Title: Stem Cell Microvesicles Transfer Cystinosin to Human Cystinotic Cells and Reduce Cystine Accumulation In Vitro
Authors: Iglesias, Diana ×
El-Kares, Reyhan
Taranta, Anna
Bellomo, Francesco
Emma, Francesco
Besouw, Martine
Levtchenko, Elena
Toelen, Jaan
van den Heuvel, Bert
Chu, LeeLee
Zhao, Jing
Young, Yoon Kow
Eliopoulos, Nicoletta
Goodyer, Paul #
Issue Date: 13-Aug-2012
Publisher: Public Library of Sciene
Series Title: PLoS One vol:7 issue:8
Article number: e42840
Abstract: Cystinosis is a rare disease caused by homozygous mutations of the CTNS gene, encoding a cystine efflux channel in the lysosomal membrane. In Ctns knockout mice, the pathologic intralysosomal accumulation of cystine that drives progressive organ damage can be reversed by infusion of wildtype bone marrow-derived stem cells, but the mechanism involved is unclear since the exogeneous stem cells are rarely integrated into renal tubules. Here we show that human mesenchymal stem cells, from amniotic fluid or bone marrow, reduce pathologic cystine accumulation in co-cultured CTNS mutant fibroblasts or proximal tubular cells from cystinosis patients. This paracrine effect is associated with release into the culture medium of stem cell microvesicles (100-400 nm diameter) containing wildtype cystinosin protein and CTNS mRNA. Isolated stem cell microvesicles reduce target cell cystine accumulation in a dose-dependent, Annexin V-sensitive manner. Microvesicles from stem cells expressing CTNS(Red) transfer tagged CTNS protein to the lysosome/endosome compartment of cystinotic fibroblasts. Our observations suggest that exogenous stem cells may reprogram the biology of mutant tissues by direct microvesicle transfer of membrane-associated wildtype molecules.
ISSN: 1932-6203
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Organ Systems (+)
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science