Potential Of MSC-derived Extracellular Vesicles Research Articles

Bioengineered Mesenchymal Stem/Stromal Cells in Anti-Cancer Therapy: Current Trends and Future Prospects.

Mesenchymal stem/stromal cells (MSCs) are one of the most widely used cell types in advanced therapies due to their therapeutic potential in the regulation of tissue repair and homeostasis, and immune modulation. However, their use in cancer therapy is controversial: they can inhibit cancer cell proliferation, but also potentially promote tumour growth by supporting angiogenesis, modulation of the immune milieu and increasing cancer stem cell invasiveness. This opposite behaviour highlights the need for careful and nuanced use of MSCs in cancer treatment. To optimize their anti-cancer effects, diverse strategies have bioengineered MSCs to enhance their tumour targeting and therapeutic properties or to deliver anti-cancer drugs. In this review, we highlight the advanced uses of MSCs in cancer therapy, particularly as carriers of targeted treatments due to their natural tumour-homing capabilities. We also discuss the potential of MSC-derived extracellular vesicles to improve the efficiency of drug or molecule delivery to cancer cells. Ongoing clinical trials are evaluating the therapeutic potential of these cells and setting the stage for future advances in MSC-based cancer treatment. It is critical to identify the broad and potent applications of bioengineered MSCs in solid tumour targeting and anti-cancer agent delivery to position them as effective therapeutics in the evolving field of cancer therapy.

Mesenchymal-Stem-Cell-Derived Extracellular Vesicles Mitigate Trained Immunity in the Brain.

Trained immunity was recently discovered in innate immune cells and shown to facilitate the clearance of pathogens at the time of occurrence of the second insult. However, it exacerbates several aspects of neuropathologies, and proper therapy is needed to rectify this abnormal immune reaction. Mesenchymal-stem cells (MSCs) exhibit a distinct capability for brain repair but are associated with safety concerns. Extracellular vesicles derived from MSCs are a promising alternative therapy. In this study, we used lipopolysaccharides to activate trained immunity in the brain and examined the therapeutic potential of MSC-derived extracellular vesicles in mitigating the trained-immunity-induced exacerbated neuropathology. We found that MSC-derived extracellular vesicles showed comparable effects to those of MSCs in the mitigation of trained immunity in the brain. Moreover, the administration of MCS-derived extracellular vesicles mitigated the aggregated inflammatory responses in the acute stage of stroke and alleviated the trained-immunity-induced increased load of amyloid-β in APP/PS1 mice. We further investigated the molecular machinery of MSC-derived extracellular vesicles and found that IL-10 is important for the mediation of the therapeutic potential of MSC-derived extracellular vesicles toward the alleviation of trained immunity. Our study indicates that extracellular-vesicle-based regenerative strategies might be useful to mitigate trained immunity in the brain.

Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Treatment of Diabetic Foot Ulcers: Application and Challenges.

Diabetic foot ischemia and ulcer (DFU) persists as a serious diabetes mellitus complication in spite of increased understanding of the pathophysiology and the cellular and molecular responses. Contributing to this pessimistic situation is the lack of effective treatments that are slow to heal the deep chronic wounds and microvascular obstruction. Mesenchymal stromal cells (MSCs) have been tested as a promising cell-based therapy for diabetes in vitro and in vivo, which is able to accelerate wound closure with increased epithelialization, granulation tissue formation and angiogenesis by differentiation into skin cells and paracrine pathways to repair injured cells. The secretomes of MSCs, including cytokines, growth factors, chemokines, and extracellular vesicles containing mRNA, proteins and microRNAs, have immunomodulatory and regenerative effects. This review will shed new light on the therapeutic potential of MSC-derived extracellular vesicles (MSC-EVs) for the treatment of diabetes-induced lower limb ischemia and ulcers. The identification of underlying mechanisms for MSC-EVs regulation on impaired diabetic wound healing might provide a new direction for MSC-centered treatment for diabetic lower limb ischemia and ulcers. Immunomodulatory and angiogenic effects of MSC-derived extracellular vesicles on diabetic foot ulcer.

Taking advantage of the potential of mesenchymal stromal cells in liver regeneration: Cells and extracellular vesicles as therapeutic strategies.

Cell-based therapies for acute and chronic liver diseases are under continuous progress. Mesenchymal stem/stromal cells (MSCs) are multipotent cells able to migrate selectively to damaged tissue and contribute to its healing and regeneration. The MSC pro-regenerative effect occurs due to their immunomodulatory capacity and their ability to produce factors that promote cell protection and survival. Likewise, it has been observed that part of their paracrine effect is mediated by MSC-derived extracellular vesicles (EVs). EVs contain proteins, lipids and nucleic acids (DNA, mRNA, miRNA, lncRNA) from the cell of origin, allowing for intercellular communication. Recently, different studies have demonstrated that MSC-derived EVs could reproduce, at least in part, the biological effects obtained by MSC-based therapies. Moreover, due to EVs’ stability for long periods of time and easy isolation methods they have become a therapeutic option to MSCs treatments. This review summarizes the latest results achieved in clinical trials using MSCs as cell therapy for liver regeneration, the role of EVs in liver physiopathology and the potential of MSCderived EVs as intercellular mediators and therapeutic tools in liver diseases.