hESC-derived immune suppressive dendritic cells induce immune tolerance of parental hESC-derived allografts
Year: 2020
Type: article
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).
Source: EBioMedicine
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,500
Funders: California Institute for Regenerative Medicine, National Natural Science Foundation of China, Science, Technology and Innovation Commission of Shenzhen Municipality, Development and Reform Commission of Shenzhen Municipality, Leading Talents Program of Guangdong Province, Sanming Project of Medicine in Shenzhen, National High-tech Research and Development Program, Special Project for Research and Development in Key areas of Guangdong Province
OpenAlex ID: W3108332750