Center for Reproductive Medicine, Department of Obstetrics, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 310000 Hangzhou, Zhejiang, China.
Department of Gynaecology, Affiliated Hospital of Jiaxing University, 314000 Jiaxing, Zhejiang, China.
Front Biosci (Landmark Ed). 2024 Apr 3;29(4):139. doi: 10.31083/j.fbl2904139.
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.
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.
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.
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.
缺氧缺血性脑病（HIE）是新生儿残疾和死亡的主要原因。虽然低温治疗提供了一定的神经保护作用，但神经功能的恢复是有限的。因此，需要新的协同治疗方法来改善预后。基于间充质干细胞的治疗方法正成为治疗 HIE 的一种有前途的治疗选择。在这项研究中，我们研究了人胎盘来源的间充质干细胞（PD-MSCs）在 HIE 大鼠模型中的治疗效果，并分析了潜在的治疗机制。
将大鼠分为 6 组（每组 9 只）：对照组、HIE 模型组、HIE+生理盐水组和产后 7、14 和 28 天 PD-MSC 移植组。PD-MSC 移植后，通过转棒试验、牵引试验和 Morris 水迷宫试验评估神经行为。通过组织学检查和尼氏染色评估脑组织损伤程度。通过 Western blot 和酶联免疫吸附试验定量测定凋亡相关蛋白和炎症因子的表达水平。免疫荧光用于研究 PD-MSC 修复缺氧缺血（HI）损伤海马神经元形态和功能的能力。
PD-MSC 移植可增强 HIE 大鼠的运动协调性和肌肉力量。这种治疗还通过修复病理性损伤和防止大脑皮质神经元丢失来改善空间记忆能力。在 HIE+PD-MSC 移植第 7 天组中观察到最有效的治疗效果。与 HIE 组相比，HIE+PD-MSC 治疗组微管相关蛋白-2（MAP-2）、B 细胞淋巴瘤-2（BCL-2）、白细胞介素（IL）-10 和转化生长因子-β1（TGF-β1）的表达水平显著升高，而 BCL-2 相关 X 蛋白（BAX）、BCL-2 相关细胞死亡激动剂（BAD）、白细胞介素-1β和肿瘤坏死因子-α（TNF-α）的表达水平显著降低。
我们证明，在宫内 HI 损伤后 7、14 和 28 天，静脉注射 PD-MSC 可改善学习、记忆和运动功能，可能通过抑制细胞凋亡和炎症损伤。这些发现表明，自体 PD-MSC 治疗可能具有治疗 HIE 的应用潜力。
