Modulation of Graft Arteriosclerosis in a Rat Carotid Transplantation Model

Zdoroveac, Andrei; Doebis, Cornelia; Laube, Horst; Brösel, S.; Schmitt-Knosalla, Isabela; Volk, Hans‐Dieter; Seifert, Martina

doi:10.1016/j.jss.2007.08.031

Cited by 9 publications

(5 citation statements)

References 34 publications

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“…Our findings, however, do not concur with other studies reporting engraftment of MHC class I − cells in xenogeneic or allogeneic recipients without active suppression of NK cell activity [28]–[32], [56]. In view of the different strategies used in these studies (i.e.…”

Section: Discussioncontrasting

confidence: 99%

“…Along the same line, adipose tissue-derived hMSCs that had lost MHC class I surface expression during long-term culture, effectively contributed to skeletal muscle repair in immunocompetent dystrophic mice [31]. Recently, Zdoroveac and co-workers [32] demonstrated reduced immune responses to carotid allografts genetically modified to decrease surface levels of MHC class I antigens through an endoplasmic reticulum-targeted MHC class I-specific intrabody.…”

Section: Introductionmentioning

confidence: 99%

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Exploitation of Herpesvirus Immune Evasion Strategies to Modify the Immunogenicity of Human Mesenchymal Stem Cell Transplants

et al. 2011

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BackgroundMesenchymal stem cells (MSCs) are multipotent cells residing in the connective tissue of many organs and holding great potential for tissue repair. In culture, human MSCs (hMSCs) are capable of extensive proliferation without showing chromosomal aberrations. Large numbers of hMSCs can thus be acquired from small samples of easily obtainable tissues like fat and bone marrow. MSCs can contribute to regeneration indirectly by secretion of cytokines or directly by differentiation into specialized cell types. The latter mechanism requires their long-term acceptance by the recipient. Although MSCs do not elicit immune responses in vitro, animal studies have revealed that allogeneic and xenogeneic MSCs are rejected.Methodology/Principal FindingsWe aim to overcome MSC immune rejection through permanent down-regulation of major histocompatibility complex (MHC) class I proteins on the surface of these MHC class II-negative cells through the use of viral immune evasion proteins. Transduction of hMSCs with a retroviral vector encoding the human cytomegalovirus US11 protein resulted in strong inhibition of MHC class I surface expression. When transplanted into immunocompetent mice, persistence of the US11-expressing and HLA-ABC-negative hMSCs at levels resembling those found in immunodeficient (i.e., NOD/SCID) mice could be attained provided that recipients' natural killer (NK) cells were depleted prior to cell transplantation.Conclusions/SignificanceOur findings demonstrate the potential utility of herpesviral immunoevasins to prevent rejection of xenogeneic MSCs. The observation that down-regulation of MHC class I surface expression renders hMSCs vulnerable to NK cell recognition and cytolysis implies that multiple viral immune evasion proteins are likely required to make hMSCs non-immunogenic and thereby universally transplantable.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exploitation of Herpesvirus Immune Evasion Strategies to Modify the Immunogenicity of Human Mesenchymal Stem Cell Transplants

et al. 2011

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“…Since intrabody was successfully captured in the lumen of the ER by KDEL ER-retention signal sequence, it is possible that the intrabody binds to CD147 and retains these molecules in the membrane of the ER compartment and subsequently diminishes CD147 expression on the cell surface. In other studies, targeting of intrabodies to the ER has been successfully applied to knockdown major histocompatibility complex I (MHC-I) expression (Mhashilkar et al, 2002;Beyer et al, 2004;Zdoroveac et al, 2008) and inactivate various neoplastic cell-surface receptors (Wheeler et al, 2003;Jendreyko et al, 2005;Peng et al, 2007). Additionally, the same strategy was used to block cell surface expression of the CCR5 receptor which is important for cell entry of HIV-1 (Steinberger et al, 2000).…”

Section: Article In Pressmentioning

confidence: 99%

Potent inhibition of OKT3-induced T cell proliferation and suppression of CD147 cell surface expression in HeLa cells by scFv-M6-1B9

Intasai¹,

Tragoolpua²,

Pingmuang³

et al. 2009

Immunobiology

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“…Second, recipient APCs present donor MHC and minor antigens from the allograft to recipient T cells. This requires recognition of the allogens as peptides bound to recipient MHC II molecules [39,40] .…”

Section: Discussionmentioning

confidence: 99%

Glycerol-Preserved Arterial Allografts Evaluated in the Infrarenal Rat Aorta

Fahner

Idu²,

Gulik³

et al. 2008

Eur Surg Res

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Background: Vascular transplantation has become an alternative for prosthetic grafts. Suitable storage methods for vascular allografts are therefore necessary. For small caliber arterial allografts, cryopreservation and cold storage showed discouraging results. Since glycerol preservation proved effective for the storage of skin allografts, this preservation method was investigated for vascular allografts using a rat aortic transplantation model. Methods: Glycerol-preserved allografts (GA) were transplanted to the infrarenal aorta (n = 18) in Wistar rats. A control group (n = 18) underwent immediate autotransplantation (AU) of an equal length of aorta. Results: Cumulative graft patency at 90 days’ follow-up was 93% for AU and 78% for GA (ns). No aneurysm formation was detected in both groups. Intraluminal endothelial cell coverage, integrity of the media and smooth muscle cell repopulation were comparable in both groups. Intimal thickness was less in GA than in AU and inflammatory reaction in the adventitia was diminished in GA. Conclusion: GA were successfully grafted with acceptable patency rates compared to autografts, while intima hyperplasia and adventitial inflammatory reaction were less.

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Modulation of Graft Arteriosclerosis in a Rat Carotid Transplantation Model

Cited by 9 publications

References 34 publications

Exploitation of Herpesvirus Immune Evasion Strategies to Modify the Immunogenicity of Human Mesenchymal Stem Cell Transplants

Exploitation of Herpesvirus Immune Evasion Strategies to Modify the Immunogenicity of Human Mesenchymal Stem Cell Transplants

Potent inhibition of OKT3-induced T cell proliferation and suppression of CD147 cell surface expression in HeLa cells by scFv-M6-1B9

Glycerol-Preserved Arterial Allografts Evaluated in the Infrarenal Rat Aorta

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