Neurovascular effects of umbilical cord blood-derived stem cells in growth-restricted newborn lambs

Stem Cell Research & Therapy

Michael C. Fahey¹  Atul Malhotra²  Graham Jenkin³  Ilias Nitsos³  Beth J. Allison³  Amy E. Sutherland³  Graeme R. Polglase³  Yen Pham³  Margie Castillo-Melendez³  Courtney A. McDonald³  Suzanne L. Miller³ 

[1] Department of Paediatrics, Monash University;Monash Newborn, Monash Children’s Hospital;The Ritchie Centre, Hudson Institute of Medical Research;

关键词: Brain injury;    Intrauterine growth restriction;    IUGR;    FGR;    Preterm;    Ventilation;   

DOI  :  10.1186/s13287-019-1526-0

来源: DOAJ

【 摘 要 】

Abstract Background Neonatal ventilation exacerbates brain injury in lambs with fetal growth restriction (FGR), characterized by neuroinflammation and reduced blood-brain barrier integrity, which is normally maintained by the neurovascular unit. We examined whether umbilical cord blood stem cell (UCBC) treatment stabilized the neurovascular unit and reduced brain injury in preterm ventilated FGR lambs. Methods Surgery was performed in twin-bearing pregnant ewes at 88 days’ gestation to induce FGR in one fetus. At 127 days, FGR and appropriate for gestational age (AGA) lambs were delivered, carotid artery flow probes and umbilical lines inserted, lambs intubated and commenced on gentle ventilation. Allogeneic ovine UCBCs (25 × 106 cells/kg) were administered intravenously to lambs at 1 h of life. Lambs were ventilated for 24 h and then euthanized. Results FGR (n = 6) and FGR+UCBC (n = 6) lambs were growth restricted compared to AGA (n = 6) and AGA+UCBC (n = 6) lambs (combined weight, FGR 2.3 ± 0.4 vs. AGA 3.0 ± 0.3 kg; p = 0.0002). UCBC therapy did not alter mean arterial blood pressure or carotid blood flow but decreased cerebrovascular resistance in FGR+UCBC lambs. Circulating TNF-α cytokine levels were lower in FGR+UCBC vs. FGR lambs (p < 0.05). Brain histopathology showed decreased neuroinflammation and oxidative stress, increased endothelial cell proliferation, pericyte stability, and greater integrity of the neurovascular unit in FGR+UCBC vs. FGR lambs. Conclusions Umbilical cord blood stem cell therapy mitigates perinatal brain injury due to FGR and ventilation, and the neuroprotective benefits may be mediated by stabilization of the neurovascular unit.

【 授权许可】

Unknown