Use of Amniotic Microparticles Coated with Fibroblasts Overexpressing SDF-1a to Create an Environment Conducive to Neovascularization for Repair of Full-Thickness Skin Defects

As angiogenesis and vasculogenesis involve the complex network structures of various types of cells, extracellular matrix components, and cytokines, it is still difficult to exactly mimic the microenvironment of vascularization in vivo. In our study, we constructed a complex containing highly prolif...

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Main Authors: Yun-Qing Zhang, Shi-Zhao Ji, He Fang, Yong-Jun Zheng, Peng-Fei Luo, Hai-Bin Wu, Min-Juan Wu, Zhi-Hong Wang, Shi-Chu Xiao, Zhao-Fan Xia
Format: Article
Language:English
Published: SAGE Publishing 2016-02-01
Series:Cell Transplantation
Online Access:https://doi.org/10.3727/096368915X687930
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author Yun-Qing Zhang
Shi-Zhao Ji
He Fang
Yong-Jun Zheng
Peng-Fei Luo
Hai-Bin Wu
Min-Juan Wu
Zhi-Hong Wang
Shi-Chu Xiao
Zhao-Fan Xia
author_facet Yun-Qing Zhang
Shi-Zhao Ji
He Fang
Yong-Jun Zheng
Peng-Fei Luo
Hai-Bin Wu
Min-Juan Wu
Zhi-Hong Wang
Shi-Chu Xiao
Zhao-Fan Xia
author_sort Yun-Qing Zhang
collection DOAJ
description As angiogenesis and vasculogenesis involve the complex network structures of various types of cells, extracellular matrix components, and cytokines, it is still difficult to exactly mimic the microenvironment of vascularization in vivo. In our study, we constructed a complex containing highly proliferative fibroblasts that can secrete extracellular matrix components and growth factors to chemotaxize endothelial progenitor cells (EPCs) in an attempt to create an ideal microenvironment for quick vascularization. Amniotic membrane microparticles (mAM) rich in type IV collagen (COL IV) and laminin (LN) were prepared, and human dermal fibroblasts (HDF) were infected with lentivirus (LV) of overexpression of SDF-1α to construct SDF-1α ov HDF. Using the rotary cell culture system (RCCS), mAM was loaded with HDF or SDF-1α ov HDF to construct HDF-mAM and SDF-1α ov HDF-mAM complexes. The complexes were able to secrete various types of active peptides (IL-6, IL-8, TGF-β, and bFGF) during in vitro culture. In addition, SDF-1α ov HDF-mAM complex highly expressed SDF-1α. Transwell assay showed SDF-1α ov HDF-mAM complex had an apparent chemotactic effect on EPCs. Transplantation of complexes onto full-thickness skin defects of C57BL mice further demonstrated that SDF-1α expression and the number of peripheral EPCs at days 3, 5, and 7 in the SDF-1α ov HDF-mAM group were significantly higher than that in other groups ( p < 0.01). The local microvascular density at day 10 of transplantation showed that the microvascular density in the SDF-1α ov HDF-mAM group was significantly higher than that in HDF-mAM group ( p < 0.01). In conclusion, HDF-mAM had a strong proliferative activity and could be used to create a sound microenvironment for quick vascularization by secreting multiple cytokines and extracellular matrix components. Overexpression of SDF-1α could chemotaxize EPCs to reach local wounds, thus further accelerating angiogenesis in the transplant site. The technique described may prove to be a new model for accelerating vascularization of tissue and organ transplants and chronic ischemic wounds.
