Stem Cell and Biomaterials

Extracellular Vesicles (EVs) released by stem cells carry transcriptional regulators and secreted RNAs and may transfer these encapsulated molecules to target cells, inducing phenotypic changes. It has been shown that EVs derived from stem cells, and in particular those derived from mesenchymal stromal cells (MSC), may reprogram injured cells and activate regenerative processes resulting  in repair of acute tissue injury. We herein investigate the potential therapeutic effect of EVs, shed by human bone marrow MSCs and by human liver stem-like cells (HLSCs), on the progression and reversion of fibrosis in two mouse models, diabetic nephropathy model, induced by streptozotocin and aristolochic acid-induced kidney fibrosis.

The stem cell-derived EV treatment, but not the fibroblast-EV treatment that was used as a control, significantly ameliorated renal functional parameters, such as albumin/creatinine excretion, plasma creatinine and blood urea nitrogen, which are altered in diabetic mice. Moreover, the renal fibrosis that develops during diabetic nephropathy progression was significantly inhibited in stem cell EV-treated quantified by histology and molecular analysis. A correlation between the down regulation of several pro-fibrotic genes, such as collagen, alpha-sma and TGF-beta in renal tissues, and the anti-fibrotic effect of HLSC and MSC EVs was found. A comparative analysis of HLSC and MSC EV miRNA content highlighted some common and some specific patterns of miRNAs that target predicted pro-fibrotic genes.