Alzheimer’s disease (AD) is characterized by the accumulation of amyloid plaques and neurofibrillary tangles accompanied by cognitive dysfunction. The aim of the present study was to elucidate preventive and therapeutic potential of stem cells for AD. Among stem cells, autologous human adipose-derived stem cells (hASCs) elicit no immune rejection responses, tumorigenesis, or ethical problems. We found that intravenously transplanted hASCs passed through the BBB and migrated into the brain. The learning, memory and pathology in an AD mouse model (Tg2576) mice greatly improved for at least 4 months after intravenous injection of hASC. The number of amyloid plaques and Aβ levels decreased significantly in the brains of hASC-injected Tg mice compared to those of Tg-sham mice. Here, we first report that intravenously or intracerebrally transplanted hASCs significantly rescues memory deficit and neuropathology, in the brains of Tg mice by up-regulating IL-10 and VEGF and be a possible use for the prevention and treatment of AD.
The use of non-chemical methods to differentiate stem cells has attracted
researchers from multiple disciplines, including the engineering and the
biomedical fields. No doubt, growth factor based methods are still the most
dominant of achieving some level of proliferation and differentiation control -
however, chemical based methods are still limited by the quality, source, and
amount of the utilized reagents. Well-defined non-chemical methods to
differentiate stem cells allow stem cell scientists to control stem cell biology
by precisely administering the pre-defined parameters, whether they are
structural cues, substrate stiffness, or in the form of current flow. We have
developed a culture system that allows normal stem cell growth and the option of
applying continuous and defined levels of electric current to alter the cell
biology of growing cells. This biphasic current stimulator chip employing ITO
electrodes generates both positive and negative currents in the same culture
chamber without affecting surface chemistry. We found that biphasic electrical
currents (BECs) significantly increased the proliferation of fetal neural stem
cells (NSCs). Furthermore, BECs also promoted the differentiation of fetal NSCs
into neuronal cells, as assessed using immunocytochemistry. Our results clearly
show that BECs promote both the proliferation and neuronal differentiation of
fetal NSCs. It may apply to the development of strategies that employ NSCs in
the treatment of various neurodegenerative diseases, such as Alzheimer's
and Parkinson's diseases.
Amyloid beta peptide (Abeta) is a neurotoxic metabolic product of the amyloid precursor protein (APP). Abeta is strongly implicated in the pathology of Alzheimer's disease (AD) and can be formed intracellularly. In this study, we show that the addition of Abeta to isolated mouse brain mitochondria can directly induce cytochrome c (Cyt c) release and mitochondrial swelling, which were partially inhibited by cyclosporin A (CsA). These results suggest that the Abetaaccumulated intracellularly by APP processing might exert neurotoxicity by interacting with mitochondria and inducing mitochondrial swelling and release of Cyt c, which activates caspase-3 and finally can lead to apoptosis in neuronal cells and to neurodegeneration in AD.
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