Extracellular Vesicle-microRNAs as Diagnostic Biomarkers in Preterm Neonates
Abstract
:1. Introduction
2. Definition of an Effective Diagnostic Biomarker
3. EVs as Effective Diagnostic Biomarkers
Methods of EV Characterization and miRNA Extraction
4. EV-miRNAs in Necrotizing Enterocolitis
5. EV-miRNAs in Bronchopulmonary Dysplasia
6. EV-miRNAs in Hypoxic-Ischemic Brain Damage
7. Next Steps in EV-miRNAs Biomarker Development in Premature Infants
7.1. Determine the Best Sample Source for Discovering Diagnostic Biomarkers from Neonatal EVs
7.2. Validation of EV-miRNAs as Reliable Diagnostic Biomarkers in the Premature Population
7.3. Determine the Feasibility of Implementing EV Diagnostic Testing: Testing Population and Role of EV Biomarkers in Clinical Decision Making
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Condition | Study | Study Population (n) | EV Source | EV Isolation (I) & Analysis (A) | EV-miRNA Isolation | miRNA | Statistical Performance |
---|---|---|---|---|---|---|---|
NEC | [64] | Neonates < 34 weeks GA NEC (12) Age-matched healthy controls (22) | Urine | I: ExoUrine EV Isolation Kit (System Biosciences) A: NTA, western blot, TEM | ExoRNEasy Midi Kits & Qiagen Qiaquick small RNA Kit (Qiagen Inc.) | 139-3p 604 5186 5703 | p < 0.05 p < 0.05 p < 0.05 p < 0.05 |
BPD | [66] | Neonates < 32 weeks GA, DOL 28 BPD (39) Non-BPD controls (34) Neonatal Mice Exposed to hyperoxia (4) Exposed to air (controls) (3) | Serum | I: ExoQuick precipitation solution (System Biosciences) A: NTA & ExoScreen, western blot | mirVana miRNA Isolation kit (Ambion Applied Biosystems) | 21 | p = 0.001 AUC = 0.850 p < 0.01 |
[67] | Neonates < 32 weeks GA BPD (12) Non-BPD controls (14) | UC Serum | I: PEG precipitation A: NTA & ExoScreen, western blot, TEM | SeraMir Exosome RNA Purification Kit (System Biosciences) | 17-5p 20b-5p 103a-3p 185-5p 200a-3p 765 | p < 0.05 p < 0.05 p < 0.05 p < 0.05 p < 0.05 p < 0.05 | |
[68] | Neonates 36 weeks PMA with BPD (25) GA-matched, FT controls, intubated for surgery (25) Neonates < 28 weeks GA BPD (15) Non-BPD controls (15) Neonatal Mice Exposed to hyperoxia (5-7) Exposed to air (controls) (5-7) | TA TA BALF | I: Ultracentrifugation A: NTA | miRCURY RNA Isolation Kit Cell and Plant with miRNA primers (Exiqon) | 876-3p | p = 0.001 p < 0.05 AUC = 0.917 p < 0.05 | |
[69] | Neonatal Rats Exposed to hyperoxia (10) Exposed to air (controls) (10) | Lung Homogenate | I: Total exosome isolation reagent (Thermo Scientific) A: NTA, western blot, TEM | Trizol kits with miR primer (Beijing Dingguo Changsheng Biotechnology Co.) | 425 | p < 0.01 | |
HIBD | [70] | Neonatal Mice, 24 hours post-surgery Unilateral carotid ligation + hypoxia (HIBD) (12) Sham surgery + normoxia (controls) (12) | Brain Homogenate | NA | NA | 182-5p * 342-3p * | p < 0.05 p < 0.05 |
[71] | Neonates, FT Moderate to severe HIBD (7) Healthy control (7) | UC Serum | NA | NA | 92b-3p * 342-3p * | p = 0.016793 p = 0.00059 | |
[72] | Neonatal Mice Hypoxia-preconditioned (3) | Brain homogenate | I: Ultracentrifugation and Sucrose Step Gradient A: NTA, western blot, electron microscopy | RNeasy Lipid Tissue Mini Kit (Qiagen) miRNA-Seq with NEXTFLEX small RNA kit (PerkinElmer) | 92b-3p 182-5p 342-3p | NA | |
[73] | Neonates, FT HIBD (102) Healthy controls (60) | Serum | NA | NA | 410 * | p < 0.01 AUC = 0.886 | |
[74] | Neonatal Rats Unilateral carotid ligation + hypoxia (HIBD) (12) Sham surgery + normoxia (controls) (12) | Brain homogenate | NA | NA | 124-3p * | p < 0.05 |
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Schiller, E.A.; Cohen, K.; Lin, X.; El-Khawam, R.; Hanna, N. Extracellular Vesicle-microRNAs as Diagnostic Biomarkers in Preterm Neonates. Int. J. Mol. Sci. 2023, 24, 2622. https://doi.org/10.3390/ijms24032622
Schiller EA, Cohen K, Lin X, El-Khawam R, Hanna N. Extracellular Vesicle-microRNAs as Diagnostic Biomarkers in Preterm Neonates. International Journal of Molecular Sciences. 2023; 24(3):2622. https://doi.org/10.3390/ijms24032622
Chicago/Turabian StyleSchiller, Emily A., Koral Cohen, Xinhua Lin, Rania El-Khawam, and Nazeeh Hanna. 2023. "Extracellular Vesicle-microRNAs as Diagnostic Biomarkers in Preterm Neonates" International Journal of Molecular Sciences 24, no. 3: 2622. https://doi.org/10.3390/ijms24032622