Exosomes: an emerging strategy to treat autoimmune and inflammatory diseases

Abstract

Current treatment options for autoimmune and in ammatory diseases are scarce and consist of broad immunosuppressive agents that have no impact on reverting the already existing damage, and might even ultimately lead to severe side effects. To avert these drawbacks, some progress has been made on developing new treatment strategies by exploiting host cells, nanoparticles, genes. In this context, exosomes have recently emerged as potential new treatment modality in the management of autoimmune and in ammatory diseases. They are nano-sized vesicles that are secreted by most of cell types. It has been shown that these vesicles are keyplayers in cell communication and preserve the cell phenotype from which they derived. Indeed, increasing evidence supports that exosomes can convey important molecules to recipient cells and modulate their function. Additionally, because they can easily overcome biological barriers, have natural homing speci cities, are better tolerated, and easily engineered to comprise other molecules such as drugs, besides being considered as cellular surrogates they can be exploited as drug delivery carriers. Although their role is better understood in cancer setting, only modest progress has been made in gaining better knowledge of exosomes in autoimmune diseases. The present review is an attempt to summarize the current status of the application of exosome-based drug delivery systems as well as cell-derived exosomes to treat autoimmune diseases, what are their advantages and main challenges that this approach might pose during its clinical translation. Our aim is that, with this review, researchers can quickly be brought up to speed with, and improve, the state of the art.

Os atuais tratamentos para doen cas autoimunes e in amat orias s~ao escassos e consistem em agentes imunosupressores gerais, que n~ao t^em qualquer impacto em reverter danos, e at e podem originar graves efeitos adversos. Para culmatar estas desvantagens, algum progresso tem sido feito para desenvolver novas estrat egias terap^euticas recorrendo para tal a c elulas, nanopart culas, genes. Neste contexto, os exossomas surgiram recentemente como potencial nova modalidade terap^eutica para a gest~ao de doen cas autoimunes e in amat orias. Exossomas s~ao nano-ves culas que transportam moleculas importantes para as c elulas alvo e modulam a sua fun c~ao. Adicionalmente, uma vez que conseguem facilmente atravessar barreiras biol og- icas, t^em prefer^encias intr nsicas de transporte, s~ao melhor tolerados, e facilmente alterados para transportar outras moleculas como f armacos, para al em de serem considerados como substitutos celulares, estes podem ser explorados como sistemas de transporte para f armacos. Apesar do seu papel ser melhor conhecido no cancro, apenas um modesto progresso foi feito para conhecer melhor os exosomes nas doen cas autoimunes. Esta review e uma tentativa de sumarizar o conhecimento atual sobre a aplica c~ao dos exosomas como sistemas de transporte de f armacos, bem como dos exosomas derivados de c elulas para tratar as doen cas autoimunes, quais s~ao as suas vantagens e desa os que a implementa c~ao desta abordagem na cl nica pode trazer. O nosso objetivo, com esta review, e que outros cientistas quem a conhecer melhor esta abordagem, de modo a que possam tamb em eles contribuir futuramente para o estado da arte.