Journal Article},
  language     = {eng},
  month        = {05},
  number       = {9},
  pages        = {14--802},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology - Lung Cellular and Molecular Physiology},
  title        = {Microparticles as biomarkers of lung disease : enumeration in biological fluids using lipid bilayer microspheres},
  url          = {http://dx.doi.org/10.1152/ajplung.00369.2015},
  volume       = {310},
  year         = {2016},
}