Intravenous injection of umbilical cord-derived mesenchymal stromal cells attenuates reactive gliosis and hypomyelination in a neonatal intraventricular hemorrhage model. (4th July 2017)

• Record Type: Journal Article
• Authors: Mukai, Takeo; Mori, Yuka; Shimazu, Takahisa; Takahashi, Atsuko; Tsunoda, Hajime; Yamaguchi, Satoru; Kiryu, Shigeru; Tojo, Arinobu; Nagamura-Inoue, Tokiko
• Is Part Of: Neuroscience. Volume 355(2017)
• Page Start: 175
• Page End: 187
• Publication Date: 2017-07-04
• Subjects: APC allophycocyanin -- BBB blood–brain barrier -- BDNF brain-derived neurotrophic factor -- BM bone marrow -- CB cord blood -- CSF cerebrospinal fluid -- FBS fetal bovine serum -- FITC fluorescein isothiocyanate -- GAPDH glyceraldehyde 3-phosphate dehydrogenase -- GFAP glial fibrillary acidic protein -- HGF hepatocyte growth factor -- IVH intraventricular hemorrhage -- MBP myelin basic protein -- MRI magnetic resonance imaging -- MSCs mesenchymal stromal cells -- NGF nerve growth factor -- PE phycoerythrin -- TUNEL terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling -- UC umbilical cord; mesenchymal stromal cell -- umbilical cord -- intraventricular hemorrhage -- cerebral palsy -- brain-derived neurotrophic factor -- Hepatocyte growth factor; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2017.05.006
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Intravenously administered UC-MSCs cultured in serum-free medium improve motor abilities in the IVH model. UC-MSCs migrate to the injured brain and improve reactive gliosis and hypomyelination. UC-MSCs secrete trophic factors in the IVH model. Abstract: 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 × 10 5 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 24 h 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.