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The application of patient-derived induced pluripotent stem cells for modeling and treatment of Alzheimer’s disease

Brain Science Advances 2019年第1期5卷 21-40页

作者： Fabin Han Chuanguo Liu Jin Huang Juanli Chen Chuanfei Wei Xiwen Geng Yanming Liu Dong Han Mengpeng Li The Institute for Tissue Engineering and Regenerative Medicine Liaocheng University/Liaocheng People’s HospitalShandong 252000China The Translational Research Lab for Stem Cells and Traditional Chinese Medicine Shandong University of Traditional Chinese MedicineJinanShandong 250355China Key Laboratory of Tissue Repair and Regeneration of PLA and Beijing Key Research Laboratory of Skin Injury Repair and RegenerationThe Fourth Medical Centre of PLA General HospitalBeijing 100048China Shandong Molecular Diagnostics&Cell Therapeutic Biotechnology Corporation Ji’nanShandong 250001China

Alzheimer’s disease(AD)is the most prevalent age-related neurodegenerative disease which is mainly caused by aggregated protein plaques in degenerating neurons of the brain.These aggregated protein plaques are mainly consisting of amyloidβ(Aβ)fibrils and neurofibrillary tangles(NFTs)of phosphorylated tau protein.Even though the transgenic murine models can recapitulate some of the AD phenotypes,they are not the human cell models of AD.Recent breakthrough in somatic cell reprogramming made it available to use induced pluripotent stem cells(i PSCs)for patientspecific disease modeling and autologous transplantation therapy.Human i PSCs provide alternative ways to obtain specific human brain cells of AD patients to study the molecular mechanisms and therapeutic approaches for familial and sporadic forms of AD.After differentiation into neuronal cells,i PSCs have enabled the investigation of the complex aetiology and timescale over which AD develops in human brain.Here,we first go over the pathological process of and transgenic models of AD.Then we discuss the application of i PSC for disease model and cell transplantation.At last the challenges and future applications of i PSCs for AD will be summarized to propose cell-based approaches for the treatment of this devastating disorder.

关键词： Alzheimer’s disease(AD) induced pluripotent stem cell(iPSC) amyloid-beta plaque(Aβplaque) neural stem cell(NSC) transplantation mutation

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