High‐yield Platelet units revealed immediate pH decline and delayed mitochondrial dysfunction during storage in 100% plasma as compared with storage in SSP+

Sandgren, Per; Stjepanovic, A.

doi:10.1111/j.1423-0410.2011.01581.x

Cited by 12 publications

(14 citation statements)

References 47 publications

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“…33 Also the expression level of the GPIb-IX-V complex 34,35 and maintenance of the PECAM-1 (CD31) levels of filtered PLTs 36,37 strengthens the conclusion that filtration does not adversely affect PLT quality. Moreover, our results on the filtered PLTs seem to agree with the functional integrity of the OrbiSac-produced PLTs proven earlier in a series of in vitro assays 2,22,23,29,30,37 and more than 10 years of clinical experience including more than 1.5 million units produced worldwide.…”

Section: Effect Of Storage Postrecovery Filtration and Activated Masupporting

confidence: 90%

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In vitro affinity reduction of biologic response modifiers from production buffy coat platelets exposed to recombinant protein receptors

Sandgren¹,

Rönnmark²,

Axelsson³

2015

Transfusion

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Section: Effect Of Storage Postrecovery Filtration and Activated Masupporting

confidence: 90%

“…All methods, including staining, were performed as described in recent publications. 23,29,30 Secretion markers and cytokine analysis …”

Section: Analysis Of Cellular Metabolic In Vitro Functional and Phementioning

confidence: 99%

In vitro affinity reduction of biologic response modifiers from production buffy coat platelets exposed to recombinant protein receptors

Sandgren¹,

Rönnmark²,

Axelsson³

2015

Transfusion

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“…Measurements of extracellular parameters offer, on one hand, valuable insights into the equilibrium among the cytosolic pathways and the mitochondrial oxidative pathways of PLTs during storage, as changes caused by PLTs may disturb metabolic homeostasis are linked to increased cytosolic glycolysis , PLT activation , aggregation and release reactions . On the other hand, other physiological challenges, not related to increased glycolytic flux and accelerated cellular metabolism, may affect metabolic homeostasis.…”

Section: Discussionmentioning

confidence: 99%

“…This proton gradient uncoupling agent quickly reduces the electrochemical potential across the inner mitochondrial membrane, resulting in a rapid intracellular mitochondrial depolarization event. Maintenance of MMP is expressed as JC‐1‐positive PLTs as described earlier .…”

Section: Methodsmentioning

confidence: 99%

Pathogen inactivation of double‐dose buffy‐coat platelet concentrates photochemically treated with amotosalen and UVA light: preservation of in vitro function

Sandgren

Diedrich

2014

Vox Sanguinis

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Background The INTERCEPT Blood System for Platelets (PLT) utilizes amotosalen (S-59) in combination with ultraviolet A (UVA) light to inactivate viruses, bacteria, protozoa and leucocytes that may contaminate PLT concentrates. However, limited data are available on the quality of INTERCEPT-treated double-dose (DD) buffy-coat (BC) PLT units allowing a single treatment procedure to produce two pathogen-inactivated PLT units for transfusion. Study Design and MethodsThe objective of this study was to evaluate potential in vitro effects of the INTERCEPT treatment on pools of 7 BCs as compared to untreated units. Functional, phenotypic and mitochondrial properties of DD BC PLTs during storage over 7 days were studied.Results For some parameters measured, small yet significant differences were observed including PLT count (P < 0Á05), pH, pCO 2 and glucose concentration. Throughout storage, no significant differences were observed in ATP levels, ESC, HSR reactivity and CD62P expression. Similarly, no differences were observed in the expression of PAC-1, CD42b and PECAM-1 at any time-points. The mitochondrial membrane potential (MMP) determined by JC-1-labelling was well maintained until day 7 in all treated and untreated units (>90%). The release of sCD40L increased over time (P < 0Á01) in all units but without any significant differences between treated and untreated PLTs.Conclusion Our data demonstrate that photochemical pathogen inactivation of DD-BC PLT concentrates with the INTERCEPT Blood System had no influence on the PLT in vitro quality over the 7 day of storage. However, whether in vivo efficacy of INTERCEPT-treated PLTs is affected may require clinical evaluation.

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“…They are one of the life-saving transfusion products in controlling bleeding associated with surgery, trauma, and accident victims in day-to-day life. During storage under standard blood bank conditions, platelets normally start to lose their quality with time and it has been identified that one of the reasons for this loss of quality is due to mitochondrial dysfunction [1–3]. Understanding the molecular mechanisms underlying mitochondrial dysfunction and ATP regulation in platelets during storage would facilitate developing targeted strategies toward enhancing the shelf-life of ex vivo stored platelets.…”

Section: Introductionmentioning

confidence: 99%

miR-570 interacts with mitochondrial ATPase subunit g (ATP5L) encoding mRNA in stored platelets

et al. 2016

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Loss of platelet quality during ex vivo storage is a major concern in the transfusion medicine field and it has been known that platelet mitochondrial dysfunction is associated with storage time. In the last decade, small noncoding RNAs also known as microRNAs (miRNAs) have been reported to regulate key cellular processes through their target sequence interactions with selected mRNAs. In this study, we focused on understanding the mechanisms of platelet mitochondrial dysfunction during storage through miRNA regulation of mRNAs. RNA was isolated from day 0, day 5, and day 9 of stored human leukocyte-depleted platelets and subjected to differential miRNA and mRNA profiling. The miRNA profiling identified several miRNAs at low levels including a set of 12 different miR-548 family members (miR-548a-3p, miR-548aa, miR-548x, miR-548ac, miR-548c-3p, miR-603, miR-548aj, miR-548ae, miR-548z, miR-548u, miR-548al, and miR-570-3p). The mRNA profiling identified, among many, the mitochondrial ATP synthase subunit g (ATP5L) mRNA at high levels during storage. Target Scan algorithm for potential targets of miR-570-3p also identified ATP5L as one of its targets. We further identified two target sites for miR-570-3p in the 3′ untranslated region (3′UTR) of ATP5L mRNA. While ATP5L is a subunit of F0ATPase complex, its function is not established yet. Overexpression of miR-570-3p in platelets resulted in reduced levels of ATP5L mRNA and concomitant ATP loss. These experimental results provide first-time insights into the miRNA–mRNA interactions underlying mitochondrial dysfunction in ex vivo stored platelets and warrants further investigation.

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High‐yield Platelet units revealed immediate pH decline and delayed mitochondrial dysfunction during storage in 100% plasma as compared with storage in SSP+

Abstract: The use of SSP+ instead of plasma may reduce the risk of triggering pro-apoptotic events in high-yield PLT units. A rapid decline in pH in PLT units cannot be explained with initial elevated and prolonged high carbon dioxide levels and mitochondrial dysfunction.

Cited by 12 publications

References 47 publications

In vitro affinity reduction of biologic response modifiers from production buffy coat platelets exposed to recombinant protein receptors

In vitro affinity reduction of biologic response modifiers from production buffy coat platelets exposed to recombinant protein receptors

Pathogen inactivation of double‐dose buffy‐coat platelet concentrates photochemically treated with amotosalen and UVA light: preservation of in vitro function

miR-570 interacts with mitochondrial ATPase subunit g (ATP5L) encoding mRNA in stored platelets

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