Prolonged survival of GalT‐KO swine skin on baboons

Weiner, Joshua; Yamada, Kazuhiko; Ishikawa, Yoshinori; Moran, Shannon; Etter, Justin; Shimizu, Akira; Smith, Rex Neal; Sachs, David H.

doi:10.1111/j.1399-3089.2010.00576.x

Cited by 21 publications

(31 citation statements)

References 27 publications

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“…Nevertheless, the presence of these additional antigens did not lead to an accelerated rejection of the xenogeneic grafts, suggesting that these additional antigens are of less importance for the cellular than for the humoral immune response. Thus, in the absence of Gal antigens, to which the most potent natural antibody reactivities are seen (17), it would appear that primary skin graft rejection is primarily a result of the cellular immune response and is comparable for allogeneic and xenogeneic skin grafts as indicated by similar graft survivals.…”

Section: Discussionmentioning

confidence: 99%

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Lack of Cross-Sensitization Between α-1,3-Galactosyltransferase Knockout Porcine and Allogeneic Skin Grafts Permits Serial Grafting

et al. 2014

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Background The current standard of care for burns requiring operative treatment consists of early burn excision and autologous split-thickness skin grafting. However, in large burns, sufficient donor sites may not be available to achieve total coverage, necessitating temporary coverage with allogeneic human cadaver skin grafts or synthetic skin substitutes. A previous study from this laboratory demonstrated that skin grafts from alpha-1,3 galactosyltransferase knockout (GalT-KO) miniature swine enjoyed survival comparable to that of allogeneic skin grafts in baboons. Methods In the present study, we have evaluated the immune response against sequential GalT-KO and allogeneic skin grafts to determine whether such serial grafts could extend the period of temporary wound coverage before definitive grafting with autologous skin. Results We report that rejection of primary GalT-KO skin grafts led to an anti-xenogeneic humoral response with no evidence for sensitization to alloantigens nor acceleration of rejection of allogeneic skin grafts. Similarly, presensitization with allogeneic skin did not lead to accelerated rejection of xenogeneic skin. Conclusions These data suggest that GalT-KO skin grafts could provide an early first-line treatment in the management of severe burns that would not preclude subsequent use of allografts, and that serial grafting of GalT-KO skin and allogeneic skin could potentially be used to provide an extended period of temporary burn wound coverage.

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Section: Discussionmentioning

confidence: 99%

“…We have previously reported prolonged survival of skin from these animals transplanted across a pig-to-baboon barrier (17). In those studies, we have shown that skin grafts from these GalT-KO swine enjoy comparable survival to allogeneic skin in baboons and thus might provide a new source of vital skin grafts for the acute treatment of severe burns.…”

mentioning

confidence: 97%

Lack of Cross-Sensitization Between α-1,3-Galactosyltransferase Knockout Porcine and Allogeneic Skin Grafts Permits Serial Grafting

et al. 2014

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“…Therefore, confirming that grafts stored for this purpose can be effectively thawed and transplanted without adverse implications is of critical importance in interpreting other experimental results. Given the well-established similarity between human and porcine skin, 6,8–15 we expect that the findings in these studies should have relevance to the clinical practice of skin grafting.…”

Section: Introductionmentioning

confidence: 85%

A Comparative Examination of the Clinical Outcome and Histological Appearance of Cryopreserved and Fresh Split-Thickness Skin Grafts

Holzer

Leonard

Shanmugarajah

et al. 2017

Journal of Burn Care & Research

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Objective The clinical use of frozen, human allogeneic skin grafts is considered a suitable alternative to freshly harvested allogeneic skin grafts when the latter are not available. However, limited functional and histologic information exists regarding the effects of cryopreservation on allogeneic skin grafts, especially those across mismatched histocompatibility barriers. Thus, we performed a side-by-side comparative study of fresh vs. frozen skin grafts, across both minor and major histocompatibility barriers, in a miniature swine model. Since porcine skin shares many physical and immunologic properties with human skin, our findings have relevance to current clinical practices involving allogeneic grafting, and may support future, temporary wound therapies involving frozen xenografts, comprised of genetically modified porcine skin. Methods Four miniature swine underwent harvest and grafting of split thickness skin, with and without cryopreservation, in order to observe autologous grafts and grafts across minor and major histocompatibility barriers. Grafts were biopsied at regular intervals for study of architecture, vascularization, and outcomes. Results All grafts vascularized without technical complications. Differences were noted in the early appearance of some fresh vs. frozen grafts but no significant difference was observed in overall survival times in any of the experimental groups. Conclusion These results demonstrate that despite early observable differences in the healing process, cryopreservation and thawing does not significantly affect long-term graft survival or time to rejection, thus supporting the clinical and experimental use of fresh and frozen split thickness skin grafts as comparable and interchangeable.

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“…In a short communication, Weiner et al. [6] evaluated survival of skin grafts from α1,3‐galactosyltransferase gene knockout (GT‐KO) pigs on baboons. Two adult baboons that had fully recovered from previous T‐cell depletion received simultaneous skin grafts from GT‐KO pigs, galactose‐α1,3‐galactose (Gal)‐positive pigs, a third‐party baboon, and self (control) and were treated with cyclosporine for 12 days.…”

Section: Preclinicalmentioning

confidence: 99%