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Isolation and Characterization of Human Umbilical Cord-derived Mesenchymal Stem Cells from Preterm and Term Infants
Published on: January 26, 2019
Preterm umbilical cord blood derived mesenchymal stem/stromal cells protect preterm white matter brain development
Jingang Li1, Tamara Yawno1, Amy E Sutherland1
1The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia.
Insights
Mesenchymal stem/stromal cells (MSC) from preterm umbilical cord blood protected preterm sheep brains from injury. MSC therapy preserved white matter and reduced inflammation, offering neuroprotection.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Neonatal Research
Background:
- Preterm infants face high risks of white matter injury and neurodevelopmental issues.
- Mesenchymal stem/stromal cells (MSC) show potential for neural repair due to anti-inflammatory and immunomodulatory properties.
Purpose of the Study:
- To investigate the neuroprotective effects of allogeneic MSC derived from preterm umbilical cord blood (UCB).
- To assess MSC efficacy in a preterm sheep model of white matter injury.
Main Methods:
- UCB-derived MSC confirmed for differentiation, clonogenicity, and self-renewal.
- Preterm sheep fetuses (0.7 gestation) underwent hypoxia-ischemia (HI) or sham-HI.
- MSC (10 million) or saline administered intravenously 12 hours post-HI; brains collected 10 days later for analysis.
Main Results:
- HI induced white matter injury, reducing myelin density and increasing microglial activation.
- MSC administration preserved myelination, modulated microglial activation, and promoted macrophage migration and cell proliferation.
- MSC increased cerebral CXCL10 and reduced systemic TNFα, indicating anti-inflammatory effects.
Conclusions:
- UCB-derived MSC therapy preserved white matter structure in preterm lambs post-HI.
- MSC therapy suppressed microglial activation, promoted macrophage migration, and enhanced self-repair.
- MSC demonstrated neuroprotection through peripheral and cerebral anti-inflammatory and immunomodulatory mechanisms.
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 25 min hypoxia-ischemia (HI) to induce preterm brain injury, or sham-HI. Ten million MSC, or saline, were administered iv to fetuses at 12 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 (P < .05 vs control). MSC administration following HI preserved myelination (P < .05), modified microglial activation, and promoted macrophage migration (CD163) and cell proliferation (Ki-67) within cerebral white matter (P < .05). Cerebral CXCL10 concentration was increased following MSC administration (P < .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 (P < .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.
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