Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced Neovascularization

Background/Aims: Transplantation of mesenchymal stem cells (MSCs) improves post-injury cardiac muscle repair using ill-defined mechanisms. Recently, we have shown that production and secretion of placental growth factor (PLGF) by MSCs play a critical role in the MSCs-mediated post-injury cardiac mus...

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Main Authors: Jianfeng Zhang, Anqing Chen, Yicheng Wu, Qiang Zhao
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2015-06-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:http://www.karger.com/Article/FullText/430269
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author Jianfeng Zhang
Anqing Chen
Yicheng Wu
Qiang Zhao
author_facet Jianfeng Zhang
Anqing Chen
Yicheng Wu
Qiang Zhao
author_sort Jianfeng Zhang
collection DOAJ
description Background/Aims: Transplantation of mesenchymal stem cells (MSCs) improves post-injury cardiac muscle repair using ill-defined mechanisms. Recently, we have shown that production and secretion of placental growth factor (PLGF) by MSCs play a critical role in the MSCs-mediated post-injury cardiac muscle repair. In this study, we addressed the underlying molecular mechanisms, focusing specifically on the interactions between MSCs, macrophages and endothelial cells. Methods: We isolated macrophages (BM-MΦ) from mouse bone-marrow derived cells based on F4/80 expression by flow cytometry. BM-MΦ were treated with different doses of PLGF. Cell number was analyzed by a MTT assay. Macrophage polarization was examined based on CD206 expression by flow cytometry. PLGF levels in macrophage subpopulations were analyzed by RT-qPCR and ELISA. Effects of macrophages on vascularization were evaluated by a collagen gel assay using Human umbilical vein endothelial cells (HUVECs) co-cultured with PLGF-treated macrophages. Results: PLGF did not increase macrophage number, but dose-dependently polarized macrophages into a M2 subpopulation. M2 macrophages expressed high levels of PLGF. PLGF-polarized M2 macrophages significantly increased tubular structures in the collagen gel assay. Conclusion: Our data suggest that MSCs-derived PLGF may induce macrophage polarization into a M2 subpopulation, which in turn releases more PLGF to promote local neovascularization for augmenting post-injury cardiac muscle repair. This study thus sheds novel light on the role of PLGF in cardiac muscle regeneration.
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spelling doaj.art-67e152eb89db4b1c83bfd4c58166fce72022-12-21T18:26:37ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-06-0136394795510.1159/000430269430269Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced NeovascularizationJianfeng ZhangAnqing ChenYicheng WuQiang ZhaoBackground/Aims: Transplantation of mesenchymal stem cells (MSCs) improves post-injury cardiac muscle repair using ill-defined mechanisms. Recently, we have shown that production and secretion of placental growth factor (PLGF) by MSCs play a critical role in the MSCs-mediated post-injury cardiac muscle repair. In this study, we addressed the underlying molecular mechanisms, focusing specifically on the interactions between MSCs, macrophages and endothelial cells. Methods: We isolated macrophages (BM-MΦ) from mouse bone-marrow derived cells based on F4/80 expression by flow cytometry. BM-MΦ were treated with different doses of PLGF. Cell number was analyzed by a MTT assay. Macrophage polarization was examined based on CD206 expression by flow cytometry. PLGF levels in macrophage subpopulations were analyzed by RT-qPCR and ELISA. Effects of macrophages on vascularization were evaluated by a collagen gel assay using Human umbilical vein endothelial cells (HUVECs) co-cultured with PLGF-treated macrophages. Results: PLGF did not increase macrophage number, but dose-dependently polarized macrophages into a M2 subpopulation. M2 macrophages expressed high levels of PLGF. PLGF-polarized M2 macrophages significantly increased tubular structures in the collagen gel assay. Conclusion: Our data suggest that MSCs-derived PLGF may induce macrophage polarization into a M2 subpopulation, which in turn releases more PLGF to promote local neovascularization for augmenting post-injury cardiac muscle repair. This study thus sheds novel light on the role of PLGF in cardiac muscle regeneration.http://www.karger.com/Article/FullText/430269Mesenchymal stem cells (MSCs)Cardiac muscle repairPlacental growth factor (PLGF)Macrophage polarization
spellingShingle Jianfeng Zhang
Anqing Chen
Yicheng Wu
Qiang Zhao
Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced Neovascularization
Cellular Physiology and Biochemistry
Mesenchymal stem cells (MSCs)
Cardiac muscle repair
Placental growth factor (PLGF)
Macrophage polarization
title Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced Neovascularization
title_full Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced Neovascularization
title_fullStr Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced Neovascularization
title_full_unstemmed Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced Neovascularization
title_short Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced Neovascularization
title_sort placental growth factor promotes cardiac muscle repair via enhanced neovascularization
topic Mesenchymal stem cells (MSCs)
Cardiac muscle repair
Placental growth factor (PLGF)
Macrophage polarization
url http://www.karger.com/Article/FullText/430269
work_keys_str_mv AT jianfengzhang placentalgrowthfactorpromotescardiacmusclerepairviaenhancedneovascularization
AT anqingchen placentalgrowthfactorpromotescardiacmusclerepairviaenhancedneovascularization
AT yichengwu placentalgrowthfactorpromotescardiacmusclerepairviaenhancedneovascularization
AT qiangzhao placentalgrowthfactorpromotescardiacmusclerepairviaenhancedneovascularization