Therapeutic roles of mesenchymal stem cell-derived extracellular vesicles in cancer.

Extracellular vesicles (EVs) are cell-derived membrane structures enclosing proteins, lipids, RNAs, metabolites, growth factors, and cytokines. EVs have emerged as essential intercellular communication regulators in multiple physiological and pathological processes. Previous studies revealed that mesenchymal stem cells (MSCs) could either support or suppress tumor progression in different cancers by paracrine signaling via MSC-derived EVs. Evidence suggested that MSC-derived EVs could mimic their parental cells, possessing pro-tumor and anti-tumor effects, and inherent tumor tropism. Therefore, MSC-derived EVs can be a cell-free cancer treatment alternative. This review discusses different insights regarding MSC-derived EVs' roles in cancer treatment and summarizes bioengineered MSC-derived EVs' applications as safe and versatile anti-tumor agent delivery platforms. Meanwhile, current hurdles of moving MSC-derived EVs from bench to bedside are also discussed.

Weng Z ，Zhang B ，Wu C ，Yu F ，Han B ，Li B ，Li L ... -  《Journal of Hematology & Oncology》

Mesenchymal Stem Cell-Derived Extracellular Vesicles to the Rescue of Renal Injury.

Birtwistle L ，Chen XM ，Pollock C 《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Functional proteins of mesenchymal stem cell-derived extracellular vesicles.

Qiu G ，Zheng G ，Ge M ，Wang J ，Huang R ，Shu Q ，Xu J ... -  《Stem Cell Research & Therapy》

Human mesenchymal stroma/stem-like cell-derived taxol-loaded EVs/exosomes transfer anti-tumor microRNA signatures and express enhanced SDF-1-mediated tumor tropism.

The release of extracellular vesicles (EVs) including exosomes from human mesenchymal stroma/stem-like cells (MSC) represents valuable cell-free carriers for the delivery of regenerative and medicinal compounds. EVs/exosomes were isolated by differential centrifugation from four individual MSC as controls and after treatment with a sub-lethal concentration of 10 mM taxol for 24 h, respectively. The isolated EVs/exosomes were characterized and quantified by nano-tracking-analysis and by Western blots. MicroRNAs (miRs) were isolated from the different EVs/exosome populations and expression levels were quantified by qPCR using 1246 miR templates. Cytotoxic effects of the different MSC-derived taxol-loaded EVs/exosomes were determined in five different GFP-transduced cancer cell lines and quantified by a fluoroscan assay with a GFP-detecting fluorimeter. The presence of stroma cell-derived factor 1 (SDF-1) in MSC-derived EVs/exosomes and its enhanced expression in the vesicles after taxol treatment of MSC was quantified by a specific ELISA. EVs/exosomes isolated from four individual taxol-treated MSC displayed a larger size and higher yields as the control EVs/exosomes and were used as anti-tumor therapeutic vehicles. Application of each of the four MSC-derived taxol-loaded EVs/exosome populations revealed significant cytotoxic effects in cell lines of five different tumor entities (carcinomas of lung, breast, ovar, colon, astrocytoma) in a concentration-dependent manner. Expression analysis of 1246 miRs in these taxol-loaded EVs/exosomes as compared to the corresponding MSC-derived control EVs/exosomes unraveled a taxol-mediated up-regulation of 11 miRs with predominantly anti-tumorigenic properties. Moreover, various constitutively expressed protein levels were unanimously altered in the MSC cultures. Taxol treatment of the different MSC revealed an up-regulation of tetraspanins and a 2.2-fold to 5.4-fold increased expression of SDF-1 among others. Treatment of cancer cells with MSC-derived taxol-loaded EVs/exosomes in the presence of a neutralizing SDF-1 antibody significantly abolished the cytotoxic effects between 20.3% and 27%. These findings suggested a taxol-mediated increase of anti-cancer properties in MSC that enhance the tropism of derived EVs/exosomes to tumors, thereby specifically focusing the therapeutic effects of the delivered products.

Hass R ，von der Ohe J ，Luo T 《Cell Communication and Signaling》

Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles as novel cell-free therapy for treatment of autoimmune disorders.

Over the past decades, new light has been shed on the efficiency of Mesenchymal Stem Cells (MSCs) in the treatment of autoimmune diseases. The therapeutic functions of MSCs partly stem from their well-recognized ability to efficiently modulate immune responses and it is well substantiated that MSC secretory components, in particular extracellular vesicles (EVs), play a critical role in this immunomodulation. In fact, almost any cell type can generate and release EVs under both pathological and physiological conditions and these nano-sized particles are believed to greatly contribute to homeostasis and cell-cell communication through transportation of a wide variety of biomolecules including nucleic acid, signaling lipids, regulatory proteins, transcription factors, cytokines, and growth factors. Lamentably, despite exhibiting promising results in both animal experiments and clinical trials, MSC therapy is still largely restricted to the experimental stage due to its critical pitfalls and drawbacks such as safety issues, poor cell survival, immune rejection and high cost. On the other hand, MSC-derived EVs, which ideally reflect the exact biophysical features of MSCs, are considered to be much safer and more effective than MSCs themselves. Therefore, introducing alternative approaches based on MSC-derived EVs can offer appreciable promise in overcoming the limitations and practical challenges observed in cell-based therapy and thus the extracellular vesicles of MSCs may also provide a far more potent therapeutic strategy for immune-related disorders. In this review, we first focus on the properties of MSC-derived EVs and then we shall provide valuable insight regarding their beneficial therapeutic opportunities to further compare this alternative approach with conventional MSC therapy. Finally, we will attempt to summarize the current findings on the influences of MSC-derived EVs on autoimmune disorders, offering a potential alternative avenue towards treatment of autoimmune diseases.

Kahmini FR ，Shahgaldi S 《-》