Synthetic PreImplantation Factor (sPIF)# neuroprotective role in intracranial stem cell transplantation: Encephalopathy of prematurity rat model

Background: Premature birth is a major cause of neonatal morbidity and mortality. Although improvements in perinatal and neonatal care reduce mortality, morbidity remains a serious challenge. Survivors of premature birth will confront enormous neurological problems. Wharton's jelly-derived mesenchymal stem cells (WJ-MSC) are a promising source for cell transplant. Embryo-derived PIF modulates systemic maternal immunity without suppression. PIF also reverses neuroinflammation (severe paralysis) while imparting neuroprotective/neurogenerative activity (multiple sclerosis models) and prevents juvenile diabetes while preserving islet function, by reducing oxidative stress and protein misfolding and controlling macrophages.

Material and methods: This pilot study investigates the effect of intracranial transplantation of WJ-MSC ± sPIF a rat model of severe encephalopathy of prematurity in a sham controlled design. Subcutaneous administration of LPS from E. coli followed by ligation of the left carotid artery and hypoxia (8% O₂, 65 min) was performed on anesthetized rats (P3). Two days later 250,000 WJ-MSC were injected into the lateral ventricle using a stereotactic frame ± subcutaneous sPIF injections (0.75 mg/kg twice-daily until brain harvesting). To evaluate encephalopathy of prematurity and the neuroprotective activity on postnatal day 11, histology and immunohistochemistry were used.

Results: The survival rate was 68% and mainly due to the prolonged hypoxic period. The induced damage was characterized by astrogliosis and neuro-axonal impairment in association with myelination deficiency. We detected grafted intact stem cells throughout brain tissue, confirming integration in the host's brain tissue.

Conclusion: Study suggests sPIF neuroprotective potential extends to intracranial transplantation of WJ-MSC.