Fresenius Medical Care achieves preclinical milestone for its nano-extracellular vesicles in chronic kidney disease

Fresenius Medical Care, the world’s largest provider of dialysis products and services, announced today that its subsidiary Unicyte AG has achieved a key preclinical milestone in its regenerative medicine program for chronic kidney disease. The company was able to confirm a disease modifying potential for its proprietary nano-Extracellular Vesicles (“nEVs” are stem cell-derived particles that support communication between cells) in a second preclinical model of chronic kidney disease.

When administered to mice with fast progressing kidney disease, Unicyte’s nEVs prevented renal fibrosis, a hallmark of chronic kidney disease. In particular, nEVs significantly reduced interstitial fibrosis and tubular necrosis while also inhibiting infiltration of various cells. This resulted in near-to-normal recovery of kidney function. The study conducted in collaboration with Prof. Giovanni Camussi of the University of Turin, Italy, has been accepted for publication in the peer-reviewed journal Frontiers of Immunology.

These new results support previous findings in a preclinical model of slowly progressing kidney disease (diabetic nephropathy), a major pathology that often leads to end-stage renal disease. Combined results of these studies demonstrate the efficacy and the underlying mechanism of action of nEVs in preventing renal fibrosis and subsequent progression to end-stage renal disease. Unicyte will continue the preclinical and clinical development of its proprietary nEVs for treatment of chronic and acute kidney diseases.

Human liver stem cell-derived extracellular vesicles (HLSC-EVs) downregulate pro-fibrotic genes in mkCF in an in vitro model of aristolochic acid nephropathy


mTECs pre-treated with 100 µM aristolochic acid (AA) for 4 h were cocultured with mouse fibroblasts in the presence or absence of HLSC-EVs or Fibro-EVs (50,000 EVs/cell) for 5 days at 37°C. Post experimental analyses revealed an upregulation of the fibrotic markers: (A) α-sma, (B) Tgfb1, and (C) Col1a1 in mkCF cocultured with AA-treated mTECs (AA). Treatment with HLSC-EVs, but not Fibro-EVs, significantly downregulated all three genes compared to control. The data represent mean ± SEM of three independent experiments performed in quadruplicate. *p < 0.05, **p < 0.01, ***p < 0.001 mTEC + AA vs Control, or HLSC-EVs vs mTEC + AA. No significant differences were observed between mTEC + AA vs Fibro-EVs. A one-way analyses of variance with Bonferroni’s multi comparison test was performed. (D) Representative confocal microscopy depicting the uptake of 1 × 1010 Dil dye-labelled HLSC-EVs by mkCF after 6 h of co-incubation at 37°C. Z stack analyses shows the presence of EVs within the cytoplasm (phalloidin staining, green) of the cells indicating an effective internalisation of vesicles (in red); scale bar = 50 μm. Data represent one of the three experiments performed with similar results.

Source – Fresenius Medical Care

Kholia S et al. (2018) Human Liver Stem Cell-Derived Extracellular Vesicles Prevent Aristolochic Acid-Induced Kidney Fibrosis. Front Immunol [Epub ahead of print]. [article]

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