Cell viability during platelet storage in correlation to cellular metabolism after different pathogen reduction technologies

Picker, Susanne M.; Schneider, Volker; Oustianskaia, Larissa; Gathof, Birgit

doi:10.1111/j.1537-2995.2009.02316.x

Cited by 52 publications

(54 citation statements)

References 34 publications

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“…[8][9][10] Mitochondrial membrane depolarization occurs in PCs during blood bank storage and further increases upon PI treatment. [11][12][13] Recently, we and other groups have demonstrated that apoptotic events including phosphatidylserine (PS) exposure, increased proapoptotic protein expression, and caspase activation are triggered by RF/UV treatment in stored PCs, further supporting the model that apoptosis is involved in development of the PLT storage lesion. 14,15 However, the detailed biochemical mechanism(s) triggered by RF/UV are still unclear.…”

mentioning

confidence: 82%

p38 mitogen‐activated protein kinase regulates mitochondrial function and microvesicle release in riboflavin‐ and ultraviolet light–treated apheresis platelet concentrates

et al. 2017

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BACKGROUND: Biochemical analyses of mechanisms triggered in platelets (PLTs) upon pathogen inactivation (PI) are crucial to further understand the impact of PI on PLT functionality and, subsequently, quality. STUDY DESIGN AND METHODS: PLT concentrates(PCs) were split into four small illumination bags: 1) untreated control, 2) treated with riboflavin and ultraviolet light (RF/UV), and spiked with 3) solvent control dimethyl sulfoxide and 4) p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 before RF/UV treatment. Flow cytometry was used to monitor PLT mitochondrial potential (DW m ); generation of intracellular reactive oxygen species (ROS); and release of microvesicles (MVs), mitochondria (MT), and MVs containing MT (MVs/ MT). Quantitative polymerase chain reaction (qPCR) was used to quantify extracellular mitochondrial DNA (mtDNA). Translocation of selected mitochondrial proteins was analyzed in subcellular fractions by immunoblot.RESULTS: RF/UV treatment triggered an increased mitochondrial translocation of both Bax and Bid (p < 0.05, Day 7) and cytochrome c release (p < 0.01, Day 7), loss of DW m (p < 0.05, Day 5 and Day 7), and ROS generation (p < 0.01, Day 5 and Day 7) in PCs compared to the untreated control during storage. These PI-triggered changes were inhibited by SB203580 (p < 0.05). The release of MVs, MT, and MVs/MT was increased upon the RF/UV treatment during storage (p < 0.05) and, with the exception of MT, the release was decreased by the inhibitor (p < 0.05). qPCR analysis showed that RF/UV does not trigger mtDNA release during storage. CONCLUSION:These findings further our understanding of mechanisms in PLTs initiated by the RF/UV treatment, demonstrating that this treatment induces p38 MAPK-dependent mitochondrial signaling and MV release in apheresis PCs. R iboflavin and ultraviolet light (RF/UV) treatment is one of several pathogen inactivation (PI) technologies currently available.1 These treatments aim to target the replication and/or proliferation mechanism of pathogens and to destroy residual white blood cells (WBCs) to improve the safety of blood 14,15,25 The aim of this study was to evaluate the effects of RF/UV treatment on PLT mitochondrial function and signaling, including the recently discovered release of MT by PLTs, and to determine whether p38 is involved in the modulation of these mechanisms. MATERIALS AND METHODS MaterialsCommon chemicals were purchased from Sigma-Aldrich or Fisher Scientific. SB203580, a p38 MAPK inhibitor, was purchased from Santa Cruz Biotechnology. Apheresis PC preparationThis study was approved by the research ethics board of Canadian Blood Services and informed consent was obtained from all healthy volunteers before blood donation. Phlebotomy and plateletpheresis were carried out by the NetCAD development laboratory of Canadian Blood Services (Vancouver, Canada) using a Trima Accel (TerumoBCT). RF/UV treatment and inhibitor studyThe SB inhibitor stock solution in dimethyl sulfoxide (DMSO) was diluted in phosphate-buffered saline (PBS) and...

