Scientific Reports, 03 March 2026
Objectives
White-Matter Injury (WMI) is a prevalent and severe neurological condition in preterm infants, leading to permanent sequelae such as cerebral palsy and cognitive impairment. This study aims to evaluate the therapeutic potential of human umbilical cord mesenchymal stem cells (hUC-MSCs) and elucidate their immunomodulatory mechanisms against neuroinflammatory responses in a neonatal rat model of hypoxic-ischemic (HI) injury.
Methods
– Experimental Model: 3-day-old Sprague–Dawley rats underwent unilateral carotid artery ligation combined with hypoxia exposure (8% O2) to establish the HI brain injury model.
– Intervention: hUC-MSCs (2 x 105 cells) were administered via intraventricular injection into the lateral ventricle 8 hours post-injury.
– Evaluation: Brain structure and cognitive functions were assessed using TTC staining, HE staining, electron microscopy, Western blot analysis, and the Morris Water Maze (MWM) behavioral test.
Key Results
– Reduction in Brain Damage: hUC-MSC treatment significantly reduced infarct volume, preserved axonal integrity, and promoted remyelination (upregulated expression of Myelin Basic Protein – MBP and Proteolipid Protein – PLP). Behavioral tests showed marked improvements in spatial learning and memory.
– Inflammatory Modulation: Stem cell therapy inhibited the activation of the NLRP3 (nucleotide-binding domain leucine-rich repeat containing protein 3) inflammasome, thereby reducing pro-inflammatory cytokines (IL-1β, TNF-α).
– Microglial Phenotypic Switch: The study demonstrated that hUC-MSCs drive microglial polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory and neuro-reparative M2 phenotype.
– Role of the TLR4 Signaling Pathway: Experimental data indicated that the neuroprotective effects of hUC-MSCs were reversed upon activation of the TLR4 receptor, confirming it as a pivotal signaling pathway in the therapeutic mechanism.
Conclusion and Clinical Significance
This study provides robust experimental evidence that hUC-MSCs function not only as a cell replacement therapy but also as a sophisticated immunomodulatory agent. By targeting the TLR4/NLRP3 axis, hUC-MSCs create a favorable microenvironment for early-stage neural repair. These findings establish an important scientific foundation for future clinical trials in treating neonatal brain injuries.
References
Wang, C., Xu, Q. Q., Zhang, S. J., & Zhu, Y. P. (2026). Human umbilical cord mesenchymal stem cells alleviate hypoxic-ischemia-induced white-matter injury in neonatal rats by regulating polarization of microglia. Scientific Reports.
Source: Scientific Reports
Link: https://doi.org/10.1038/s41598-026-42445-8
