期刊
BIOMATERIALS
卷 248, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2020.120013
关键词
Pluripotent stem cell therapy; Allograft; Immunogenicity; Humanized antibodies; Humanized mice; Pancreatic beta-like cells
资金
- Research Grants Council of Hong Kong [C4024-16W, C4026-17WF]
- National Natural Science Foundation of China [81922077]
- Croucher Foundation
- Lui Chi Woo Institute of Innovative Medicine
- CUHK
We have previously demonstrated that short-term coreceptor blockade with non-lyric monoclonal antibodies enables the long-term survival of fully allogeneic embryonic stem cell (ESC) transplants in mice. Here, we describe the use of Hu-PBL humanized mice to determine whether short-term coreceptor blockade with humanized anti-human CD4 and CD8 antibodies can achieve the same outcome towards human ESC derivatives. While control Hu-PBL mice rejected allogeneic hESC-derived transplants within weeks, mice treated with coreceptor blocking antibodies held their grafts for 7 weeks, the duration of the study. Rejection in the control mice was associated with demonstrable infiltrates of human CD45 white blood cells, predominantly of CD8 T-cells, whereas anti-CD4, but not anti-CD8 antibody treated mice showed remarkably reduced lymphocyte infiltration and prolonged allograft survival, indicating that the CD4(+) T-cells were crucial to the rejection process. Our results give support to the principle that short-term blockade of T-cell co-receptors can achieve long-term acceptance of regenerative cell transplants in humans.
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