Establishment of universal human embryonic stem cell lines

The potential application of human embryonic stem cells in regenerative medicine using cell, tissue or organ transplantation has aroused great interest. However, HLA incompatibility between donor cells or tissues and the recipient is a primary obstacle to the use of unmatched human embryonic stem cells and their derivatives as donor 'grafts' for patient treatment without some form of immunosuppressive therapy. This is because, for most tissues, which express HLA Class I antigens, the recipient patient's immune system will recognize the difference between their and the donor's HLA types, leading to graft rejection in the absence of immunosuppressive therapy. One approach to overcoming this obstacle and enabling the use of a single or limited range of suitably selected human embryonic stem cells and their derivatives without needing extensive HLA matching is to use gene-editing technology to establish a universally or widely HLA compatible human embryonic stem cell line, thereby providing a potentially unlimited source of cells for future cell, tissue or organ transplantation. This article reviews current strategies and methods for establishing such universal or near universally HLA compatible human embryonic stem cell lines.