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Stem Cell Technology for (Epi)genetic Brain Disorders

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Neuroepigenomics in Aging and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((PMISB,volume 978))

Abstract

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).

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Acknowledgments

Renzo J. M. Riemens is supported by Maastricht University (Maastricht, The Netherlands) and Julius Maximilians University (Würzburg, Germany). Edilene Siqueira Soares is supported by the National Council for Scientific and Technological Development (CNPQ; grant n. 202074/2015-3), Ministry of Science, Brazil. The work of laboratory is supported by, among other institutions, the EU Joint Programme – Neurodegenerative Disease Research (JPND), Cellex Foundation, the Health and Science Departments of the Catalan Government (Generalitat de Catalunya), the E-Rare (ERA-Net for research programs on rare diseases), and EuroRETT (a European network on Rett syndrome, funded by the European Commission under its 6th Framework Program since 2006). Dr. Manel Esteller is an ICREA Research Professor.

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Authors and Affiliations

  1. Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Duran i Reynals Hospital, 3rd floor, Gran Via de L’Hospitalet 199-203, L’Hospitalet de Llobregat, Barcelona, Catalonia, 08908, Spain

    Renzo J. M. Riemens M.Sc, Edilene S. Soares, Manel Esteller M.D., Ph.D. & Raul Delgado-Morales Ph.D.

  2. Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, The Netherlands

    Renzo J. M. Riemens M.Sc & Raul Delgado-Morales Ph.D.

  3. Institute of Human Genetics, Julius Maximilians University, Biozentrum, Am Hubland, Wurzburg, 97074, Germany

    Renzo J. M. Riemens M.Sc

  4. Department of Physiological Sciences II, School of Medicine, University of Barcelona, Carrer de Casanova, 143, Barcelona, Catalonia, Spain

    Manel Esteller M.D., Ph.D.

  5. Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys 23, Barcelona, Catalonia, 08010, Spain

    Manel Esteller M.D., Ph.D.

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  1. Renzo J. M. Riemens M.Sc
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  2. Edilene S. Soares
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  3. Manel Esteller M.D., Ph.D.
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  4. Raul Delgado-Morales Ph.D.
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  1. Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), CATALONIA, Spain

    Raul Delgado-Morales

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Riemens, R.J.M., Soares, E.S., Esteller, M., Delgado-Morales, R. (2017). Stem Cell Technology for (Epi)genetic Brain Disorders. In: Delgado-Morales, R. (eds) Neuroepigenomics in Aging and Disease. Advances in Experimental Medicine and Biology(), vol 978. Springer, Cham. https://doi.org/10.1007/978-3-319-53889-1_23

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