Umbilical Cord Blood-Derived Exosomes From Very Preterm Infants With Bronchopulmonary Dysplasia Impaired Endothelial

Xin-Qi Zhong1,2, Qin Yan3, Zhuang-Gui Chen4

  • 1Department of Neonatology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Insights

Exosomes from umbilical cord blood of infants with bronchopulmonary dysplasia (BPD) impair blood vessel development. Specific exosomal microRNAs (EXO-miRNAs) within these exosomes are linked to BPD pathogenesis and may serve as biomarkers.

Area of Science:

  • Neonatal Medicine
  • Molecular Biology
  • Biomarker Discovery

Background:

  • Bronchopulmonary dysplasia (BPD) is a common complication in premature infants, characterized by impaired lung development.
  • Exosomes and their microRNA cargo (EXO-miRNAs) are implicated in BPD pathogenesis.
  • The role of umbilical cord blood exosomes and EXO-miRNAs in BPD-related angiogenesis remains unclear.

Purpose of the Study:

  • To investigate the impact of umbilical cord blood-derived exosomes from BPD infants on angiogenesis.
  • To identify differentially expressed EXO-miRNAs in BPD infants and their association with angiogenesis pathways.
  • To explore the functional role of specific EXO-miRNAs in endothelial cell function.

Main Methods:

  • Umbilical cord blood exosomes were isolated from preterm infants with and without BPD.
  • In vitro angiogenesis assays were performed using these exosomes.
  • Next-generation sequencing identified differentially expressed EXO-miRNAs.
  • Quantitative PCR and cell culture experiments assessed the function of specific miRNAs in human umbilical vein endothelial cells (HUVECs).

Main Results:

  • Exosomes from BPD infants significantly impaired angiogenesis in vitro.
  • 418 differentially expressed EXO-miRNAs were identified, enriched in PI3K/Akt and angiogenesis pathways.
  • BPD was associated with decreased hsa-miR-103a-3p and hsa-miR-185-5p, and increased hsa-miR-200a-3p.
  • Overexpression of hsa-miR-103a-3p and hsa-miR-185-5p promoted HUVEC proliferation, migration, and tube formation, while hsa-miR-200a-3p inhibited these processes.

Conclusions:

  • Umbilical cord blood exosomes from BPD infants negatively regulate angiogenesis.
  • Differentially expressed EXO-miRNAs, particularly hsa-miR-103a-3p, hsa-miR-185-5p, and hsa-miR-200a-3p, are involved in BPD-associated angiogenesis dysfunction.
  • These findings suggest a potential role for EXO-miRNAs as biomarkers and therapeutic targets for BPD.