Résumé :
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Purpose: Islet-1+ cells are cardiogenic and angiogenic progenitors participating to heart formation. The first aim was to locate and quantify these cells in view of potential pre-clinical developments. The second aim was to compare their presence and localisation in normal animals and in a model of dilated cardiomyopathy, the Lmna-H222P mouse carrying a lamin A/C gene mutation. Methods: We set up a time-course study in C57BL/6J, SVJ129, KI-LmnaH22P/H222P mice and wild type littermates. Animals were sacrificed at days 1, 5, 10, 15, 20, 25, then every month (from 3rd to 12th) and Islet-1+ cells detected by immunohistofluorescence on consecutive cryostat sections of whole heart. Results: Islet-1+ cells are gathered in one cluster in C57BL/6J animals. Cells are located in the proximal (basal) portion encompassing 8 to 20% of the organ height in outflow tract, atria, ventricles, septa. Approximately 150 to 300 cells are observed in each heart, from birth to 7 month. In the KI-Lmna mice (C57BL/6J x SVJ129) and wild-type SVJ129, cells are more restricted to atria and septa, and persist beyond 10 months. Importantly, a second cluster located in a more proximal (basal) position contains numerous cells (800-1800) of smaller size, and is no longer observed after the age of 4 months. The cells in this second cluster express sarcomeric actin and are intricated within the resident cardiac tissue. No significant differences are observed between the KI-LmnaH222P/H222P mice and their wild-type littermates. Ki67 expression is not detected, suggesting that islet1+ cells are not proliferating. Conclusions: The presence and localisation of Islet-1+ cells in the heart of young adult mice is linked to the genetic background. However, their low amounts and specific localisation make Islet-1+ cells unlikely to soon become practical tools in a therapeutic perspective. Supported by grants from Leducq Foundation (CaPTAA network) and AFM.
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