Cargando…

Human embryonic stem cells extracellular vesicles and their effects on immortalized human retinal Müller cells

Extracellular vesicles (EVs) released by virtually every cell of all organisms are involved in processes of intercellular communication through the delivery of their functional mRNAs, proteins and bioactive lipids. We previously demonstrated that mouse embryonic stem cell-released EVs (mESEVs) are a...

Descripción completa

Detalles Bibliográficos
Autores principales: Peng, Yingqian, Baulier, Edouard, Ke, Yifeng, Young, Alejandra, Ahmedli, Novruz B., Schwartz, Steven D., Farber, Debora B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5851617/
https://www.ncbi.nlm.nih.gov/pubmed/29538408
http://dx.doi.org/10.1371/journal.pone.0194004
_version_ 1783306418690981888
author Peng, Yingqian
Baulier, Edouard
Ke, Yifeng
Young, Alejandra
Ahmedli, Novruz B.
Schwartz, Steven D.
Farber, Debora B.
author_facet Peng, Yingqian
Baulier, Edouard
Ke, Yifeng
Young, Alejandra
Ahmedli, Novruz B.
Schwartz, Steven D.
Farber, Debora B.
author_sort Peng, Yingqian
collection PubMed
description Extracellular vesicles (EVs) released by virtually every cell of all organisms are involved in processes of intercellular communication through the delivery of their functional mRNAs, proteins and bioactive lipids. We previously demonstrated that mouse embryonic stem cell-released EVs (mESEVs) are able to transfer their content to different target retinal cells, inducing morphological and biochemical changes in them. The main objective of this paper is to characterize EVs derived from human embryonic stem cells (hESEVs) and investigate the effects that they have on cultured retinal glial, progenitor Müller cells, which are known to give rise to retinal neurons under specific conditions. This would allow us to establish if hESEVs have a pro-regenerative potential not yet described that could be used in the future for treatment of human retinal degenerative diseases. Initially, we showed that hESEVs are heterogeneous in size, contain mRNAs and proteins involved in the induction and maintenance of stem cell pluripotency and can be internalized by cultured Müller cells. After a single exposure to hESEVs these cells display changes in their gene expression profile, and with multiple exposures they de-differentiate and trans-differentiate into retinal neuronal precursors. hESEVs were then fractionated into microvesicles (MVs) and exosomes (EXOs), which were characterized by size, specific surface proteins and biochemical/molecular components. We demonstrate that despite the similar internalization of non-fractionated hESEVs, MVs and EXOs by Müller progenitor cells, in vitro, only the release of MVs’ cargo into the cells’ cytoplasm induces specific changes in their levels of pluripotency mRNAs and early retinal proteins. EXOs do not produce any detectable effect. Thus, we conclude that MVs and MVs-containing hESEVs are promising agents that possibly could promote the regeneration of diseased or damaged retinas in vivo through inducing glial Müller cells to become replacement neurons.
format Online
Article
Text
id pubmed-5851617
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-58516172018-03-23 Human embryonic stem cells extracellular vesicles and their effects on immortalized human retinal Müller cells Peng, Yingqian Baulier, Edouard Ke, Yifeng Young, Alejandra Ahmedli, Novruz B. Schwartz, Steven D. Farber, Debora B. PLoS One Research Article Extracellular vesicles (EVs) released by virtually every cell of all organisms are involved in processes of intercellular communication through the delivery of their functional mRNAs, proteins and bioactive lipids. We previously demonstrated that mouse embryonic stem cell-released EVs (mESEVs) are able to transfer their content to different target retinal cells, inducing morphological and biochemical changes in them. The main objective of this paper is to characterize EVs derived from human embryonic stem cells (hESEVs) and investigate the effects that they have on cultured retinal glial, progenitor Müller cells, which are known to give rise to retinal neurons under specific conditions. This would allow us to establish if hESEVs have a pro-regenerative potential not yet described that could be used in the future for treatment of human retinal degenerative diseases. Initially, we showed that hESEVs are heterogeneous in size, contain mRNAs and proteins involved in the induction and maintenance of stem cell pluripotency and can be internalized by cultured Müller cells. After a single exposure to hESEVs these cells display changes in their gene expression profile, and with multiple exposures they de-differentiate and trans-differentiate into retinal neuronal precursors. hESEVs were then fractionated into microvesicles (MVs) and exosomes (EXOs), which were characterized by size, specific surface proteins and biochemical/molecular components. We demonstrate that despite the similar internalization of non-fractionated hESEVs, MVs and EXOs by Müller progenitor cells, in vitro, only the release of MVs’ cargo into the cells’ cytoplasm induces specific changes in their levels of pluripotency mRNAs and early retinal proteins. EXOs do not produce any detectable effect. Thus, we conclude that MVs and MVs-containing hESEVs are promising agents that possibly could promote the regeneration of diseased or damaged retinas in vivo through inducing glial Müller cells to become replacement neurons. Public Library of Science 2018-03-14 /pmc/articles/PMC5851617/ /pubmed/29538408 http://dx.doi.org/10.1371/journal.pone.0194004 Text en © 2018 Peng et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Peng, Yingqian
Baulier, Edouard
Ke, Yifeng
Young, Alejandra
Ahmedli, Novruz B.
Schwartz, Steven D.
Farber, Debora B.
Human embryonic stem cells extracellular vesicles and their effects on immortalized human retinal Müller cells
title Human embryonic stem cells extracellular vesicles and their effects on immortalized human retinal Müller cells
title_full Human embryonic stem cells extracellular vesicles and their effects on immortalized human retinal Müller cells
title_fullStr Human embryonic stem cells extracellular vesicles and their effects on immortalized human retinal Müller cells
title_full_unstemmed Human embryonic stem cells extracellular vesicles and their effects on immortalized human retinal Müller cells
title_short Human embryonic stem cells extracellular vesicles and their effects on immortalized human retinal Müller cells
title_sort human embryonic stem cells extracellular vesicles and their effects on immortalized human retinal müller cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5851617/
https://www.ncbi.nlm.nih.gov/pubmed/29538408
http://dx.doi.org/10.1371/journal.pone.0194004
work_keys_str_mv AT pengyingqian humanembryonicstemcellsextracellularvesiclesandtheireffectsonimmortalizedhumanretinalmullercells
AT baulieredouard humanembryonicstemcellsextracellularvesiclesandtheireffectsonimmortalizedhumanretinalmullercells
AT keyifeng humanembryonicstemcellsextracellularvesiclesandtheireffectsonimmortalizedhumanretinalmullercells
AT youngalejandra humanembryonicstemcellsextracellularvesiclesandtheireffectsonimmortalizedhumanretinalmullercells
AT ahmedlinovruzb humanembryonicstemcellsextracellularvesiclesandtheireffectsonimmortalizedhumanretinalmullercells
AT schwartzstevend humanembryonicstemcellsextracellularvesiclesandtheireffectsonimmortalizedhumanretinalmullercells
AT farberdeborab humanembryonicstemcellsextracellularvesiclesandtheireffectsonimmortalizedhumanretinalmullercells