Stem Cell Technology for (Epi)genetic Brain Disorders.
Despite the enormous efforts of the scientific community over the years, effective therapeutics for many (epi)genetic brain disorders remain unidentified. The common and persistent failures to translate preclinical findings into clinical success are partially attributed to the limited efficiency of current disease models. Although animal and cellular models have substantially improved our knowledge of the pathological processes involved in these disorders, human brain research has generally been hampered by a lack of satisfactory humanized model systems. This, together with our incomplete knowledge of the multifactorial causes in the majority of these disorders, as well as a thorough understanding of associated (epi)genetic alterations, has been impeding progress in gaining more mechanistic insights from translational studies. Over the last years, however, stem cell technology has been offering an alternative approach to study and treat human brain disorders. Owing to this technology, we are now able to obtain a theoretically inexhaustible source of human neural cells and precursors in vitro that offer a platform for disease modeling and the establishment of therapeutic interventions. In addition to the potential to increase our general understanding of how (epi)genetic alterations contribute to the pathology of brain disorders, stem cells and derivatives allow for high-throughput drugs and toxicity testing, and provide a cell source for transplant therapies in regenerative medicine. In the current chapter, we will demonstrate the validity of human stem cell-based models and address the utility of other stem cell-based applications for several human brain disorders with multifactorial and (epi)genetic bases, including Parkinson's disease (PD), Alzheimer's disease (AD), fragile X syndrome (FXS), Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Rett syndrome (RTT).
['Riemens|Renzo J M|RJM|', 'Soares|Edilene S|ES|', 'Esteller|Manel|M|', 'Delgado-Morales|Raul|R|']
D000818:Animals D001927:Brain Diseases D016380:Brain Tissue Transplantation D004195:Disease Models, Animal D004353:Drug Evaluation, Preclinical D044127:Epigenesis, Genetic D016332:Fetal Tissue Transplantation D005544:Forecasting D030342:Genetic Diseases, Inborn D006801:Humans D057026:Induced Pluripotent Stem Cells D009419:Nerve Tissue Proteins D019636:Neurodegenerative Diseases D044968:Regenerative Medicine D057905:Stem Cell Research D033581:Stem Cell Transplantation D013234:Stem Cells
Stem cells Brain disorders Disease modeling Regenerative medicine Drug screening Epigenetics iPSCs