Most disease-modifying therapeutic approaches in Alzheimer's disease (AD) aim to reduce the accumulation of neurotoxic amyloid-beta (Aβ) peptides as a hallmark of AD pathogenesis. Here we report the in vitro basis for a potential autologous stem cell-based strategy for widespread delivery of enzymatic activities against Aβ formation in the brain. We detected the functional induction of two genes upon neuroectodermal conversion of human adult mesenchymal stem cells (MSCs), namely F-spondin and neprilysin (CD10), with a 4,992 ± 697-fold and 692 ± 226-fold increase of mRNA levels in converted cells compared to MSCs, respectively (n = 3; P < 0.01). These genes are known to be involved in the formation and degradation of Aβ peptides, respectively. Consistently, co-incubation of the neuroectodermally converted MSCs with HEK-293 cells stably expressing amyloid precursor protein (APP) lead to a significant cell dose-dependent decrease of Aβ peptides. These in vitro results indicate that MSCs might be useful vehicles for delivering anti-Aβ activity depicting a causal stem cell-based therapeutic approach to treat AD.
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