Human cord blood cells attenuate post-infarct remodelling processes in NOD/scid-mice

Objectives: We tested the hypothesis that intravenously administered human umbilical cord blood (hUCB) cells contribute to repair processes following myocardial infarction.

Material and Methods: hUCB cells containing 0.11% to 1.1% CD34+ cells were injected in the tail vein of NOD/scid mice 24h following LAD ligation (n=24). Control mice received no cells (n=11). rtPCR using human-specific primers of Locus D7Z1 served as a screening test for hUCB-derived cells in myocardium. Immunohistology was used for phenotypic analysis. Capillary density, infarct size, collagen deposition, and myocardial mass were measured after 3weeks.

Results: hDNA in myocardium was detected in the 53% of the hUCB-treated animals. Infarct size was smaller in cell-treated MI+ mice (38.7 versus 47.8% in control hearts, p=0.01). There was less collagen deposition in the ischemic myocardium (p=0.02) of hUCB-treated mice, and the heart weight/body weight ratio was also lower (6.7±0.3 vs. 7.1±0.3, p=0.03), indicating less compensatory myocardial hypertrophy. Capillary density in the infarct border zone was approximately 20% higher (p=0.02), and clusters of hUCB-derived cells were detected in the perivascular interstitium. Occasionally, chimeric capillaries composed of human and mouse endothelial cells were found, but the vast majority of neo-vessels appeared to consist of mouse cells only. There was no evidence of cardiomyocyte differentiation as determined by co-localization of hNUC or HLA with GATA-4 or Connexin 43, and 70% of the cord blood-derived cells in the heart were CD45+.

Conclusions: hUCB cells migrate to infarcted myocardium, participate in neoangiogenesis, and attenuate remodelling processes. Cord blood cells may hence be useful for cell therapy of ischemic heart disease.