Stem cell-derived extracellular vesicles inhibit and revert fibrosis progression in a mouse model of diabetic nephropathy.
Animals
Cells, Cultured
Creatinine
/ metabolism
Diabetes Mellitus, Experimental
/ chemically induced
Diabetic Nephropathies
/ metabolism
Disease Models, Animal
Disease Progression
Extracellular Vesicles
/ transplantation
Humans
Liver
/ cytology
Male
Mesenchymal Stem Cells
/ cytology
Mice
Serum Albumin
/ metabolism
Streptozocin
Treatment Outcome
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
14 03 2019
14 03 2019
Historique:
received:
14
11
2018
accepted:
21
02
2019
entrez:
16
3
2019
pubmed:
16
3
2019
medline:
2
10
2020
Statut:
epublish
Résumé
Extracellular vesicles (EVs) that are derived from mesenchymal stromal cells (MSCs) have been shown to reprogram injured cells by activating regenerative processes. 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 a mouse model of diabetic nephropathy, as induced by streptozotocin. After the development of nephropathy, stem cell-derived EVs were administered weekly to diabetic mice for four weeks. The stem cell-derived EV treatment, but not the fibroblast EV treatment that was used as a control, significantly ameliorated 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 animals. A correlation was found between the down regulation of several pro-fibrotic genes in renal tissues and the anti-fibrotic effect of HLSC and MSC EVs. 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. In conclusion, stem cell-derived EVs inhibit fibrosis and prevent its progression in a model of diabetes-induced chronic kidney injury.
Identifiants
pubmed: 30872726
doi: 10.1038/s41598-019-41100-9
pii: 10.1038/s41598-019-41100-9
pmc: PMC6418239
doi:
Substances chimiques
Serum Albumin
0
Streptozocin
5W494URQ81
Creatinine
AYI8EX34EU
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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