title: Neuronal differentiation of human mesenchymal stromal cells increases their resistance to Aβ42 aggregate toxicity.
abstract: Cell therapy is a promising approach for the treatment of neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. However, the presence of toxic aggregates in tissue raises the question of whether grafted stem cells are susceptible to amyloid toxicity before they differentiate into mature neurons. To address this question, we investigated the relative vulnerability of human mesenchymal stromal cells and their neuronally differentiated counterparts to Aβ(42) oligomers and whether susceptibility correlates with membrane GM1 content, a key player in oligomer toxicity. We found that our cell model was highly susceptible to aggregate toxicity, whereas neuronal differentiation induced resistance to amyloid species. This data correlated well with the content of membrane GM1, levels of which decreased considerably in differentiated cells. These findings extend our knowledge of stem cell vulnerability to amyloid species, which remains a controversial issue, and confirm that amyloid-GM1 interactions play an important role in cell impairment.
authors.affiliation: Department of Biochemical Sciences, and Research Centre on the Molecular Basis of Neurodegeneration (CIMN), Florence, Italy. cristina.cecchi@unifi.it
authors.forename: Cristina
authors.initials: C
authors.lastname: Cecchi
authors.forename: Elisa
authors.initials: E
authors.lastname: Evangelisti
authors.forename: Roberta
authors.initials: R
authors.lastname: Cascella
authors.forename: Mariagioia
authors.initials: M
authors.lastname: Zampagni
authors.forename: Susanna
authors.initials: S
authors.lastname: Benvenuti
authors.forename: Paola
authors.initials: P
authors.lastname: Luciani
authors.forename: Cristiana
authors.initials: C
authors.lastname: Deledda
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cellai
authors.forename: Daniel
authors.initials: D
authors.lastname: Wright
authors.forename: Riccardo
authors.initials: R
authors.lastname: Saccardi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Peri
authors.forename: Massimo
authors.initials: M
authors.lastname: Stefani
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D005677:G(M1) Ganglioside / Q000633:toxicity; D006801:Humans; D008563:Membrane Lipids / Q000633:toxicity; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity*
chemical_list: D016229:Amyloid beta-Peptides; D008563:Membrane Lipids; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D005677:G(M1) Ganglioside