ヒト神経細胞と神経変性疾患 ―iPS、iN細胞の未来― Human Induced Neuronal Cells and Neurodegenerative Diseases -The Next Stage of iPS and iN Cells in Neuroscience Field-
S3-1-3-1 Presentation Cancelled	S3-1-3-2 ヒト神経細胞を用いたアルツハイマー病病態解析 Human induced neuron from Alzheimer's disease patients display disease phenotype ○藤田亮介1 ○Ryousuke Fujita1, Asa Abeliovich1 コロンビア大学　病理学・細胞生物学分野1 Departments of Pathology and Cell biology, Columbia University1 Now, the technology of iPS and direct conversion are able to use human neuron in neurodegenerative disease model. Alzheimer's disease is the most common cause of age-associated dementia, and its prevalence is predicted to increase rapidly as the world population ages. Recently, to pursue cellular mechanism of familial and sporadic Alzheimer disease (FAD and SAD), we generate human induced neurons (hiN) by direct conversion of skin fibroblasts from FAD and SAD patients. hiN cells from FAD and SAD exhibit altered processing and localization of amyloid precursor protein (APP) and changes in production of Aβ, relative to the patient fibroblast or to hiN cell from unaffected individuals. Taken together, our findings demonstrate directed conversion of human fibroblasts to a neuronal phenotype and reveal cell type-selective pathology in hiN cells derived from AD patients. In the end, we would like to discuss the ability and utility of hiN cell model for the therapy of AD or other neurodegenerative diseases in this symposium.
S3-1-3-3 パーキンソン病に対する幹細胞移植治療への挑戦 Challenges towards stem cell therapy for Parkinson's disease ○高橋淳1 ○Jun Takahashi1 京都大学　iPS細胞研究所　臨床応用研究部門1 Department of Clinical Application, Center for iPS Cell and Application, Kyoto University1 Considering cell therapy with embryonic stem cells (ESCs) for Parkinson's disease into clinical application, formation of a graft cell-derived tumor is a major concern about safety of the therapy. We and others have reported transplantation of monkey ESC-derived neural cells or human neural progenitor cells into the brain of monkey Parkinson's disease models, but tumor formation in primates has never been studied. Thus, it is important to determine whether human ESCs are able to form tumors in the primate brain, and to examine the characteristics of the tumors. To answer this question, we compared the growth of cells with different stages of pre-differentiation: neural cell preparations, with or without undifferentiated ESCs. We induced neural progenitor cells from human ESC lines (KhES-1, -2) by the modified SDIA (stromal cell-derived inducing activity) method for 14 to 42 days. Then, the cells were transplanted into the bilateral striatum of monkey models of Parkinson's disease. In this talk, we will show that residual undifferentiated cells expressing ESC markers can proliferate as long as nine months and form tumors in the monkey brain. No signs of malignancy were found, and the tumors mainly consisted of immature neural cells with no teratomatous components. In contrast, cell preparations with sufficient maturation for 42 days did not form tumors, and survived as dopaminergic (DA) neurons proved by immunofluorescence and PET studies. In addition, the monkeys showed behavioral improvement from 3 to 12 months. We also generated DA neurons from human induced pluripotent stem cells (iPSCs) without feeder cells, and confirmed that these cells could survive as long as 6 months in the monkey brain. These results support the idea that human ESCs/iPSCs, after appropriate differentiation towards DA neurons, can be used as a source for cell replacement therapy of Parkinson's disease.	S3-1-3-4 iPS細胞をもちいた高齢発症神経変性疾患研究の進展 Advances in induced pluripotent stem cell research for age-related neurodegenerative diseases ○伊東大介1, 鈴木則宏1 ○Daisuke Ito1, Norihiro Suzuki1 慶應義塾大学医学部神経内科1 Department of Neurology, Keio University School of Medicine1 Progress in molecular biology has led to steady progress in the elucidation of the pathological mechanisms of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). In contrast, progress in the development of disease-modifying therapies has been slower, and there are currently no treatments available to even delay the progression of neurodegenerative diseases. Ideally, research into the development of