Is umbilical cord blood therapy an effective treatment for early lung injury in growthrestricted newborn lambs?.

Background: Foetal growth restriction (FGR) and prematurity are often co-morbidities with both risk factors for lung disease. Despite advances in treatment, rates of ventilation-induced lung injury (VILI) remain high. Stem cell therapy can attenuate inflammation and injury associated with VILI in preterm animals. However, no studies have looked at the effects of stem cell therapy in FGR VILI. We aimed to determine if stem cell treatment could attenuate VILI in FGR lambs. Method(s): Preterm foetal sheep (0.6 gestation) underwent single umbilical artery ligation (SUAL) to induce FGR. Lambs were delivered preterm at ~126dGA (term 150d), and randomised to either immediate euthanasia (unventilated controls; AGUVC & FGRUVC) or 24hr ventilation (AGV & FGRV) with a cohort receiving umbilical cord blood (UCB) treatment (AGCELLS, FGRCELLS). Lungs were collected at post-mortem for histological and biochemical examination. Result(s): Ventilation caused lung injury in AG lambs which was attenuated with UCB therapy. Ventilated FGR lambs also had lung injury, albeit with different indices compared to AG lambs. Following ventilation septal crests, alpha smooth muscle actin and cell proliferation were all decreased (P<0.05) in FGR lungs. UCB treatment in ventilated FGR lambs further decreased septal crest density and increased collagen deposition, however also increased angiogenesis. Conclusion(s): Our data demonstrate that the uterine environment can impact on treatment efficacy. Our findings show potential differential pathways for therapeutic potential of UCB depending on the growth status of the newborn, and warrant further investigation to determine how growth status can modulate these effects.