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. Topography plays a major role on surface-cell interaction beside the surface chemistry. We investigated the effect of the nanotopography on vascular cell adhesion and proliferation in order to improve endothelialisation for restenosis treatment. In this context, Al2O3 nanowires (NWs) composed of a stable Al2O3 shell and an Al core were synthesized by chemical vapour deposition (CVD) of the molecular precursor (tBuOAlH2)2. After the detailed material characterization, human umbilical vein endothelial cells (HUVEC) and human umbilical vein smooth muscle cells (HUVSMC) were seeded and cultivated on these surfaces. Our preliminary results showed that there is a preference of HUVEC adhesion on NWs in comparison to that of HUVSMC. The control of the cell–surface interaction by the topography may represent a key issue for the future stent material design.

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The clinical application of xenotransplantation evokes immunological and microbiological as well as virological challenges. Porcine pathogens that do not show any symptoms in their natural host could exhibit a risk of fatal infections to humans. The presence of pig infectious agents including zoonotic and dissimilar agents should be reduced by specific pathogen free (spf) breeding of donor animals. However, the genetic information of porcine endogenous retroviruses (PERV) is integrated in the pig genome and can not be eradicated by spf breeding. The concerns about PERV for human xenograft recipients are based on data of in vitro replication of PERV in some human cell lines. So far, viral replication of PERV has been difficult to demonstrate in non‐human primate cell lines and in preclinical studies of non‐human primates receiving porcine xenografts, respectively. In this regard, natural and effective mechanisms of human and porcine cells counteracting productive infections caused by PERV are important to investigate. Intracellular proteins and components of the innate immune system including endogenous “antiretroviral restriction factors” act at various steps in retroviral replication. The cellular front is composed by several constitutively expressed genes which prevent or suppress retroviral infections. Some of these factors such as members of the tripartite motif (TRIM) and the apolipoprotein B mRNA‐editing polypeptide (APOBEC) families as well as tetherin and zinc‐finger antiviral protein (ZAP) could be useful in the management of PERV in xenotransplantation. The risks of infection and the potential role of antiretroviral restriction factors in xenotransplantation are presented in detail.

Zoonoses pose a threat to mammalian species. Cross‐species transmission of viruses have given rise to fatal diseases because the host organism is not prepared to resist a new pathogen. Mammals have developed several strategies of defense against viruses, including an intracellular antiretroviral defense, a part of innate immunity. In addition to the conventional innate and acquired immune responses, complex organisms such as mice and primates have evolved an array of dominant, constitutively expressed genes that suppress or prevent retroviral infections. Several of these antiretroviral restriction mechanisms have recently been identified, with two particularly well described factors being members of the tripartite motif (TRIM) and APOBEC families. The TRIM5 class of inhibitors appears to target incoming retroviral capsids and the APOBEC class of cytidine deaminases hypermutates and destabilizes retroviral genomes. Lentiviruses such as HIV‐1 have developed countermeasures that allow them to replicate despite the human host factors. In the course of risk assessment for pig‐to‐human xenotransplantation the capacity of human cells to counteract infections of gamma‐type porcine endogenous retroviruses (PERV) should be analyzed. We raised the question as to whether PERV is affected by APOBEC3 proteins. Initial data indicate that human and porcine cytidine deaminases inhibit PERV replication, thereby possibly reducing the risk for infection of human cells by PERV as a consequence of pig‐to‐human xenotransplantation. The exact mechanism of the TRIM5 mediated restriction has not been clarified up to now. At current, we investigate how many TRIM5 genes are located in the pig genome. Furthermore, the properties of porcine TRIM5α isoform proteins will be tested and we will check the potential of the human TRIM5α to restrict PERVs in order to determine the risk of virus transmission.

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