Greetings, I am looking for your input on the following question: We are trying to design a study where we will inject sEVs (exosomes) isolated from human plasma and tissue biopsies to mice to look for some biological effects. However, there is a concern regarding the immune response that human sEVs might trigger in mice, and that this might impact the study outcomes. Did anyone try something like that or perhaps see a published study doing something of that sort?
How would one minimize such a response if it does occur? Thank you in advance for any advice!
Hello Dmitri,
We have evaluated the safety and toxicity profile of human embryonic kidney-derived EVs after intravenous administration in mice. Overall, we did not see toxicity effects or immunogenicity associated with our EV treatment. Article Extracellular Vesicles Induce Minimal Hepatotoxicity and Imm...
Similar results were also reported by other groups (here is a nice study). Article Comprehensive toxicity and immunogenicity studies reveal min...
However, many factors including the EV dose, source of the cells, frequency of EV administration, administration route, etc. can have an impact on the overall toxicity of EVs. I would recommend you to perform a small safety study before your experiments to be sure that your EVs do not induce toxicity and immunogenicity in vivo. I hope this helps.
Best wishes,
Elisa
Hello Dmitri,
We have evaluated the safety and toxicity profile of human embryonic kidney-derived EVs after intravenous administration in mice. Overall, we did not see toxicity effects or immunogenicity associated with our EV treatment. Article Extracellular Vesicles Induce Minimal Hepatotoxicity and Imm...
Similar results were also reported by other groups (here is a nice study). Article Comprehensive toxicity and immunogenicity studies reveal min...
However, many factors including the EV dose, source of the cells, frequency of EV administration, administration route, etc. can have an impact on the overall toxicity of EVs. I would recommend you to perform a small safety study before your experiments to be sure that your EVs do not induce toxicity and immunogenicity in vivo. I hope this helps.
Best wishes,
Elisa
Hello Dmitri,
Thanks for your question!
In our study, all model rats, including that in blank, untreated and exo-treated group, received cyclosporine A to minimize the immune rejection, which is consistent to the treatment in NPC transplantation study.Article Organoid-derived C-Kit + /SSEA4 − human retinal progenitor c...
Article Neural stem cells transplanted to the subretinal space of rd...
You may also consider to use relative drug to avoid or minimize the rejection reaction (of course, the animals in control groups should receive at the same time). Much thanks to Elisa Lazaro-Ibañez for your suggestion and sharing the excellent works. There are some studies evaluated the immunogenicity from xenograft of EVs, finding that they were well tolerated without adverse immune responses even without any immunosuppressive agents.
Article Generation and testing of clinical-grade exosomes for pancre...
But most of these studies focused on the EVs derived from the one single type cell lines or purified primary cells, which is not that diversified compared to the that from plasma and tissue biopsies. It should be considered that most all type of cells release EVs including immune cells in the blood and tissue. You might as well set up the immunosuppressive group to evaluate the differences. And it should be pointed out that some EVs have the regulative effect on T-cells, NK cells and other immune cells, which might be a part of the biological effects, the pre-treatment on immune cells should be avoided.Article Exosome Targeting of Tumor Antigens Expressed by Cancer Vacc...
Hope this helps.
Best wishes,
Bian