The therapeutic potential of human umbilical cord blood-derived mesenchymal stem cells in Alzheimer's disease.
The neuropathological hallmarks of Alzheimer's disease (AD) include the presence of extracellular amyloid-beta peptide (Abeta) in the form of amyloid plaques in the brain parenchyma and neuronal loss. The mechanism associated with neuronal death by amyloid plaques is unclear but oxidative stress and glial activation has been implicated. Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) are being scrutinized as a potential therapeutic tool to prevent various neurodegenerative diseases including AD. However, the therapeutic impact of hUCB-MSCs in AD has not yet been reported. Here we undertook in vitro work to examine the potential impact of hUCB-MSCs treatment on neuronal loss using a paradigm of cultured hippocampal neurons treated with Abeta. We confirmed that hUCB-MSCs co-culture reduced the hippocampal apoptosis induced by Abeta treatment. Moreover, in an acute AD mouse model to directly test the efficacy of hUCB-MSCs treatment on AD-related cognitive and neuropathological outcomes, we demonstrated that markers of glial activation, oxidative stress and apoptosis levels were decreased in AD mouse brain. Interestingly, hUCB-MSCs treated AD mice demonstrated cognitive rescue with restoration of learning/memory function. These data suggest that hUCB-MSCs warrant further investigation as a potential therapeutic agent in AD.
Lee
Hyun Ju
HJ
Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, South Korea.
Lee
Jong Kil
JK
Lee
Hyun
H
Shin
Ji-woong
JW
Carter
Janet E
JE
Sakamoto
Toshiro
T
Jin
Hee Kyung
HK
Bae
Jae-sung
JS
D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005312:Fetal Blood / Q000166:cytology*; D005333:Fetus; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D020287:In Situ Nick-End Labeling / Q000379:methods; D007211:Indoles; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000473:pathology*
D016229:Amyloid beta-Peptides; D007211:Indoles; C007293:DAPI