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最小免疫抑制同种基因工程猪模型全层与板层猪猴角膜异种移植的移植物存活率比较。

Comparison of Graft Survival Between Full-Thickness and Lamellar Pig-to-Monkey Corneal Xenotransplantation from the Same Genetically Engineered Pig Model with Minimal Immunosuppression.

机构信息

Department of Surgery, Konkuk University School of Medicine, Seoul, South Korea.

Department of Ophthalmology, Konkuk University Medical Center, Seoul, South Korea.

出版信息

Transplant Proc. 2023 May;55(4):1036-1042. doi: 10.1016/j.transproceed.2023.03.065. Epub 2023 May 3.

DOI:10.1016/j.transproceed.2023.03.065
PMID:37147194
Abstract

BACKGROUND

The graft survival rate of full-thickness corneal xenotransplantation (XTP) with minimal immunosuppression in genetically engineered pigs is unknown, whereas lamellar corneal XTP shows satisfactory results. We compared graft survival between full-thickness and lamellar transplantations in the same genetically engineered pig.

METHODS

Six pig-to-monkey corneal transplantations were performed on 3 transgenic pigs. Two corneas harvested from 1 pig were transplanted into 2 monkeys using full-thickness and lamellar corneal xenotransplantation. The transgenic donor pigs used were α1,3-galactosyltransferase gene-knockout + membrane cofactor protein (GTKO+CD46) in one recipient and GTKO+CD46+ thrombomodulin (TBM) in the other.

RESULTS

The graft survival time for GTKO+CD46 XTP was 28 days. With the addition of TBM, the survival differences between lamellar and full-thickness XTP were 98 days versus 14 days and >463 days (ongoing) versus 21 days, respectively. An excessive number of inflammatory cells was observed in failed grafts, but none were in the recipient's stromal bed.

CONCLUSIONS

Unlike full-thickness corneal XTP, lamellar xenocorneal transplantation does not exhibit surgical complications, such as retrocorneal membrane or anterior synechia. The graft survival of lamellar XTP in this study was not as good as in our previous experiments, although the survival period was superior to that of full-thickness XTP. The difference in graft survival based on transgenic type is not definitive. Further studies using transgenic pigs and minimal immunosuppression need to focus on improving graft survival of lamellar XTP and using a larger sample size to determine the potential of full-thickness corneal XTP.

摘要

背景

在基因工程猪中进行最小免疫抑制的全厚角膜异种移植(XTP)的移植物存活率尚不清楚,而板层角膜 XTP 则显示出满意的结果。我们比较了同一基因工程猪中全厚和板层移植的移植物存活率。

方法

在 3 只转基因猪上进行了 6 例猪到猴角膜移植。从 1 只猪收获的 2 个角膜通过全厚和板层角膜异种移植分别移植到 2 只猴子中。使用的转基因供体猪在 1 只受体中为α1,3-半乳糖基转移酶基因敲除+膜辅助蛋白(GTKO+CD46),在另 1 只受体中为 GTKO+CD46+血栓调节蛋白(TBM)。

结果

GTKO+CD46 XTP 的移植物存活时间为 28 天。添加 TBM 后,板层和全厚 XTP 的存活差异分别为 98 天与 14 天和>463 天(持续中)与 21 天。失败的移植物中观察到大量炎症细胞,但在受体的基质床上没有。

结论

与全厚角膜 XTP 不同,板层异种角膜移植不会出现后弹力层膜或前粘连等手术并发症。本研究中板层 XTP 的移植物存活率不如我们之前的实验,但存活时间优于全厚 XTP。基于转基因类型的移植物存活率差异不明确。使用转基因猪和最小免疫抑制的进一步研究需要集中于改善板层 XTP 的移植物存活率,并使用更大的样本量来确定全厚角膜 XTP 的潜力。

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