Advances in cellular reprogramming: moving toward a reprieve from immunogenicity.
Somatic cell nuclear reprogramming is opening new doors for the modeling of human disease phenotypes in vitro, the identification of novel therapeutic compounds and diagnostic factors as well as future autologous cell replacement therapies. Despite the potential that reprogramming technologies bring, there are remaining concerns preventing their broad application in the short-term. One of them is the safety concern associated with the use of stem cell derivatives, those generated by reprogramming or even when embryonic stem cells are employed. Here we summarize the current knowledge in the field of stem cells and reprogramming with a particular focus on the pitfalls preventing rapid translation of stem cell technologies into the clinic. We discuss the most recent findings on immunogenicity and tumorigenicity of reprogrammed cells. We additionally provide an overview on the potential applications that reprogramming approaches might bring to the immunological field and elaborate on the use of induced pluripotent stem cells (iPSCs) with pre-arranged immune receptors for the development of future immunotherapeutic approaches. The use of reprogramming approaches can represent and provide groundbreaking strategies previously unachievable for stem cell engineering aimed at modulating immune responses. In summary, we provide an overview on the different topics related to the use of stem cells and highlight the most provocative, yet perhaps currently underappreciated, aspect of combining immunological and reprogramming strategies for the treatment of human disease.
Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Thomas F
TF
Gallegos
Ignacio
I
Sancho-Martinez
Juan Carlos
JC
Izpisua Belmonte
D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D065150:Cellular Reprogramming / Q000276:immunology; D053595:Embryonic Stem Cells / Q000276:immunology*; D015316:Genetic Therapy; D006801:Humans; D007109:Immunity / Q000235:genetics; D057026:Induced Pluripotent Stem Cells / Q000276:immunology*; D009369:Neoplasms / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D011183:Postoperative Complications / Q000276:immunology* / Q000517:prevention & control; D015202:Protein Engineering; D011946:Receptors, Antigen / Q000235:genetics / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000378:metabolism; D055746:Stage-Specific Embryonic Antigens / Q000276:immunology; D033581:Stem Cell Transplantation
D011946:Receptors, Antigen; D051192:Receptors, Pattern Recognition; D055746:Stage-Specific Embryonic Antigens
Immunogenicity; Lineage conversion; Reprogramming; Tumorigenicity; iPSC