BACKGROUND: Infants born preterm following exposure to in utero inflammation/chorioamnionitis are at high risk of brain injury and life-long neurological deficits. In this study, we assessed the efficacy of early intervention umbilical cord blood (UCB) cell therapy in a large animal model of preterm brain inflammation and injury. We hypothesised that UCB treatment would be neuroprotective for the preterm brain following subclinical fetal inflammation. METHODS: Chronically instrumented fetal sheep at 0.65 gestation were administered lipopolysaccharide (LPS, 150 ng, 055:B5) intravenously over 3 consecutive days, followed by 100 million human UCB mononuclear cells 6 h after the final LPS dose. Controls were administered saline instead of LPS and cells. Ten days after the first LPS dose, the fetal brain and cerebrospinal fluid were collected for analysis of subcortical and periventricular white matter injury and inflammation. RESULTS: LPS administration increased microglial aggregate size, neutrophil recruitment, astrogliosis and cell death compared with controls. LPS also reduced total oligodendrocyte count and decreased mature myelinating oligodendrocytes. UCB cell therapy attenuated cell death and inflammation, and recovered total and mature oligodendrocytes, compared with LPS. CONCLUSIONS: UCB cell treatment following inflammation reduces preterm white matter brain injury, likely mediated via anti-inflammatory actions.
BACKGROUND:Infants born preterm following exposure to in utero inflammation/chorioamnionitis are at high risk of brain injury and life-long neurological deficits. In this study, we assessed the efficacy of early intervention umbilical cord blood (UCB) cell therapy in a large animal model of preterm brain inflammation and injury. We hypothesised that UCB treatment would be neuroprotective for the preterm brain following subclinical fetal inflammation. METHODS: Chronically instrumented fetal sheep at 0.65 gestation were administered lipopolysaccharide (LPS, 150 ng, 055:B5) intravenously over 3 consecutive days, followed by 100 million human UCB mononuclear cells 6 h after the final LPS dose. Controls were administered saline instead of LPS and cells. Ten days after the first LPS dose, the fetal brain and cerebrospinal fluid were collected for analysis of subcortical and periventricular white matter injury and inflammation. RESULTS:LPS administration increased microglial aggregate size, neutrophil recruitment, astrogliosis and cell death compared with controls. LPS also reduced total oligodendrocyte count and decreased mature myelinating oligodendrocytes. UCB cell therapy attenuated cell death and inflammation, and recovered total and mature oligodendrocytes, compared with LPS. CONCLUSIONS: UCB cell treatment following inflammation reduces preterm white matter brain injury, likely mediated via anti-inflammatory actions.
Authors: Fraser Nott; J Jane Pillow; MarJanna Dahl; Sharmony B Kelly; Jacqueline Melville; Courtney McDonald; Ilias Nitsos; Rebecca Lim; Euan M Wallace; Graham Jenkin; Graeme R Polglase; Timothy J Moss; Robert Galinsky Journal: Pediatr Res Date: 2020-03-02 Impact factor: 3.756
Authors: Atul Malhotra; Margie Castillo-Melendez; Beth J Allison; Amy E Sutherland; Ilias Nitsos; Yen Pham; Courtney A McDonald; Michael C Fahey; Graeme R Polglase; Graham Jenkin; Suzanne L Miller Journal: Stem Cell Res Ther Date: 2020-01-08 Impact factor: 6.832
Authors: Madeleine J Smith; Kyra Y Y Chan; Paris Papagianis; Ilias Nitsos; Valerie Zahra; Beth Allison; Graeme R Polglase; Courtney A McDonald Journal: Front Physiol Date: 2020-02-21 Impact factor: 4.566
Authors: Ashalyn P Watt; Mark Kirkland; Lakshmi Nekkanti; Yen Pham; Courtney McDonald; Atul Malhotra; Guy Moeneclaey; Suzanne L Miller; Graham Jenkin Journal: Cell Tissue Res Date: 2022-02-02 Impact factor: 5.249