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Human umbilical cord-derived mesenchymal stem cells promote repair of neonatal brain injury caused by hypoxia/ischemia in rats. 2022

Yang Jiao, and Yue-Tong Sun, and Nai-Fei Chen, and Li-Na Zhou, and Xin Guan, and Jia-Yi Wang, and Wen-Juan Wei, and Chao Han, and Xiao-Lei Jiang, and Ya-Chen Wang, and Wei Zou, and Jing Liu
Stem Cell Clinical Research Center, National Joint Engineering Laboratory, Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University; Dalian Innovation Institute of Stem Cells and Precision Medicine; Department of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China.

Administration of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) is believed to be an effective method for treating neurodevelopmental disorders. In this study, we investigated the possibility of hUC-MSCs treatment of neonatal hypoxic/ischemic brain injury associated with maternal immune activation and the underlying mechanism. We established neonatal rat models of hypoxic/ischemic brain injury by exposing pregnant rats to lipopolysaccharide on day 16 or 17 of pregnancy. Rat offspring were intranasally administered hUC-MSCs on postnatal day 14. We found that polypyrimidine tract-binding protein-1 (PTBP-1) participated in the regulation of lipopolysaccharide-induced maternal immune activation, which led to neonatal hypoxic/ischemic brain injury. Intranasal delivery of hUC-MSCs inhibited PTBP-1 expression, alleviated neonatal brain injury-related inflammation, and regulated the number and function of glial fibrillary acidic protein-positive astrocytes, thereby promoting plastic regeneration of neurons and improving brain function. These findings suggest that hUC-MSCs can effectively promote the repair of neonatal hypoxic/ischemic brain injury related to maternal immune activation through inhibition of PTBP-1 expression and astrocyte activation.

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