title: Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model.
abstract: OBJECTIVE
  The potential for beneficial effects of adipose-derived stem cells (ASCs) on myocardial perfusion and left ventricular dysfunction in myocardial ischemia (MI) has not been tested following intravenous delivery.
  
  
  METHODS
  Surviving pigs following induction of MI were randomly assigned to 1 of 3 different groups: the placebo group (n = 7), the single bolus group (SB) (n = 7, 15 × 10(7) ASCs), or the divided dose group (DD) (n = 7, 5 × 10(7) ASCs/day for three consecutive days). Myocardial perfusion defect area and coronary flow reserve (CFR) were compared during the 28-day follow-up. Also, serial changes in the absolute number of circulating CD4(+) T and CD8(+) T cells were measured.
  
  
  RESULTS
  The increases in ejection fraction were significantly greater in both the SB and the DD groups compared to the placebo group (5.4 ± 0.9%, 3.7 ± 0.7%, and -0.4 ± 0.6%, respectively), and the decrease in the perfusion defect area was significantly greater in the SB group than the placebo group (-36.3 ± 1.8 and -11.5 ± 2.8). CFR increased to a greater degree in the SB and the DD groups than in the placebo group (0.9 ± 0.2, 0.8 ± 0.1, and 0.2 ± 0.2, respectively). The circulating number of CD8(+) T cells was significantly greater in the SB and DD groups than the placebo group at day 7 (3,687 ± 317/µL, 3,454 ± 787/µL, and 1,928 ± 457/µL, respectively). The numbers of small vessels were significantly greater in the SB and the DD groups than the placebo group in the peri-infarct area.
  
  
  CONCLUSIONS
  Both intravenous SB and DD delivery of ASCs are effective modalities for the treatment of MI in swine. Intravenous delivery of ASCs, with its immunomodulatory and angiogenic effects, is an attractive noninvasive approach for myocardial rescue.
authors.affiliation: Krannert Institute of Cardiology, Indiana University, Indianapolis, Indiana.|Indiana Center for Vascular Biology and Medicine, Indianapolis, Indiana.|Indiana University School of Medicine, Indianapolis, Indiana.|R.L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana.|Korea University Anam Hospital, Seoul, Korea.
authors.forename: Soon
authors.initials: S
authors.lastname: Jun Hong
authors.affiliation: Krannert Institute of Cardiology, Indiana University, Indianapolis, Indiana.|Indiana Center for Vascular Biology and Medicine, Indianapolis, Indiana.|Indiana University School of Medicine, Indianapolis, Indiana.|R.L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana.
authors.forename: Pamela I
authors.initials: PI
authors.lastname: Rogers
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: John
authors.initials: J
authors.lastname: Kihlken
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Jessica
authors.initials: J
authors.lastname: Warfel
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Chris
authors.initials: C
authors.lastname: Bull
authors.affiliation: Krannert Institute of Cardiology, Indiana University, Indianapolis, Indiana.|Indiana Center for Vascular Biology and Medicine, Indianapolis, Indiana.|Indiana University School of Medicine, Indianapolis, Indiana.|R.L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana.
authors.forename: Maja
authors.initials: M
authors.lastname: Deuter-Reinhard
authors.affiliation: Krannert Institute of Cardiology, Indiana University, Indianapolis, Indiana.|Indiana Center for Vascular Biology and Medicine, Indianapolis, Indiana.|Indiana University School of Medicine, Indianapolis, Indiana.|R.L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana.
authors.forename: Dongni
authors.initials: D
authors.lastname: Feng
authors.affiliation: Krannert Institute of Cardiology, Indiana University, Indianapolis, Indiana.|Indiana Center for Vascular Biology and Medicine, Indianapolis, Indiana.|Indiana University School of Medicine, Indianapolis, Indiana.|R.L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana.
authors.forename: Jie
authors.initials: J
authors.lastname: Xie
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Aaron
authors.initials: A
authors.lastname: Kyle
authors.affiliation: Krannert Institute of Cardiology, Indiana University, Indianapolis, Indiana.|Indiana Center for Vascular Biology and Medicine, Indianapolis, Indiana.|Indiana University School of Medicine, Indianapolis, Indiana.|R.L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Merfeld-Clauss
authors.affiliation: Krannert Institute of Cardiology, Indiana University, Indianapolis, Indiana.|Indiana Center for Vascular Biology and Medicine, Indianapolis, Indiana.|Indiana University School of Medicine, Indianapolis, Indiana.|R.L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Johnstone
authors.affiliation: Krannert Institute of Cardiology, Indiana University, Indianapolis, Indiana.|Indiana Center for Vascular Biology and Medicine, Indianapolis, Indiana.|Indiana University School of Medicine, Indianapolis, Indiana.|R.L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana.
authors.forename: Dmitry O
authors.initials: DO
authors.lastname: Traktuev
authors.affiliation: Krannert Institute of Cardiology, Indiana University, Indianapolis, Indiana.|Indiana Center for Vascular Biology and Medicine, Indianapolis, Indiana.|Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
authors.affiliation: Oregon Health and Science University, Portland, Oregon.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lindner
authors.affiliation: Krannert Institute of Cardiology, Indiana University, Indianapolis, Indiana.|Indiana Center for Vascular Biology and Medicine, Indianapolis, Indiana.|Indiana University School of Medicine, Indianapolis, Indiana.|R.L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana.
authors.forename: Keith L
authors.initials: KL
authors.lastname: March
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D008833:Microcirculation; D055806:Microvessels / Q000503:physiopathology*; D009203:Myocardial Infarction / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology / Q000601:surgery*; D055414:Myocardial Perfusion Imaging; D018919:Neovascularization, Physiologic; D055495:Neurogenesis; D020127:Recovery of Function; D033581:Stem Cell Transplantation; D013318:Stroke Volume; D034421:Sus scrofa; D013997:Time Factors; D016277:Ventricular Function, Left; D018879:Ventricular Premature Complexes / Q000503:physiopathology / Q000517:prevention & control; D055815:Young Adult
keywords: adipose stem cell; intravenous injection; myocardial infarction; myocardial perfusion; ventricular dysfunction