Abstract
Background and objectives. 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.
Acknowledgements
We thank Petros Minasi for his help in this project.
Declaration of interest: This work was supported in part by the UCSF Translational Cardiac Stem Cell Foundation and a grant from the Wayne and Gladys Valley Foundation to Y.Y.; and grants from the following to J.W.K.: Sigrid Juselius Foundation, Finnish Foundation for Cardiovascular Research, Paavo Nurmi Foundation, Varsinais-Suomi Regional Fund of Finnish Cultural Foundation and The Finnish Medical Foundation. The authors report no conflicts of interest.