Abstract
Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth. Up to 1/3 of children with BPD develop pulmonary hypertension (PH). PH increases mortality, the risk of adverse neurodevelopmental outcome and lacks effective treatment. Current vasodilator therapies address symptoms, but not the underlying arrested vascular development. Recent insights into placental biology and novel technological advances enabling the study of normal and impaired lung development at the single cell level support the concept of a vascular phenotype of BPD. Dysregulation of growth factor pathways results in depletion and dysfunction of putative distal pulmonary endothelial progenitor cells including Cap1, Cap2, and endothelial colony-forming cells (ECFCs), a subset of vascular progenitor cells with self-renewal and de novo angiogenic capacity. Preclinical data demonstrate effectiveness of ECFCs and ECFC-derived particles including extracellular vesicles (EVs) in promoting lung vascular growth and reversing PH, but the mechanism is unknown. The lack of engraftment suggests a paracrine mode of action mediated by EVs that contain miRNA. Aberrant miRNA signaling contributes to arrested pulmonary vascular development, hence using EV- and miRNA-based therapies is a promising strategy to prevent the development of BPD-PH. More needs to be learned about disrupted pathways, timing of intervention, and mode of delivery.
Impact
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Single-cell RNA sequencing studies provide new in-depth view of developmental endothelial depletion underlying BPD-PH.
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Aberrant miRNA expression is a major cause of arrested pulmonary development.
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EV- and miRNA-based therapies are very promising therapeutic strategies to improve prognosis in BPD-PH.
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Data sharing is not applicable as no datasets were generated or analyzed for this review.
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Funding
W.D. is financially supported by the Bekker Programme from the Polish National Agency for Academic Exchange – (Number BPN/BEK/2021/1/00329/ U/00001). B.T. is supported by the Canadian Institutes of Health Research (CIHR) and the Stem Cell Network.
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Durlak, W., Thébaud, B. The vascular phenotype of BPD: new basic science insights—new precision medicine approaches. Pediatr Res 96, 1162–1171 (2024). https://doi.org/10.1038/s41390-022-02428-7
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DOI: https://doi.org/10.1038/s41390-022-02428-7
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