Cargando…

High-Throughput Metabolomics Platform for the Rapid Data-Driven Development of Novel Additive Solutions for Blood Storage

Red blood cell transfusion is a life-saving intervention, and storage is a logistic necessity to make ~110 million units available for transfusion every year worldwide. However, storage in the blood bank is associated with a progressive metabolic decline, which correlates with the accumulation of mo...

Descripción completa

Detalles Bibliográficos
Autores principales: Nemkov, Travis, Yoshida, Tatsuro, Nikulina, Maria, D’Alessandro, Angelo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964052/
https://www.ncbi.nlm.nih.gov/pubmed/35360223
http://dx.doi.org/10.3389/fphys.2022.833242
_version_ 1784678124664913920
author Nemkov, Travis
Yoshida, Tatsuro
Nikulina, Maria
D’Alessandro, Angelo
author_facet Nemkov, Travis
Yoshida, Tatsuro
Nikulina, Maria
D’Alessandro, Angelo
author_sort Nemkov, Travis
collection PubMed
description Red blood cell transfusion is a life-saving intervention, and storage is a logistic necessity to make ~110 million units available for transfusion every year worldwide. However, storage in the blood bank is associated with a progressive metabolic decline, which correlates with the accumulation of morphological lesions, increased intra- and extra-vascular hemolysis upon transfusion, and altered oxygen binding/off-loading kinetics. Prior to storage, red blood cells are suspended in nutrient formulations known as additive solutions to prolong cellular viability. Despite a thorough expansion of knowledge regarding red blood cell biology over the past few decades, only a single new additive solution has been approved by the Food and Drug Administration this century, owing in part to the limited capacity for development of novel formulations. As a proof of principle, we leveraged a novel high-throughput metabolomics technology as a platform for rapid data-driven development and screening of novel additive solutions for blood storage under both normoxic and hypoxic conditions. To this end, we obtained leukocyte-filtered red blood cells (RBCs) and stored them under normoxic or hypoxic conditions in 96 well plates (containing polyvinylchloride plasticized with diethylhexylphthalate to concentrations comparable to full size storage units) in the presence of an additive solution supplemented with six different compounds. To inform this data-driven strategy, we relied on previously identified metabolic markers of the RBC storage lesion that associates with measures of hemolysis and post-transfusion recovery, which are the FDA gold standards to predict stored blood quality, as well as and metabolic predictors of oxygen binding/off-loading parameters. Direct quantitation of these predictors of RBC storage quality were used here—along with detailed pathway analysis of central energy and redox metabolism—as a decision-making tool to screen novel additive formulations in a multiplexed fashion. Candidate supplements are shown here that boost-specific pathways. These metabolic effects are only in part dependent on the SO(2) storage conditions. Through this platform, we anticipate testing thousands of novel additives and combinations thereof in the upcoming months.
format Online
Article
Text
id pubmed-8964052
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-89640522022-03-30 High-Throughput Metabolomics Platform for the Rapid Data-Driven Development of Novel Additive Solutions for Blood Storage Nemkov, Travis Yoshida, Tatsuro Nikulina, Maria D’Alessandro, Angelo Front Physiol Physiology Red blood cell transfusion is a life-saving intervention, and storage is a logistic necessity to make ~110 million units available for transfusion every year worldwide. However, storage in the blood bank is associated with a progressive metabolic decline, which correlates with the accumulation of morphological lesions, increased intra- and extra-vascular hemolysis upon transfusion, and altered oxygen binding/off-loading kinetics. Prior to storage, red blood cells are suspended in nutrient formulations known as additive solutions to prolong cellular viability. Despite a thorough expansion of knowledge regarding red blood cell biology over the past few decades, only a single new additive solution has been approved by the Food and Drug Administration this century, owing in part to the limited capacity for development of novel formulations. As a proof of principle, we leveraged a novel high-throughput metabolomics technology as a platform for rapid data-driven development and screening of novel additive solutions for blood storage under both normoxic and hypoxic conditions. To this end, we obtained leukocyte-filtered red blood cells (RBCs) and stored them under normoxic or hypoxic conditions in 96 well plates (containing polyvinylchloride plasticized with diethylhexylphthalate to concentrations comparable to full size storage units) in the presence of an additive solution supplemented with six different compounds. To inform this data-driven strategy, we relied on previously identified metabolic markers of the RBC storage lesion that associates with measures of hemolysis and post-transfusion recovery, which are the FDA gold standards to predict stored blood quality, as well as and metabolic predictors of oxygen binding/off-loading parameters. Direct quantitation of these predictors of RBC storage quality were used here—along with detailed pathway analysis of central energy and redox metabolism—as a decision-making tool to screen novel additive formulations in a multiplexed fashion. Candidate supplements are shown here that boost-specific pathways. These metabolic effects are only in part dependent on the SO(2) storage conditions. Through this platform, we anticipate testing thousands of novel additives and combinations thereof in the upcoming months. Frontiers Media S.A. 2022-03-14 /pmc/articles/PMC8964052/ /pubmed/35360223 http://dx.doi.org/10.3389/fphys.2022.833242 Text en Copyright © 2022 Nemkov, Yoshida, Nikulina and D’Alessandro. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Nemkov, Travis
Yoshida, Tatsuro
Nikulina, Maria
D’Alessandro, Angelo
High-Throughput Metabolomics Platform for the Rapid Data-Driven Development of Novel Additive Solutions for Blood Storage
title High-Throughput Metabolomics Platform for the Rapid Data-Driven Development of Novel Additive Solutions for Blood Storage
title_full High-Throughput Metabolomics Platform for the Rapid Data-Driven Development of Novel Additive Solutions for Blood Storage
title_fullStr High-Throughput Metabolomics Platform for the Rapid Data-Driven Development of Novel Additive Solutions for Blood Storage
title_full_unstemmed High-Throughput Metabolomics Platform for the Rapid Data-Driven Development of Novel Additive Solutions for Blood Storage
title_short High-Throughput Metabolomics Platform for the Rapid Data-Driven Development of Novel Additive Solutions for Blood Storage
title_sort high-throughput metabolomics platform for the rapid data-driven development of novel additive solutions for blood storage
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964052/
https://www.ncbi.nlm.nih.gov/pubmed/35360223
http://dx.doi.org/10.3389/fphys.2022.833242
work_keys_str_mv AT nemkovtravis highthroughputmetabolomicsplatformfortherapiddatadrivendevelopmentofnoveladditivesolutionsforbloodstorage
AT yoshidatatsuro highthroughputmetabolomicsplatformfortherapiddatadrivendevelopmentofnoveladditivesolutionsforbloodstorage
AT nikulinamaria highthroughputmetabolomicsplatformfortherapiddatadrivendevelopmentofnoveladditivesolutionsforbloodstorage
AT dalessandroangelo highthroughputmetabolomicsplatformfortherapiddatadrivendevelopmentofnoveladditivesolutionsforbloodstorage