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Human Cord Blood-Derived Unrestricted Somatic Stem Cell Infusion Improves Neurobehavioral Outcome in a Rabbit Model

Govindaiah Vinukonda1,2, Yanling Liao1, Furong Hu1

  • 1Department of Pediatrics, New York Medical College, Valhalla, New York, USA.

Stem Cells Translational Medicine
|July 20, 2019
PubMed

Insights

Unrestricted somatic stem cells (USSCs) show promise in treating preterm birth complications like intraventricular hemorrhage (IVH). USSC treatment reduced inflammation and improved white matter integrity and neurobehavioral outcomes in rabbit pups.

Area of Science:

  • Neonatal Neurology
  • Stem Cell Therapy
  • Neuroinflammation

Background:

  • Intraventricular hemorrhage (IVH) is a major complication of preterm birth with no cure, leading to severe neurological deficits.
  • Unrestricted somatic stem cells (USSCs) demonstrate reparative potential in preclinical models of central nervous system injury.

Purpose of the Study:

  • To evaluate the efficacy of USSCs in mitigating white matter damage and improving neurobehavioral outcomes in a rabbit model of IVH.
  • To compare the effects of intracerebroventricular (ICV) versus intravenous (IV) administration of USSCs.

Main Methods:

  • Premature rabbit pups received glycerol-induced IVH and were treated with USSCs via ICV or IV routes 24 hours post-injury.
  • Cell distribution, white matter integrity, glial activation, apoptosis, cytokine levels, and neurobehavioral performance were assessed at postnatal days 3, 7, and 14.
  • In vivo bioluminescence imaging and immunohistochemistry were employed.

Main Results:

  • USSCs were detected in the injured parenchyma (IV route) and adjacent to ventricles (ICV route) without adverse events.
  • USSC treatment attenuated microglial infiltration, reduced apoptotic cell death, and decreased reactive astrocytes and inflammatory cytokines (TNFα, IL1β).
  • Treated animals showed improved myelin preservation, increased myelin gene expression, and enhanced locomotor function.

Conclusions:

  • USSCs exert significant anti-inflammatory effects in the context of IVH, mitigating key pathological consequences.
  • Both IV and ICV administration routes showed therapeutic potential, with IV cells distributing more widely in the parenchyma.
  • USSC therapy represents a promising strategy for managing neurological damage associated with intraventricular hemorrhage in preterm infants.

Keywords:
Bioluminescence imagingIntraventricular hemorrhageLocomotor functionMyelinationUnrestricted somatic stem cells (USSCs)White matter injury

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