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increase the purity of samples, but there are no generally accepted guidelines for such manipulations.49 In consider- ation of these limitations, we utilized the PureExo Exosome Isolation kit for vesicle extraction because the ultra-centrifugation step can be eliminated and exosomes can be obtained from small volume biological samples.
Biomarkers allow better evaluation of disease in general and improve prognosis, thus helping clinicians in the deci- sion-making process. In SAA, age, sex, and pre-treatment PB counts are established as prognostically valuable mark- ers for response to IST.50 In the current study, we observed positive correlation of some exosomal miRNAs with WBC and Plt counts, and LDH levels at diagnosis in SAA, but not with pre-treatment PB counts. These results sug- gest that their expression was not affected by transfusion history or disease severity, and that miRNAs could be used as independent diagnostic or prognostic markers. Similarly, positive correlation of miRNAs with clinical parameters was also seen in MDS.
Exosomal miRNAs are available from PB, and they are considered reliable biomarkers because they are protected from degradation and specifically loaded into vesicles from proliferating or apoptotic cells. We propose further study of measurement of exosomal miRNAs in marrow
failure syndromes in general. We have identified different miRNA signatures in SAA and MDS, and a candidate bio- marker of responsiveness to IST. However, a larger cohort of patients combined with an ultra-pure exosome isola- tion technique are needed to validate the clinical utility of exosomal miRNAs.
Acknowledgments
The authors would like to acknowledge the support of the Electron Microscopy Core of the National Heart, Lung, and Blood Institute (NHLBI) at National Institutes of Health (NIH, Bethesda, MD, USA). The authors would like to thank Xingmin Feng and Sawa Ito (Hematology Branch, NHLBI, NIH), Nastaran Rezaie and Anisha Kharkia (Qiagen, Germantown, MD, USA), and Leonid Margolis (National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA) for technical assistance; and Kinneret Broder and Therese Intrater (Hematology Branch, NHLBI, NIH) for assistance in obtaining samples from healthy volunteers.
Funding
This research was supported by the Intramural Research Program of the NIH, National Heart, Lung, and Blood Institute.
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