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 (Abeta) 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 Abeta 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 + or - 697-fold and 692 + or - 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 Abeta peptides, respectively. Consistently, coincubation of the neuroectodermally converted MSCs with HEK-293 cells stably expressing amyloid precursor protein (APP) lead to a significant cell dose-dependent decrease of Abeta peptides. These in vitro results indicate that MSCs might be useful vehicles for delivering anti-Abeta activity depicting a causal stem cell-based therapeutic approach to treat AD.
Habisch
Hans-Jörg
HJ
Department of Neurology, University of Ulm, Ulm, Germany.
Schmid
Benjamin
B
von Arnim
Christine A F
CA
Ludolph
Albert C
AC
Brenner
Rolf
R
Storch
Alexander
A
D000293:Adolescent; D000328:Adult; D000544:Alzheimer Disease / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D018920:Coculture Techniques; D016326:Extracellular Matrix Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D015260:Neprilysin / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology; D054258:Neural Plate / Q000166:cytology*; D012333:RNA, Messenger / Q000032:analysis; D015533:Transcriptional Activation; D055815:Young Adult
D016229:Amyloid beta-Peptides; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; C429104:SPON1 protein, human; D015260:Neprilysin