Mesenchymal Stem Cell-Conditioned Medium Improves Mitochondrial Dysfunction and Suppresses Apoptosis in Okadaic Acid-Treated SH-SY5Y Cells by Extracellular Vesicle Mitochondrial Transfer.
BACKGROUND
Mesenchymal stem cells-conditioned medium (MSC-CM) provides a promising cell-free therapy for Alzheimer's disease (AD) mainly due to the paracrine of MSCs, but the precise mechanisms remain unclear. Studies suggests that mitochondrial dysfunction precedes the accumulation of amyloid-β plaques and neurofibrillary tangles, and involves in the onset and development of AD.


OBJECTIVE
In the present study, we evaluated the protective effects and explored the related-mitochondrial mechanisms of human umbilical cord derived MSC-CM (hucMSC-CM) in an AD model in vitro.


METHODS
To this end, an AD cellular model was firstly established by okadaic acid (OA)-treated SH-SY5Y cells, and then treated by hucMSC-CM to assess the oxidative stress, mitochondrial function, apoptosis, AD-related genes, and signaling pathways.


RESULTS
hucMSC-CM significantly deceased tau phosphorylated at Thr181 (p181-tau) level, which was increased in AD. hucMSC-CM also alleviated intracellular and mitochondrial oxidative stress in OA-treated SH-SY5Y cells. In addition, hucMSC-CM suppressed apoptosis and improved mitochondrial function in OA-treated SH-SY5Y cells. Flow cytometric analysis indicated that hucMSC-CM exerted the protective effects relying on or partly extracellular vesicle (EV) mitochondrial transfer from hucMSCs to OA-treated SH-SY5Y cells. Moreover, RNA sequencing data further demonstrated that hucMSC-CM regulated many AD-related genes, signaling pathways and mitochondrial function.


CONCLUSION
These results indicated that MSC-CM or MSC-EVs containing abundant mitochondria may provide a novel potential therapeutic approach for AD.
['Zhang|Zhihua|Z|', 'Sheng|Hongxia|H|', 'Liao|Li|L|', 'Xu|Chen|C|', 'Zhang|Ang|A|', 'Yang|Yang|Y|', 'Zhao|Long|L|', 'Duan|Lian|L|', 'Chen|Hu|H|', 'Zhang|Bin|B|']
D000544:Alzheimer Disease D017209:Apoptosis D045744:Cell Line, Tumor D002470:Cell Survival D017077:Culture Media, Conditioned D003576:Electron Transport Complex IV D004791:Enzyme Inhibitors D000067128:Extracellular Vesicles D006801:Humans D066298:In Vitro Techniques D053078:Membrane Potential, Mitochondrial D059630:Mesenchymal Stem Cells D008928:Mitochondria D009474:Neurons D019319:Okadaic Acid D018384:Oxidative Stress D017382:Reactive Oxygen Species D014470:Umbilical Cord D016875:tau Proteins
mesenchymal stem cell-conditioned medium mitochondrial dysfunction apoptosis mitochondrial transfer Alzheimer’s disease