Three Dimensional Human Neuro-Spheroid Model of Alzheimer’s Disease Based on Differentiated Induced Pluripotent Stem Cells
Publication Date
September 29, 2016
Journal
PLOS ONE
Authors
Han Kyu Lee, Clara Velazquez Sanchez, Mei Chen, Peter J. Morin, et al
Volume
11
Issue
9
Pages
e0163072
DOI
https://dx.plos.org/10.1371/journal.pone.0163072
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0163072
Scopus
84991717019
Mendeley
http://www.mendeley.com/research/three-dimensional-human-neurospheroid-model-alzheimers-disease-based-differentiated-induced-pluripot
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Mendeley | Further Information

{"title"=>"Three Dimensional Human Neuro-Spheroid Model of Alzheimer’s Disease Based on Differentiated Induced Pluripotent Stem Cells", "type"=>"journal", "authors"=>[{"first_name"=>"Han-Kyu", "last_name"=>"Lee"}, {"first_name"=>"Clara", "last_name"=>"Velazquez Sanchez"}, {"first_name"=>"Mei", "last_name"=>"Chen"}, {"first_name"=>"Peter J.", "last_name"=>"Morin"}, {"first_name"=>"John M.", "last_name"=>"Wells"}, {"first_name"=>"Eugene B.", "last_name"=>"Hanlon"}, {"first_name"=>"Weiming", "last_name"=>"Xia"}], "year"=>2016, "source"=>"PLOS ONE", "identifiers"=>{"sgr"=>"84991717019", "doi"=>"10.1371/journal.pone.0163072", "pui"=>"612795444", "pmid"=>"27684569", "isbn"=>"19326203", "issn"=>"1932-6203"}, "id"=>"3a79ec63-d6e6-3029-acdc-07f73b39fcbc", "abstract"=>"The testing of candidate drugs to slow progression of Alzheimer's disease (AD) requires clinical trials that are lengthy and expensive. Efforts to model the biochemical milieu of the AD brain may be greatly facilitated by combining two cutting edge technologies to generate three-dimensional (3D) human neuro-spheroid from induced pluripotent stem cells (iPSC) derived from AD subjects. We created iPSC from blood cells of five AD patients and differentiated them into 3D human neuronal culture. We characterized neuronal markers of our 3D neurons by immunocytochemical staining to validate the differentiation status. To block the generation of pathologic amyloid β peptides (Aβ), the 3D-differentiated AD neurons were treated with inhibitors targeting β-secretase (BACE1) and γ-secretases. As predicted, both BACE1 and γ-secretase inhibitors dramatically decreased Aβ generation in iPSC-derived neural cells derived from all five AD patients, under standard two-dimensional (2D) differentiation conditions. However, BACE1 and γ-secretase inhibitors showed less potency in decreasing Aβ levels in neural cells differentiated under 3D culture conditions. Interestingly, in a single subject AD1, we found that BACE1 inhibitor treatment was not able to significantly reduce Aβ42 levels. To investigate underlying molecular mechanisms, we performed proteomic analysis of 3D AD human neuronal cultures including AD1. Proteomic analysis revealed specific reduction of several proteins that might contribute to a poor inhibition of BACE1 in subject AD1. To our knowledge, this is the first iPSC-differentiated 3D neuro-spheroid model derived from AD patients' blood. Our results demonstrate that our 3D human neuro-spheroid model can be a physiologically relevant and valid model for testing efficacy of AD drug.", "link"=>"http://www.mendeley.com/research/three-dimensional-human-neurospheroid-model-alzheimers-disease-based-differentiated-induced-pluripot", "reader_count"=>54, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Researcher"=>10, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>2, "Student > Master"=>14, "Student > Bachelor"=>9, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Researcher"=>10, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>2, "Student > Master"=>14, "Student > Bachelor"=>9, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>7, "Unspecified"=>5, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>12, "Materials Science"=>1, "Agricultural and Biological Sciences"=>16, "Medicine and Dentistry"=>1, "Neuroscience"=>7, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1, "Psychology"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>7}, "Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>7}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Psychology"=>{"Psychology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>12}, "Unspecified"=>{"Unspecified"=>5}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United Kingdom"=>1, "Germany"=>1}, "group_count"=>5}

CrossRef

Scopus | Further Information

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