title: The safety of human pluripotent stem cells in clinical treatment.
abstract: Human pluripotent stem cells (hPSCs) have practically unlimited proliferation potential and a capability to differentiate into any cell type in the human body. Since the first derivation in 1998, they have been an attractive source of cells for regenerative medicine. Numerous ethical, technological, and regulatory complications have been hampering hPSC use in clinical applications. Human embryonic stem cells (ESCs), parthenogenetic human ESCs, human nuclear transfer ESCs, and induced pluripotent stem cells are four types of hPSCs that are different in many clinically relevant features such as propensity to epigenetic abnormalities, generation methods, and ability for development of autologous cell lines. Propensity to genetic mutations and tumorigenicity are common features of all pluripotent cells that complicate hPSC-based therapies. Several recent advances in methods of derivation, culturing, and monitoring of hPSCs have addressed many ethical concerns and technological challenges in development of clinical-grade hPSC lines. Generation of banks of such lines may be useful to minimize immune rejection of hPSC-derived allografts. In this review, we discuss different sources of hPSCs available at the moment, various safety risks associated with them, and possible solutions for successful use of hPSCs in the clinic. We also discuss ongoing clinical trials of hPSC-based treatments.
authors.affiliation: a Division of Cardiothoracic Surgery and Anesthesiology, Department of Molecular Medicine and Surgery , Karolinska Institutet, Karolinska University Hospital , 171 77 Stockholm , Sweden.
authors.forename: Oscar E
authors.initials: OE
authors.lastname: Simonson
authors.forename: Anna
authors.initials: A
authors.lastname: Domogatskaya
authors.forename: Pavel
authors.initials: P
authors.lastname: Volchkov
authors.forename: Sergey
authors.initials: S
authors.lastname: Rodin
mesh_terms: D018070:Biological Specimen Banks / Q000941:ethics; D018929:Cell Culture Techniques; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002986:Clinical Trials as Topic; D044127:Epigenesis, Genetic; D006084:Graft Rejection / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000276:immunology / Q000637:transplantation; D044968:Regenerative Medicine; D057905:Stem Cell Research / Q000941:ethics* / Q000331:legislation & jurisprudence
chemical_list: D006680:HLA Antigens
keywords: Epigenetic aberrations; good manufacturing practices; human embryonic stem cells (hESCs); human induced pluripotent stem cells (hiPSCs); human nuclear transfer embryonic stem cells (NT-ESCs); human pluripotent stem cells (hPSCs); immune rejection; parthenogenetic human embryonic stem cells (phESCs); stem cell bank; tumorigenicity