Neural Regeneration Research ›› 2022, Vol. 17 ›› Issue (11): 2518-2525.doi: 10.4103/1673-5374.339002

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

Yang Jiao1, 2, 3, Yue-Tong Sun4, Nai-Fei Chen4, Li-Na Zhou1, 3, Xin Guan1, 2, Jia-Yi Wang1, 2, Wen-Juan Wei1, 2, Chao Han1, 2, Xiao-Lei Jiang4, Ya-Chen Wang1, 2, Wei Zou2, 4, *, Jing Liu1, 2, *#br#   

  1. 1Stem Cell Clinical Research Center, National Joint Engineering Laboratory, Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China; 2Dalian Innovation Institute of Stem Cells and Precision Medicine, Dalian, Liaoning Province, China; 3Department of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China; 4College of Life Science, Liaoning Normal University, Dalian, Liaoning Province, China
  • Online:2022-11-15 Published:2022-04-23
  • Contact: Jing Liu, PhD, liujing@dmu.edu.cn; Wei Zou, PhD, weizou60@126.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81471308 (to JL); Stem cell Clinical Research Registry Program, No. CMR-20161129-1003 (to JL); Liaoning Province Excellent Talent Program Project of China, No. XLYC1902031 (to JL); Dalian Innovation Fund of China, No. 2018J11CY025 (to JL); and National Defense Science and Technology New Special Zone Contract, No. 19-163-00-kx-003-001-01(to JL).

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Abstract: 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.

Key words: developmental brain disease model, disease-associated astrocytes, intranasal administration, lipopolysaccharide, maternal immune activation, neonatal brain injury, neuroplasticity repair, polypyrimidine tract-binding protein-1, stem cell therapy, umbilical cord-derived mesenchymal stem cells