title: Intravenous Followed by X-ray Fused with MRI-Guided Transendocardial Mesenchymal Stem Cell Injection Improves Contractility Reserve in a Swine Model of Myocardial Infarction.
abstract: The aim of this study is to determine the effects of early intravenous (IV) infusion later followed by transendocardial (TE) injection of allogeneic mesenchymal stem cells (MSCs) following myocardial infarction (MI). Twenty-four swine underwent balloon occlusion reperfusion MI and were randomized into 4 groups: IV MSC (or placebo) infusion (post-MI day 2) and TE MSC (or placebo) injection targeting the infarct border with 2D X-ray fluoroscopy fused to 3D magnetic resonance (XFM) co-registration (post-MI day 14). Continuous ECG recording, MRI, and invasive pressure-volume analyses were performed. IV MSC plus TE MSC treated group was superior to other groups for contractility reserve (p = 0.02) and freedom from VT (p = 0.03) but had more lymphocytic foci localized to the peri-infarct region (p = 0.002). No differences were observed in post-MI remodeling parameters. IV followed by XFM targeted TE MSC therapy improves contractility reserve and suppresses VT but does not affect post-MI remodeling and may cause an immune response.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Schmuck
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Koch
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Hacker
authors.affiliation: Division of Cardiovascular Medicine, Department of Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, H4/568 Clinical Sciences Center, 600 Highland Ave, Madison, WI, 53792-3248, USA.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Hatt
authors.affiliation: Division of Cardiovascular Medicine, Department of Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, H4/568 Clinical Sciences Center, 600 Highland Ave, Madison, WI, 53792-3248, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Tomkowiak
authors.affiliation: Division of Radiology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Karl K
authors.initials: KK
authors.lastname: Vigen
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Hendren
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Cathlyn
authors.initials: C
authors.lastname: Leitzke
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Ying-Qi
authors.initials: YQ
authors.lastname: Zhao
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Zhanhai
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Centanni
authors.affiliation: Waisman Biomanufacturing Facility, Madison, WI, USA.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Hei
authors.affiliation: Research Animal Resources Center, University of Wisconsin, Madison, WI, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Schwahn
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Jaehyup
authors.initials: J
authors.lastname: Kim
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Peiman
authors.initials: P
authors.lastname: Hematti
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. anr@medicine.wisc.edu.|Division of Cardiovascular Medicine, Department of Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, H4/568 Clinical Sciences Center, 600 Highland Ave, Madison, WI, 53792-3248, USA. anr@medicine.wisc.edu.
authors.forename: Amish N
authors.initials: AN
authors.lastname: Raval
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000175:diagnosis; D002469:Cell Separation / Q000379:methods; D004699:Endocardium; D006439:Hemodynamics; D007267:Injections / Q000379:methods; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000528:radiation effects*; D009200:Myocardial Contraction / Q000502:physiology*; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery*; D011897:Random Allocation; D013552:Swine
keywords: Allogeneic; Immune response; Intravenous; Mesenchymal stem cell; Multiple dose; Myocardial infarction; Stem cell; Swine; Transendocardial