title: Magnetic nanosensor for detection and profiling of erythrocyte-derived microvesicles.
abstract: During the course of their lifespan, erythrocytes actively shed phospholipid-bound microvesicles (MVs). In stored blood, the number of these erythrocyte-derived MVs has been observed to increase over time, suggesting their potential value as a quality metric for blood products. The lack of sensitive, standardized MV assays, however, poses a significant barrier to implementing MV analyses into clinical settings. Here, we report on a new nanotechnology platform capable of rapid and sensitive MV detection in packed red blood cell (pRBC) units. A filter-assisted microfluidic device was designed to enrich MVs directly from pRBC units, and label them with target-specific magnetic nanoparticles. Subsequent detection using a miniaturized nuclear magnetic resonance system enabled accurate MV quantification as well as the detection of key molecular markers (CD44, CD47, CD55). When the developed platform was applied, MVs in stored blood units could also be monitored longitudinally. Our results showed that MV counts increase over time and, thus, could serve as an effective metric of blood aging. Furthermore, our studies found that MVs have the capacity to generate oxidative stress and consume nitric oxide. By advancing our understanding of MV biology, we expect that the developed platform will lead to improved blood product quality and transfusion safety.
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital , 185 Cambridge Street, CPZN 5206, Boston, Massachusetts 02114, United States.
authors.forename: Junsung
authors.initials: J
authors.lastname: Rho
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Chung
authors.forename: Hyungsoon
authors.initials: H
authors.lastname: Im
authors.forename: Monty
authors.initials: M
authors.lastname: Liong
authors.forename: Huilin
authors.initials: H
authors.lastname: Shao
authors.forename: Cesar M
authors.initials: CM
authors.lastname: Castro
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Hakho
authors.initials: H
authors.lastname: Lee
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001803:Blood Transfusion; D051928:CD47 Antigen / Q000378:metabolism; D018958:CD55 Antigens / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000737:chemistry*; D004867:Equipment Design; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000737:chemistry* / Q000166:cytology*; D006454:Hemoglobins / Q000737:chemistry; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008280:Magnetics; D046210:Microfluidic Analytical Techniques; D044085:Microfluidics; D053758:Nanoparticles / Q000737:chemistry; D036103:Nanotechnology; D009569:Nitric Oxide / Q000737:chemistry; D018384:Oxidative Stress; D010743:Phospholipids / Q000737:chemistry; D017382:Reactive Oxygen Species
chemical_list: D015415:Biomarkers; D051928:CD47 Antigen; D018958:CD55 Antigens; D006454:Hemoglobins; D018960:Hyaluronan Receptors; D010743:Phospholipids; D017382:Reactive Oxygen Species; D009569:Nitric Oxide