| |
Therapeutic effect of placenta-derived mesenchymal stem cells on hypoxic-ischemic brain damage in rats
Hong-Fang Ding, Hui Zhang, Hui-Fang Ding, Dong Li, Xin-Hao Yi, Xin-Yi Gao, Wei-Wei Mou, Xiu-Li Ju
Jinan, China
Author Affiliations: Department of Pediatrics, Qilu Hospital, Shandong University, Jinan 250012, China (Ding HF, Li D, Ju XL); Department of Pediatrics, Shengli Oil Field Central Hospital, Dongying 257034, China (Ding HF, Ding H, Yi XH, Gao XY, Mou WW); Department of Neurology, Qingdao Municipal Hospital, Qingdao 266000, China (Zhang H)
Corresponding Author: Xiu-Li Ju, PhD, Department of Pediatrics, Qilu Hospital, Shandong University, No. 107 West Wenhua Road, Jinan 250012, China (Tel: +86 0546 8770581; Fax: +86 0546 8555760; Email: qlyyjxl@163.com)
doi: 10.1007/s12519-014-0531-8
Background: Oxidative stress is involved in the development of hypoxic-ischemic brain damage (HIBD). In this study, we investigated the therapeutic effects of placenta-derived mesenchymal stem cells (PD-MSCs) and explored the NF-E2-related factor-2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway in treating HIBD.
Methods: P7 rats were subjected to hypoxic-ischemic brain injury and randomly divided into four groups (control, HIBD, HIBD+PD-MSCs, and HIBD+fibroblasts). Forty-eight hours after the induction of HIBD, 5¡Á105 of PD-MSCs were injected into cerebral tissue in the HIBD+PD-MSCs group, while the same dose of fibroblasts were injected in the HIBD+fibroblasts group. Morris Water Maze, gross and pathological changes were tested at P28. The level of malondialdehyde (MDA) was detected in rats' hippocampus. RT-PCR and western blot analysis were used to evaluate the changes of Nrf2/HO-1.
Results: The HIBD group showed significantly longer escape latency and a lower frequency of original platform crossing in the Morris Water Maze compared with the control group. Rats receiving PD-MSCs showed significant improvement of HIBD. The pathological changes were evident after HIBD, but ameliorated in the PD-MSCs group. Compared with the control group, HO-1 and Nrf2 were up-regulated at gene and protein levels in the HI brain, beginning at 6 hours and peaking at 48 hours (P<0.05). The expression of HO-1 and Nrf2 in the PD-MSCs treatment group was more pronounced than in the HIBD group (P<0.01). PD-MSCs also decreased MDA production in the brain tissue.
Conclusion: These results demonstrate that PD-MSCs have neuroprotective effect during the treatment of HIBD and that the mechanism may be partly due to alleviating oxidative stress.
World J Pediatr 2015;11(1):74-82
Key words: hypoxia-ischemia;
mesenchymal stem cells;
neonatal rat;
oxidative stress
|
