title: Mesenchymal stem cells rescue the Alzheimer's disease cell model from cell death induced by misfolded truncated tau.
abstract: We have developed a stably transfected human cell model for Alzheimer's disease with doxycycline-inducible expression of human misfolded truncated tau protein (AT tau). We have showed that AT tau reduced the metabolic activity of the AT tau cells, slowed down cell proliferation, and induced caspase-3-independent apoptosis-like programmed cell death, tauoptosis. The aim of this study was to test the possible capability of rat mesenchymal stem cells (MSCs) to interfere with AT tau protein-induced cell death. AT tau cells after treatment with 10 μM all-trans retinoic acid were either co-cultivated with MSCs or supplemented with MSC secretome for 6 and 9 days. We found that both MSCs and MSC secretome promoted survival and increased the metabolic activity of the cells. Moreover stem cells induced cell differentiation and formation of neurites with numerous varicosities. Strikingly, treatment had no effect on tau expression suggesting that MSC induced self-protecting mechanism that prevented AT tau cells from tauoptosis. Our results showed that mesenchymal stem cells and their secretome are able to rescue the Alzheimer's disease cell model from cell death induced by misfolded truncated tau. We suggest that cell therapy may represent an alternative therapeutic avenue for treatment of human Alzheimer's disease and related tauopathies.
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Dubravska cesta 9, 845 10 Bratislava, Slovak Republic.
authors.forename: N
authors.initials: N
authors.lastname: Zilka
authors.forename: M
authors.initials: M
authors.lastname: Zilkova
authors.forename: Z
authors.initials: Z
authors.lastname: Kazmerova
authors.forename: M
authors.initials: M
authors.lastname: Sarissky
authors.forename: V
authors.initials: V
authors.lastname: Cigankova
authors.forename: M
authors.initials: M
authors.lastname: Novak
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002470:Cell Survival; D018920:Coculture Techniques; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology; D009447:Neuroblastoma; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014212:Tretinoin / Q000494:pharmacology; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D009414:Nerve Growth Factors; D016875:tau Proteins; D014212:Tretinoin; D000255:Adenosine Triphosphate; D053148:Caspase 3