The exosome of adipose-derived stem cells reduces beta-amyloid pathology and apoptosis of neuronal cells derived from the transgenic mouse model of Alzheimer's disease

Adipose-derived stem cells (ADSC) have a therapeutic potential for the treatment of neurodegenerative disorders such as Alzheimer's disease (AD). Exosomes are extracellular vesicles secreted from various types of cells, and stem cell-derived exosomes are known to have beneficial effects in many diseases. Many studies have suggested that amyloid beta (A beta) peptides have a pivotal role in AD progression, by mitochondrial dysfunction of neuronal cells. We examined the therapeutic potential of exosomes derived from ADSCs (ADSC-Exo) in preventing the disease phenotypes induced by the A beta cascade in an AD in vitro model. Neuronal stem cells (NSCs) from the brains of TG2576 AD mice were used to examine the effects of ADSC-Exo on AD phenotypes. NSCs from AD mice can be grown as a neurosphere and differentiated. Differentiated NSCs of TG2576 mice showed increase of A beta 42 and A beta 40 levels, and A beta 42/40 ratio. Apoptotic molecules such as p53, Bax and caspase-3 were increased and Bc12, an anti-apoptotic molecule, was decreased in AD cells compared with wild-type littermate cells. Lower viable cell population and higher necrotic cells were examined in AD neuronal cells. ELISA result showed that ADSC-Exo treatment resulted in reduced A beta 42 levels, Ap40 levels, and the A beta 42/40 ratio of AD cells. Increased apoptotic molecules, p53, Bax, pro-caspase-3 and cleaved-caspase-3, and decreased BcI-2 protein level were normalized by ADSC-Exo treatment. Flow cytometry analysis revealed that increased cell apoptosis of AD neuronal cells was reduced by ADSC-Exo. In addition, neurite growth, which is impaired by A beta in the brains of patients with AD, was augmented by ADSC-Exo treatment. Taken together, these findings implicate the disease-modulating effects of ADSC-Exo in the transgenic mice-derived AD in vitro model, and ADSC-Exo can be a therapeutic source to ameliorate the progression of A beta-induced neuronal death and AD. (C) 2018 Elsevier B.V. All rights reserved.