Abstract 853: Bone Marrow-derived Stem Cells Can Transform Into Cardiac Progenitor Cells To Maintain Homeostasis Of The Stem Cell Pool In The Adult Heart
Background: Cardiac stem cells, otherwise known as progenitor cells, have been identified in the adult hearts of mice, rats, and humans, but their precise origin and characterization remain unclear. We tested the hypothesis that cardiac stem cells originate from bone marrow, and investigated their phenotype changes and population dynamics.
Methods and Results: Female wild-type and male GFP-transgenic C57/BL6 mice (10 –12 weeks old) were used for this study. We counted approximately 5000~10000 Sca-1+ and c-kit+ stem cells per heart. To identify the origination of cardiac progenitor cells from bone marrow, wild-type mice were subjected to whole body irradiation and the transplantation of GFP+ bone marrow cells. Histological analysis confirmed GFP-positivity in about 30% of the Sca-1+ cardiac stem cells in these mice, 12 weeks after bone marrow transplantation. Using a heterotopic mouse heart transplantation model, we investigated the phenotype changes and population dynamics of cardiac stem cells. Donor hearts from wild-type mice were transplanted into GFP-transgenic mice, and then collected 0, 2, 4, 8, and 12 weeks after transplantation. We detected extra-cardiac GFP+ stem cells in the donor hearts 2 weeks after transplantation. Quantitative flow cytometry analysis showed that the percentage of GFP+ stem cells in the donor hearts was about 40%~60% (36.0±2.7% of Sca-1+ and 56.0±5.0% of c-kit+) at 2 weeks, which increased further to about 80% (82.2±2.6% of Sca-1+ and 79.5±3.9% c-kit+) by 4 weeks. Immunostaining revealed that these GFP+ stem cells in the donor hearts gradually lost expression of the hematopoietic markers of CD45 and CD34, and shifted to express the cardiac specific transcription factors of GATA-4 and NKx2.5 at 4~8 weeks. Furthermore, some of the GFP+ cells in the donor hearts finally acquired the mature cardiac phenotype in the absence of cell fusion with donor cardiomyocytes at 12 weeks.
Conclusion: These results provide evidence that extra-cardiac stem cells of bone marrow origin can transform into cardiac progenitor cells to maintain the homeostasis of the stem cell pool in the adult heart.