Microvascular integrity plays an important role for graft survival after experimental skin transplantation

•We transplanted skin from C57BL/6 (H-2b) to CBA/J (H-2k) mice.•The recipient mice received clopidogrel, everolimus or both drugs.•The treatment prolonged the survival of the skin grafts.•The treatment increased the density of the microvessels in the graft.•The treatment reduced the amount of activated complement in the graft.

BackgroundEvery transplanted organ relies on a reliable and sound vascular system. Therefore, our study focused on the investigation if platelet inhibition alone or combined with mTOR-inhibition has a beneficial effect on the microvascular integrity in allogeneic murine skin grafts.MethodsSkin transplantation was performed from fully MHC-mismatched C57BL/6 (H-2b) donors to CBA/J (H-2k) recipient mice. Skin allograft recipients were assigned to several experimental groups and either treated with clopidogrel alone, everolimus alone or a combination of both. Graft survival was evaluated and transplants were harvested after 8 days and analyzed for CD31 and C4d by immunohistochemistry.ResultsUntreated allografts showed a reduced amount of CD31 on postoperative day 8 as well as an increase in C4d compared to isografts. All treated animals showed a significant improvement regarding CD31 [1577.7 ± 200.4 (clopidogrel)/1702.8 ± 151.1 (clopidogrel + everolimus) vs. 479.7 ± 184.2 (control), n = 8, p < 0.05] and C4d [420.9 ± 70.9 (clopidogrel)/324.5 ± 77.3 (clopidogrel + everolimus) vs. 772.4 ± 159.7 (control), n = 8, p < 0.05]. In addition, skin grafts of animals treated with clopidogrel and everolimus survived significantly longer compared to untreated controls [19.2 ± 4.2 d vs. 12.8 ± 2.4 d, n = 10, p < 0.05].ConclusionIn this study we could show that clopidogrel alone and in combination with everolimus substantially improved microvascular integrity and resulted in increased survival time of skin grafts.