Mesenchymal stem cells can prevent alterations in behavior and neurogenesis induced by Aß25-35 administration.
Mesenchymal stem cells (MSCs) are known to enhance neurogenesis in the dentate gyrus, as well as to modulate immune cell activity and inflammation. Easily obtained and expanded from the bone marrow and other tissues, MSCs have been proposed as candidates for stem cell therapy in various neurodegenerartive diseases. In the present study, we sought to explore these therapeutic properties of MSC on Aß25-35-induced pathology when coadministered together. Apparently, coadministration of MSC prevented mild cognitive deficits observed following Aß administration alone, by promoting microglial activation and rapid clearance of injected Aß aggregates. Surprisingly, increased hippocampal neurogenesis was observed in the Aß-injected animals and was normal in MSC-coadministered animals just as in control animals. The observed increase in neurogenesis can be explained as a compensating mechanism responsible for the mild and temporary cognitive deficits observed in the Morris water maze assay in Aß-injected animals. Interestingly, MSC engrafted not only to the hippocampus but were also detected in the choroid plexus. We thus conclude that MSC may act in multiple pathways to protect the CNS from Aß pathology, while neurogenesis is a possible compensating mechanism; it is not always activated by MSC, which in turn may interact with local immune cells to regulate Aß accumulation.
Department of Molecular Biology, Laboratory of Stem Cell Research, Milken Campus, Ariel University, Ariel, 40700, Israel.
Keren Nicole
KN
Hamisha
Matanel
M
Tfilin
Joseph
J
Yanai
Gadi
G
Turgeman
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D002831:Choroid Plexus / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control* / Q000628:therapy; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018782:Maze Learning; D008568:Memory; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis; D010446:Peptide Fragments / Q000633:toxicity*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35)