MSC-Derived Extracellular Vesicles in Tumors and Therapy

Simple Summary Therapeutic functions of mesenchymal stroma-/stem-like cells (MSCs) are mediated predominantly through paracrine effects by the release of various different components. Upon recruitment of MSCs to damaged tissue sites or tumors, several bioactive molecules and organelles that are secreted by MSCs among others are cytokines, chemokines, metabolites, and extracellular vesicles including exosomes. The MSC-mediated cargo of released exosomes contains specific proteins and nucleic acids with varying regulatory microRNAs according to the tissue origin and the MSC microenvironment. These MSC-released exosomes are taken up by different target cells in damaged tissues to promote a regulatory network of tissue repair, including immune modulation and induction of angiogenesis. Conversely, in tumors, MSC-derived exosomes can confer predominant signals to suppress neovascularization and to relay further tumor-inhibitory effects. However, MSCs that adapted to the tumor tissue by mutual interaction with cancer cells progressively alter to an aberrant phenotype with the release of exosomes carrying tumor-supportive material. Exosomes derived from mesenchymal stroma-/stem-like cells (MSCs) as part of extracellular vesicles are considered cell-free biocompatible nanovesicles that promote repair activities of damaged tissues or organs by exhibiting low immunogenic and cytotoxic effects. Contributions to regenerative activities include wound healing, maintenance of stem cell niches, beneficial regenerative effects in various diseases, and reduction of senescence. However, the mode of action in MSC-derived exosomes strongly depends on the biological content like different regulatory microRNAs that are determined by the tissue origin of MSCs. In tumors, MSCs use indirect and direct pathways in a communication network to interact with cancer cells. This leads to mutual functional changes with the acquisition of an aberrant tumor-associated MSC phenotype accompanied by altered cargo in the exosomes. Consequently, MSC-derived exosomes either from normal tissue-originating MSCs or from aberrant tumor-associated MSCs can confer different actions on tumor development. These processes exhibiting tumor-inhibitory and tumor-supportive effects with a focus on exosome microRNA content will be discriminated and discussed within this review.

Automated summary

Therapeutic functions of MSCs are largely mediated through paracrine effects by releasing various components such as cytokines, chemokines, and metabolites, among which exosomes play a significant role in tissue repair and immune modulation. However, MSC-derived exosomes can exhibit both tumor-inhibitory and tumor-supportive effects, depending on their interactions with cancer cells. The microRNA content of exosomes is crucial in determining their specific actions in different tissues and diseases.