Human umbilical cord blood mononuclear cells for the treatment of acute myocardial infarction.
Cell transplantation is a new treatment to improve cardiac function in hearts that have been damaged by myocardial infarction. We have investigated the use of human umbilical cord blood mononuclear progenitor cells (HUCBC) for the treatment of acute myocardial infarction. The control group consisted of 24 normal rats with no interventions. The infarct + vehicle group consisted of 33 rats that underwent left anterior descending coronary artery (LAD) ligation and after 1 h were given Isolyte in the border of the infarction. The infarct + HUCBC group consisted of 38 rats that underwent LAD ligation and after 1 h were given 10(6) HUCBC in Isolyte directly into the infarct border. Immunosuppression was not given to any rat. Measurements of left ventricular (LV) ejection fraction, LV pressure, dP/dt, and infarct size were determined at baseline and 1, 2, 3, and 4 months. The ejection fraction in the controls decreased from 88+/-3% to 78+/-4% at 4 months (p = 0.03) as a result of normal aging. Following infarction in the infarct + vehicle group, the ejection fraction decreased from 87+/-4% to 51+/-3% between 1 and 4 months (p < 0.01). In contrast, the ejection fraction of the infarcted + HUCBC-treated rat hearts decreased from 87+/-4% to 63+/-3% at 1 month, but progressively increased to 69+/-6% at 3 and 4 months, which was different from infarct + vehicle group rats (p < 0.02) but similar to the controls. At 4 months, anteroseptal wall thickening in infarct + HUCBC group was 57.9+/-11.6%, which was nearly identical to the control anteroseptal thickening of 59.2+/-8.9%, but was significantly greater than the infarct + vehicle group, which was 27.8+/-7% (p < 0.02). dP/dt(max) increased by 130% in controls with 5.0 microg of phenylephrine (PE)/min (p < 0.001). In the infarct + vehicle group, dP/dt(max) increased by 91% with PE (p = 0.01). In contrast, in the infarct + HUCBC group, dP/dt(max) increased with PE by 182% (p < 0.001), which was significantly greater than the increase in dP/dt(max) in the infarct + vehicle group (p = 0.03) and similar to the increase in the controls. Infarct sizes in the infarct + HUCBC group were smaller than the infarct + vehicle group and averaged 3.0+/-2.8% for the infarct + HUCBC group versus 22.1+/-5.6% for infarct + vehicle group at 3 months (p < 0.01); at 4 months they averaged 9.2+/-2.0% for infarct + HUCBC group versus 40.0+/-9.2% for the infarct + vehicle group (p < 0.001). The present experiments demonstrate that HUCBC substantially reduce infarction size in rats without requirements for immunosuppression. As a consequence, LV function measurements, determined by LV ejection fraction, wall thickening, and dP/dt, are significantly greater than the same measurements in rats with untreated infarctions.
Henning
Robert J
RJ
Department of Medicine, University of South Florida College of Medicine, Tampa, FL 33612, USA. rhenning@hsc.usf.edu
Abu-Ali
Hamdi
H
Balis
John U
JU
Morgan
Michael B
MB
Willing
Alison E
AE
Sanberg
Paul R
PR
D000208:Acute Disease; D000818:Animals; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods* / Q000639:trends; D004195:Disease Models, Animal; D005240:Feasibility Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000639:trends; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D012038:Regeneration / Q000502:physiology; D013318:Stroke Volume / Q000502:physiology; D014183:Transplantation, Heterologous; D016277:Ventricular Function, Left / Q000502:physiology