Stable corneal regeneration four years after implantation of a cell-free recombinant human collagen scaffold
Stable corneal regeneration four years after implantation of a cell-free recombinant human collagen scaffold
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DOI：
10.1016/j.biomaterials.2013.11.079
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发表时间：
2014-03-01
期刊：
影响因子：
14
通讯作者：
Griffith, May
中科院分区：
文献类型：
--
作者：
Fagerholm, Per;Lagali, Neil S.;Griffith, May
我们开发了含有碳二亚胺交联型重组人胶原(RHC)的无细胞植入物，通过内源性细胞募集实现角膜再生，以解决全球供体角膜短缺的问题。患者接受RHC植入物移植。在四年多的时间里，再生的新角膜稳定地结合在一起，没有排斥反应，没有供体角膜患者所需的长期免疫抑制疗法。没有炎性树突状细胞募集到植入区，然而，即使在免疫抑制的情况下，供体角膜受体仍显示树突状细胞迁移到中央角膜，并观察到排斥反应。再生，如持续的神经和基质细胞再生在四年中发生的，接近健康角膜的微结构。重新移植患者再生的透明角膜的组织病理学显示正常的角膜结构。供体人角膜移植眼神经异常弯曲，基质细胞死亡。植入的患者4年平均矫正视力为20/54，并在眼表上获得了5条以上的Snellen视线。使用更坚固的材料可以提高视力，从而更好地保持形状。然而，这些RHC植入物可以实现稳定的再生，因此，是一种潜在的安全的替代供体器官移植的选择。(C)2013年提交人。爱思唯尔有限公司出版。保留所有权利。
We developed cell-free implants, comprising carbodiimide crosslinked recombinant human collagen (RHC), to enable corneal regeneration by endogenous cell recruitment, to address the worldwide shortage of donor corneas. Patients were grafted with RHC implants. Over four years, the regenerated neo-corneas were stably integrated without rejection, without the long immunosuppression regime needed by donor cornea patients. There was no recruitment of inflammatory dendritic cells into the implant area, whereas, even with immunosuppression, donor cornea recipients showed dendritic cell migration into the central cornea and a rejection episode was observed. Regeneration as evidenced by continued nerve and stromal cell repopulation occurred over the four years to approximate the micro-architecture of healthy corneas. Histopathology of a regenerated, clear cornea from a regrafted patient showed normal corneal architecture. Donor human cornea grafted eyes had abnormally tortuous nerves and stromal cell death was found. Implanted patients had a 4-year average corrected visual acuity of 20/54 and gained more than 5 Snellen lines of vision on an eye chart. The visual acuity can be improved with more robust materials for better shape retention. Nevertheless, these RHC implants can achieve stable regeneration and therefore, represent a potentially safe alternative to donor organ transplantation. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.