title: A comparison in therapeutic efficacy of several time points of intravenous StemBell administration in a rat model of acute myocardial infarction.
abstract: Adipose-derived stromal cells (ASCs) are a promising new therapeutic option for patients with acute myocardial infarction (AMI). Previously, we found that ASCs coupled to antibody-targeted microbubbles (StemBells [StBs]) improved cardiac function when administered intravenously 7 days post-AMI in rats. In this study, we compared the efficacy of intravenous StB administration at different administration time points following AMI in rats.
  
  
  
  AMI, followed by reperfusion, was induced in four groups of male Wistar rats, which subsequently received an intravenous 1 × 106StB bolus 1 day post-AMI (StB1; n = 8), 7 days post-AMI (StB7; n = 9), at both time points (StB1+7; n = 7) or neither (Control; n = 7). The effect onrdiac function was determined using echocardiography prior to AMI, 7 days post-AMI and 42 days post-AMI. The effect on infarct size and macrophages in the infarct core were determined (immuno)histochemically 42 days post-AMI.
  
  
  
  At 42 days post-AMI, all three StB groups had a significantly improved fractional shortening compared with the control group. Between the StB-treated groups, the effects did not differ significantly at 42 days post-AMI. At 7 days post-AMI, the StB1 group had a significantly improved fractional shortening compared with the control and StB7 groups. No significant changes in infarct size or macrophage numbers were found compared with the control group for any StB group.
  
  
  
  StB administration resulted in long-term improvement of cardiac function, independent of the time point of administration. When administered at 1 day post-AMI, this improvement was already evident at 7 days post-AMI.
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, the Netherlands, Amsterdam, The Netherlands. Electronic address: r.emmens@vumc.nl.
authors.forename: Reindert W
authors.initials: RW
authors.lastname: Emmens
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Maikel
authors.initials: M
authors.lastname: Oedayrajsingh-Varma
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Linde
authors.initials: L
authors.lastname: Woudstra
authors.affiliation: Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands; Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
authors.forename: Otto
authors.initials: O
authors.lastname: Kamp
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Elisa
authors.initials: E
authors.lastname: Meinster
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Annemieke
authors.initials: A
authors.lastname: van Dijk
authors.affiliation: Department of Orthopedics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marco N
authors.initials: MN
authors.lastname: Helder
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, the Netherlands, Amsterdam, The Netherlands.
authors.forename: Diana
authors.initials: D
authors.lastname: Wouters
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, the Netherlands, Amsterdam, The Netherlands; Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Sacha
authors.initials: S
authors.lastname: Zeerleder
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, the Netherlands, Amsterdam, The Netherlands.
authors.forename: S Marieke
authors.initials: SM
authors.lastname: van Ham
authors.affiliation: Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands; Department of Biomedical Engineering, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: de Jong
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands; Department of Cardiac Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Hans W M
authors.initials: HW
authors.lastname: Niessen
authors.affiliation: Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands; Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
authors.forename: Lynda J M
authors.initials: LJ
authors.lastname: Juffermans
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Paul A J
authors.initials: PA
authors.lastname: Krijnen
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D061605:Administration, Intravenous; D000818:Animals; D002478:Cells, Cultured; D004452:Echocardiography; D008297:Male; D045423:Microbubbles; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000628:therapy*; D017208:Rats, Wistar; D017154:Stromal Cells / Q000637:transplantation; D013997:Time Factors
keywords: adipose tissue; intravenous administration; microbubbles; myocardial infarction; stromal cells