title: Intracoronary Transplantation of Mesenchymal Stem Cells with Overexpressed Integrin-Linked Kinase Improves Cardiac Function in Porcine Myocardial Infarction.
abstract: The effect of mesenchymal stem cell (MSCs)-based therapy on treating acute myocardial infarction (MI) is limited due to poor engraftment and limited regenerative potential. Here we engineered MSCs with integrin-linked kinase (ILK), a pleiotropic protein critically regulating cell survival, proliferation, differentiation, and angiogenesis. We firstly combined ferumoxytol with poly-L-lysine (PLL), and found this combination promisingly enabled MRI visualization of MSCs in vitro and in vivo with good safety. We provided visually direct evidence that intracoronary ILK-MSCs had substantially enhanced homing capacity to infarct myocardium in porcine following cardiac catheterization induced MI. Intracoronary transplantation of allogeneic ILK-MSCs, but not vector-MSCs, significantly enhanced global left ventricular ejection fraction (LVEF) by 7.8% compared with baseline, by 10.3% compared with vehicles, and inhibited myocardial remodeling compared with vehicles at 15-day follow-up. Compared with vector-MSCs, ILK-MSCs significantly improved regional LV contractile function, reduced scar size, fibrosis, cell apoptosis, and increased regional myocardial perfusion and cell proliferation. This preclinical study indicates that ILK-engineered MSCs might promote the clinical translation of MSC-based therapy in post-MI patients, and provides evidence that ferumoxytol labeling of cells combined with PLL is feasible in in vivo cell tracking.
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.|Department of Radiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Mu
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Xin-Lin
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Yuan
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Guan-Nan
authors.initials: GN
authors.lastname: Li
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Jian-Rong
authors.initials: JR
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Mao
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Radiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Le
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Radiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Mai
authors.affiliation: Department of Pathology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Radiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Chuan-Shuai
authors.initials: CS
authors.lastname: Tian
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Kang
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Gu
authors.affiliation: Department of Radiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
mesh_terms: D000818:Animals; D058948:Cell Tracking; D003326:Coronary Circulation; D004195:Disease Models, Animal; D015870:Gene Expression; D017930:Genes, Reporter; D015316:Genetic Therapy; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D057054:Molecular Imaging; D009203:Myocardial Infarction / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D032383:Myocytes, Cardiac / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013552:Swine; D016277:Ventricular Function, Left; D000099200:Scaffold Protein ILK
chemical_list: D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK