Bahar Mohammad Ali, Nabai Layla, Ghahary Aziz
Burn Research Center (BRC), Iran University of Medical Science and Health Services, Tehran, Iran.
J Burn Care Res. 2012 May-Jun;33(3):364-70. doi: 10.1097/BCR.0b013e318235836e.
Delayed wound healing can significantly impact survival of patients who suffer from severe thermal injury. In general, the use of a wound coverage, particularly with those of bilayer skin substitute, would be ideal to promote healing and prevent infection and fluid loss. Although the use of an autologous skin substitute is desirable, its preparation is time consuming and its immediate availability is impossible. To overcome this difficulty, the authors have previously demonstrated that the expression of indoleamine 2,3 dioxygenase (IDO) could function as a local immune suppressive factor in protecting allogenic fibroblasts and keratinocytes without using any immunosuppressive medication in a wound healing animal model. IDO, which is naturally expressed in the placenta by trophoblast cells during pregnancy, plays an essential role in maternal tolerance toward the fetus. The potent and selective local immunosuppressive function of IDO makes this enzyme a very promising tool for engineering a nonrejectable skin allograft. Here, the authors reviewed and discussed how the expression of IDO by the primary cells of our skin substitute can serve as a source of IDO enzyme activity and generate a tryptophan-deficient environment. Under this condition, only skin cells but not immune cells (CD4(+) and CD8(+) cells) would survive and protect engraftment of this engineered and shelf-ready skin substitute to be used not only as wound coverage but also as a rich source of wound healing promoting factors. Therefore, this review summarizes the body of work on immunoprotective role of IDO in engraftment of allogenic skin substitute in wound healing, which has recently been reported by the authors' research group and others.
伤口愈合延迟会对严重热损伤患者的生存产生重大影响。一般来说，使用伤口覆盖物，特别是双层皮肤替代物，对于促进愈合、预防感染和减少体液流失是理想的选择。尽管使用自体皮肤替代物是可取的，但其制备耗时且无法立即获得。为克服这一困难，作者先前已证明，在伤口愈合动物模型中，吲哚胺2,3-双加氧酶（IDO）的表达可作为一种局部免疫抑制因子，在不使用任何免疫抑制药物的情况下保护同种异体成纤维细胞和角质形成细胞。IDO在孕期由胎盘滋养层细胞自然表达，在母体对胎儿的耐受性中起重要作用。IDO强大且具有选择性的局部免疫抑制功能，使其成为构建不可排斥皮肤同种异体移植物的极具前景的工具。在此，作者回顾并讨论了我们皮肤替代物的原代细胞中IDO的表达如何作为IDO酶活性的来源，并产生色氨酸缺乏的环境。在这种条件下，只有皮肤细胞而非免疫细胞（CD4(+)和CD8(+)细胞）能够存活，并保护这种经过工程改造且可立即使用的皮肤替代物的植入，该替代物不仅可作为伤口覆盖物，还可作为促进伤口愈合因子的丰富来源。因此，本综述总结了作者研究小组及其他团队最近报道的关于IDO在伤口愈合中同种异体皮肤替代物植入的免疫保护作用的研究工作。
