[98] This might be of relevance to recent studies that have found

[98] This might be of relevance to recent studies that have found increased glycoprotein B7-1 to nephrin mRNA ratios PI3K Inhibitor Library high throughput in urinary sediments from patients with minimal change disease compared with FSGS[99] and to the finding that urinary granzyme A mRNA levels can potentially distinguish patients with cellular rejection from those with AKI.[100] Harnessing

exosomal delivery mechanisms to therapeutic ends could have far-reaching consequences. The exploitation of ‘custom-made’ exosomes as a delivery tool for pharmacological agents could allow the precise targeting of those molecules to certain cell types. Exosomes are potentially ideal gene delivery vectors. Their small size and flexibility enables them to cross biological membranes, while their bi-lipid structure protects the mRNA, miRNA and protein cargo from degradation, facilitating delivery to its target. A proof of concept study has used modified

murine exosomes to successfully deliver siRNA resulting in gene-specific silencing in the brain.[101] For many kidney-related diseases a prime target for potential exosome-based therapy could be endothelial cells, which have essential roles in regulation of blood pressure, Opaganib clinical trial local regulation of blood flow, regulation of thrombosis and clearance of plasma lipids and are easily accessible to exosomes from the circulation. The artificial engineering of exosomes is a natural extension of the success of some liposomal therapies and can be used for delivery of specific RNAi molecules.[101] Furthermore, the purification and use of exosomes from particular cells or generated under certain stresses may be useful therapeutically. An example of this has developed from the interest in the mechanism underlying the potential of mesenchymal stem cells to promote tissue

repair and mediate check regeneration. Several studies have demonstrated that mesenchymal stem cells have the capacity to reverse acute and chronic kidney injury in different experimental models. These effects appear to be at least in part paracrine and can be largely mediated by the RNA cargo of exosomes and/or microvesicles.[102, 103] A potential approach to cancer immunotherapy based on exosomes has arisen from initial studies showing that dendritic cell-derived exosomes loaded with tumour peptides are capable of priming cytotoxic T cells. This can then mediate the rejection of tumours expressing the relevant antigens in mice.[104] These exosomes also promote natural killer (NK) cell activation in immunocompetent mice and NK cell-dependent anti-tumour effects. Based on these results, clinical trials are in progress. Vaccination strategies could also be envisioned using exosomes from tumour cells that carry tumour antigens.

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