PMID- 24144439
OWN - NLM
STAT- MEDLINE
DCOM- 20160125
LR  - 20150507
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Linking)
VI  - 24
IP  - 5
DP  - 2015
TI  - Characteristic expression of major histocompatibility complex and immune 
      privilege genes in human pluripotent stem cells and their derivatives.
PG  - 845-64
LID - 10.3727/096368913X674639 [doi]
AB  - 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, beta2-microglobulin, and HLA-E in undifferentiated stem 
      cells. The levels were increased after cotreatment with interferon-gamma 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-beta2, 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.
FAU - Chen, Hsin-Fu
AU  - Chen HF
AD  - Division of Reproductive Endocrinology and Infertility, Department of Obstetrics 
      and Gynecology, College of Medicine and the Hospital, National Taiwan University, 
      Taipei, Taiwan.
FAU - Yu, Chun-Ying
AU  - Yu CY
FAU - Chen, Mei-Jou
AU  - Chen MJ
FAU - Chou, Shiu-Huey
AU  - Chou SH
FAU - Chiang, Ming-Shan
AU  - Chiang MS
FAU - Chou, Wen-Hsi
AU  - Chou WH
FAU - Ko, Bor-Sheng
AU  - Ko BS
FAU - Huang, Hsiang-Po
AU  - Huang HP
FAU - Kuo, Hung-Chih
AU  - Kuo HC
FAU - Ho, Hong-Nerng
AU  - Ho HN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131018
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
RN  - 0 (Antigens, Differentiation)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Antigens, Differentiation/biosynthesis/*immunology
MH  - Cell Differentiation/*immunology
MH  - Cells, Cultured
MH  - Gene Expression Regulation/*immunology
MH  - HLA Antigens/biosynthesis/*immunology
MH  - Humans
MH  - Induced Pluripotent Stem Cells/cytology/*immunology/metabolism
EDAT- 2013/10/23 06:00
MHDA- 2016/01/26 06:00
CRDT- 2013/10/23 06:00
PHST- 2013/10/23 06:00 [entrez]
PHST- 2013/10/23 06:00 [pubmed]
PHST- 2016/01/26 06:00 [medline]
AID - content-ct0882Chen [pii]
AID - 10.3727/096368913X674639 [doi]
PST - ppublish
SO  - Cell Transplant. 2015;24(5):845-64. doi: 10.3727/096368913X674639. Epub 2013 Oct 
      18.