Characteristic Expression of Major Histocompatibility Complex and Immune Privilege Genes in Human Pluripotent Stem Cells and Their Derivatives

Cell Transplantation

Article

Bor-Sheng Ko¹  Shiu-Huey Chou²  Ming-Shan Chiang³  Mei-Jou Chen³  Wen-Hsi Chou³  Hsin-Fu Chen⁴  Hong-Nerng Ho⁵  Hsiang-Po Huang⁶  Chun-Ying Yu⁷  Hung-Chih Kuo⁷ 

[1] Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Institute of Cellular and Systemic Medicine, National Health Research Institute, Miaoli County, Taiwan;Department of Life Science, Fu-Jen Catholic University, Taipei, Taiwan;Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University, Taipei, Taiwan;Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University, Taipei, Taiwan; Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan;Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University, Taipei, Taiwan; Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan;Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan;Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan;Institute of Cellular and Organismic Biology and Genomics Research Center, Academia Sinica, Taipei, Taiwan;

关键词: Pluripotent stem cells;    Embryonic stem cells;    Induced pluripotent stem cells;    Immunogenicity;    Major histocompatibility complex (MHC);    Immune privilege;   

DOI  :  10.3727/096368913X674639

 received in 2012-04-18, accepted in 2013-10-09,  发布年份 2015

来源: Sage Journals

【 摘 要 】

Pluripotent stem cells, including human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), have been regarded as useful sources for cell-based transplantation therapy. However, immunogenicity of the cells remains the major determinant for successful clinical application. We report the examination of several hESC lines (NTU1 and H9), hiPSC lines, and their derivatives (including stem cell-derived hepatocytes) for the expression of major histocompatibility complex (MHC), natural killer (NK) cell receptor (NKp30, NKp44, NKp46) ligand, immune-related genes, human leukocyte antigen (HLA) haplotyping, and the effects in functional mixed lymphocyte reaction (MLR). Flow cytometry showed lower levels (percentages and fluorescence intensities) of MHC class I (MHC-I) molecules, β2-microglobulin, and HLA-E in undifferentiated stem cells. The levels were increased after cotreatment with interferon-γ and/or in vitro differentiation. Antigen-presenting cell markers (CD11c, CD80, and CD86) and MHC-II (HLA-DP, -DQ, and -DR) remained low throughout the treatments. Recognition of stem cells/derivatives by NK lysis receptors were lower or absent. Activation of responder lymphocytes was significantly lower by undifferentiated stem cells than by allogeneic lymphocytes in MLR, but differentiated NTU1 hESCs induced a cell number-dependent lymphocyte proliferation comparable with that by allogeneic lymphocytes. Interestingly, activation of lymphocytes by differentiated hiPSCs or H9 cells became blunted at higher cell numbers. Real-time reverse transcriptase PCR (RT-PCR) showed significant differential expression of immune privilege genes (TGF-β2, Arginase 2, Indole 1, GATA3, POMC, VIP, CALCA, CALCB, IL-1RN, CD95L, CR1L, Serpine 1, HMOX1, IL6, LGALS3, HEBP1, THBS1, CD59, and LGALS1) in pluripotent stem cells/derivatives when compared to somatic cells. It was concluded that pluripotent stem cells/derivatives are predicted to be immunogenic, though evidence suggests some level of potential immune privilege. In addition, differential immunogenicity may exist between different pluripotent stem cell lines and their derivatives.

【 授权许可】

Unknown   
© 2015 Cognizant Comm. Corp.

【 图 表 】

Figure 1.

Figure 5

Figure 3

Figure 3

Figure 2

Figure 5.