Early Growth Response Genes Signaling Supports Strong Paracrine Capability of Mesenchymal Stem Cells

MSCs provide a promising method for cell therapy through their wound healing and tissue regenerative properties. Originally, MSCs' role in wound healing was thought to be tied to their multipotency, but it is now accepted that MSCs mediate the healing process through their strong paracrine capa...

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Main Authors: Kenichi Tamama, Dominique J. Barbeau
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2012/428403
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author Kenichi Tamama
Dominique J. Barbeau
author_facet Kenichi Tamama
Dominique J. Barbeau
author_sort Kenichi Tamama
collection DOAJ
description MSCs provide a promising method for cell therapy through their wound healing and tissue regenerative properties. Originally, MSCs' role in wound healing was thought to be tied to their multipotency, but it is now accepted that MSCs mediate the healing process through their strong paracrine capability. EGF was shown to facilitate in vitro expansion of MSCs without altering multipotency. Our previous data suggest that the molecular machinery underlying MSCs' strong paracrine capability lies downstream of EGFR signaling, and we focus on transcription factors EGR1 and EGR2. Evidence suggests that EGR1 regulates angiogenic and fibrogenic factor production in MSCs, and an EGFR-EGR1-EGFR ligands autocrine loop is one of the underlying mechanisms supporting their strong paracrine machinery through EGR1. EGR2 appears to regulate the expression of immunomodulatory molecules. Chronic nonhealing wounds are ischemic, inflammatory, and often fibrotic, and the hypoxic micro-environment of these wounds may compromise MSCs' wound healing properties in vivo by upregulating the EGR1's fibrogenic effects and downregulating the EGR2's immuno-modulatory effects. Thus, these transcription factors can be potential targets in the optimization of cell-based therapies. Further study in vitro is required to understand MSCs' paracrine machinery and to optimize it as a tool for effective cell-based therapies.
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spelling doaj-art-442ce3a8c2184b279a1f50d724d1f0082025-02-03T05:50:14ZengWileyStem Cells International1687-966X1687-96782012-01-01201210.1155/2012/428403428403Early Growth Response Genes Signaling Supports Strong Paracrine Capability of Mesenchymal Stem CellsKenichi Tamama0Dominique J. Barbeau1Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USAMSCs provide a promising method for cell therapy through their wound healing and tissue regenerative properties. Originally, MSCs' role in wound healing was thought to be tied to their multipotency, but it is now accepted that MSCs mediate the healing process through their strong paracrine capability. EGF was shown to facilitate in vitro expansion of MSCs without altering multipotency. Our previous data suggest that the molecular machinery underlying MSCs' strong paracrine capability lies downstream of EGFR signaling, and we focus on transcription factors EGR1 and EGR2. Evidence suggests that EGR1 regulates angiogenic and fibrogenic factor production in MSCs, and an EGFR-EGR1-EGFR ligands autocrine loop is one of the underlying mechanisms supporting their strong paracrine machinery through EGR1. EGR2 appears to regulate the expression of immunomodulatory molecules. Chronic nonhealing wounds are ischemic, inflammatory, and often fibrotic, and the hypoxic micro-environment of these wounds may compromise MSCs' wound healing properties in vivo by upregulating the EGR1's fibrogenic effects and downregulating the EGR2's immuno-modulatory effects. Thus, these transcription factors can be potential targets in the optimization of cell-based therapies. Further study in vitro is required to understand MSCs' paracrine machinery and to optimize it as a tool for effective cell-based therapies.http://dx.doi.org/10.1155/2012/428403
spellingShingle Kenichi Tamama
Dominique J. Barbeau
Early Growth Response Genes Signaling Supports Strong Paracrine Capability of Mesenchymal Stem Cells
Stem Cells International
title Early Growth Response Genes Signaling Supports Strong Paracrine Capability of Mesenchymal Stem Cells
title_full Early Growth Response Genes Signaling Supports Strong Paracrine Capability of Mesenchymal Stem Cells
title_fullStr Early Growth Response Genes Signaling Supports Strong Paracrine Capability of Mesenchymal Stem Cells
title_full_unstemmed Early Growth Response Genes Signaling Supports Strong Paracrine Capability of Mesenchymal Stem Cells
title_short Early Growth Response Genes Signaling Supports Strong Paracrine Capability of Mesenchymal Stem Cells
title_sort early growth response genes signaling supports strong paracrine capability of mesenchymal stem cells
url http://dx.doi.org/10.1155/2012/428403
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