Time-course analysis on the differentiation of bone marrow-derived progenitor cells into smooth muscle cells during neointima formation.
OBJECTIVE
Bone marrow-derived progenitor cells have been implicated to contribute to neointima formation, but the time course and extent of their accumulation and differentiation into vascular cells and, most importantly, the long-term contribution of bone marrow-derived progenitor cells to the vascular lesion remain undefined.


RESULTS
Wire-induced injury of the femoral artery was performed on chimeric C57BL/6 mice transplanted with bone marrow from transgenic mice expressing enhanced green fluorescence protein, and vessels were harvested at 3 days, 1, 2, 3, 4, 6, and 16 weeks after dilatation (n=8 animals per time point). Using high-resolution microscopy, we unexpectedly found that the expression of smooth muscle cell or endothelial cell markers in enhanced green fluorescence protein positive cells was a very rare event. Indeed, most of the enhanced green fluorescence protein positive cells that accumulated during the acute inflammatory response were identified as monocytes/macrophages, and their number declined at later time points. In contrast, a substantial fraction of highly proliferative stem cell antigen-1 and CD34(+) but enhanced green fluorescence protein negative and thus locally derived cells were detected in the adventitia.


CONCLUSIONS
These data provide evidence that the differentiation of bone marrow-derived progenitor cells into smooth muscle cell or endothelial cell lineages seems to be an exceedingly rare event. Moreover, the contribution of bone marrow-derived cells to the cellular compartment of the neointima is limited to a transient period of the inflammatory response.
Daniel
Jan-Marcus
JM
Department of Cardiology, Justus-Liebig-University, Giessen, Germany.
Bielenberg
Wiebke
W
Stieger
Philipp
P
Weinert
Soenke
S
Tillmanns
Harald
H
Sedding
Daniel G
DG
D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D003238:Connective Tissue / Q000473:pathology; D005263:Femoral Artery / Q000293:injuries / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000473:pathology*; D009389:Neovascularization, Pathologic; D011994:Recombinant Proteins / Q000235:genetics; D013997:Time Factors; D017539:Tunica Intima / Q000293:injuries / Q000473:pathology*
D011994:Recombinant Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins