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DOI: 10.1055/s-2004-816761
Cardiac homing of human cord blood cells following myocardial infarction in a SCID-mouse model
Objectives: Multipotent stem cells may serve to regenerate myocardium following acute myocardial infarction (AMI). We tested the potential of human cord blood mononuclear cells (hMNCs) cells to populate the heart following intravenous injection
Material and Methods: Cord blood samples were harvested from healthy neonates, and a mononuclear cell suspension was prepared by Ficoll density gradient centrifugation. As determined by FACS analysis, 1–2% hMNCs were CD34+. AMI was induced in NOD/SCID mice by ligation of the left anterior descending coronary artery, and extensive myocardial infarction was confirmed by ECG and subsequent histology (n=30). 1×10E7 cord blood hMNCs (1×10E5 CD34+ cells) were injected in the tail vein one day after surgery. In control mice hMNCs were injected without prior AMI Mice were sacrificed after 24h, 1 week, or 3 weeks. DNA was isolated from heart, bone marrow and brain tissue, and PCR analysis was performed using a human-specific primer.
Results: hMNCs quantitatively homed to the bone marrow, and hMNC-DNA was present in marrow at all time points. In brain tissue, hMNC-DNA was found in all treated animals and also persisted up to 3 weeks. In control mice without AMI, we found no hMNC-DNA in the heart at any of the time points. Following AMI, however, hMNC-DNA was identified in 70% of the animals at 24h, but was absent after 1week and 3 weeks.
Conclusions: Myocardial infarction attracts cord blood hMNCs to the heart during the acute phase, but does not induce permanent myocardial colonization. Therefore, local stem cell implantation may be necessary to achieve stem cell-induced myocardial regeneration