Hypoimmunogenic human pluripotent stem cells are valid cell sources for cell therapeutics with normal self-renewal and multilineage differentiation capacity

被引:0
|
作者
Yifan Chen
Yanjie Zhou
Zhongshu Zhou
Yujiang Fang
Lin Ma
Xiaoqing Zhang
Jie Xiong
Ling Liu
机构
[1] Tongji University,Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, School of Medicine
[2] Orthopaedic Department of Tongji Hospital,Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education
[3] Shanghai Institute of Stem Cell Research and Clinical Translation,Key Laboratory of Neuroregeneration of Shanghai Universities, School of Medicine
[4] Tongji University,Clinical Center for Brain and Spinal Cord Research
[5] Tongji University,Tsingtao Advanced Research Institute
[6] Tongji University,undefined
来源
Stem Cell Research & Therapy | / 14卷
关键词
Hypoimmunogenic hPSCs; Self-renewal; Multilineage differentiation; Functional maturity;
D O I
暂无
中图分类号
学科分类号
摘要
Hypoimmunogenic human pluripotent stem cells (hPSCs) are expected to serve as an unlimited cell source for generating universally compatible “off-the-shelf” cell grafts. However, whether the engineered hypoimmunogenic hPSCs still preserve their advantages of unlimited self-renewal and multilineage differentiation to yield functional tissue cells remains unclear. Here, we systematically studied the self-renewal and differentiation potency of three types of hypoimmunogenic hPSCs, established through the biallelic lesion of B2M gene to remove all surface expression of classical and nonclassical HLA class I molecules (B2Mnull), biallelic homologous recombination of nonclassical HLA-G1 to the B2M loci to knockout B2M while expressing membrane-bound β2m-HLA-G1 fusion proteins (B2MmHLAG), and ectopic expression of soluble and secreted β2m-HLA-G5 fusion proteins in B2MmHLAG hPSCs (B2Mm/sHLAG) in the most widely used WA09 human embryonic stem cells. Our results showed that hypoimmunogenic hPSCs with variable expression patterns of HLA molecules and immune compromising spectrums retained their normal self-renewal capacity and three-germ-layer differentiation potency. More importantly, as exemplified by neurons, cardiomyocytes and hepatocytes, hypoimmunogenic hPSC-derived tissue cells were fully functional as of their morphology, electrophysiological properties, macromolecule transportation and metabolic regulation. Our findings thus indicate that engineered hypoimmunogenic hPSCs hold great promise of serving as an unlimited universal cell source for cell therapeutics.
引用
收藏
相关论文
共 50 条
  • [21] Assessing self-renewal and differentiation in human embryonic stem cell lines
    Cai, Jingli
    Chen, Jia
    Liu, Ying
    Miura, Takumi
    Luo, Yongquan
    Loring, Jeanne F.
    Freed, William J.
    Rao, Mahendra S.
    Zeng, Xianmin
    STEM CELLS, 2006, 24 (03) : 516 - 530
  • [22] Human trophoblast stem cell self-renewal and differentiation: Role of decorin
    Nandi, Pinki
    Lim, Hyobin
    Torres-Garcia, Eloy Jose
    Lala, Peeyush K.
    SCIENTIFIC REPORTS, 2018, 8
  • [23] Direct evidence of multilineage differentiation and self-renewal division of individual human hematopoietic stem cell clones in vivo.
    Yahata, T
    Yumino, S
    Miyatake, H
    Tomoko, U
    Sheng, Y
    Muguruma, Y
    Ito, M
    Miyoshi, H
    Kato, S
    Hotta, T
    Ando, K
    BLOOD, 2005, 106 (11) : 491A - 491A
  • [24] Self-renewal and differentiation capacity of young and aged stem cells
    Roobrouck, Valerie D.
    Ulloa-Montoya, Fernando
    Verfaillie, Catherine M.
    EXPERIMENTAL CELL RESEARCH, 2008, 314 (09) : 1937 - 1944
  • [25] The role of the chromatin remodeler Mi-2β in hematopoietic stem cell self-renewal and multilineage differentiation
    Yoshida, Toshimi
    Hazan, Idit
    Zhang, Jiangwen
    Ng, Samuel Y.
    Naito, Taku
    Snippert, Hugo J.
    Heller, Elizabeth J.
    Qi, Xiaoqing
    Lawton, Lee N.
    Williams, Christine J.
    Georgopoulos, Katia
    GENES & DEVELOPMENT, 2008, 22 (09) : 1174 - 1189
  • [26] Small molecules in stem cell self-renewal and differentiation
    Schugar, R. C.
    Robbins, P. D.
    Deasy, B. M.
    GENE THERAPY, 2008, 15 (02) : 126 - 135
  • [27] Hematopoietic stem cell: self-renewal versus differentiation
    Seita, Jun
    Weissman, Irving L.
    WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE, 2010, 2 (06) : 640 - 653
  • [28] ALTERNATIVE SPLICING IN STEM CELL SELF-RENEWAL AND DIFFERENTIATION
    Nelles, David A.
    Yeo, Gene W.
    CELL BIOLOGY OF STEM CELLS, 2010, 695 : 92 - 104
  • [29] Designing stem cell niches for differentiation and self-renewal
    Donnelly, Hannah
    Salmeron-Sanchez, Manuel
    Dalby, Matthew J.
    JOURNAL OF THE ROYAL SOCIETY INTERFACE, 2018, 15 (145)
  • [30] Quantitative assessment of the stem cell self-renewal capacity
    Nakauchi, H
    Sudo, K
    Ema, H
    HEMATOPOIETIC STEM CELLS 2000 BASIC AND CLINICAL SCIENCES, 2001, 938 : 18 - 25