Endothelial colony forming cell administration promotes neurovascular unit development in growth restricted and appropriately grown fetal lambs

Stem Cell Research & Therapy

Research

Margie Castillo-Melendez¹  Ashalyn P. Watt¹  Amy E. Sutherland¹  Yen Pham¹  Alexander Bell²  Beth J. Allison²  Courtney A. McDonald²  Ingrid Dudink²  Suzanne L. Miller²  Graham Jenkin²  Tamara Yawno³  Atul Malhotra⁴ 

[1] The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Australia;The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Australia;Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia;The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Australia;Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia;Department of Paediatrics, Monash University, 246 Clayton Road, 3168, Clayton, Melbourne, VIC, Australia;The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Australia;Department of Paediatrics, Monash University, 246 Clayton Road, 3168, Clayton, Melbourne, VIC, Australia;Monash Newborn, Monash Children’s Hospital, Melbourne, Australia;

关键词: Brain injury;    Blood brain barrier;    Cord blood;    Endothelial progenitor cells;    ECFC;    FGR;    Repair;    Stem cells;   

DOI  :  10.1186/s13287-023-03249-z

 received in 2022-08-16, accepted in 2023-02-01,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundFetal 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.MethodsTwin-bearing ewes had surgery performed at 88–90 days’ gestation, inducing FGR in one fetus. At 113 days, ECFCs (1 × 107 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.ResultsTwenty-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.ConclusionsECFC 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.

【 授权许可】

CC BY   
© The Author(s) 2023

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