Preterm umbilical cord blood derived mesenchymal stem/stromal cells protect preterm white matter brain development against hypoxia-ischemia.
Exp Neurol
; 308: 120-131, 2018 10.
Article
em En
| MEDLINE
| ID: mdl-30012511
ABSTRACT
INTRODUCTION:
Preterm infants are at high risk for white matter injury and subsequent neurodevelopmental impairments. Mesenchymal stem/stromal cells (MSC) have anti-inflammatory/immunomodulatory actions and are of interest for neural repair in adults and newborns. This study examined the neuroprotective effects of allogeneic MSC, derived from preterm umbilical cord blood (UCB), in a preterm sheep model of white matter injury.METHODS:
Quad-lineage differentiation, clonogenicity and self-renewal ability of UCB-derived MSC were confirmed. Chronically instrumented fetal sheep (0.7 gestation) received either 25â¯min hypoxia-ischemia (HI) to induce preterm brain injury, or sham-HI. Ten million MSC, or saline, were administered iv to fetuses at 12â¯h after HI. Fetal brains were collected 10d after HI for histopathology and immunocytochemistry.RESULTS:
HI induced white matter injury, as indicated by a reduction in CNPase-positive myelin fiber density. HI also induced microglial activation (Iba-1) in the periventricular white matter and internal capsule (Pâ¯<â¯.05 vs control). MSC administration following HI preserved myelination (Pâ¯<â¯.05), modified microglial activation, and promoted macrophage migration (CD163) and cell proliferation (Ki-67) within cerebral white matter (Pâ¯<â¯.05). Cerebral CXCL10 concentration was increased following MSC administration (Pâ¯<â¯.05), which was likely associated with macrophage migration and cell proliferation within the preterm brain. Additionally, MSC administration reduced systemic pro-inflammatory cytokine TNFα at 3d post-HI (Pâ¯<â¯.05).CONCLUSIONS:
UCB-derived MSC therapy preserved white matter brain structure following preterm HI, mediated by a suppression of microglial activation, promotion of macrophage migration and acceleration of self-repair within the preterm brain. UCB-derived MSC are neuroprotective, acting via peripheral and cerebral anti-inflammatory and immunomodulatory mechanisms.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Hipóxia-Isquemia Encefálica
/
Transplante de Células-Tronco de Sangue do Cordão Umbilical
/
Transplante de Células-Tronco Mesenquimais
Tipo de estudo:
Etiology_studies
Limite:
Animals
/
Pregnancy
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article