Enhanced therapeutic effects on acute myocardial infarction with multiple intravenous transplantation of human cord blood mononuclear cells

Abstract

Background: Cell transplantation of human cord blood mononuclear progenitor cells (HCBMCs) is a new treatment that could restore cardiac functions after acute myocardial infarction (AMI). We hypothesize that multiple doses of HCBMCs might increase homing of transplanted cells to infarcted region, and improve outcome of AMI via inhibition of ischemic-induced inflammatory responses.

Methods and results: HCBMCs were injected intravenously to rabbits that previously underwent ligation of left anterior coronary artery (LAD). Single dose of HCBMCs was intravenously delivered on the 7th day or multiple doses of HCBMCs were delivered on the 7th, 9th, 11th and 13th day after AMI. Homing of HCBMCs was determined by 5-bromodeoxyuridine (BrdU) labeling. The amount of grafted cells homed and retained in the infarcted area was significantly increased in the rabbits that received multiple doses. More viable cardiomyocytes and less collagen deposition were observed also in the group with more injections. Cardiac functions were assessed by echocardiography and hemodynamics. Multiple doses of HCBMCs showed significant benefits in preservation of cardiac functions. In infarcted myocardium, multiple transplantations of HCBMCs showed a significant increase in the myocardial level of anti-inflammatory IL-10 and a marked decrease in the level of the pro-inflammatory IL-6.

Conclusions: Multiple injections of HCBMCs markedly increased the amount of grafted cells, beneficially improving cardiac functions after AMI. The findings suggest that multiple doses of HCBMCs might be a novel strategy in the cell therapy for AMI.

Keywords: Acute myocardial infarction (AMI); Cardiac function; Cardiac remolding; Human cord blood mononuclear cells (HCBMCs); Inflammatory responses; Multiple cell transplantation.