Stem cell microvesicles transfer cystinosin to human cystinotic cells and reduce cystine accumulation in vitro.

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 ma...

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Autores principales:	Diana M Iglesias, Reyhan El-Kares, Anna Taranta, Francesco Bellomo, Francesco Emma, Martine Besouw, Elena Levtchenko, Jaan Toelen, Lambertus van den Heuvel, Leelee Chu, Jing Zhao, Yoon Kow Young, Nicoletta Eliopoulos, Paul Goodyer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/353a18b5afee4d52adc1fd7c0dda280d
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spelling	oai:doaj.org-article:353a18b5afee4d52adc1fd7c0dda280d2021-11-18T07:08:57ZStem cell microvesicles transfer cystinosin to human cystinotic cells and reduce cystine accumulation in vitro.1932-620310.1371/journal.pone.0042840https://doaj.org/article/353a18b5afee4d52adc1fd7c0dda280d2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22912749/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Cystinosis 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.Diana M IglesiasReyhan El-KaresAnna TarantaFrancesco BellomoFrancesco EmmaMartine BesouwElena LevtchenkoJaan ToelenLambertus van den HeuvelLeelee ChuJing ZhaoYoon Kow YoungNicoletta EliopoulosPaul GoodyerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e42840 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Diana M Iglesias Reyhan El-Kares Anna Taranta Francesco Bellomo Francesco Emma Martine Besouw Elena Levtchenko Jaan Toelen Lambertus van den Heuvel Leelee Chu Jing Zhao Yoon Kow Young Nicoletta Eliopoulos Paul Goodyer Stem cell microvesicles transfer cystinosin to human cystinotic cells and reduce cystine accumulation in vitro.
description	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.
format	article
author	Diana M Iglesias Reyhan El-Kares Anna Taranta Francesco Bellomo Francesco Emma Martine Besouw Elena Levtchenko Jaan Toelen Lambertus van den Heuvel Leelee Chu Jing Zhao Yoon Kow Young Nicoletta Eliopoulos Paul Goodyer
author_facet	Diana M Iglesias Reyhan El-Kares Anna Taranta Francesco Bellomo Francesco Emma Martine Besouw Elena Levtchenko Jaan Toelen Lambertus van den Heuvel Leelee Chu Jing Zhao Yoon Kow Young Nicoletta Eliopoulos Paul Goodyer
author_sort	Diana M Iglesias
title	Stem cell microvesicles transfer cystinosin to human cystinotic cells and reduce cystine accumulation in vitro.
title_short	Stem cell microvesicles transfer cystinosin to human cystinotic cells and reduce cystine accumulation in vitro.
title_full	Stem cell microvesicles transfer cystinosin to human cystinotic cells and reduce cystine accumulation in vitro.
title_fullStr	Stem cell microvesicles transfer cystinosin to human cystinotic cells and reduce cystine accumulation in vitro.
title_full_unstemmed	Stem cell microvesicles transfer cystinosin to human cystinotic cells and reduce cystine accumulation in vitro.
title_sort	stem cell microvesicles transfer cystinosin to human cystinotic cells and reduce cystine accumulation in vitro.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/353a18b5afee4d52adc1fd7c0dda280d
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Stem cell microvesicles transfer cystinosin to human cystinotic cells and reduce cystine accumulation in vitro.

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