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.
Abstract

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