Human cord blood progenitors with high aldehyde dehydrogenase activity improve vascular density in a model of acute myocardial infarction
1 Department of Molecular Biology, Department of Hematology and Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
2 Program in Regenerative Medicine, Krembil Centre for Stem Cell Biology, Vascular Biology Group, Robarts Research Institute and the University of Western Ontario, London, ON, Canada
3 Department of Molecular Biology and Pharmacology, Molecular Imaging Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, USA
4 Department of Surgery, Center for Cardiovascular Research, Washington University School of Medicine, St Louis, MO, USA
5 Division of Oncology, Hematopoietic Development and Malignancy Program, Washington University School of Medicine, St Louis, MO, USA
6 Department of Pathology, Umbilical Cord Blood Bank, Cardinal Glennon Children's Hospital, St Louis, MO, USA
7 Department of Internal Medicine, Stem Cell Program and Institute for Regenerative Cures, University of California, Davis, Sacramento CA, USA
Journal of Translational Medicine 2010, 8:24 doi:10.1186/1479-5876-8-24Published: 9 March 2010
Human stem cells from adult sources have been shown to contribute to the regeneration of muscle, liver, heart, and vasculature. The mechanisms by which this is accomplished are, however, still not well understood. We tested the engraftment and regenerative potential of human umbilical cord blood-derived ALDHhiLin-, and ALDHloLin- cells following transplantation to NOD/SCID or NOD/SCID β2m null mice with experimentally induced acute myocardial infarction. We used combined nanoparticle labeling and whole organ fluorescent imaging to detect human cells in multiple organs 48 hours post transplantation. Engraftment and regenerative effects of cell treatment were assessed four weeks post transplantation. We found that ALDHhiLin- stem cells specifically located to the site of injury 48 hours post transplantation and engrafted the infarcted heart at higher frequencies than ALDHloLin- committed progenitor cells four weeks post transplantation. We found no donor derived cardiomyocytes and few endothelial cells of donor origin. Cell treatment was not associated with any detectable functional improvement at the four week endpoint. There was, however, a significant increase in vascular density in the central infarct zone of ALDHhiLin- cell-treated mice, as compared to PBS and ALDHloLin- cell-treated mice.
Our data indicate that adult human stem cells do not become a significant part of the regenerating tissue, but rapidly home to and persist only temporarily at the site of hypoxic injury to exert trophic effects on tissue repair thereby enhancing vascular recovery.