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spelling doaj.art-3d09dc6d27a74d018731760df04d34c72022-12-22T00:16:53ZengSAGE PublishingCell Transplantation0963-68971555-38922016-02-012510.3727/096368915X687930Use of Amniotic Microparticles Coated with Fibroblasts Overexpressing SDF-1a to Create an Environment Conducive to Neovascularization for Repair of Full-Thickness Skin DefectsYun-Qing Zhang0Shi-Zhao Ji1He Fang2Yong-Jun Zheng3Peng-Fei Luo4Hai-Bin Wu5Min-Juan Wu6Zhi-Hong Wang7Shi-Chu Xiao8Zhao-Fan Xia9 Burns Institute of People's Liberation Army, Changhai Hospital, the Second Military Medical University, Shanghai, People's Republic of China Burns Institute of People's Liberation Army, Changhai Hospital, the Second Military Medical University, Shanghai, People's Republic of China Burns Institute of People's Liberation Army, Changhai Hospital, the Second Military Medical University, Shanghai, People's Republic of China Burns Institute of People's Liberation Army, Changhai Hospital, the Second Military Medical University, Shanghai, People's Republic of China Burns Institute of People's Liberation Army, Changhai Hospital, the Second Military Medical University, Shanghai, People's Republic of China Burns Institute of People's Liberation Army, Changhai Hospital, the Second Military Medical University, Shanghai, People's Republic of China Department of Histology and Embryology, College of Basic Medical Science, the Second Military Medical University, Shanghai, People's Republic of China Burns Institute of People's Liberation Army, Changhai Hospital, the Second Military Medical University, Shanghai, People's Republic of China Burns Institute of People's Liberation Army, Changhai Hospital, the Second Military Medical University, Shanghai, People's Republic of China Burns Institute of People's Liberation Army, Changhai Hospital, the Second Military Medical University, Shanghai, People's Republic of ChinaAs angiogenesis and vasculogenesis involve the complex network structures of various types of cells, extracellular matrix components, and cytokines, it is still difficult to exactly mimic the microenvironment of vascularization in vivo. In our study, we constructed a complex containing highly proliferative fibroblasts that can secrete extracellular matrix components and growth factors to chemotaxize endothelial progenitor cells (EPCs) in an attempt to create an ideal microenvironment for quick vascularization. Amniotic membrane microparticles (mAM) rich in type IV collagen (COL IV) and laminin (LN) were prepared, and human dermal fibroblasts (HDF) were infected with lentivirus (LV) of overexpression of SDF-1α to construct SDF-1α ov HDF. Using the rotary cell culture system (RCCS), mAM was loaded with HDF or SDF-1α ov HDF to construct HDF-mAM and SDF-1α ov HDF-mAM complexes. The complexes were able to secrete various types of active peptides (IL-6, IL-8, TGF-β, and bFGF) during in vitro culture. In addition, SDF-1α ov HDF-mAM complex highly expressed SDF-1α. Transwell assay showed SDF-1α ov HDF-mAM complex had an apparent chemotactic effect on EPCs. Transplantation of complexes onto full-thickness skin defects of C57BL mice further demonstrated that SDF-1α expression and the number of peripheral EPCs at days 3, 5, and 7 in the SDF-1α ov HDF-mAM group were significantly higher than that in other groups ( p < 0.01). The local microvascular density at day 10 of transplantation showed that the microvascular density in the SDF-1α ov HDF-mAM group was significantly higher than that in HDF-mAM group ( p < 0.01). In conclusion, HDF-mAM had a strong proliferative activity and could be used to create a sound microenvironment for quick vascularization by secreting multiple cytokines and extracellular matrix components. Overexpression of SDF-1α could chemotaxize EPCs to reach local wounds, thus further accelerating angiogenesis in the transplant site. The technique described may prove to be a new model for accelerating vascularization of tissue and organ transplants and chronic ischemic wounds.https://doi.org/10.3727/096368915X687930
spellingShingle Yun-Qing Zhang
Shi-Zhao Ji
He Fang
Yong-Jun Zheng
Peng-Fei Luo
Hai-Bin Wu
Min-Juan Wu
Zhi-Hong Wang
Shi-Chu Xiao
Zhao-Fan Xia
Use of Amniotic Microparticles Coated with Fibroblasts Overexpressing SDF-1a to Create an Environment Conducive to Neovascularization for Repair of Full-Thickness Skin Defects
Cell Transplantation
title Use of Amniotic Microparticles Coated with Fibroblasts Overexpressing SDF-1a to Create an Environment Conducive to Neovascularization for Repair of Full-Thickness Skin Defects
title_full Use of Amniotic Microparticles Coated with Fibroblasts Overexpressing SDF-1a to Create an Environment Conducive to Neovascularization for Repair of Full-Thickness Skin Defects
title_fullStr Use of Amniotic Microparticles Coated with Fibroblasts Overexpressing SDF-1a to Create an Environment Conducive to Neovascularization for Repair of Full-Thickness Skin Defects
title_full_unstemmed Use of Amniotic Microparticles Coated with Fibroblasts Overexpressing SDF-1a to Create an Environment Conducive to Neovascularization for Repair of Full-Thickness Skin Defects
title_short Use of Amniotic Microparticles Coated with Fibroblasts Overexpressing SDF-1a to Create an Environment Conducive to Neovascularization for Repair of Full-Thickness Skin Defects
title_sort use of amniotic microparticles coated with fibroblasts overexpressing sdf 1a to create an environment conducive to neovascularization for repair of full thickness skin defects
url https://doi.org/10.3727/096368915X687930
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