title: Clinical potential of human-induced pluripotent stem cells : Perspectives of induced pluripotent stem cells.
abstract: The recent establishment of induced pluripotent stem (iPS) cells promises the development of autologous cell therapies for degenerative diseases, without the ethical concerns associated with human embryonic stem (ES) cells. Initially, iPS cells were generated by retroviral transduction of somatic cells with core reprogramming genes. To avoid potential genotoxic effects associated with retroviral transfection, more recently, alternative non-viral gene transfer approaches were developed. Before a potential clinical application of iPS cell-derived therapies can be planned, it must be ensured that the reprogramming to pluripotency is not associated with genome mutagenesis or epigenetic aberrations. This may include direct effects of the reprogramming method or "off-target" effects associated with the reprogramming or the culture conditions. Thus, a rigorous safety testing of iPS or iPS-derived cells is imperative, including long-term studies in model animals. This will include not only rodents but also larger mammalian model species to allow for assessing long-term stability of the transplanted cells, functional integration into the host tissue, and freedom from undifferentiated iPS cells. Determination of the necessary cell dose is also critical; it is assumed that a minimum of 1 billion transplantable cells is required to achieve a therapeutic effect. This will request medium to long-term in vitro cultivation and dozens of cell divisions, bearing the risk of accumulating replication errors. Here, we review the clinical potential of human iPS cells and evaluate which are the most suitable approaches to overcome or minimize risks associated with the application of iPS cell-derived cell therapies.
authors.affiliation: Animal Physiology and Reproduction Division, ICAR-Central Institute for Research on Buffaloes, Hisar, Haryana, 125001, India.
authors.forename: Dharmendra
authors.initials: D
authors.lastname: Kumar
authors.affiliation: NCVTCC, ICAR-National Research Centre on Equines, Hisar, Haryana, 125001, India.
authors.forename: Taruna
authors.initials: T
authors.lastname: Anand
authors.affiliation: Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Federal Reseach Institute for Animal Health, Höltystr. 10, 31535, Neustadt, Germany. wilfried.kues@fli.de.
authors.forename: Wilfried A
authors.initials: WA
authors.lastname: Kues
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000637:transplantation*; D018570:Risk Assessment; D012307:Risk Factors; D033581:Stem Cell Transplantation
keywords: Cell fate; Cell therapy; Cellular reprogramming; Genotoxicity; Integrational mutagenesis; Ontogenesis; Transposition