中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (11): 2518-2525.doi: 10.4103/1673-5374.339002

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

人脐带源间充质干细胞促进缺氧缺血性幼鼠脑损伤的修复

  

  • 出版日期:2022-11-15 发布日期:2022-04-23
  • 基金资助:
    国家自然科学基金项目(81471308),干细胞临床研究注册计划项目(CMR-20161129-1003);辽宁省优秀人才计划项目(XLYC1902031);大连市创新基金项目(2018J11CY025);国防科技新区合同项目(19-163-00-kx-003-001-01)

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).

摘要:

有研究认为脐带源间充质干细胞移植被认为是治疗神经发育障碍的潜在方法,因而实验拟探索以脐带源间充质干细胞移植治疗母体免疫激活反应相关的新生儿缺氧缺血性脑损伤的可能与相关机制。首先实验于孕鼠孕16或17天时暴露脂多糖,构建缺氧缺血性幼鼠脑损伤模型,出生后第14天鼻内滴注人脐带源间充质干细胞。结果显示,多聚嘧啶区结合蛋白1可参与调控脂多糖诱导的产后免疫激活反应,进而导致新生儿缺氧缺血性脑损伤。人脐带间充质干细胞鼻腔滴注可通过抑制多聚嘧啶区结合蛋白1的表达、减轻脑部的炎症损伤及调节神经纤维酸性蛋白阳性星形胶质细胞的数量和功能,以促进神经元的塑性再生并改善脑功能。结果提示人脐带源间充质干细胞可通过抑制多聚嘧啶区结合蛋白1表达和星形胶质细胞活化,有效促进母体免疫激活反应相关的新生儿缺氧缺血性脑损伤的修复。

https://orcid.org/0000-0002-0493-296X (Jing Liu); https://orcid.org/0000-0002-2203-8347(Wei Zou); https://orcid.org/0000-0001-8476-7978 (Yang Jiao)

关键词: 干细胞治疗, 新生儿脑损伤, 多聚嘧啶区结合蛋白1, 脂多糖, 母体免疫激活, 鼻内滴注, 脐带间充质干细胞, 疾病相关星形胶质细胞, 神经可塑性修复, 发育性脑病

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