Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (9): 2027-2035.doi: 10.4103/1673-5374.390952

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Transplantation of human placental chorionic plate-derived mesenchymal stem cells for repair of neurological damage in neonatal hypoxic-ischemic encephalopathy

Lulu Xue1, 2, #, Ruolan Du3, #, Ning Bi4, Qiuxia Xiao3, Yifei Sun3, Ruize Niu4, Yaxin Tan6, Li Chen3, Jia Liu4, Tinghua Wang1, 2, 3, 4, *, Liulin Xiong1, 5, *   

  1. 1Transformation Research Laboratory, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China; 2State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan Province, China; 3Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China; 4Department of Animal Zoology, Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan Province, China; 5Department of Anesthesiology, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China; 6Department of Pediatrics, the People’s Liberation Army Rocket Force Characteristic Medical Center, Beijing, China
  • Online:2024-09-15 Published:2024-01-26
  • Contact: Liulin Xiong, PhD, 499465010@qq.com; Tinghua Wang, PhD, Wangth_email@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 82001604; Guizhou Provincial Higher Education Science and Technology Innovation Team, No. [2023]072; Guizhou Province Distinguished Young Scientific and Technological Talent Program, No. YQK[2023]040; Guizhou Provincial Basic Research Program (Natural Science), No. ZK[2021]-368 (all to LXiong), and Zunyi City Innovative Talent Team Training Plan, No. [2022]-2.

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Abstract: Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy, neurosensory impairments, and cognitive deficits, and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy. The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored. However, the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated. In this study, we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function. Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats. Following transplantation of human placental chorionic plate-derived mesenchymal stem cells, interleukin-3 expression was downregulated. To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy, we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA. We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown. Furthermore, interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy. The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy, and this effect was mediated by interleukin-3-dependent neurological function.

Key words: behavioral evaluations, gene knockout, human neuroblastoma cells (SH-SY5Y), human placental chorionic derived mesenchymal stem cells, interleukin-3, neonatal hypoxic-ischemic encephalopathy, nerve injury, oxygen-glucose deprivation, protein chip, small interfering RNA