(F1158) MULTIFACETED ACTIVITIES OF HUMAN PLURIPOTENT STEM CELL-DERIVED ECTOMESENCHYMAL STROMAL CELLS FOR THE TREATMENT OF HYPOXIC-ISCHEMIC ENCEPHALOPATHY
STUDENT The Chinese University of Hong Kong (CUHK) city of Hong Kong, Hong Kong
Abstract: MULTIFACETED ACTIVITIES OF HUMAN PLURIPOTENT STEM CELL-DERIVED ECTOMESENCHYMAL STROMAL CELLS FOR THE TREATMENT OF HYPOXIC-ISCHEMIC ENCEPHALOPATHY
Hypoxic-ischemic encephalopathy (HIE), affecting 0.1–0.8% of newborns, can lead to severe outcomes such as cerebral palsy and neurobehavioral impairments. The primary pathological changes in HIE involve gray and white matter injuries characterized by axon degeneration and a deficiency of mature oligodendrocytes (OLs). Although neural progenitor cells (NPCs) and oligodendrocyte precursor cells (OPCs) increase in response to injury, their differentiation toward a mature state is often hindered in HIE, highlighting the necessity for treatments that promote endogenous repair through neurogenesis and oligodendrogenesis.
Mesenchymal stromal cell (MSC) therapy is emerging as a promising treatment for HIE. However, clinical application is limited by cell heterogeneity, low isolation efficiency, and unpredictable effectiveness. This study investigates the therapeutic effects and underlying mechanisms of human pluripotent stem cell-derived ectomesenchymal stromal cells (hPSC-EMSCs) in a rat model of HIE.
Our findings demonstrate that hPSC-EMSCs provides greater neuroprotective potential and better functional recovery compared to hUC-MSCs in rats following hypoxia-ischaemia (HI). Intranasal delivery of the secretome derived from hPSC-EMSCs significantly reduced brain lesion size, mitigated inflammatory responses, promoted endogenous neurogenesis, improved remyelination， and improved functional recovery in rats with HIE. Mechanistically, the secretome derived from hPSC-EMSCs was found to potentiate NGF-induced neurite outgrowth and the neuronal differentiation of NPCs via the ERK/CREB pathway, while also promoting OPC differentiation mediated by the Periostin/Integrin-β3 axis. In summary, hPSC-EMSCs not only repairs gray matter injury but also addresses white matter injury, offering promising avenues for new treatment strategies aimed at restoring neuronal and myelin function in patients with HIE and other neurological diseases.
