Elzafir Elsheikh, Rami Genead, Christian Danielsson, Eva Wärdell, Agneta Andersson, Anders Kjaeldgaard, Erik Sundström, Tolga Sutlu, Karl-Henrik Grinnemo and Christer Sylvén
Background: The optimal stem cell source for regenerative therapy of the failing heart has not been settled. Embryonic stem cells, bone marrow derived cells, skeletal myoblasts, as well as cells derived from adult cardiac biopsies have been explored. Here we investigated the option to generate heart progenitor cells from the early human embryonic heart (hEHPCs) for the treatment of acute myocardial infarction. Methods: Two hearts (8 and 8.5 gestational weeks) from human abortion material were used for the clonal expansion of hEHPCs after stage specific embryonic antigen 1 (SSEA-1) enrichment by magnetic beads isolation. GFP-transduced hEHPCs- were transplanted into 18 SCID mice intramyocardially after induction of myocardial infarction. Hearts were harvested every 72 hours. Results: In this study we succeeded to isolate clones of hEHPCs with similar characteristics twice from two different early human embryonic hearts (8 and 8.5 gestational weeks) based on SSEA-1, a multipotent stem cell marker. Isolated clones were found to be positive for the multipotent stem cell marker (c-kit), the cardiac progenitors transcription factors GATA4, NKX2.5, TBX5 as well as the endothelial progenitors markers (CD133, CD34 and KDR). After transplantation into the peri-infarcted region they survived up to 12 days, and formed tubule-like structures in the mouse heart. Conclusions: These data demonstrate that the SSEA-1+ enriched cell population provides a potential basis to find the optimal cardiac progenitor cell population.
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