title: The quest for an effective and safe personalized cell therapy using epigenetic tools.
abstract: In the presence of different environmental cues that are able to trigger specific responses, a given genotype has the ability to originate a variety of different phenotypes. This property is defined as plasticity and allows cell fate definition and tissue specialization. Fundamental epigenetic mechanisms drive these modifications in gene expression and include DNA methylation, histone modifications, chromatin remodeling, and microRNAs. Understanding these mechanisms can provide powerful tools to switch cell phenotype and implement cell therapy. Environmentally influenced epigenetic changes have also been associated to many diseases such as cancer and neurodegenerative disorders, with patients that do not respond, or only poorly respond, to conventional therapy. It is clear that disorders based on an individual's personal genomic/epigenomic profile can rarely be successfully treated with standard therapies due to genetic heterogeneity and epigenetic alterations and a personalized medicine approach is far more appropriate to manage these patients. We here discuss the recent advances in small molecule approaches for personalized medicine, drug targeting, and generation of new cells for medical application. We also provide prospective views of the possibility to directly convert one cell type into another, in a safe and robust way, for cell-based clinical trials and regenerative medicine.
authors.affiliation: Laboratory of Biomedical Embryology, Unistem, Università degli Studi di Milano, Via Celoria 10, 20133 Milan, Italy.
authors.forename: T A L
authors.initials: TA
authors.lastname: Brevini
authors.affiliation: Laboratory of Biomedical Embryology, Unistem, Università degli Studi di Milano, Via Celoria 10, 20133 Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Pennarossa
authors.affiliation: Laboratory of Biomedical Embryology, Unistem, Università degli Studi di Milano, Via Celoria 10, 20133 Milan, Italy.
authors.forename: E F M
authors.initials: EF
authors.lastname: Manzoni
authors.affiliation: Laboratory of Biomedical Embryology, Unistem, Università degli Studi di Milano, Via Celoria 10, 20133 Milan, Italy.
authors.forename: C E
authors.initials: CE
authors.lastname: Gandolfi
authors.affiliation: Laboratory of Biomedical Embryology, Unistem, Università degli Studi di Milano, Via Celoria 10, 20133 Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Zenobi
authors.affiliation: Laboratory of Biomedical Embryology, Unistem, Università degli Studi di Milano, Via Celoria 10, 20133 Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Gandolfi
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D016503:Drug Delivery Systems; D044127:Epigenesis, Genetic; D018740:Genetic Heterogeneity; D006801:Humans; D057285:Precision Medicine / Q000379:methods*; D054852:Small Molecule Libraries / Q000494:pharmacology* / Q000627:therapeutic use; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects
chemical_list: D054852:Small Molecule Libraries
keywords: Epigenetic conversion; Epigenetics; Molecular medicine; Personalized medicine; Regenerative medicine; Small molecules; iPSCs