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猪-恒河猴角膜板层异种移植的疗效。

Efficacy of pig-to-rhesus lamellar corneal xenotransplantation.

机构信息

Department of Ophthalmology, Healthcare System Gangnam Center, Seoul, Korea.

出版信息

Invest Ophthalmol Vis Sci. 2011 Aug 22;52(9):6643-50. doi: 10.1167/iovs.11-7273.

DOI:10.1167/iovs.11-7273
PMID:21743020
Abstract

PURPOSE. To solve the shortage of donor corneas, a decellularizing method based on hypertonic saline treatment was introduced, and a favorable outcome was observed in pig-to-rabbit lamellar corneal transplantation. This study was an investigation of the efficacy of pig-to-nonhuman primate lamellar corneal transplantation, using both decellularized and fresh porcine corneas to assess feasibility as a substitute for human corneas. METHODS. Nine Chinese rhesus macaques underwent lamellar corneal transplantation using both decellularized (n = 5) and fresh (n = 4) porcine corneas. Clinically acceptable graft size (7.5 mm in diameter) and minimal immunosuppression based on topical and systemic corticosteroids were applied. Rejection signs, histology of porcine grafts, and serial changes in recipients' blood profile, including memory T-cell subset, anti-α-Gal and donor pig-specific antibodies, and complement were evaluated. Changes in aqueous complement concentration were also assessed at 4 weeks after transplantation. RESULTS. Of the decellularized porcine lamellar grafts, 80% remained transparent for more than 6 months, whereas half of the fresh porcine lamellar grafts developed chronic rejection. Rejected grafts showed extensive cellular infiltration, predominantly CD8(+) T lymphocytes and macrophages. Immunologic profiles of the recipients with rejected grafts showed a significant increase in the concentration of aqueous complement, an enhancement of memory T cells, and an abrupt increase in donor pig-specific antibodies. CONCLUSIONS. The findings suggested that decellularized porcine cornea could be a promising substitute for human corneal allograft. Fresh porcine cornea may be a feasible option for a substitute if combined with more potent immunosuppression or if obtained from transgenic pigs with complement-regulatory proteins.

摘要

目的。为了解决供体角膜短缺的问题,引入了一种基于高渗盐水处理的脱细胞方法,在猪-兔板层角膜移植中观察到了良好的结果。本研究旨在探讨猪-非人灵长类板层角膜移植的效果,使用脱细胞和新鲜猪角膜来评估作为人角膜替代物的可行性。

方法。9 只中国猕猴接受了脱细胞(n=5)和新鲜(n=4)猪角膜的板层角膜移植。采用临床可接受的移植物大小(直径 7.5mm)和基于局部和全身皮质类固醇的最小免疫抑制。评估排斥迹象、猪移植物的组织学、受者血液特征的连续变化,包括记忆 T 细胞亚群、抗-α-Gal 和供体猪特异性抗体以及补体,以及移植后 4 周时房水中补体浓度的变化。

结果。脱细胞猪板层移植物中有 80%在 6 个月以上保持透明,而一半的新鲜猪板层移植物发生慢性排斥。排斥的移植物显示出广泛的细胞浸润,主要是 CD8(+)T 淋巴细胞和巨噬细胞。排斥移植物受者的免疫特征显示,房水中补体浓度显著增加,记忆 T 细胞增强,供体猪特异性抗体急剧增加。

结论。研究结果表明,脱细胞猪角膜可能是一种有前途的人角膜同种异体移植物替代品。如果与更有效的免疫抑制结合使用,或者如果从具有补体调节蛋白的转基因猪获得,新鲜猪角膜可能是一种可行的替代品。

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