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The paradigm that cardiac myocytes are non-proliferating, terminally differentiatedcells was recently challenged by studies reporting the ability of bone marrow-derivedcells (BMCs) to differentiate into cardiomyocytes after myocardial damage. However,little knowledge exists about the role of BMCs in the heart during physiologicalaging. Twelve-week-old mice (n=36) were sublethally irradiated and bone marrowfrom littermates transgenic for enhanced green fluorescent protein (eGFP) wastransplanted. After 4 weeks, 18 mice were sacrificed at the age of 4 months andserved as controls (group A); the remaining mice were sacrificed at the age of18 months (group B). Group A did not exhibit a significant number of eGFP+ cells,whereas 9.4±2.8 eGFP+ cells/mm2 was documented in group B. In total, only fiveeGFP+ cardiomyocytes were detected in 20 examined hearts, excluding a functionalrole of BM differentiation in cardiomyocytes. Similarly, a relevant differentiationof BMCs in endothelial or smooth muscle cells was excluded. In contrast, numerousBM-derived fibroblasts and myofibroblasts were observed in group B, but none weredetected in group  A. The present study demonstrates that BMCs transdifferentiateinto fibroblasts and myofibroblasts in the aging murine myocardium, suggestingtheir contribution to the preservation of the structural integrity of the myocardium,while they do not account for regenerative processes of the heart.

Bone marrow-derived cells contribute to cell turnover in aging murine hearts