Dynamics of medial smooth muscle changes after carotid artery transplantation in transgenic mice expressing green fluorescent protein.
BACKGROUND
Recent observations have demonstrated the importance of host cells in neointima formation after transplantation. Because little is known regarding the dynamics of host-derived cells in the graft media, we investigated this question in a mouse carotid artery transplantation model.


METHODS
C57BL/6 carotid arteries were orthotopically transplanted into BALB/c mice ubiquitously expressing enhanced green fluorescent protein. Grafts were harvested at 1, 2, 4, and 8 weeks after transplantation for histologic examination. No immunosuppression was used.


RESULTS
Immunostaining and semiquantitative analysis of cross sections showed that donor medial smooth muscle cells decreased over time in the graft media, whereas green fluorescent protein-positive/smooth muscle alpha-actin-positive cells (i.e., cells of host origin) increased over time. Interestingly, host cells were located only in the inner media and the neointima at 2 weeks and thereafter also in the outer media, indicating that the host-derived cells entered the media from the luminal side rather than from the adventitia. In longitudinal sections, there were no differences in the accumulation of donor- and host-derived cells between the end and middle regions of the graft media at 8 weeks.


CONCLUSIONS
After transplantation, medial cells were replaced by alpha-actin-expressing host cells that were probably derived from circulating precursor cells. Our observations differ from the traditional view of a major contribution of donor medial smooth muscle cells to the neointima formation. Thus, circulating progenitor cells may be important for graft vessel disease.
Matsumoto
Yuji
Y
Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
Hof
Akiko
A
Baumlin
Yves
Y
Müller
Matthias
M
Prescott
Margaret F
MF
Hof
Robert P
RP
D000818:Animals; D002339:Carotid Arteries / Q000473:pathology / Q000637:transplantation*; D005260:Female; D005455:Fluorescent Antibody Technique; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D011994:Recombinant Proteins / Q000032:analysis; D014184:Transplantation, Homologous / Q000473:pathology*; D017540:Tunica Media / Q000473:pathology / Q000637:transplantation*
D008164:Luminescent Proteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins