Contributions
Abstract: EP728
Type: E-Poster Presentation
Session title: Gene therapy, cellular immunotherapy and vaccination - Biology & Translational Research
Background
There exist kinds of limitations of MSCs during its application, while exosome derived from MSCs has shown promising future.
Aims
To verify the effects and mechanisms of natural MSCs-exosome in treating acute GVHD in mice, then explore and establish a method for targeted modification of MSCs-exosome and verify the functions of the modified MSCs-exosome.
Methods
In different doses of MSCs-exosome groups and MSCs group, the weight loss of acute GVHD mice was observed, then the proliferation levels of activated T cells were measured through T cell activation experiment in vitro and OVA antigen specific T cell activation experiment in vivo. AAV2YF3 mutants carrying PD-L1 and PD-L1-ITGB1 was obtained after the construction of recombinant expression vectors and then was applied to infect human MSCs to modify their exosome. The immunoregulatory functions of the modified MSCs-exosome were measured with methods as above.
Results
1) Mouse MSCs-exosome (300ug*3 times) and MSCs (1e6*3 times) effectively alleviated the weight loss of acute GVHD mice. 2) Compared with IL2, 10ug, 25ug and 50ug human MSCs-exosome inhibited the proliferation of activated T cells in vitro, respectively 86.01% (IL2), 40%, 39.61% and 42.84%; compared with PBS, 50ug, 100ug and 200ug mouse MSCs-exosome inhibited the proliferation of antigen-specifically activated OT-1 cells in vivo, respectively 42.6%, 33.1%, 14.2% and 10.6%. 3) After the infection of AAV2YF3 mutant carrying PD-L1 or PD-L1-ITGB1, the positive proportion of MSCs-exosome exceeds 40% and 60%, respectively. 4) Compared with the natural state, human MSCs-exosome modified by PD-L1 or PD-L1-ITGB1 showed better proliferation inhibitory effect in vivo, and increased the proportion of Treg cells in vitro.
Conclusion
MSCs-exosome exhibited similar immunomodulatory effects with MSCs. MSCs-exosome after PD-L1 and PD-L1-ITGB1 targeted modification effectively inhibited the proliferation of activated T cells and increased the proportion of Treg cells.
Keyword(s): AAV, Graft-versus-host disease (GVHD), Mesenchymal stem cell
Abstract: EP728
Type: E-Poster Presentation
Session title: Gene therapy, cellular immunotherapy and vaccination - Biology & Translational Research
Background
There exist kinds of limitations of MSCs during its application, while exosome derived from MSCs has shown promising future.
Aims
To verify the effects and mechanisms of natural MSCs-exosome in treating acute GVHD in mice, then explore and establish a method for targeted modification of MSCs-exosome and verify the functions of the modified MSCs-exosome.
Methods
In different doses of MSCs-exosome groups and MSCs group, the weight loss of acute GVHD mice was observed, then the proliferation levels of activated T cells were measured through T cell activation experiment in vitro and OVA antigen specific T cell activation experiment in vivo. AAV2YF3 mutants carrying PD-L1 and PD-L1-ITGB1 was obtained after the construction of recombinant expression vectors and then was applied to infect human MSCs to modify their exosome. The immunoregulatory functions of the modified MSCs-exosome were measured with methods as above.
Results
1) Mouse MSCs-exosome (300ug*3 times) and MSCs (1e6*3 times) effectively alleviated the weight loss of acute GVHD mice. 2) Compared with IL2, 10ug, 25ug and 50ug human MSCs-exosome inhibited the proliferation of activated T cells in vitro, respectively 86.01% (IL2), 40%, 39.61% and 42.84%; compared with PBS, 50ug, 100ug and 200ug mouse MSCs-exosome inhibited the proliferation of antigen-specifically activated OT-1 cells in vivo, respectively 42.6%, 33.1%, 14.2% and 10.6%. 3) After the infection of AAV2YF3 mutant carrying PD-L1 or PD-L1-ITGB1, the positive proportion of MSCs-exosome exceeds 40% and 60%, respectively. 4) Compared with the natural state, human MSCs-exosome modified by PD-L1 or PD-L1-ITGB1 showed better proliferation inhibitory effect in vivo, and increased the proportion of Treg cells in vitro.
Conclusion
MSCs-exosome exhibited similar immunomodulatory effects with MSCs. MSCs-exosome after PD-L1 and PD-L1-ITGB1 targeted modification effectively inhibited the proliferation of activated T cells and increased the proportion of Treg cells.
Keyword(s): AAV, Graft-versus-host disease (GVHD), Mesenchymal stem cell