Xenotransplantation

Kemp, E

doi:10.1046/j.1365-2796.1996.380747000.x

Cited by 15 publications

(10 citation statements)

References 26 publications

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“…The concept of cross-species tissue transplantation has intrigued medical science for decades by its prospect of alleviating the constantly growing need for donor tissue (Reemtsma 1964; Kemp, 1996). The xenotransplantation paradigm is, however, severely hampered by the fact that cross-species grafts are invariably rejected in immunocompetent hosts.…”

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confidence: 99%

Neuroretinal xenotransplantation to immunocompetent hosts in a discordant species combination

2008

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In spite of its immune privileged state, xenotransplantation within the CNS is associated with rapid graft destruction in immunocompetent hosts. Efforts to enhance graft survival have mostly focused on host immune response, whereas relatively little attention has been paid to donor tissue characteristics. In the present paper, we explore long-term survival of xenogeneic full-thickness neuroretinal transplants in immunocompetent hosts and investigate the significance of tissue integrity in relation to graft survival.Adult rabbits receiving no immunosuppression were used as hosts and fetal Sprague-Dowley rat neuroretina as donors. Using vitreoretinal surgical techniques, rabbits received either a full thickness or a fragmented neuroretinal graft to the subretinal space of one eye. Eyes receiving full-thickness grafts were examined morphologically after 91 days and fragmented grafts after 7-14 days.Surviving full thickness grafts were found in 6 out of 8 eyes, 4 of which displayed the normal laminated appearance. Major Histocompatibility Complex (MHC) up-regulation in surviving grafts was minimal and they contained a well organized photoreceptor layer, Protein Kinase C (PKC) labeled rod bipolar cells, parvalbumin labeled AII amacrine cells and glial fibrillary acidic protein (GFAP) labeled Müller cells. Fragmented grafts (n=6) were all destroyed or showed severe signs of rejection. A mass of inflammatory cells derived from the choroid was evident in these specimens, and no labeling of retina-specific cells were seen.We conclude that full-thickness rat neuroretina can survive for several months after subretinal transplantation to the subretinal space of immunocompetent rabbits, while fragmented counterparts are rapidly rejected. Surviving full-thickness grafts can develop many of the normal retinal morphological characteristics, indicating a thriving relationship between the initially immature donor tissue and its foreign host. Our results strongly indicates that donor tissue integrity is a crucial factor for graft survival in CNS xenotransplantation.

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Neuroretinal xenotransplantation to immunocompetent hosts in a discordant species combination

2008

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“…of respiratory mechanics in healthy pigs is needed. The potential use of porcine lung for xenotransplantation merits increased knowledge about these lungs [10].…”

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confidence: 99%

Elastic pressure-volume curves of the respiratory system reveal a high tendency to lung collapse in young pigs

et al. 1999

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“…Elucidating the exact mechanisms behind DXR would lead to rational treatment strategies in order to prevent graft destruction. It is essential to evaluate the effect of xenotransplantation on GT‐Ko organs, since organ physiology may accentuate organ damage during DXR (1). It has been postulated that α1,3Gal carbohydrate epitopes on endothelial cells may activate complement via the coupling to anti‐donor anti‐α1,3Gal Abs.…”

Section: Discussionmentioning

confidence: 99%

“…Delayed xenograft rejection (DXR), also known as acute vascular rejection, can occur after inhibition of hyperacute rejection (HAR) during disconcordant xenotransplantation or as an initial rejection form during concordant xenotransplantation (1). DXR is characterized by endothelial activation, thrombosis, graft infiltration by inflammatory cells and graft destruction within days (2).…”

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The resistance of delayed xenograft rejection to α(1,3)‐galactosyltransferase gene inactivation and CD4 depletion in a mouse‐to‐rat model

Hansen

Kirkeby²,

Aasted³

et al. 2003

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Critical to the prevention of xenograft loss is the prevention of delayed xenograft rejection (DXR), due to its resistance to conventional immunosuppression. The role of the carbohydrate galactose-alpha1,3-galactose (alpha1,3Gal) has been a matter of great debate and it has been proposed that the reaction between alpha1,3Gal epitopes on donor endothelial cells and recipient anti-alpha1,3Gal antibodies (Abs) may damage the graft during DXR. Recipient anti-alpha1,3Gal Abs are produced by CD4-dependent B cells. To test the above-mentioned hypothesis, hearts from alpha1,3Gal-free mice (GT-Ko mice), generated by alpha1,3-galacto-syltransferase gene disruption, were transplanted to anti-alpha1,3Gal antibody-free Lew/Mol rats. This model consists of an alpha1,3Gal/alpha1,3Gal-antibody-free environment, eliminating a possible influence of this specific system on DXR. A subgroup of recipients were furthermore CD4 depleted in order to inhibit CD4-dependent B-cell antibody production. Rejected hearts were evaluated by light- and immunofluorescence microscopy. Treatment effects on recipient T-cell subsets and cytokine expression were analyzed by flow cytometry, while antibody production was measured by ELISA. All recipients developed DXR with no differences among the groups. DXR was related to thrombosis with IgG and IgM desposition in vessel walls, as well as macrophage and granulocyte accumulation in the myocardium. No complement C3, CD4 cells or NK cells were found. Flow cytometric analysis confirmed peripheral blood CD4 depletion and IFN-gamma suppression in CD4 Ab-treated recipients. Finally, ELISA showed that specific anti-alpha1,3Gal Ab production was absent. However, Ab(s) against an unidentified Galalpha 1 were found among recipients. In our model, DXR is resistant to alpha1,3-galactosyltransferase gene inactivation and CD4 depletion. However, other Galalpha 1 epitopes and antibodies may play a role during DXR. Further studies are needed to elucidate the precise pathways leading to DXR.

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Xenotransplantation

Cited by 15 publications

References 26 publications

Neuroretinal xenotransplantation to immunocompetent hosts in a discordant species combination

Neuroretinal xenotransplantation to immunocompetent hosts in a discordant species combination

Elastic pressure-volume curves of the respiratory system reveal a high tendency to lung collapse in young pigs

The resistance of delayed xenograft rejection to α(1,3)‐galactosyltransferase gene inactivation and CD4 depletion in a mouse‐to‐rat model

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