Mesenchymal stem cells, exosomes and exosome-mimics as smart drug carriers for targeted cancer therapy

Mesenchymal stem cells (MSCs) are multipotent stem cells with the capacity to differentiate into several cell types under appropriate conditions. They also possess remarkable antitumor features that make them a novel choice to treat cancers. Accumulating evidence suggest that the MSCs-derived extracellular vesicles, known as exosomes, play an essential role in the therapeutic effects of MSCs mainly by carrying biologically active factors. However, limitations such as low yield of exosomes and difficulty in isolation and purification hinder their clinical applications. To overcome these issues, research on development of exosome-mimics has attracted great attention. This systematic review represents, to the best of our knowledge, the first thorough evaluations of the innate antineoplastic features of MSCs-derived exosomes or exosome-mimics, the methods of drug loading, application as drug delivery system and their impacts on targeted cancer therapy. Importantly, we dissect the commonalities and differences as well as address the shortcomings of work accumulated over the last two decades and discuss how this information can serve as a guide map for optimal experimental design implementation ultimately aiding the effective transition into clinical trials.