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Endothelial colony forming cell administration promotes neurovascular unit development in growth restricted and appropriately grown fetal lambs
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Endothelial colony forming cell administration promotes neurovascular unit development in growth restricted and appropriately grown fetal lambs
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Journal Article
Endothelial colony forming cell administration promotes neurovascular unit development in growth restricted and appropriately grown fetal lambs
2023
Overview
Background
Fetal growth restriction (FGR) is associated with deficits in the developing brain, including neurovascular unit (NVU) dysfunction. Endothelial colony forming cells (ECFC) can mediate improved vascular stability, and have demonstrated potential to enhance vascular development and protection. This investigation examined whether ECFCs from human umbilical cord blood (UCB) enhanced NVU development in FGR and appropriate for gestational age (AGA) fetal sheep.
Methods
Twin-bearing ewes had surgery performed at 88–90 days’ gestation, inducing FGR in one fetus. At 113 days, ECFCs (1 × 10
7
cells) cultured from human UCB were administered intravenously to fetal sheep in utero. At 127 days, ewes and their fetuses were euthanised, fetal brains collected, and NVU components analysed by immunohistochemistry.
Results
Twenty-four fetal lambs, arranged in four groups: AGA (n = 7), FGR (n = 5), AGA + ECFC (n = 6), and FGR + ECFC (n = 6), were included in analyses. FGR resulted in lower body weight than AGA (P = 0.002) with higher brain/body weight ratio (P = 0.003). ECFC treatment was associated with increased vascular density throughout the brain in both AGA + ECFC and FGR + ECFC groups, as well as increased vascular–astrocyte coverage and VEGF expression in the cortex (P = 0.003, P = 0.0006, respectively) and in the subcortical white matter (P = 0.01, P = 0.0002, respectively) when compared with the untreated groups.
Conclusions
ECFC administration enhanced development of NVU components in both the AGA and FGR fetal brain. Further investigation is required to assess how to optimise the enhanced angiogenic capabilities of ECFCs to provide a therapeutic strategy to protect the developing NVU against vulnerabilities associated with FGR.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Analysis
/ Animals
/ Biomedical and Life Sciences
/ Biomedical Engineering and Bioengineering
/ Brain
/ Colonies
/ ECFC
/ Endothelial progenitor cells
/ Ethics
/ Female
/ Fetal Growth Retardation - metabolism
/ Fetus
/ Fetuses
/ FGR
/ Growth
/ Humans
/ Injuries
/ Ischemia
/ Regenerative Medicine/Tissue Engineering
/ Scientific equipment and supplies industry
/ Sheep
/ Uterus