treatments should involve disease-specific tissues obtained from patients. However, in the case of neurological diseases, it is difficult to perform highly invasive brain biopsies from living persons, or to obtain brain tissues suitable for biochemical analysis from autopsy specimens due to rapid postmortem changes. In 2006, Takahashi et al. directly reprogrammed somatic cells into induced pluripotent stem cells (iPSCs), thereby opening a novel approach to disease modeling and drug discovery. The availability of iPSCs is particularly advantageous for research involving neurological diseases, since it is difficult to obtain affected tissues from living patients. A new era in in vitro modeling of neurodegenerative diseases recently began when iPSC technology was used to recapitulate the phenotypes of several late-onset neurodegenerative diseases, such as AD and PD, in which clinical signs appear on or after presenium. These findings show that the phenotype of neurodegenerative disorder can be recapitulated in iPSCs described neuronal cells which are reflected the early developmental stages, indicating cellular abnormality exist from prenatal period despite late-onset diseases.In this presentation, we will talk about the accelerating progress in iPS cell research for age-related neurodegenerative disorders, and discuss the possibilities of clarification of the mechanisms underlying the neurodegenerative disorder, and discovery of new drugs.
S3-1-3-5 iPS細胞技術を用いた神経変性疾患の研究 Neurodegenerative disease-specific iPS cell research ○井上治久1,2 ○Haruhisa Inoue1,2 京都大学iPS 細胞研究所　臨床応用研究部門　神経変性研究チーム1 Center for iPS Cell Research and Application (CiRA), Kyoto University1, CREST, Japan Science and Technology Agency, Kawaguchi, Japan2 Molecular-biological analyses are advancing our understanding of intractable neurodegenerative diseases, but radical care is still to be established. iPSC technology is expected to provide innovative tools for disease modeling, using differentiated cells from neurodegenerative-disease patient-derived iPSCs. This disease-modeling approach should also augment our understanding of disease progression and biology in specific cell types, possibly leading to a redefining of the known aspects of diseases. In regard to the disease modeling of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease, we aim to analyze cellular and molecular phenotypes of motor neurons using patient-specific iPSCs with the perspective of translating these findings into developing methods of treatment and/or prevention of the diseases. In this symposium, I will talk about our recent progress, and discuss our comprehensive understanding of the diseases.	S3-1-3-6 iPS細胞技術を用いた小児神経疾患の病態解析 Modeling pediatric neurological diseases using iPSCs technologies ○岡野栄之1 ○Hideyuki Okano1 慶應義塾大学医学部生理学教室1 Department of Physiology, Keio University School of Medicine1 It came to be realized that diseases model mice do not always recapitulate the pathophysiology of human diseases. This is true particularly in neurological disorders. It is extremely difficult to investigate what is taking place in vivo at the onset of the diseases. Furthermore, there is a low accessibility to the pathological foci in the brain. Based on these factors, investigation of pathogenesis of human neurological diseases is extremely difficult, although there is a rapid progress in the human genome research using next generation sequencer. Thus, it is reasonable that there is an increasing interest in modeling diseases by taking advantages of induced pluripotent stem cells (iPSCs)-technologies. So far, we have established iPSCs from somatic cells of various neurological diseases, which can be categorized into i) diseases caused by disordered gene regulation, ii) diseases with structural abnormalities of the nervous systems, iii) diseases with abnormal neural functions, iv) diseases with abnormal metabolic pathways and v) late onset neurological diseases including Parkinson diseases and Alzheimer diseases. We found that characterization of iPS cells derived from neurological disorders could recapitulate the diseases processes at least partially. In this symposium, I will talk about our updated results on pediatric neurological disorders.

上部に戻る

前に戻る