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

Benjamin Motsch, Christian Heim, Nina Koch, Martina Ramsperger-Gleixner, Michael Weyand, Stephan M. Ensminger*

*Corresponding author for this work
4 Citations (Scopus)


Background: Every transplanted organ relies on a reliable and sound vascular system. Therefore, our study focused on the investigation if platelet inhibition alone or combinedwith mTOR-inhibition has a beneficial effect on the microvascular integrity in allogeneic murine skin grafts. Methods: Skin 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. Results: Untreated allografts showed a reduced amount of CD31 on postoperative day 8 aswell 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]. Conclusion: In 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.

Original languageEnglish
JournalTransplant Immunology
Issue number3
Pages (from-to)204-209
Number of pages6
Publication statusPublished - 11.2015


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