title: Fractionation of mouse bone-marrow cells limits functional efficacy in non-reperfused mouse model of acute myocardial infarction.
abstract: OBJECTIVE
  Clinical trials of bone-marrow (BM)-derived cells for therapy after acute myocardial infarct (MI) have been controversial. The most commonly used cells for these trials have been mononuclear cells (MNC), obtained by fractionation of BM cells (BMCs) via different protocols. In this study, we performed a head-to-head comparison of: 1) whole BMC; 2) fractionated BM (fBM) using the commonly used Ficoll protocol; 3) the extract derived from the fBM (fBM extract) versus 4) saline (HBSS) control for treatment of acute MI.
  
  
  METHODS
  In total, 155 male C57BL/6J (10-12-week old) mice were included. Echocardiography was performed at baseline and 2 days after permanent ligation of the left anterior descending artery to induce MI. Echocardiography and histology were employed to measure outcome at 28 days post-MI.
  
  
  RESULTS
  Whole BMC therapy improved left ventricular ejection fraction (LVEF) post-MI, but fBM or fBM extract was not beneficial compared to control (change of LVEF of 4.9% ±4.6% (P = 0.02), -0.4% ±5.8% (P = 0.86), -2.0% ±6.2% (P = 0.97) versus -1.4% ±5.3%, respectively). The histological infarct size or numbers of arterioles or capillaries at infarct or border zone did not differ between the groups.
  
  
  CONCLUSIONS
  Clinical studies should be performed to test whether whole BMC therapy translates into better outcome also after human MI.
authors.affiliation: Division of Cardiology, Department of Medicine, University of California , San Francisco, San Francisco, CA, USA. juhkos@utu.fi
authors.forename: Juha W
authors.initials: JW
authors.lastname: Koskenvuo
authors.forename: Richard E
authors.initials: RE
authors.lastname: Sievers
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Franca S
authors.initials: FS
authors.lastname: Angeli
authors.forename: Brian
authors.initials: B
authors.lastname: Lee
authors.forename: Henry
authors.initials: H
authors.lastname: Shih
authors.forename: Jianqin
authors.initials: J
authors.lastname: Ye
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Boyle
authors.forename: Yerem
authors.initials: Y
authors.lastname: Yeghiazarians
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016026:Bone Marrow Transplantation; D002458:Cell Fractionation; D004452:Echocardiography; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D009929:Organ Size; D013318:Stroke Volume; D020257:Ventricular Remodeling