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confidence: 82%

p38 mitogen‐activated protein kinase regulates mitochondrial function and microvesicle release in riboflavin‐ and ultraviolet light–treated apheresis platelet concentrates

et al. 2017

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“…Marschner/Goodrich spite the fact that mitochondrial DNA is fragmented by the treatment [11], the wavelength of UV light used in the process is distinct from the one where cytochrome C, FMN and FAD absorb (370-450 nm) [46], resulting in intact electron transfer processes within mitochondrial membranes. Low oxygen levels in the treated products are a simple measurement and indication of functional mitochondria, since oxygen is consumed and ATP produced during mitochondrial respiration [44,45]. Additional evidence that mitochondria are intact after Mirasol treatment comes from the use of PAS, in which acetate is used as a substitute for glucose.…”

Section: Pathogen Reduction and Leukocyte Inactivation Performancementioning

confidence: 99%

“…However, shearinduced adhesion is maintained in Mirasol-treated platelets [41][42][43], and mitochondrial function is preserved [44,45]. De- Overview of the Mirasol ® Pathogen Reduction Technology System 13 tween the Mirasol-treated and control group were detected for mean number of days between transfusions, mean number of platelet transfusions per patient and dose of platelets transfused.…”

Section: Mirasol Prt System For Plateletsmentioning

confidence: 99%

Pathogen Reduction Technology Treatment of Platelets, Plasma and Whole Blood Using Riboflavin and UV Light

Marschner¹,

Goodrich²

2011

Transfus Med Hemother

181

186

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Bacterial contamination and emerging infections combined with increased international travel pose a great risk to the safety of the blood supply. Tests to detect the presence of infection in a donor have a ‘window period’ during which infections cannot be detected but the donor may be infectious. Agents and their transmission routes need to be recognized before specific tests can be developed. Pathogen reduction of blood components represents a means to address these concerns and is a proactive approach for the prevention of transfusion-transmitted diseases. The expectation of a pathogen reduction system is that it achieves high enough levels of pathogen reduction to reduce or prevent the likelihood of disease transmission while preserving adequate cell and protein quality. In addition the system needs to be nontoxic, non-mutagenic and should be simple to use. The Mirasol® Pathogen Reduction Technology (PRT) System for Platelets and Plasma uses riboflavin (vitamin B2) plus UV light to induce damage in nucleic acid-containing agents. The system has been shown to be effective against clinically relevant pathogens and inactivates leukocytes without significantly compromising the efficacy of the product or resulting in product loss. Riboflavin is a naturally occurring vitamin with a well-known and well-characterized safety profile. The same methodology is currently under development for the treatment of whole blood, making pathogen reduction of all blood products using one system achievable. This review gives an overview of the Mirasol PRT System, summarizing the mechanism of action, toxicology profile, pathogen reduction performance and clinical efficacy of the process.

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“…With this stain, polarized mitochondria appear red and depolarized green. Analysis of JC-1 fluorescence was performed using FACS analysis [27]. As also shown in our study, platelet storage causes a slight decrease in mitochondrial functionality.…”

Section: Resultsmentioning

confidence: 99%

Real-Time Live Confocal Fluorescence Microscopy as a New Tool for Assessing Platelet Vitality

Hermann

Nussbaumer²,

Knöfler

et al. 2010

Transfus Med Hemother

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Background: Assessment of platelet vitality is important for patients presenting with inherited or acquired disorders of platelet function and for quality assessment of platelet concentrates. Methods: Herein we combined live stains with intra-vital confocal fluorescence microscopy in order to obtain an imaging method that allows fast and accurate assessment of platelet vitality. Three fluorescent dyes, FITC-coupled wheat germ agglutinin (WGA), tetramethylrhodamine methyl ester perchlorate (TMRM) and acetoxymethylester (Rhod-2), were used to assess platelet morphology, mitochondrial activity and intra-platelet calcium levels. Microscopy was performed with a microlens-enhanced Nipkow spinning disk-based system allowing live confocal imaging. Results: Comparison of ten samples of donor platelets collected before apheresis and platelets collected on days 5 and 7 of storage showed an increase in the percentage of Rhod-2positive platelets from 3.6 to 47 and finally to 71%. Mitochondrial potential was demonstrated in 95.4% of donor platelets and in 92.5% of platelets stored for 7 days. Conclusion: Such fast and accurate visualization of known key parameters of platelet function could be of relevance for studies addressing the quality of platelets after storage and additional manipulation, such as pathogen inactivation, as well as for the analysis of inherited platelet function disorders.

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Cell viability during platelet storage in correlation to cellular metabolism after different pathogen reduction technologies

Cited by 52 publications

References 34 publications

p38 mitogen‐activated protein kinase regulates mitochondrial function and microvesicle release in riboflavin‐ and ultraviolet light–treated apheresis platelet concentrates

p38 mitogen‐activated protein kinase regulates mitochondrial function and microvesicle release in riboflavin‐ and ultraviolet light–treated apheresis platelet concentrates

Pathogen Reduction Technology Treatment of Platelets, Plasma and Whole Blood Using Riboflavin and UV Light

Real-Time Live Confocal Fluorescence Microscopy as a New Tool for Assessing Platelet Vitality

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