AUTHOR=Sackett Sara D. , Kaplan Samuel J. , Mitchell Samantha A. , Brown Matthew E. , Burrack Adam L. , Grey Shane , Huangfu Danwei , Odorico Jon TITLE=Genetic Engineering of Immune Evasive Stem Cell-Derived Islets JOURNAL=Transplant International VOLUME=35 YEAR=2022 URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2022.10817 DOI=10.3389/ti.2022.10817 ISSN=1432-2277 ABSTRACT=

Genome editing has the potential to revolutionize many investigative and therapeutic strategies in biology and medicine. In the field of regenerative medicine, one of the leading applications of genome engineering technology is the generation of immune evasive pluripotent stem cell-derived somatic cells for transplantation. In particular, as more functional and therapeutically relevant human pluripotent stem cell-derived islets (SCDI) are produced in many labs and studied in clinical trials, there is keen interest in studying the immunogenicity of these cells and modulating allogeneic and autoimmune immune responses for therapeutic benefit. Significant experimental work has already suggested that elimination of Human Leukocytes Antigen (HLA) expression and overexpression of immunomodulatory genes can impact survival of a variety of pluripotent stem cell-derived somatic cell types. Limited work published to date focuses on stem cell-derived islets and work in a number of labs is ongoing. Rapid progress is occurring in the genome editing of human pluripotent stem cells and their progeny focused on evading destruction by the immune system in transplantation models, and while much research is still needed, there is no doubt the combined technologies of genome editing and stem cell therapy will profoundly impact transplantation medicine in the future.