| Objective This study aims to investigate the TIMP2 modified human umbilical cord mesenchymal stem cells(hUB-MSCs-TIMP2)and its influence on Alzheimer’s disease(AD)mice.Methods hUB-MSCs-TIMP2 were obtained by the use of an AAV gene expression vector and human umbilical mesenchymal stem cells(hUB-MSCs).It was characterized and confirmed by ELISA,flow cytometry,adipogenesis,osteogenesis and chondrogenesis.Seven-month-old AD mice were randomly allocated into PBS group,hUB-MSCs group,hUB-MSCs-TIMP2 group.The mice were injected with 0.2 ml PBS via tail vein in the PBS group,with 0.2 ml hUB-MSCs suspension of 1×106 cells/ml in the hUB-MSCs group,with 0.2 ml hUB-MSCs-TIMP2 suspension of 1×106 cells/ml in the hUB-MSCs-TIMP2 group,once a week for eight weeks.From the 1st to 4th week,the memory and cognitive ability of mice were evaluated by open field experiment,new object recognition experiment and Barnes maze experiment(n=9);at the 5th week,the mice were dissected and the hippocampal tissues were taken for transcriptome sequencing analysis(n=3).Results The escape latency of the 1st training on the first day of Barnes maze experiment in hUB-MSCs-TIMP2 group was 76±93 vs 148±83 vs 150±89 compared to hUB-MSCs group and PBS group;the escape latency of the 1st training on the first day of Barnes maze experiment in hUB-MSCs-TIMP2 group was significantly lower than that in hUB-MSCs group and PBS group(P<0.05,P<0.05).The escape latency of the 4th training on the first day of Barnes maze experiment in hUB-MSCs-TIMP2 group was 52±46 vs 87±87 vs 96±78 compared to hUB-MSCs group and PBS group;the escape latency of the 4th training on the first day of Barnes maze experiment in hUB-MSCs-TIMP2 group was significantly lower than that in the PBS group(P<0.05).In the long-term memory test on the 12th day,the number of times that mice entered the target hole in hUB-MSCs-TIMP2 group was 17±9.6 vs 12.0±5.3 vs 10.0±7.7 compared to hUB-MSCs group and PBS group;the number of times that mice entered the target hole in hUB-MSCs-TIMP2 group was significantly higher than that in PBS group(P<0.05).Conclusion hUB-MSCs-TIMP2 improve the memory ability and cognitive ability of AD mice to some extent. |
