Mechanism of human umbilical cord mesenchymal stem cells in the treatment of germinal matrix hemorrhage-intraventricular hemorrhage.

Abstract

Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) is a severe complication frequently occurring in preterm infants, often resulting in permanent neurological impairment and persistent functional deficits. Human umbilical cord-derived mesenchymal stem cells have shown significant promise as a therapeutic approach in neonatal brain injury due to their robust paracrine effects, multipotent differentiation potential, and minimal immunogenic properties. The protective roles of human umbilical cord mesenchymal stem cells (hUC-MSCs) involve multiple synergistic pathways, such as suppressing neuroinflammatory responses, inducing apoptotic processes, stimulating neurogenesis and angiogenesis, and enhancing blood-brain barrier integrity. Additionally, hUC-MSCs and their extracellular vesicles (EVs) confer protective benefits through the secretion and delivery of bioactive substances, including cytokines and microRNAs (miRNAs), which can alleviate brain damage and subsequently enhance motor and cognitive outcomes. Although further large-scale clinical investigations are required to validate their effectiveness, current preclinical and animal studies provide preliminary evidence affirming the safety profile and therapeutic efficacy of hUC-MSCs treatment as an innovative strategy for managing GMH-IVH. LITERATURE SEARCH STRATEGY: We conducted a systematic literature search to identify relevant publications. The primary databases were PubMed and Web of Science, with the search period extending through October 2025. The search combined the following keywords and, where applicable, MeSH terms: "Germinal matrix hemorrhage," "Intraventricular hemorrhage," "GMH-IVH," "White matter injury," "Hydrocephalus," "mesenchymal stem cells," "MSC," "umbilical cord," "mechanism," "therapy," "neuroprotection," and "clinical trials." We also searched ClinicalTrials.gov for ongoing or completed trials of MSCs for neonatal brain injury. The selection prioritized original research, high-quality reviews, and meta-analyses. After an initial title-and-abstract screening, full texts of potentially relevant articles were examined. Studies offering the most significant insight into the mechanisms of hUC-MSC therapy in GMH-IVH were chosen for in-depth discussion in this review.