Human umbilical cord mesenchymal stem cell-derived exosomes improve brain tissue and functional recovery in mice with cerebral palsy

Abstract Cerebral palsy (CP) is a neurodevelopmental and motor disorder syndrome threatening children’s physical and mental health. Hypoxic-ischemic brain injury and inflammation have been considered as the main causes of CP. Mesenchymal stem cells (MSCs) can repair brain tissue damage, and many studies have proved that exosomes from MSCs have a critical advantage in the central nervous system (CNS) disease. Therefore, this study aimed to explore the improvement effect of human umbilical cord MSC (hUC-MSC)-derived exosomes on CP and whether synergistic action existed when combined with mouse nerve growth factor (mNGF). Therefore, the exosomes were isolated from hUC-MSCs and examined using electron microscopy, particle size, and Western blot (WB). A CP model was constructed by hypoxic induction after unilateral common carotid artery ligation combined with lipopolysaccharide (LPS) infection. The pathological damage of neuron tissue and synaptic structure in the hippocampus was determined using a light microscope after hematoxylin-eosin (HE) staining and transmission electron microscopy, respectively. The survival of neurons was analyzed using Nissl staining. The WB analysis was performed to monitor postsynaptic density 95(PSD-95) and synaptophysin(SYN) protein levels. The results showed that exosomes released by hUC-MSCs could ameliorate the motor function in mice with CP by rescuing the impaired brain tissue, synaptic structure, and neuronal function with increased PSD-95 and SYN levels. When the exosome was combined with mNGF, an improvement in CP was found. The results indicated that the intravenously injected hUC-MSC-exosomes and intraperitoneal administration of mNGF alleviated the nerve function injury in mice with CP.