title: Bone marrow-derived cells contribute to cell turnover in aging murine             hearts.
abstract: The paradigm that cardiac myocytes are non-proliferating, terminally differentiated             cells was recently challenged by studies reporting the ability of bone marrow-derived             cells (BMCs) to differentiate into cardiomyocytes after myocardial damage. However,             little knowledge exists about the role of BMCs in the heart during physiological             aging. Twelve-week-old mice (n=36) were sublethally irradiated and bone marrow             from littermates transgenic for enhanced green fluorescent protein (eGFP) was             transplanted. After 4 weeks, 18 mice were sacrificed at the age of 4 months and             served as controls (group A); the remaining mice were sacrificed at the age of             18 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 five             eGFP+ cardiomyocytes were detected in 20 examined hearts, excluding a functional             role of BM differentiation in cardiomyocytes. Similarly, a relevant differentiation             of BMCs in endothelial or smooth muscle cells was excluded. In contrast, numerous             BM-derived fibroblasts and myofibroblasts were observed in group B, but none were             detected in group  A. The present study demonstrates that BMCs transdifferentiate             into fibroblasts and myofibroblasts in the aging murine myocardium, suggesting             their contribution to the preservation of the structural integrity of the myocardium,             while they do not account for regenerative processes of the heart.
authors.affiliation: Department of Cardiology, Kerckhoff Heart Center, D-61231 Bad                     Nauheim, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Szardien
authors.forename: Holger M
authors.initials: HM
authors.lastname: Nef
authors.forename: Christian
authors.initials: C
authors.lastname: Troidl
authors.forename: Matthias
authors.initials: M
authors.lastname: Willmer
authors.forename: Sandra
authors.initials: S
authors.lastname: Voss
authors.forename: Christoph
authors.initials: C
authors.lastname: Liebetrau
authors.forename: Jedrzej
authors.initials: J
authors.lastname: Hoffmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Rolf
authors.forename: Johannes
authors.initials: J
authors.lastname: Rixe
authors.forename: Albrecht
authors.initials: A
authors.lastname: Elsässer
authors.forename: Christian W
authors.initials: CW
authors.lastname: Hamm
authors.forename: Helge
authors.initials: H
authors.lastname: Möllmann
mesh_terms: D000375:Aging; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D054338:Cell Transdifferentiation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype