Spizzo Thomas, Denner Joachim, Gazda Lawrence, Martin Michael, Nathu Divya, Scobie Linda, Takeuchi Yasuhiro
Spring Point Project, Minneapolis, MN, USA.
Robert Koch Institut, Berlin, Germany.
Xenotransplantation. 2016 Jan-Feb;23(1):25-31. doi: 10.1111/xen.12223. Epub 2016 Mar 4.
Chapter 2 of the original consensus statement published in 2009 by IXA represents an excellent basis for the production of safe donor pigs and pig-derived materials for porcine islet xenotransplantation. It was intended that the consensus statement was to be reviewed at interval to remain relevant. Indeed, many of the original salient points remain relevant today, especially when porcine islet xenotransplantation is performed in conjunction with immunosuppressants. However, progress in the field including demonstrated safe clinical porcine xenograft studies, increased understanding of risks including those posed by PERV, and advancement of diagnostic capabilities now allow for further consideration. Agents of known and unknown pathogenic significance continue to be identified and should be considered on a geographic, risk-based, dynamic, and product-specific basis, where appropriate using validated, advanced diagnostic techniques. PERV risk can be sufficiently reduced via multicomponent profiling including subtype expression levels in combination with infectivity assays. Barrier facilities built and operated against the AAALAC Ag Guide or suitable alternative criteria should be considered for source animal production as long as cGMPs and SOPs are followed. Bovine material-free feed for source animals should be considered appropriate instead of mammalian free materials to sufficiently reduce TSE risks. Finally, the sponsor retention period for archival samples of donor materials was deemed sufficient until the death of the recipient if conclusively determined to be of unrelated and non-infectious cause or for a reasonable period, that is, five to 10 yrs. In summary, the safe and economical production of suitable pigs and porcine islet xenograft materials, under appropriate guidance and regulatory control, is believed to be a viable means of addressing the unmet need for clinical islet replacement materials.
国际异种移植协会（IXA）2009年发布的原始共识声明第二章，为生产用于猪胰岛异种移植的安全供体猪和猪源材料奠定了良好基础。该共识声明原本计划定期进行审查，以确保其相关性。事实上，许多原始要点如今仍然适用，尤其是在猪胰岛异种移植与免疫抑制剂联合使用时。然而，该领域的进展，包括已开展的安全临床猪异种移植研究、对包括猪内源性逆转录病毒（PERV）所带来风险在内的风险有了更多了解，以及诊断能力的提升，现在使得我们能够进行进一步思考。具有已知和未知致病意义的病原体仍在不断被发现，应在适当情况下，基于地理、风险、动态和产品特异性等因素，采用经过验证的先进诊断技术进行考量。通过多组分分析，包括亚型表达水平与感染性检测相结合，可以充分降低PERV风险。只要遵循药品生产质量管理规范（cGMPs）和标准操作规程（SOPs），就应考虑按照实验动物评估与认可委员会（AAALAC）实验动物饲养与使用指南或合适的替代标准建造和运营屏障设施来生产供体动物。应考虑为供体动物提供不含牛源成分的饲料，而非不含哺乳动物成分的饲料，以充分降低传染性海绵状脑病（TSE）风险。最后，如果最终确定供体材料的存档样本与受体死亡无关且无传染性，或者在合理期限内（即5至10年），那么在受体死亡之前，供体材料存档样本的主办方保留期被认为是足够的。总之，在适当的指导和监管控制下，安全且经济地生产合适的猪和猪胰岛异种移植材料，被认为是满足临床胰岛替代材料未满足需求的可行方法。
