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

IF 3.2 2区 医学 Q1 SURGERY
Plastic and reconstructive surgery Pub Date : 2025-01-01 Epub Date: 2024-03-29 DOI:10.1097/PRS.0000000000011441
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
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引用次数: 0

摘要

背景:从转基因α1,3-半乳糖基转移酶基因敲除猪(GalT-KO)身上获得的神经异种移植物缺乏导致猪对灵长类动物移植超急性排斥反应的表位。目前还不清楚这些冷保存神经移植物在免疫抑制期间和之后是否支持其他物种的轴突再生。在这项研究中,我们比较了大鼠坐骨神经间隙修复模型中自体移植和冷冻异种移植的结果:50只雄性Lewis大鼠用以下方法修复了1厘米的坐骨神经缺损:自体移植物和缝合(n=10);1周或4周冷保存异种移植物和缝合(每组n=10);1周或4周冷保存异种移植物和使用人羊膜包裹的光化学组织粘合(PTB/HAM)(每组n=10)。接受异种移植的大鼠在术后 4 个月前服用他克莫司。在 4 个月和 7 个月时,对大鼠实施安乐死并采集神经切片。计算每月坐骨神经功能指数(SFI)得分:结果:所有组的 SFI 评分在 4 个月和 7 个月时都有所提高。自体移植缝合组在 4 个月和 7 个月时的轴突密度最高。冷保存一周的 PTB/HAM 组的轴突密度在 4 至 7 个月期间下降幅度最大。各组 SFI 评分的唯一显著差异出现在 5 个月时,冷保存 1 周组的评分均显著低于冷保存 4 周缝合组:我们在大鼠坐骨神经模型中的研究结果表明,GalT-KO 神经异种移植物可能是自体移植物的可行替代品,并证明有必要进一步研究长间隙修复以及与无细胞神经异体移植物的比较:这项在大鼠坐骨神经模型中进行的概念验证研究表明,冷保存的 GalT-KO 猪异种神经移植物支持轴突再生,并在免疫抑制撤除后支持轴突存活。这些结果进一步表明,低温保存和光化学组织粘合在调节神经修复部位的免疫反应中发挥作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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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来源期刊
CiteScore
5.00
自引率
13.90%
发文量
1436
审稿时长
1.5 months
期刊介绍: For more than 70 years Plastic and Reconstructive Surgery® has been the one consistently excellent reference for every specialist who uses plastic surgery techniques or works in conjunction with a plastic surgeon. Plastic and Reconstructive Surgery® , the official journal of the American Society of Plastic Surgeons, is a benefit of Society membership, and is also available on a subscription basis. Plastic and Reconstructive Surgery® brings subscribers up-to-the-minute reports on the latest techniques and follow-up for all areas of plastic and reconstructive surgery, including breast reconstruction, experimental studies, maxillofacial reconstruction, hand and microsurgery, burn repair, cosmetic surgery, as well as news on medicolegal issues. The cosmetic section provides expanded coverage on new procedures and techniques and offers more cosmetic-specific content than any other journal. All subscribers enjoy full access to the Journal''s website, which features broadcast quality videos of reconstructive and cosmetic procedures, podcasts, comprehensive article archives dating to 1946, and additional benefits offered by the newly-redesigned website.
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