title: A VEGF delivery system targeting MI improves angiogenesis and cardiac function based on the tropism of MSCs and layer-by-layer self-assembly.
abstract: Myocardial infarction (MI) is a serious ischemic condition affecting many individuals around the world. Vascular endothelial growth factor (VEGF) is considered a promising factor for enhancing cardiac function by promoting angiogenesis. However, the lack of a suitable method of VEGF delivery to the MI area is a serious challenge. In this study, we screened a suitable delivery carrier with favorable biocompatibility that targeted the MI area using the strategy of an inherent structure derived from the body and that was based on characteristics of the MI. Mesenchymal stem cells (MSCs) are important infiltrating cells that are derived from blood and have an inherent tropism for the MI zone. We hypothesized that VEGF-encapsulated MSCs targeting MI tissue could improve cardiac function by angiogenesis based on the tropism of the MSCs to the MI area. We first developed VEGF-encapsulated MSCs using self-assembled gelatin and alginate polyelectrolytes to improve angiogenesis and cardiac function. In vitro, the results showed that VEGF-encapsulated MSCs had a sustained release of VEGF and tropism to SDF-1. In vivo, VEGF-encapsulated MSCs migrated to the MI area, enhanced cardiac function, perfused the infarcted area and promoted angiogenesis. These preclinical findings suggest that VEGF-loaded layer-by-layer self-assembled encapsulated MSCs may be a promising and minimally invasive therapy for treating MI. Furthermore, other drugs loaded to layer-by-layer self-assembled encapsulated MSCs may be promising therapies for treating other diseases.
authors.affiliation: Department of Anatomy, National & Regional Engineering Laboratory of Tissue Engineering, State and Local Joint Engineering Laboratory for Vascular Implants, Key Lab for Biomechanics and Tissue Engineering of Chongqing, State Key Laboratory of Trauma, burn and Combined injury, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Anatomy, National & Regional Engineering Laboratory of Tissue Engineering, State and Local Joint Engineering Laboratory for Vascular Implants, Key Lab for Biomechanics and Tissue Engineering of Chongqing, State Key Laboratory of Trauma, burn and Combined injury, Third Military Medical University, Chongqing 400038, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Anatomy, National & Regional Engineering Laboratory of Tissue Engineering, State and Local Joint Engineering Laboratory for Vascular Implants, Key Lab for Biomechanics and Tissue Engineering of Chongqing, State Key Laboratory of Trauma, burn and Combined injury, Third Military Medical University, Chongqing 400038, China.
authors.forename: Da
authors.initials: D
authors.lastname: Huo
authors.affiliation: Department of Anatomy, National & Regional Engineering Laboratory of Tissue Engineering, State and Local Joint Engineering Laboratory for Vascular Implants, Key Lab for Biomechanics and Tissue Engineering of Chongqing, State Key Laboratory of Trauma, burn and Combined injury, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yanzhao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anatomy, National & Regional Engineering Laboratory of Tissue Engineering, State and Local Joint Engineering Laboratory for Vascular Implants, Key Lab for Biomechanics and Tissue Engineering of Chongqing, State Key Laboratory of Trauma, burn and Combined injury, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yangxiao
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Anatomy, National & Regional Engineering Laboratory of Tissue Engineering, State and Local Joint Engineering Laboratory for Vascular Implants, Key Lab for Biomechanics and Tissue Engineering of Chongqing, State Key Laboratory of Trauma, burn and Combined injury, Third Military Medical University, Chongqing 400038, China.
authors.forename: Lingqing
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Anatomy, National & Regional Engineering Laboratory of Tissue Engineering, State and Local Joint Engineering Laboratory for Vascular Implants, Key Lab for Biomechanics and Tissue Engineering of Chongqing, State Key Laboratory of Trauma, burn and Combined injury, Third Military Medical University, Chongqing 400038, China.
authors.forename: Panke
authors.initials: P
authors.lastname: Cheng
authors.affiliation: Department of Mechanical Engineering, Biochemistry & Medical Genetics, University of Manitoba, 75A Chancellors Circle, Winnipeg, Manitoba R3T 2N2, Canada; Manitoba Institute of Child Health, 715 McDermot Ave, Winnipeg, Manitoba R3E3P4, Canada.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Xing
authors.affiliation: Department of Anatomy, National & Regional Engineering Laboratory of Tissue Engineering, State and Local Joint Engineering Laboratory for Vascular Implants, Key Lab for Biomechanics and Tissue Engineering of Chongqing, State Key Laboratory of Trauma, burn and Combined injury, Third Military Medical University, Chongqing 400038, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Anatomy, National & Regional Engineering Laboratory of Tissue Engineering, State and Local Joint Engineering Laboratory for Vascular Implants, Key Lab for Biomechanics and Tissue Engineering of Chongqing, State Key Laboratory of Trauma, burn and Combined injury, Third Military Medical University, Chongqing 400038, China. Electronic address: Zhuch99@yahoo.com.
authors.forename: Chuhong
authors.initials: C
authors.lastname: Zhu
mesh_terms: D000818:Animals; D048430:Cell Shape; D054377:Chemokine CXCL12 / Q000378:metabolism; D016503:Drug Delivery Systems; D004562:Electrocardiography; D006334:Heart Function Tests; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010477:Perfusion; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000378:metabolism; D013997:Time Factors; D018523:Tropism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology / Q000627:therapeutic use*; D055114:X-Ray Microtomography
chemical_list: D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A
keywords: Layer-by-layer self-assembly; Myocardial infarction; Targeting VEGF-encapsulated MSCs; Tropism to the MI zone