title: A scalable approach to prevent teratoma formation of human embryonic stem cells.
abstract: As the renewable source of all cell types in the body, human embryonic stem cells (hESCs) hold great promise for human cell therapy. However, one major bottleneck that hinders the clinic application of hESCs is that hESCs remaining with their differentiated derivatives pose cancer risk by forming teratomas after transplantation. NANOG is a critical pluripotency factor specifically expressed in hESCs but rarely in their differentiated derivatives. By introducing a hyperactive variant of herpes simplex virus thymidine kinase gene into the 3'-untranslated region of the endogenous NANOG gene of hESCs through homologous recombination, we developed a safe and highly scalable approach to efficiently eliminate the teratoma risk associated with hESCs without apparent negative impact on their differentiated cell types. As thymidine kinase is widely used in human gene therapy trials and is the therapeutic target of U. S. Food and Drug Administration-approved drugs, our strategy could be effectively applied to the clinic development of hESC-based human cell therapy.
authors.affiliation: Division of Biological Sciences, University of California at San Diego, La Jolla, California 92093-0322, USA.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Rong
authors.forename: Xuemei
authors.initials: X
authors.lastname: Fu
authors.forename: Meiyan
authors.initials: M
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000473:pathology; D041722:Genes, Transgenic, Suicide; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051379:Mice; D000071317:Nanog Homeobox Protein; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013724:Teratoma / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D013937:Thymidine Kinase / Q000096:biosynthesis* / Q000235:genetics; D014764:Viral Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D014764:Viral Proteins; D013937:Thymidine Kinase