Abstract
Despite improvements in donor screening and increasing efforts to avoid contamination and the spread of pathogens in clinical platelet concentrates (PCs), the risks of transfusion-transmitted infections remain important. Relying on an ultraviolet photo activation system, pathogen reduction technologies (PRTs), such as Intercept and Mirasol, utilize amotosalen, and riboflavin (vitamin B2), respectively, to mediate inactivation of pathogen nucleic acids. Although they are expected to increase the safety and prolong the shelf life of clinical PCs, these PRTs might affect the quality and function of platelets, as recently reported. Upon activation, platelets release microparticles (MPs), which are involved in intercellular communications and regulation of gene expression, thereby mediating critical cellular functions. Here, we have used small RNA sequencing (RNA-Seq) to document the effect of PRT treatment on the microRNA profiles of platelets and derived MPs. PRT treatment did not affect the microRNA profile of platelets. However, we observed a specific loading of certain microRNAs into platelet MPs, which was impaired by treatment with Intercept or its Additive solution (SSP+). Whereas, Intercept had an impact on the microRNA profile of platelet-derived MPs, Mirasol did not impact the microRNA profile of platelets and derived MPs, compared to non-treated control. Considering that platelet MPs are able to transfer their microRNA content to recipient cells, and that this content may exert biological activities, those findings suggest that PRT treatment of clinical PCs may modify the bioactivity of the platelets and MPs to be transfused and argue for further investigations into PRT-induced changes in clinical PC content and function.
Highlights
Derived from giant megakaryocytes in the hematopoietic bone marrow, platelets are small discoid and anucleate blood elements [1]
We have previously reported that pathogen reduction technologies (PRTs) treatment of clinical platelet concentrates (PCs) altered the level of some platelet microRNAs [21], suggesting that it might alter the microRNA content of MPs derived from PRT-treated platelets
PCs were subjected to one of the following four conditions: [1] Control; [2] Mirasol [platelets stored in donor plasma and treated with riboflavin and ultraviolet B (UVB) light]; [3] Additive solution [platelets stored in 65% storage solutions for platelets (SSP+; MacoPharma) and 35% donor plasma]; or [4] Intercept [platelets stored in SSP+ (Additive solution) and treated with amotosalen and UVA light]
Summary
Derived from giant megakaryocytes in the hematopoietic bone marrow, platelets are small discoid and anucleate blood elements [1]. Platelets release extracellular vesicles (EVs), known as microparticles (MPs) [3], along with other particles, such as free mitochondria and PRTs Alter MPs’s MicroRNA Profile mito-MPs [4]. These MPs can mediate intercellular communications through delivery of bioactive molecules [5]. With their rich content in protein-coding messenger RNAs, non-coding RNAs (e.g., microRNAs), cytokines, and lipids, platelet MPs may play an important role in gene regulation and homeostasis [5, 6]. We reported previously that MPs released from human platelets can transfer functional microRNAs to human endothelial cells [1] and macrophages [2], in which platelet-derived microRNAs could regulate host cell gene expression
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