potential immune modulatory action of mesenchymal stem cell derived extracellular vesicles in type 1 diabetes

Several preclinical studies have shown potential immunemodulatory properties of mesenchymal stem cells (MSC) in type 1 diabetes leading to phase I/II clinical trials. Immune-modulatory properties of MSC have been mainly ascribed to their secretome. The extracellular vesicles (EV) have emerged as paracrine mediators of MSC actions. In fact, MSC-derived EV have been shown to carry proteins and nucleic acids capable to mimic the effect of originating cells. In the present short review we discuss evidences for contribution of EV to the immune-modulatory properties of MSC and mechanisms involved. In particular, EV were shown to inhibit T cell response to the glutamic acid decarboxylase (GAD) islet auto-antigen by inducing a shift of lymphocytes from Th1 to Th2 phenotype

Extracellular vesicle-mediated modulation of angiogenesis

Angiogenesis is a tightly regulated process where a number of different players are involved. Recently, a role for membrane vesicles actively released from cells has been proposed. Virtually all cell types may release non-apoptotic membrane vesicles in the nano-size range containing critical components of the cell of origin. The two main categories of these vesicles include exosomes and microvesicles that differ for biogenesis but, sharing several features and mechanisms of action, have been collectively named extracellular vesicles (EV). EV are able to transfer from one cell to another bioactive lipids, proteins and nucleic acids that may induce changes in the phenotype and functions of the recipient cells. This new mechanism of cell to cell communication has been involved in modulation of the angiogenic process. Tumor cells, inflammatory cells and stem/progenitor cells were shown to release EV with angiogenic properties, suggesting that they may act on vascular remodeling in different physiological and pathological conditions. In this review we discuss the evidence for the role and the mechanisms of action of EV in vascular homeostasis and in the angiogenic processes occurring in tumors, inflammation and tissue regeneration

Reversal of Radiation Damage to Marrow Stem Cells By Mesenchymal Stem Cell Derived Vesicles

Abstract Extracellular vesicles (exosomes and microvesicles) have been found to deliver both mRNA and transcriptional modulators to target cells and affect their phenotype. Marrow mesenchymal stem cell derived vesicles (MSC-DV) have also been shown to reverse renal and hepatic injury. We have studied the capacity of MSC-DV to reverse radiation injury to marrow stem cells. B6.SJL mice were exposed to 100 centigrade whole body radiation (WBI), and 4, 24, and 168 hours later marrow is harvested and established in culture for 24-48 hours with either human or murine marrow-derived mesenchymal stem cells (MSV-DV) or vehicle. These cells were then transplanted into 950 cGy exposed C57/BL mice and engraftment evaluated at 3 weeks to 8 months. Alternatively cells were engrafted without competition into 200 centigrade exposed mice. Significant (p&lt;0.05) restoration of engraftment was seen in each setting; restoration of secondary engraftment was also seen. Mice were also subjected to 500 cGy WBI and injected at 6, 24 and 72 hours with human MSC-DV and peripheral blood counts determined. Granulocyte levels were restored to 86% of control at 3 weeks post irradiation and significant restoration seen at multiple other time points. Restoration was seen was seen in both peripheral blood and marrow. Further studies on the murine hematopoietic cell line, FDC-P1 exposed to 500 centigrade showed dramatic recovery on exposure to murine or human MSC-DV. Additional work, employing differential ultracentrifugation as a separative technique for vesicles, showed that a preparation with both exosomes and microvesicles was superior to either microvesicles or exosomes alone. Studies with irradiated FDC-P1 cells indicated that exposure to vesicles decreased apoptosis. These studies indicate that vesicles from marrow-derived mesenchymal stem cells from different sources have the capacity to reverse radiation damage to bone marrow stem cells. Thus administration of MSC-DV to patients exposed to radiation could represent an important new strategy in radiation mitigation. Disclosures No relevant conflicts of interest to declare. </jats:sec