dc.description.abstract | Millions of people suffer from loss or damage of tissue and organ every year due to birth defect, accident, and disease. Pluripotent stem cells (PSCs) such as human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs), are considered a promising cell source for tissue regeneration and medicine engineering, because they can differentiate into any type of cell lineages. However, histocompatibility of the transplanted cells remains a major challenge to their clinical application where human leukocyte antigen (HLA) class Ia (HLA-A, -B, -C) molecules are the primary mediators of immune reaction. Nevertheless, it takes long time to generate mature hiPSCs, and hiPSCs require to be verified that there is no gene abnormality and no contamination with viruses or other pathogens, which leads to a high cost of hiPSCs therapy, with laborious and time-consuming processes to generate patient-specific hiPSCs from somatic cells of each patient. On the other hand, the hiPSCs derived from each patient do not generate immunogenicity-related problems in general after the transplantation of differentiated cells from these hiPSCs. Consequently, it is necessary to establish patient-specific stem cell line or stem cells bank having specific HLA to avoid immune response of the patients. Here I report generation method of universal hiPSCs from multiple sources of human amniotic fluids without gene editing, which do not express HLA class Ia and class II even after their differentiation. Beside the HLA-Ia and II expression, immunomodulatory factors such as PD-L1, HLA-G, and CD 47 were also evaluated for universal hiPSCs and their original source cells of amniotic fluid stem cells by flow cytometry, because these antigens could suppress the immune reaction theoretically. The universal hiPSCs and their differentiated cells (human mesenchymal stem cells) survived even after treatment with allogenic mononuclear cells containing cytotoxic CD8+ T cells, natural killer cells, and macrophages. Additionally, I investigated the specific immune response of universal hiPSCs from immune cells such as CD8+ T cells and Natural Killer (NK) cells. Universal hiPSCs (mix) should be suitable for stem cell therapy, because universal hiPSCs can theoretically be used to treat any patients using only one cell line. | en_US |