IMR Press / FBL / Volume 29 / Issue 4 / DOI: 10.31083/j.fbl2904139
Open Access Original Research
Human Placenta-Derived Mesenchymal Stem Cells Improve Neurological Function in Rats with Intrauterine Hypoxic-Ischaemic Encephalopathy by Reducing Apoptosis and Inflammatory Reactions
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1 Center for Reproductive Medicine, Department of Obstetrics, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 310000 Hangzhou, Zhejiang, China
2 Department of Gynaecology, Affiliated Hospital of Jiaxing University, 314000 Jiaxing, Zhejiang, China
3 Department of Obstetrics, Hangzhou Women’s Hospital, 310000 Hangzhou, Zhejiang, China
4 Center for Reproductive Medicine, Department of Pediatrics, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 310000 Hangzhou, Zhejiang, China
5 Institute for Cell-Based Drug Development of Zhejiang Province, S-Evans Biosciences, 310000 Hangzhou, Zhejiang, China
6 Key Laboratory of Cell-Based Drug and Applied Technology Development in Zhejiang Province, 310000 Hangzhou, Zhejiang, China
*Correspondence: (Li-Wei Yang)
These authors contributed equally.
Front. Biosci. (Landmark Ed) 2024, 29(4), 139;
Submitted: 30 September 2023 | Revised: 3 December 2023 | Accepted: 25 December 2023 | Published: 3 April 2024
Copyright: © 2024 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Hypoxic-ischaemic encephalopathy (HIE) is a major cause of neonatal disability and mortality. Although hypothermia therapy offers some neuroprotection, the recovery of neurological function is limited. Therefore, new synergistic therapies are necessary to improve the prognosis. Mesenchymal stem cell-based therapy is emerging as a promising treatment option for HIE. In this study, we studied the therapeutic efficacy of human placenta-derived mesenchymal stem cells (PD-MSCs) in the HIE rat model and analyzed the underlying therapeutic mechanisms. Methods: Rats were divided into 6 groups (n = 9 for each) as follows: control, HIE model, HIE + normal saline, and HIE + PD-MSC transplantation at days 7, 14 and 28 postpartum. Following PD-MSC transplantation, neurological behavior was evaluated using rotarod tests, traction tests, and the Morris water maze test. The degree of brain tissue damage was assessed by histological examination and Nissl staining. Expression levels of apoptosis-related proteins and inflammatory factors were quantified by Western blotting and enzyme-linked immunosorbent assays. Immunofluorescence was used to investigate the ability of PD-MSCs to repair the morphology and function of hippocampal neurons with hypoxic-ischaemic (HI) injury. Results: PD-MSC transplantation enhanced motor coordination and muscle strength in HIE rats. This treatment also improved spatial memory ability by repairing pathological damage and preventing the loss of neurons in the cerebral cortex. The most effective treatment was observed in the HIE + PD-MSC transplantation at day 7 group. Expression levels of microtubule-associated protein-2 (MAP-2), B-cell lymphoma-2 (BCL-2), interleukin (IL)-10, and transforming growth factor (TGF -β1) were significantly higher in the HIE + PD-MSC treatment groups compared to the HIE group, whereas the levels of BCL-2-associated X protein (BAX), BCL-2-associated agonist of cell death (BAD), IL-1β and tumour necrosis factor α (TNF-α) were significantly lower. Conclusions: We demonstrated that intravenous injection of PD-MSC at 7, 14 and 28 days after intrauterine HI damage in a rat model could improve learning, memory, and motor function, possibly by inhibiting apoptosis and inflammatory damage. These findings indicate that autologous PD-MSC therapy could have potential application for the treatment of HIE.

human placenta-derived mesenchymal stem cells
hypoxic-ischaemic encephalopathy
treatment option
therapeutic mechanisms
Graphical Abstract
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LGF19H040013/Natural Science Foundation of Zhejiang Province
Fig. 1.
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