Bystander effect of adipose-derived stem cell extracts on neurogenesis, neuroprotection and β-amyloid claearing

Abstract

Stem cell based therapy is regarded as a promising treatment for neurodegenerative disorders, such as Alzheimers disease (AD). Among stem cells, adipose-derived stem cells (ASCs) are a feasible source of stem cells for use in clinical applications. Recent studies have shown that stem cells have a therapeutic potential for use in treatment of various illnesses through secretion of beneficial factors; this function of stem cells is called the bystander effect. A bystander effect of stem cells needs to be confirmed since its effects on neurological disorders, including AD, have not been clearly elucidated. Amyloid plaques and neurofibrillary tangles are representative hallmarks in AD, and there are invisible changes, including β-amyloid induced impaired neurogenesis, neuronal death, and shortage of neurotrophic factors in the brain. Current objectives of stem cell therapy in AD are to promote endogenous neurogenesis and to protect neurons from disease progression using factors released by stem cells. We used whole cell extracts containing secretion factors of human adipose-derived stem cells to examine their therapeutic and preventive effects in vitro and in vivo model. To examine effects of ASCs-extracts in neural stem cells (NSCs), we investigated effects on mouse subventricular zone-derived cultured NSCs. As a result, ASCs-extracts were found to induce proliferation of NSCs under conditions of growth factor deprivation and to promote the differentiation process in NSCs. In addition, we observed that ASCs-extracts attenuated β-amyloid toxicity and oxidative stress in vitro in neuronal cells. In an β-amyloid injected mouse model, amelioration of behavioral deficit and amyloid plaque burden was observed by administration of ASCs-extracts. Findings from our studies strongly suggest that use of ASCs-extracts could result in improved memory deficit of AD via augmentation of neurogenesis, neuroprotection and β-amyloid clearing. In conclusion, ASCs-extracts could be a therapeutic candidate for use in treatment of AD and a good alternative to ASCs injection therapy.