Objective
Vascular rejection after organ transplantation is characterized by an arterial occlusive
lesion, resulting from intimal proliferation occurring in response to arterial wall
immune aggression. Our hypothesis is that an early endothelial repair may prevent
vascular graft rejection. The aim of the current study was to compare different pharmacologic
progenitor cell mobilizing treatments for their protective effects against vascular
rejection.
Methods and Results
Aortic transplants were made from balb/c donor to C57Bl/6 recipient mice. Three different
mobilizing pharmacologic agents were used: low molecular weight fucoidan (LMWF), simvastatin,
and AMD3100. The circulating levels of progenitor cells were found to be increased
by all three treatments, as determined by flow cytometry. For each treatment, the
design was: treated allografts, nontreated allografts, treated isografts, and nontreated
isografts. After 21 d, morphometric and immunohistochemical analyses were performed.
We found that the three treatments significantly reduced intimal proliferation, compared
with nontreated allografts. This was associated with intimal re-endothelialization
of the grafts. Further, in chimeric mice that had previously received GFP-transgenic
bone marrow transplantation, GFP-positive cells were found in the vascular allograft
intima, indicating that re-endothelialization was, at least partly, due to the recruitment
of bone marrow-derived, presumably endothelial progenitor circulating cells.
Conclusions
In this aortic allograft model, three different mobilizing treatments were found to
partially prevent vascular transplant rejection. Bone marrow-derived progenitor cells
mobilized by the three treatments may play a direct role in the endothelial repair
process and in the suppression of intimal proliferation.
Key Words
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Article info
Publication history
Published online: December 23, 2011
Accepted:
November 18,
2011
Received:
July 27,
2011
Identification
Copyright
© 2012 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
