Over-expression of HSP47 augments mouse embryonic stem cell smooth muscle differentiation and chemotaxis.

In the recent decade, embryonic stem cells (ESC) have emerged as an attractive cell source of smooth muscle cells (SMC) for vascular tissue engineering owing to their unlimited self-renewal and differentiation capacities. Despite their promise in therapy, their efficacy is still hampered by the lack...

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Main Authors: Mei Mei Wong, Xiaoke Yin, Claire Potter, Baoqi Yu, Hao Cai, Elisabetta Di Bernardini, Qingbo Xu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0086118
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author Mei Mei Wong
Xiaoke Yin
Claire Potter
Baoqi Yu
Hao Cai
Elisabetta Di Bernardini
Qingbo Xu
author_facet Mei Mei Wong
Xiaoke Yin
Claire Potter
Baoqi Yu
Hao Cai
Elisabetta Di Bernardini
Qingbo Xu
author_sort Mei Mei Wong
collection DOAJ
description In the recent decade, embryonic stem cells (ESC) have emerged as an attractive cell source of smooth muscle cells (SMC) for vascular tissue engineering owing to their unlimited self-renewal and differentiation capacities. Despite their promise in therapy, their efficacy is still hampered by the lack of definitive SMC differentiation mechanisms and difficulties in successful trafficking of the ESC towards a site of injury or target tissue. Heat shock protein 47 (HSP47) is a 47-kDa molecular chaperone that is required for the maturation of various types of collagen and has been shown to be a critical modulator of different pathological and physiological processes. To date, the role of HSP47 on ESC to SMC differentiation or ESC chemotaxis is not known and may represent a potential molecular approach by which ESC can be manipulated to increase their efficacy in clinic. We provide evidence that HSP47 is highly expressed during ESC differentiation into the SMC lineage and that HSP47 reduction results in an attenuation of the differentiation. Our experiments using a HSP47 plasmid transfection system show that gene over-expression is sufficient to induce ESC-SMC differentiation, even in the absence of exogenous stimuli. Furthermore, HSP47 over-expression in ESC also increases their chemotaxis and migratory responses towards a panel of chemokines, likely via the upregulation of chemokine receptors. Our findings provide direct evidence of induced ESC migration and differentiation into SMC via the over-expression of HSP47, thus identifying a novel approach of molecular manipulation that can potentially be exploited to improve stem cell therapy for vascular repair and regeneration.
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spelling doaj-art-e3fce1c9e37b45c8ab6519e1938f47882025-08-20T03:11:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8611810.1371/journal.pone.0086118Over-expression of HSP47 augments mouse embryonic stem cell smooth muscle differentiation and chemotaxis.Mei Mei WongXiaoke YinClaire PotterBaoqi YuHao CaiElisabetta Di BernardiniQingbo XuIn the recent decade, embryonic stem cells (ESC) have emerged as an attractive cell source of smooth muscle cells (SMC) for vascular tissue engineering owing to their unlimited self-renewal and differentiation capacities. Despite their promise in therapy, their efficacy is still hampered by the lack of definitive SMC differentiation mechanisms and difficulties in successful trafficking of the ESC towards a site of injury or target tissue. Heat shock protein 47 (HSP47) is a 47-kDa molecular chaperone that is required for the maturation of various types of collagen and has been shown to be a critical modulator of different pathological and physiological processes. To date, the role of HSP47 on ESC to SMC differentiation or ESC chemotaxis is not known and may represent a potential molecular approach by which ESC can be manipulated to increase their efficacy in clinic. We provide evidence that HSP47 is highly expressed during ESC differentiation into the SMC lineage and that HSP47 reduction results in an attenuation of the differentiation. Our experiments using a HSP47 plasmid transfection system show that gene over-expression is sufficient to induce ESC-SMC differentiation, even in the absence of exogenous stimuli. Furthermore, HSP47 over-expression in ESC also increases their chemotaxis and migratory responses towards a panel of chemokines, likely via the upregulation of chemokine receptors. Our findings provide direct evidence of induced ESC migration and differentiation into SMC via the over-expression of HSP47, thus identifying a novel approach of molecular manipulation that can potentially be exploited to improve stem cell therapy for vascular repair and regeneration.https://doi.org/10.1371/journal.pone.0086118
spellingShingle Mei Mei Wong
Xiaoke Yin
Claire Potter
Baoqi Yu
Hao Cai
Elisabetta Di Bernardini
Qingbo Xu
Over-expression of HSP47 augments mouse embryonic stem cell smooth muscle differentiation and chemotaxis.
PLoS ONE
title Over-expression of HSP47 augments mouse embryonic stem cell smooth muscle differentiation and chemotaxis.
title_full Over-expression of HSP47 augments mouse embryonic stem cell smooth muscle differentiation and chemotaxis.
title_fullStr Over-expression of HSP47 augments mouse embryonic stem cell smooth muscle differentiation and chemotaxis.
title_full_unstemmed Over-expression of HSP47 augments mouse embryonic stem cell smooth muscle differentiation and chemotaxis.
title_short Over-expression of HSP47 augments mouse embryonic stem cell smooth muscle differentiation and chemotaxis.
title_sort over expression of hsp47 augments mouse embryonic stem cell smooth muscle differentiation and chemotaxis
url https://doi.org/10.1371/journal.pone.0086118
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