Open AccessHGF Mediates Clinical‐Grade Human Umbilical Cord‐Derived Mesenchymal Stem Cells Improved Functional Recovery in a Senescence‐Accelerated Mouse Model of Alzheimer's Disease
Author(s) -
Jia Yali,
Cao Ning,
Zhai Jinglei,
Zeng Quan,
Zheng Pei,
Su Ruyu,
Liao Tuling,
Liu Jiajing,
Pei Haiyun,
Fan Zeng,
Zhou Junnian,
Xi Jiafei,
He Lijuan,
Chen Lin,
Nan Xue,
Yue Wen,
Pei Xuetao
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201903809
Subject(s) - mesenchymal stem cell , hepatocyte growth factor , senescence , neuroscience , stem cell , neural stem cell , hippocampus , pi3k/akt/mtor pathway , microbiology and biotechnology , biology , protein kinase b , cancer research , medicine , signal transduction , biochemistry , receptor
Abstract Stem cells have emerged as a potential therapy for a range of neural insults, but their application in Alzheimer's disease (AD) is still limited and the mechanisms underlying the cognitive benefits of stem cells remain to be elucidated. Here, the effects of clinical‐grade human umbilical cord‐derived mesenchymal stem cells (hUC‐MSCs) on the recovery of cognitive ability in SAMP8 mice, a senescence‐accelerated mouse model of AD is explored. A functional assay identifies that the core functional factor hepatocyte growth factor (HGF) secreted from hUC‐MSCs plays critical roles in hUC‐MSC‐modulated recovery of damaged neural cells by down‐regulating hyperphosphorylated tau, reversing spine loss, and promoting synaptic plasticity in an AD cell model. Mechanistically, structural and functional recovery, as well as cognitive enhancements elicited by exposure to hUC‐MSCs, are at least partially mediated by HGF in the AD hippocampus through the activation of the cMet‐AKT‐GSK3 β signaling pathway. Taken together, these data strongly implicate HGF in mediating hUC‐MSC‐induced improvements in functional recovery in AD models.