Therapeutic effect of human umbilical cord mesenchymal stem cells on neonatal rat hypoxic–ischemic encephalopathy
Therapeutic effect of human umbilical cord mesenchymal stem cells on neonatal rat hypoxic–ischemic encephalopathy
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DOI：
10.1002/jnr.23304
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发表时间：
2014-01
影响因子：
4.2
通讯作者：
Xinhua Zhang;Qinfen Zhang;Wei Li;Dekang Nie;Weiwei Chen;Chun-Cai Xu;X. Yi;Jinhong Shi;Meiling Tian;J. Qin;G. Jin;Wen-juan Tu
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文献类型：
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作者：
Xinhua Zhang;Qinfen Zhang;Wei Li;Dekang Nie;Weiwei Chen;Chun-Cai Xu;X. Yi;Jinhong Shi;Meiling Tian;J. Qin;G. Jin;Wen-juan Tu
脐带血间充质干细胞的治疗潜力已经在几种疾病中进行了研究。然而，人脐带华顿氏胶质源性间充质干细胞（hUCMSCs）可用于治疗新生儿缺氧缺血性脑病（HIE）的可能性尚未得到研究。本研究的重点是hUCMSC移植在HIE大鼠模型中的潜在治疗作用。真皮成纤维细胞作为细胞对照。在7日龄的新生大鼠中诱导HIE。然后将用Dil标记的hUCMSC通过腹膜腔或颈静脉移植到HIE后24小时或72小时的模型中。行为测试显示，与媒介物对照相比，hUCMSC移植而非真皮成纤维细胞显著改善了运动功能。手术后24小时接受细胞移植的动物显示出比72小时更显著的改善。静脉内给药后比腹膜内注射后更多的hUCMSC归巢到缺血的额叶皮质。移植的细胞分化成神经元，观察梗死区域内和周围。hUCMSC移植后，缺血区域的胶质增生显著减少。在hUCMSC治疗的基础上，给予神经节苷脂（GM1）促进了行为恢复。这些结果表明，在HIE后早期静脉移植hUCMSCs可以改善缺氧缺血大鼠的行为，减少胶质细胞增生。神经节苷脂治疗进一步增强了hUCMSC移植后神经功能的恢复。© 2013 Wiley Periodicals，Inc.
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. © 2013 Wiley Periodicals, Inc.