51. hESC-derived immune suppressive dendritic cells induce immune tolerance of parental hESC-derived allografts
- Author
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Yang Xu, Jingjin He, Dilyana Todorova, Jingfeng Liu, Yue Zhang, Xuemei Fu, and Qu Chen
- Subjects
Graft Rejection ,0301 basic medicine ,Adoptive cell transfer ,lcsh:Medicine ,Cell Communication ,Regenerative Medicine ,Regenerative medicine ,Dendritic cells ,Immune tolerance ,Cell therapy ,Mice ,0302 clinical medicine ,Smooth Muscle ,Myocytes, Cardiac ,Cells, Cultured ,lcsh:R5-920 ,Cultured ,Graft Survival ,General Medicine ,Regulatory T cells ,Allografts ,Adoptive Transfer ,030220 oncology & carcinogenesis ,Public Health and Health Services ,Human embryonic stem cells ,Development of treatments and therapeutic interventions ,lcsh:Medicine (General) ,Cardiac ,Research Paper ,Cells ,Myocytes, Smooth Muscle ,Clinical Sciences ,chemical and pharmacologic phenomena ,Germ layer ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Immunophenotyping ,Immunomodulation ,03 medical and health sciences ,Immune system ,Animals ,Humans ,Stem Cell Research - Embryonic - Human ,Myocytes ,Transplantation ,5.2 Cellular and gene therapies ,lcsh:R ,Stem Cell Research ,Embryonic stem cell ,030104 developmental biology ,Immune system humanized mice ,Immunology ,Humanized mouse ,Allogeneic immune rejection ,Biomarkers - Abstract
Background With their inherent capability of unlimited self-renewal and unique potential to differentiate into functional cells of the three germ layers, human embryonic stem cells (hESCs) hold great potential in regenerative medicine. A major challenge in the application of hESC-based cell therapy is the allogeneic immune rejection of hESC-derived allografts. Methods We derived dendritic cell-like cells (DCLs) from wild type and CTLA4-Ig/PD-L1 knock-in hESCs, denoted WT DCLs and CP DCLs. The expression of DC-related genes and surface molecules was evaluated, as well as their DCL capacity to stimulate allogeneic T cells and induce regulatory T (Treg) cells in vitro. Using an immune system humanized mouse model, we investigated whether the adoptive transfer of CP DCLs can induce long-term immune tolerance of parental hESC-derived smooth muscle and cardiomyocyte allografts. Findings CP DCLs can maintain immune suppressive properties after robust inflammatory stimulation and induce Treg cells. While CP DCLs survive transiently in vivo, they induce long-term immune tolerance of parental hESC-derived allografts. Interpretation This strategy does not cause systemic immune suppression but induces immune tolerance specific for DCL-specific HLAs, and thus it presents a safe and effective approach to induce immune tolerance of allografts derived from any clinically approved hESC line. Funding NSFC, leading talents of Guangdong Province Program (No. 00201516), Key R&D Program of Guangdong Province (2019B020235003), Science and Technology Innovation Committee of Shenzhen Municipality (JCYJ20180504170301309), National High-tech R&D Program (863 Program No. 2015AA020310), Shenzhen “Sanming” Project of Medicine (SZSM201602102), Development and Reform Commission of Shenzhen Municipality (S2016004730009), CIRM (DISC2–10559).
- Published
- 2020