Molecular strategy to reduce in vivo collagen barrier promotes entry of NCX1 positive inducible pluripotent stem cells (iPSC(NCX¹⁺)) into ischemic (or injured) myocardium.
OBJECTIVE:The purpose of this study was to assess the effect of collagen composition on engraftment of progenitor cells within infarcted myocardium. BACKGROUND:We previously reported that intramyocardial penetration of stem/progenitor cells in epicardial patches was enhanced when collagen was reduce...
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doaj-a51dc0b082b14502802745f7084e9ec42020-11-25T00:08:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7002310.1371/journal.pone.0070023Molecular strategy to reduce in vivo collagen barrier promotes entry of NCX1 positive inducible pluripotent stem cells (iPSC(NCX¹⁺)) into ischemic (or injured) myocardium.Wei HuangBo DaiZhili WenRonald W MillardXi-Yong YuKristin LutherMeifeng XuTing C ZhaoHuang-Tian YangZhihua QiKathleen LasanceMuhammad AshrafYigang WangOBJECTIVE:The purpose of this study was to assess the effect of collagen composition on engraftment of progenitor cells within infarcted myocardium. BACKGROUND:We previously reported that intramyocardial penetration of stem/progenitor cells in epicardial patches was enhanced when collagen was reduced in hearts overexpressing adenylyl cyclase-6 (AC6). In this study we hypothesized an alternative strategy wherein overexpression of microRNA-29b (miR-29b), inhibiting mRNAs that encode cardiac fibroblast proteins involved in fibrosis, would similarly facilitate progenitor cell migration into infarcted rat myocardium. METHODS:In vitro: A tri-cell patch (Tri-P) consisting of cardiac sodium-calcium exchanger-1 (NCX1) positive iPSC (iPSC(NCX1+)), endothelial cells (EC), and mouse embryonic fibroblasts (MEF) was created, co-cultured, and seeded on isolated peritoneum. The expression of fibrosis-related genes was analyzed in cardiac fibroblasts (CFb) by qPCR and Western blot. In vivo: Nude rat hearts were administered mimic miRNA-29b (miR-29b), miRNA-29b inhibitor (Anti-29b), or negative mimic (Ctrl) before creation of an ischemically induced regional myocardial infarction (MI). The Tri-P was placed over the infarcted region 7 days later. Angiomyogenesis was analyzed by micro-CT imaging and immunofluorescent staining. Echocardiography was performed weekly. RESULTS:The number of green fluorescent protein positive (GFP(+)) cells, capillary density, and heart function were significantly increased in hearts overexpressing miR-29b as compared with Ctrl and Anti-29b groups. Conversely, down-regulation of miR-29b with anti-29b in vitro and in vivo induced interstitial fibrosis and cardiac remodeling. CONCLUSION:Overexpression of miR-29b significantly reduced scar formation after MI and facilitated iPSC(NCX1+) penetration from the cell patch into the infarcted area, resulting in restoration of heart function after MI.http://europepmc.org/articles/PMC3749126?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wei Huang Bo Dai Zhili Wen Ronald W Millard Xi-Yong Yu Kristin Luther Meifeng Xu Ting C Zhao Huang-Tian Yang Zhihua Qi Kathleen Lasance Muhammad Ashraf Yigang Wang |
spellingShingle |
Wei Huang Bo Dai Zhili Wen Ronald W Millard Xi-Yong Yu Kristin Luther Meifeng Xu Ting C Zhao Huang-Tian Yang Zhihua Qi Kathleen Lasance Muhammad Ashraf Yigang Wang Molecular strategy to reduce in vivo collagen barrier promotes entry of NCX1 positive inducible pluripotent stem cells (iPSC(NCX¹⁺)) into ischemic (or injured) myocardium. PLoS ONE |
author_facet |
Wei Huang Bo Dai Zhili Wen Ronald W Millard Xi-Yong Yu Kristin Luther Meifeng Xu Ting C Zhao Huang-Tian Yang Zhihua Qi Kathleen Lasance Muhammad Ashraf Yigang Wang |
author_sort |
Wei Huang |
title |
Molecular strategy to reduce in vivo collagen barrier promotes entry of NCX1 positive inducible pluripotent stem cells (iPSC(NCX¹⁺)) into ischemic (or injured) myocardium. |
title_short |
Molecular strategy to reduce in vivo collagen barrier promotes entry of NCX1 positive inducible pluripotent stem cells (iPSC(NCX¹⁺)) into ischemic (or injured) myocardium. |
title_full |
Molecular strategy to reduce in vivo collagen barrier promotes entry of NCX1 positive inducible pluripotent stem cells (iPSC(NCX¹⁺)) into ischemic (or injured) myocardium. |
title_fullStr |
Molecular strategy to reduce in vivo collagen barrier promotes entry of NCX1 positive inducible pluripotent stem cells (iPSC(NCX¹⁺)) into ischemic (or injured) myocardium. |
title_full_unstemmed |
Molecular strategy to reduce in vivo collagen barrier promotes entry of NCX1 positive inducible pluripotent stem cells (iPSC(NCX¹⁺)) into ischemic (or injured) myocardium. |
title_sort |
molecular strategy to reduce in vivo collagen barrier promotes entry of ncx1 positive inducible pluripotent stem cells (ipsc(ncx¹⁺)) into ischemic (or injured) myocardium. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
OBJECTIVE:The purpose of this study was to assess the effect of collagen composition on engraftment of progenitor cells within infarcted myocardium. BACKGROUND:We previously reported that intramyocardial penetration of stem/progenitor cells in epicardial patches was enhanced when collagen was reduced in hearts overexpressing adenylyl cyclase-6 (AC6). In this study we hypothesized an alternative strategy wherein overexpression of microRNA-29b (miR-29b), inhibiting mRNAs that encode cardiac fibroblast proteins involved in fibrosis, would similarly facilitate progenitor cell migration into infarcted rat myocardium. METHODS:In vitro: A tri-cell patch (Tri-P) consisting of cardiac sodium-calcium exchanger-1 (NCX1) positive iPSC (iPSC(NCX1+)), endothelial cells (EC), and mouse embryonic fibroblasts (MEF) was created, co-cultured, and seeded on isolated peritoneum. The expression of fibrosis-related genes was analyzed in cardiac fibroblasts (CFb) by qPCR and Western blot. In vivo: Nude rat hearts were administered mimic miRNA-29b (miR-29b), miRNA-29b inhibitor (Anti-29b), or negative mimic (Ctrl) before creation of an ischemically induced regional myocardial infarction (MI). The Tri-P was placed over the infarcted region 7 days later. Angiomyogenesis was analyzed by micro-CT imaging and immunofluorescent staining. Echocardiography was performed weekly. RESULTS:The number of green fluorescent protein positive (GFP(+)) cells, capillary density, and heart function were significantly increased in hearts overexpressing miR-29b as compared with Ctrl and Anti-29b groups. Conversely, down-regulation of miR-29b with anti-29b in vitro and in vivo induced interstitial fibrosis and cardiac remodeling. CONCLUSION:Overexpression of miR-29b significantly reduced scar formation after MI and facilitated iPSC(NCX1+) penetration from the cell patch into the infarcted area, resulting in restoration of heart function after MI. |
url |
http://europepmc.org/articles/PMC3749126?pdf=render |
work_keys_str_mv |
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