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

Lulu Xue; Ruolan Du; Ning Bi; Qiuxia Xiao; Yifei Sun; Ruize Niu; Yaxin Tan; Li Chen; Jia Liu; Tinghua Wang; Liulin Xiong

doi:10.4103/1673-5374.390952

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

Neural Regen Res. 2024 Sep 1;19(9):2027-2035. doi: 10.4103/1673-5374.390952. Epub 2023 Dec 15.

Authors

Lulu Xue^{1

2}, Ruolan Du³, Ning Bi⁴, Qiuxia Xiao³, Yifei Sun³, Ruize Niu⁴, Yaxin Tan⁵, Li Chen³, Jia Liu⁴, Tinghua Wang^{1

2

3

4}, Liulin Xiong^{1

6}

Affiliations

¹ Transformation Research Laboratory, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China.
² State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan Province, China.
³ Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
⁴ Department of Animal Zoology, Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan Province, China.
⁵ Department of Pediatrics, the People's Liberation Army Rocket Force Characteristic Medical Center, Beijing, China.
⁶ Department of Anesthesiology, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China.

Abstract

JOURNAL/nrgr/04.03/01300535-202409000-00035/figure1/v/2024-01-16T170235Z/r/image-tiff 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.

Grants and funding

Funding: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.