PMID- 25860790
OWN - NLM
STAT- MEDLINE
DCOM- 20160418
LR  - 20220330
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 4
DP  - 2015
TI  - Comparison of arrhythmogenicity and proinflammatory activity induced by 
      intramyocardial or epicardial myoblast sheet delivery in a rat model of ischemic 
      heart failure.
PG  - e0123963
LID - 10.1371/journal.pone.0123963 [doi]
LID - e0123963
AB  - Although cell therapy of the failing heart by intramyocardial injections of 
      myoblasts to results in regenerative benefit, it has also been associated with 
      undesired and prospectively fatal arrhythmias. We hypothesized that 
      intramyocardial injections of myoblasts could enhance inflammatory reactivity and 
      facilitate electrical cardiac abnormalities that can be reduced by epicardial 
      myoblast sheet delivery. In a rat model of ischemic heart failure, myoblast 
      therapy either by intramyocardial injections or epicardial cell sheets was given 
      2 weeks after occlusion of the coronary artery. Ventricular premature 
      contractions (VPCs) were assessed, using an implanted three-lead 
      electrocardiograph at 1, 7, and 14 days after therapy, and 16-point epicardial 
      electropotential mapping (EEPM) was used to evaluate ventricular 
      arrhythmogenicity under isoproterenol stress. Cardiac functioning was assessed by 
      echocardiography. Both transplantation groups showed therapeutic benefit over 
      sham therapy. However, VPCs were more frequent in the Injection group on day 1 
      and day 14 after therapy than in animals receiving epicardial or sham therapy (p 
      < 0.05 and p < 0.01, respectively). EEPM under isoproterenol stress showed 
      macroreentry at the infarct border area, leading to ventricular tachycardias in 
      the Injection group, but not in the myoblast sheet- or sham-treated groups (p = 
      0.045). Both transplantation types modified the myocardial cytokine expression 
      profile. In animals receiving epicardial myoblast therapy, selective reductions 
      in the expressions of interferon gamma, interleukin (IL)-1beta and IL12 were 
      observed, accompanied by reduced infiltration of inflammatory CD11b- and 
      CD68-positive leukocytes, compared with animals receiving myoblasts as 
      intramyocardial injections. Intramyocardial myoblast delivery was associated with 
      enhanced inflammatory and immunomodulatory reactivity and increased frequency of 
      VPCs. In comparison to intramyocardial injection, the epicardial route may serve 
      as the preferred method of skeletal myoblast transplantation to treat heart 
      failure.
FAU - Patila, Tommi
AU  - Patila T
AD  - Department of Cardiothoracic Surgery, Osaka University Graduate School of 
      Medicine, Osaka, Japan; Department of Pediatric Cardiac Surgery, Hospital for 
      Children and Adolescents, University of Helsinki, Helsinki, Finland.
FAU - Miyagawa, Shigeru
AU  - Miyagawa S
AD  - Department of Cardiothoracic Surgery, Osaka University Graduate School of 
      Medicine, Osaka, Japan.
FAU - Imanishi, Yukiko
AU  - Imanishi Y
AD  - Department of Cardiothoracic Surgery, Osaka University Graduate School of 
      Medicine, Osaka, Japan.
FAU - Fukushima, Satsuki
AU  - Fukushima S
AD  - Department of Cardiothoracic Surgery, Osaka University Graduate School of 
      Medicine, Osaka, Japan.
FAU - Siltanen, Antti
AU  - Siltanen A
AD  - Pharmacology, University of Helsinki, Helsinki, Finland.
FAU - Mervaala, Eero
AU  - Mervaala E
AD  - Pharmacology, University of Helsinki, Helsinki, Finland.
FAU - Kankuri, Esko
AU  - Kankuri E
AD  - Pharmacology, University of Helsinki, Helsinki, Finland.
FAU - Harjula, Ari
AU  - Harjula A
AD  - Department of Cardiothoracic Surgery, University of Helsinki and Helsinki 
      University Hospital, Helsinki, Finland.
FAU - Sawa, Yoshiki
AU  - Sawa Y
AD  - Department of Cardiothoracic Surgery, Osaka University Graduate School of 
      Medicine, Osaka, Japan.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150410
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Inflammation Mediators)
SB  - IM
MH  - Animals
MH  - Arrhythmias, Cardiac/*etiology
MH  - Cell- and Tissue-Based Therapy/*adverse effects/*methods
MH  - Disease Models, Animal
MH  - Gene Expression
MH  - Heart Failure/pathology/*physiopathology/*therapy
MH  - Inflammation Mediators/metabolism
MH  - Male
MH  - Myoblasts, Skeletal/*transplantation
MH  - Myocarditis/*etiology
MH  - Myocardium/pathology
MH  - Pericardium/pathology
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Ventricular Premature Complexes/etiology
PMC - PMC4393220
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/04/11 06:00
MHDA- 2016/04/19 06:00
PMCR- 2015/04/10
CRDT- 2015/04/11 06:00
PHST- 2014/03/06 00:00 [received]
PHST- 2015/03/08 00:00 [accepted]
PHST- 2015/04/11 06:00 [entrez]
PHST- 2015/04/11 06:00 [pubmed]
PHST- 2016/04/19 06:00 [medline]
PHST- 2015/04/10 00:00 [pmc-release]
AID - PONE-D-14-10275 [pii]
AID - 10.1371/journal.pone.0123963 [doi]
PST - epublish
SO  - PLoS One. 2015 Apr 10;10(4):e0123963. doi: 10.1371/journal.pone.0123963. 
      eCollection 2015.