Efficient Processing of Alzheimer's Disease Amyloid-Beta Peptides by Neuroectodermally Converted Mesenchymal Stem Cells

Most disease-modifying therapeutic approaches in Alzheimer's disease (AD) aim to reduce the accumulation of neurotoxic amyloid-beta (A beta) 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 A beta 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 A beta 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 A beta peptides. These in vitro results indicate that MSCs might be useful vehicles for delivering anti-A beta activity depicting a causal stem cell-based therapeutic approach to treat AD.