Human cord blood cells induce angiogenesis following myocardial infarction in NOD/scid-mice.
OBJECTIVE
We tested the hypothesis that intravenously administered human umbilical cord blood (hUCB) cells contribute to repair processes following myocardial infarction.


METHODS
hUCB mononuclear cells containing 0.11% to 1.1% CD34(+) cells were injected in the tail vein of NOD/scid mice that had (MI+) or had not (MI-) previously undergone ligation of the left anterior coronary artery (LAD). Homing to bone marrow and solid organs was determined by polymerase chain reaction (PCR) for human DNA (hDNA) using human-specific primers of Locus D7Z1. Immunostaining was used for phenotypic analysis, and capillary density as well as myocardial scar formation was assessed. Moreover, expression of stromal cell-derived factor-1 (SDF-1) was studied in infarcted and in normal hearts.


RESULTS
hDNA was detected in marrow, spleen, and liver of both MI+ and MI- mice 24 h, 1 week, and 3 weeks after cell injection. In the heart, however, hDNA was detected in 10 of 19 MI+ mice but in none of the MI- mice (p=0.002). Infarct size was smaller in cell-treated MI+ mice than in untreated MI+ hearts (38.7 versus 47.8%, P<0.05), and there was also less collagen deposition. In cell-treated MI+ mice, capillary density in the infarct border zone was approximately 20% higher (p=0.03), 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. Up to 70% of the cord blood-derived cells in the heart were CD45(+). There was no evidence of cardiomyocyte differentiation as determined by co-localization of HNA or HLA-I with GATA-4 or Connexin 43. In infarcted myocardium, expression of SDF-1 mRNA was approximately 7-fold higher than in normal hearts.


CONCLUSIONS
hUCB cells migrate to infarcted, not to normal myocardium, where they engraft, participate in neoangiogenesis, and beneficially influence remodelling processes. Cord blood cells may hence be useful for cell therapy of ischemic heart disease.
Ma
Nan
N
Cardiac Surgery, University of Rostock, Rostock, Germany.
Stamm
Christof
C
Kaminski
Alexander
A
Li
Wenzhong
W
Kleine
Hans-Dieter
HD
Müller-Hilke
Brigitte
B
Zhang
Li
L
Ladilov
Yuri
Y
Egger
Dietmar
D
Steinhoff
Gustav
G
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D002196:Capillaries / Q000473:pathology; D002465:Cell Movement; D003094:Collagen / Q000032:analysis; D036101:Cord Blood Stem Cell Transplantation; D004247:DNA / Q000032:analysis; D042783:Endothelial Cells / Q000473:pathology; D006801:Humans; D007275:Injections, Intravenous; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000473:pathology* / Q000601:surgery*; D009206:Myocardium / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D018919:Neovascularization, Physiologic; D013234:Stem Cells / Q000276:immunology / Q000473:pathology; D014183:Transplantation, Heterologous
D018952:Antigens, CD34; D003094:Collagen; D004247:DNA; D017493:Leukocyte Common Antigens