Intravenous injection of umbilical cord-derived mesenchymal stromal cells attenuates reactive gliosis and hypomyelination in a neonatal intraventricular hemorrhage model.
Intraventricular hemorrhage (IVH) is a frequent complication of preterm newborns, resulting in cerebral palsy and cognitive handicap as well as hypoxic ischemic encephalopathy and periventricular leukomalacia. In this study, we investigated the restorative effect on neonatal IVH by umbilical cord-derived mesenchymal stromal cells (UC-MSCs) cultured in serum-free medium (RM medium) for clinical application. UC-MSCs were cultured with αMEM medium supplemented with FBS or RM. A neonatal IVH mouse model at postnatal day 5 was generated by intraventricular injection of autologous blood, and mice were intravenously administered 1×105 UC-MSCs two days after IVH. Brain magnetic resonance imaging was performed at postnatal day 15, 22 and neurological behavioral measurements were performed at postnatal day 23, accompanied by histopathological analysis and cytokine bead assays in serum after IVH with or without UC-MSCs. Both UC-MSCs cultured with αMEM and RM met the criteria of MSCs and improved behavioral outcome of IVH mice. Moreover the RM group exhibited significant behavioral improvement compared to the control group. Histopathological analysis revealed UC-MSCs cultured with RM significantly attenuated periventricular reactive gliosis, hypomyelination, and periventricular cell death observed after IVH. Furthermore, human brain-derived neurotrophic factor and hepatocyte growth factor were elevated in the serum, cerebrospinal fluid and brain tissue of neonatal IVH model mice 24h after UC-MSCs administration. These results suggest UC-MSCs attenuate neonatal IVH by protecting gliosis and apoptosis of the injured brain, and intravenous injection of UC-MSCs cultured in RM may be feasible for neonatal IVH in clinic.
['Mukai|Takeo|T|', 'Mori|Yuka|Y|', 'Shimazu|Takahisa|T|', 'Takahashi|Atsuko|A|', 'Tsunoda|Hajime|H|', 'Yamaguchi|Satoru|S|', 'Kiryu|Shigeru|S|', 'Tojo|Arinobu|A|', 'Nagamura-Inoue|Tokiko|T|']
D017667:Adipocytes D000818:Animals D000831:Animals, Newborn D002454:Cell Differentiation D000074042:Cerebral Intraventricular Hemorrhage D016895:Culture Media, Serum-Free D003711:Demyelinating Diseases D004195:Disease Models, Animal D005260:Female D018507:Gene Expression Regulation, Developmental D005911:Gliosis D036341:Intercellular Signaling Peptides and Proteins D008168:Lung D008297:Male D045164:Mesenchymal Stem Cell Transplantation D059630:Mesenchymal Stem Cells D051379:Mice D004676:Myelin Basic Protein D009419:Nerve Tissue Proteins D014470:Umbilical Cord
mesenchymal stromal cell intraventricular hemorrhage cerebral palsy brain-derived neurotrophic factor Hepatocyte growth factor umbilical cord