Department of Pediatrics, Changzhou Children's Hospital, Changzhou, Jiangsu, China; Department of Anatomy, Nantong University, Nantong, Jiangsu, China.
J Neurosci Res. 2014 Jan;92(1):35-45. doi: 10.1002/jnr.23304. Epub 2013 Oct 28.
The therapeutic potential of umbilical cord blood mesenchymal stem cells has been studied in several diseases. However, the possibility that human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hUCMSCs) can be used to treat neonatal hypoxic-ischemic encephalopathy (HIE) has not yet been investigated. This study focuses on the potential therapeutic effect of hUCMSC transplantation in a rat model of HIE. Dermal fibroblasts served as cell controls. HIE was induced in neonatal rats aged 7 days. hUCMSCs labeled with Dil were then transplanted into the models 24 hr or 72 hr post-HIE through the peritoneal cavity or the jugular vein. Behavioral testing revealed that hUCMSC transplantation but not the dermal fibroblast improved significantly the locomotor function vs. vehicle controls. Animals receiving cell grafts 24 hr after surgery showed a more significant improvement than at 72 hr. More hUCMSCs homed to the ischemic frontal cortex following intravenous administration than after intraperitoneal injection. Differentiation of engrafted cells into neurons was observed in and around the infarct region. Gliosis in ischemic regions was significantly reduced after hUCMSC transplantation. Administration of ganglioside (GM1) enhanced the behavioral recovery on the base of hUCMSC treatment. These results demonstrate that intravenous transplantation of hUCMSCs at an early stage after HIE can improve the behavior of hypoxic-ischemic rats and decrease gliosis. Ganglioside treatment further enhanced the recovery of neurological function following hUCMSC transplantation.
脐带血间充质干细胞的治疗潜力已在多种疾病中得到研究。然而，尚未研究人脐带华通氏胶源间充质干细胞（hUCMSCs）是否可用于治疗新生儿缺氧缺血性脑病（HIE）。本研究专注于 hUCMSC 移植在 HIE 大鼠模型中的潜在治疗效果。真皮成纤维细胞作为细胞对照。在 7 日龄新生大鼠中诱导 HIE。然后在 HIE 后 24 或 72 小时通过腹腔或颈静脉将 Dil 标记的 hUCMSCs 移植到模型中。行为测试表明，hUCMSC 移植而非真皮成纤维细胞可显著改善与载体对照相比的运动功能。手术后 24 小时接受细胞移植的动物比 72 小时后显示出更显著的改善。静脉内给药后，更多的 hUCMSCs 归巢到缺血性额皮质。在梗塞区域内和周围观察到植入细胞向神经元分化。hUCMSC 移植后，缺血区域的神经胶质增生显著减少。神经节苷脂（GM1）的给药增强了 hUCMSC 治疗的基础上的行为恢复。这些结果表明，HIE 后早期静脉内移植 hUCMSCs 可以改善缺氧缺血大鼠的行为并减少神经胶质增生。神经节苷脂治疗进一步增强了 hUCMSC 移植后的神经功能恢复。
