Novel technologies to engineer graft for tolerance induction.
Novel technologies to engineer graft for tolerance induction.
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DOI：
10.1097/mot.0000000000000270
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发表时间：
2016-02
影响因子：
2.2
通讯作者：
Shirwan H
中科院分区：
文献类型：
--
作者：
Woodward KB;Wang F;Zhao H;Yolcu ES;Shirwan H
尽管最近在免疫抑制领域取得了突破性进展，但克服同种异体移植排斥反应仍然是一个难以实现的目标。大部分问题在于长期使用全身免疫抑制药物的毒副作用，这些药物有时在控制排斥反应方面无效，但也阻碍了移植耐受的建立。在这篇综述中，我们讨论了使用免疫调节分子工程的移植物作为诱导耐受的手段的新技术。最近的几项研究表明，用免疫调节生物制剂改造细胞、组织或固体器官移植物以实现移植物的长期存活是可行的，而不需要使用慢性免疫抑制。这一方法主要改变了移植物微环境中T效应细胞与CD4+CD25+FoxP3+T调节细胞的比例，有利于实现局部耐受诱导和维持。使用生物工程同种异体移植物的局部免疫调节代表了在没有长期使用免疫抑制的情况下实现移植物长期存活的新范例。对移植物的操纵，而不是对接受者的操纵，不仅通过将免疫抑制的不利影响降至最低来确保短期和长期的安全性，而且还允许保留对接受者抗击感染和癌症的能力至关重要的免疫能力。
Conquering allograft rejection remains an elusive goal in spite of recent breakthroughs in the field of immunosuppression. Much of the problem lies in the toxicity and side effects of long-term use of systemic immunosuppressant drugs, which are sometimes ineffective in controlling rejection, but also hinder establishment of transplant tolerance. In this review, we discuss novel technologies that use grafts engineered with immunomodulatory molecules as a means of inducing tolerance. Several recent studies have demonstrated the feasibility of engineering cells, tissues, or solid organ grafts with immunoregulatory biologics to achieve long termgraft survival without the use of chronic immunosuppression. This approach was shown to primarily change the ratio of T effector versus CD4+CD25+FoxP3+ T regulatory cells within the graft microenvironment in favor of attaining localized tolerance induction and maintenance. Localized immunomodulation using biologic-engineered allografts represent a new paradigm for achieving long term graft survival in the absence of chronic use of immunosuppression. The manipulation of the graft, rather than the recipient, not only ensures short and long-term safety by minimizing the adverse effects of immunosuppression, but also allows retention of immune competency critical for the ability of the recipient to fight infections and cancer.