Pretransplant kidney-specific treatment to eliminate the need for systemic immunosuppression.
Pretransplant kidney-specific treatment to eliminate the need for systemic immunosuppression.
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DOI：
10.1097/tp.0b013e3181ffba97
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发表时间：
2010-12-27
期刊：
影响因子：
6.2
通讯作者：
Stubenitsky BM
中科院分区：
文献类型：
--
作者：
Brasile L;Glowacki P;Castracane J;Stubenitsky BM
尽管有显著的副作用，慢性全身免疫抑制仍然是临床移植的支柱。我们研究了非系统性预处理预防犬移植肾早期识别的可行性。在3小时的离体温灌注期间，用由纳米屏障膜组成的生物工程接口处理肾脉管系统。通过以下标准建立免疫封闭技术的初步可行性：在离体温灌注3小时后，可以实现用纳米屏障膜覆盖脉管系统的约90%;覆盖管腔表面防止同种异体识别，如通过混合淋巴细胞-血管内皮反应所确定的;覆盖管腔表面不会对肾功能产生负面影响，如通过自体移植结果所确定的;并且在用免疫掩蔽技术处理的犬肾中，移植物排斥被显著推迟。在不存在全身免疫抑制的情况下，未处理的对照犬在第6天发生平均排斥反应，而在肾血管腔表面修饰的处理犬中，平均排斥反应发生显著延迟至第30天。推迟或最终消除在再灌注融合时立即发生的同种异体识别的能力可以提供一个新的机会窗口，以引入辅助疗法来支持耐受诱导。据我们所知，这是第一次在没有全身免疫抑制或免疫操作的情况下，犬肾移植物的存活时间显着延长。
Despite significant side effects, chronic systemic immunosuppression remains the backbone of clinical transplantation. We investigated the feasibility of preventing early allorecognition in canine renal allografts using a nonsystemic pretreatment. The renal vasculature was treated with a bioengineered interface consisting of a nano-barrier membrane during 3 hr of ex vivo warm perfusion. Preliminary feasibility of the immunocloaking technology was established by the following criteria: it is possible to achieve approximately 90% coverage of the vasculature with nano-barrier membrane after 3 hr of ex vivo warm perfusion; covering the luminal surfaces prevents allorecognition as determined by mixed lymphocyte-vascular endothelial reaction; covering the luminal surfaces does not negatively affect renal function as determined by auto-transplant outcomes; and graft rejection is significantly postponed in canine kidneys treated with the immunocloaking technology. In the absence of systemic immunosuppression, untreated control dogs experienced a mean onset of rejection on day 6, whereas in the treated dogs with modified renal vascular luminal surfaces, the mean onset of rejection was significantly delayed until day 30. The ability to postpone, or eventually eliminate, the allorecognition that occurs immediately on reper-fusion could provide a new window of opportunity to introduce adjunct therapies to support tolerance induction. To our knowledge, this is the first time significantly prolonged canine renal allograft survival has been achieved in the absence of systemic immunosuppression or immunologic manipulation of the recipient.