TY - JOUR
T1 - Resveratrol promotes hUC-MSCs engraftment and neural repair in a mouse model of Alzheimer's disease
AU - Wang, Xinxin
AU - Ma, Shanshan
AU - Yang, Bo
AU - Huang, Tuanjie
AU - Meng, Nan
AU - Xu, Ling
AU - Xing, Qu
AU - Zhang, Yanting
AU - Zhang, Kun
AU - Li, Qinghua
AU - Zhang, Tao
AU - Wu, Junwei
AU - Yang, Greta Luyuan
AU - Guan, Fangxia
AU - Wang, Jian
N1 - Funding Information:
This study was supported by the National Natural Science Foundation of China ( 81471306 , U1404313 , 81601078 ), the Innovative Research Team in Science and Technology of the University of Henan Province ( 15IRTSTHN022 ), the Plan for Scientific Innovation Talent of Henan Province ( 154200510008 ), the International Collaboration Research Program for Talents of Henan Province ( 2016GH15 ), the Key Research Project of Higher Education of Henan Province ( 17A310012 ) and NIH ( R01NS078026,R01AT007317 , R56 NS096549 and R21 NS101614 ).
Publisher Copyright:
© 2017
PY - 2018/2/26
Y1 - 2018/2/26
N2 - Mesenchymal stem cell transplantation is a promising therapeutic approach for Alzheimer's disease (AD). However, poor engraftment and limited survival rates are major obstacles for its clinical application. Resveratrol, an activator of silent information regulator 2, homolog 1 (SIRT1), regulates cell destiny and is beneficial for neurodegenerative disorders. The present study is designed to explore whether resveratrol regulates the fate of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and whether hUC-MSCs combined with resveratrol would be efficacious in the treatment of neurodegeneration in a mouse model of AD through SIRT1 signaling. Herein, we report that resveratrol facilitates hUC-MSCs engraftment in the hippocampus of AD mice and resveratrol enhances the therapeutic effects of hUC-MSCs in this model as demonstrated by improved learning and memory in the Morris water maze, enhanced neurogenesis and alleviated neural apoptosis in the hippocampus of the AD mice. Moreover, hUC-MSCs and resveratrol jointly regulate expression of hippocampal SIRT1, PCNA, p53, ac-p53, p21, and p16. These data strongly suggests that hUC-MSCs transplantation combined with resveratrol may be an effective therapy for AD.
AB - Mesenchymal stem cell transplantation is a promising therapeutic approach for Alzheimer's disease (AD). However, poor engraftment and limited survival rates are major obstacles for its clinical application. Resveratrol, an activator of silent information regulator 2, homolog 1 (SIRT1), regulates cell destiny and is beneficial for neurodegenerative disorders. The present study is designed to explore whether resveratrol regulates the fate of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and whether hUC-MSCs combined with resveratrol would be efficacious in the treatment of neurodegeneration in a mouse model of AD through SIRT1 signaling. Herein, we report that resveratrol facilitates hUC-MSCs engraftment in the hippocampus of AD mice and resveratrol enhances the therapeutic effects of hUC-MSCs in this model as demonstrated by improved learning and memory in the Morris water maze, enhanced neurogenesis and alleviated neural apoptosis in the hippocampus of the AD mice. Moreover, hUC-MSCs and resveratrol jointly regulate expression of hippocampal SIRT1, PCNA, p53, ac-p53, p21, and p16. These data strongly suggests that hUC-MSCs transplantation combined with resveratrol may be an effective therapy for AD.
KW - Alzheimer's disease
KW - Human umbilical cord-derived mesenchymal stem cells
KW - Resveratrol, SIRT1
KW - Transgenic mice
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U2 - 10.1016/j.bbr.2017.10.032
DO - 10.1016/j.bbr.2017.10.032
M3 - Article
C2 - 29102593
AN - SCOPUS:85034456097
SN - 0166-4328
VL - 339
SP - 297
EP - 304
JO - Behavioural Brain Research
JF - Behavioural Brain Research
ER -
