Engineered exosomes: desirable target-tracking characteristics for cerebrovascular and neurodegenerative disease therapies.

As extracellular vesicles secreted by cells, exosomes are intercellular signalosomes for cell communication and pharmacological effectors. Because of their special properties, including low toxicity and immunogenicity, biodegradability, ability to encapsulate endogenous biologically active molecules and cross the blood-brain barrier (BBB), exosomes have great therapeutic potential in cerebrovascular and neurodegenerative diseases. However, the poor targeting ability of natural exosomes greatly reduces the therapeutic effect. Using engineering technology, exosomes can obtain active targeting ability to accumulate in specific cell types and tissues by attaching targeting units to the membrane surface or loading them into cavities. In this review, we outline the improved targeting functions of bioengineered exosomes, tracing and imaging techniques, administration methods, internalization in the BBB, and therapeutic effects of exosomes in cerebrovascular and neurodegenerative diseases and further evaluate the clinical opportunities and challenges in this research field.

Immune protection effect of exosomes against attack of L1210 tumor cells.

We investigated the anti-tumor immunity of L1210 cell-secreted exosomes. Exosomes were purified by ultrafiltration centrifugation and sucrose gradient ultracentrifugation. Expression of H-2D and interstitial cell adhesion molecule (ICAM(-1 was investigated by solid-phase immuno-electron microscopy and expression of Hsp70 was investigated by western blotting. DBA/2 mice were immunized with a given dose of exosomes (2.5 or 5 microg(. Transmission electron microscopy revealed that L1210-derived exosomes were membrane vesicles. They were labeled by colloidal gold H-2D and ICAM-1. Western blot analysis demonstrated the presence of Hsp70 antigens in L1210 exosomes. Exosome immunization partly inhibited the growth of implanted tumor in mice. There was a significant difference between exosome groups and the control group (P < 0.05(. In conclusion, exosomes can be considered as a candidate therapeutic vaccine for leukemia.

[Exosomes derived from dendritic cells]. / Les exosomes dérivés des cellules dendritiques.

Dendritic cells (DC) are potent antigen presenting cells and the only ones capable of inducing primary cytotoxic immune responses both in vivo and vitro. DCs secrete a 60-80 nm membrane vesicle population of endocytic origin, called exosomes. The protein composition of exosomes was analyzed using a systematic proteomic approach. Besides MHC and costimulatory molecules, exosomes bear several adhesion proteins, probably involved in their specific targeting. Exosomes also accumulate several cytosolic factors, most likely involved in exoxome's biogenesis in late endosomes. Like DCs, exosomes induce potent anti tumor immune responses in vivo. Indeed, a single injection of DC-derived exosomes sensitized with tumor peptides induced the eradication of established mouse tumors. Tumor-specific cytotoxic T lymphocytes were found in the spleen of exosome treated mice, and depletion of CD8+ T cells in vivo inhibited the anti tumor effect of exosomes. These results strongly support the implementation of human DC-derived exosomes for cancer immunotherapy.