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Identification of a Putative Cardiac Progenitor Cells in the Miniature Swine
Andrew J Meltzer, Stuart Houser, Meghan Cochrane, Jessica Sayre, James Allan, David Sachs, Joren C. Madsen, Bruce R Rosengard
Massachusetts General Hospital, Boston, MA
Introduction: Recent work demonstrates that the heart is not terminally differentiated and progenitor cells have been identified in the mammalian heart. A population of cardiac cells, marked by expression of the transcription factor islet-1 (isl1), has been characterized in mice. Is1l+ cells give rise to cardiac myocytes, smooth muscle, and endothelial cells. Identification and characterization of these cells in swine would permit development of a pre-clinical model for cellular transplantation therapy for heart failure.
Materials and Methods: Pregnant sows underwent fetal harvest sixty days post conception. Cardiectomy was performed via sternotomy. Pancreatic tissue was pooled among litters. Hearts and pancreata were washed and prepared for staining in the standard fashion. Immunohistochemistry was performed using monoclonal mouse antibody for isl-1 (University of Iowa Hybridoma Bank) and Biotinlyated anti-mouse IgG.
Results: Fetal hearts (n=3), pancreata (n=3), and adult swine heart (n=2) all demonstrated intranuclear isl-1 monoclonal antibody binding. As reported in the murine model, pancreatic expression was diffuse, whereas cardiac staining was limited to distinct clusters of cells in the atria and ventricular outflow tracts. There was limited staining of isl1+ cells in the adult heart, compared to fetal tissue, but the anatomic location was consistent.
Conclusion: The LIM homeodomain transcription factor was recently identified as an important marker of cardiac progenitor cells. Multipotency has been described in a murine model. This represents the first identification of these cardiac progenitor cells in swine. As isl1+ cells are likely targets for cellular transplantation, their identification and isolation in this animal model has important implications. Future research will involve further characterization of this progenitor population, as well as progenitor cell culture and subsequently transplantation.
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