Nicholas C King, Jane M Tsui, Maria Bejar-Chapa, Michael S Marshall, Ann S Kogosov, Yingfang Fan, Marek A Hansdorfer, Joseph J Locascio, Mark A Randolph, Jonathan M Winograd
{"title":"Gal - T 基因敲除猪神经异种移植支持啮齿动物坐骨神经模型的轴突再生","authors":"Nicholas C King, Jane M Tsui, Maria Bejar-Chapa, Michael S Marshall, Ann S Kogosov, Yingfang Fan, Marek A Hansdorfer, Joseph J Locascio, Mark A Randolph, Jonathan M Winograd","doi":"10.1097/PRS.0000000000011441","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Nerve xenografts harvested from transgenic α1,3-galactosyltransferase knockout pigs lack the epitope responsible for hyperacute rejection in pig-to-primate transplants. It is unknown whether these cold-preserved nerve grafts support axonal regeneration in another species during and after immunosuppression. The authors compared outcomes between autografts and cold-preserved xenografts in a rat sciatic model of nerve gap repair.</p><p><strong>Methods: </strong>Fifty male Lewis rats had a 1-cm sciatic nerve defect repaired using autograft and suture ( n = 10); 1-week or 4-week cold-preserved xenograft and suture ( n = 10 per group); or 1-week or 4-week cold-preserved xenograft and photochemical tissue bonding using a human amnion wrap ( n = 10 per group). Rats with xenografts were given tacrolimus until 4 months postoperatively. At 4 and 7 months, rats were killed and nerve sections were harvested. Monthly sciatic functional index (SFI) scores were calculated.</p><p><strong>Results: </strong>All groups showed increases in SFI scores by 4 and 7 months. The autograft suture group had the highest axon density at 4 and 7 months. The largest decrease in axon density from 4 to 7 months was in the group with 1-week cold-preserved photochemical tissue bonding using a human amnion wrap. The only significant difference between group SFI scores occurred at 5 months, when both 1-week cold-preserved groups had significantly lower scores than the 4-week cold-preserved suture group.</p><p><strong>Conclusions: </strong>The results suggest that α1,3-galactosyltransferase knockout nerve xenografts may be viable alternatives to autografts. Further studies of long-gap repair and comparison with acellular nerve allografts are needed.</p><p><strong>Clinical relevance statement: </strong>This proof-of-concept study in the rat sciatic model demonstrates that cold-preserved α1,3-galactosyltransferase knockout porcine xenografts support axonal regeneration and viability following immunosuppression withdrawal. These results further suggest a role for both cold preservation and photochemical tissue bonding in modulating the immunological response at the nerve repair site.</p>","PeriodicalId":20128,"journal":{"name":"Plastic and reconstructive surgery","volume":" ","pages":"91-100"},"PeriodicalIF":3.2000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"GalT Knockout Porcine Nerve Xenografts Support Axonal Regeneration in a Rodent Sciatic Nerve Model.\",\"authors\":\"Nicholas C King, Jane M Tsui, Maria Bejar-Chapa, Michael S Marshall, Ann S Kogosov, Yingfang Fan, Marek A Hansdorfer, Joseph J Locascio, Mark A Randolph, Jonathan M Winograd\",\"doi\":\"10.1097/PRS.0000000000011441\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Nerve xenografts harvested from transgenic α1,3-galactosyltransferase knockout pigs lack the epitope responsible for hyperacute rejection in pig-to-primate transplants. It is unknown whether these cold-preserved nerve grafts support axonal regeneration in another species during and after immunosuppression. The authors compared outcomes between autografts and cold-preserved xenografts in a rat sciatic model of nerve gap repair.</p><p><strong>Methods: </strong>Fifty male Lewis rats had a 1-cm sciatic nerve defect repaired using autograft and suture ( n = 10); 1-week or 4-week cold-preserved xenograft and suture ( n = 10 per group); or 1-week or 4-week cold-preserved xenograft and photochemical tissue bonding using a human amnion wrap ( n = 10 per group). Rats with xenografts were given tacrolimus until 4 months postoperatively. At 4 and 7 months, rats were killed and nerve sections were harvested. Monthly sciatic functional index (SFI) scores were calculated.</p><p><strong>Results: </strong>All groups showed increases in SFI scores by 4 and 7 months. The autograft suture group had the highest axon density at 4 and 7 months. The largest decrease in axon density from 4 to 7 months was in the group with 1-week cold-preserved photochemical tissue bonding using a human amnion wrap. The only significant difference between group SFI scores occurred at 5 months, when both 1-week cold-preserved groups had significantly lower scores than the 4-week cold-preserved suture group.</p><p><strong>Conclusions: </strong>The results suggest that α1,3-galactosyltransferase knockout nerve xenografts may be viable alternatives to autografts. Further studies of long-gap repair and comparison with acellular nerve allografts are needed.</p><p><strong>Clinical relevance statement: </strong>This proof-of-concept study in the rat sciatic model demonstrates that cold-preserved α1,3-galactosyltransferase knockout porcine xenografts support axonal regeneration and viability following immunosuppression withdrawal. These results further suggest a role for both cold preservation and photochemical tissue bonding in modulating the immunological response at the nerve repair site.</p>\",\"PeriodicalId\":20128,\"journal\":{\"name\":\"Plastic and reconstructive surgery\",\"volume\":\" \",\"pages\":\"91-100\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Plastic and reconstructive surgery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/PRS.0000000000011441\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/3/29 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"SURGERY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Plastic and reconstructive surgery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/PRS.0000000000011441","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/29 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"SURGERY","Score":null,"Total":0}
GalT Knockout Porcine Nerve Xenografts Support Axonal Regeneration in a Rodent Sciatic Nerve Model.
Background: Nerve xenografts harvested from transgenic α1,3-galactosyltransferase knockout pigs lack the epitope responsible for hyperacute rejection in pig-to-primate transplants. It is unknown whether these cold-preserved nerve grafts support axonal regeneration in another species during and after immunosuppression. The authors compared outcomes between autografts and cold-preserved xenografts in a rat sciatic model of nerve gap repair.
Methods: Fifty male Lewis rats had a 1-cm sciatic nerve defect repaired using autograft and suture ( n = 10); 1-week or 4-week cold-preserved xenograft and suture ( n = 10 per group); or 1-week or 4-week cold-preserved xenograft and photochemical tissue bonding using a human amnion wrap ( n = 10 per group). Rats with xenografts were given tacrolimus until 4 months postoperatively. At 4 and 7 months, rats were killed and nerve sections were harvested. Monthly sciatic functional index (SFI) scores were calculated.
Results: All groups showed increases in SFI scores by 4 and 7 months. The autograft suture group had the highest axon density at 4 and 7 months. The largest decrease in axon density from 4 to 7 months was in the group with 1-week cold-preserved photochemical tissue bonding using a human amnion wrap. The only significant difference between group SFI scores occurred at 5 months, when both 1-week cold-preserved groups had significantly lower scores than the 4-week cold-preserved suture group.
Conclusions: The results suggest that α1,3-galactosyltransferase knockout nerve xenografts may be viable alternatives to autografts. Further studies of long-gap repair and comparison with acellular nerve allografts are needed.
Clinical relevance statement: This proof-of-concept study in the rat sciatic model demonstrates that cold-preserved α1,3-galactosyltransferase knockout porcine xenografts support axonal regeneration and viability following immunosuppression withdrawal. These results further suggest a role for both cold preservation and photochemical tissue bonding in modulating the immunological response at the nerve repair site.
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