Cozzi Emanuele, Bosio Erika, Seveso Michela, Vadori Marta, Ancona Ermanno
Department of Medical and Surgical Sciences, University of Padua, Clinica Chirurgica III, Via Giustiniani, 2, 35128 Padova, Italy.
Br Med Bull. 2006 May 24;75-76:99-114. doi: 10.1093/bmb/ldh061. Print 2005.
Research efforts have shed light on the immunological obstacles to long-term survival of pig organs transplanted into primates and allowed the identification of targets for specific immune intervention. Accordingly, the development of genetically engineered animals has overcome the hyperacute rejection barrier, with acute humoral xenograft rejection (AHXR) currently remaining the most important immunological obstacle. At this stage, a better control of the elicited anti-pig humoral immune response and avoidance of coagulation disorders are the two primary research fronts being pursued in order to overcome AHXR. Nonetheless, it is encouraging that porcine xenografts can sustain the life of non-human primates for several months. Proactive research aimed at the development of a safer organ source is also underway. It is anticipated that ongoing research in several fields, including accommodation, tolerance, immune suppression and genetic engineering, will result in further improvements in non-human primate survival. However, until convincing efficacy data and a more favourable risk/benefit ratio can be established in relevant animal models, progression to the clinic should not be viewed as an option.
研究工作已揭示了猪器官移植到灵长类动物体内长期存活所面临的免疫障碍,并确定了特异性免疫干预的靶点。因此,基因工程动物的发展克服了超急性排斥障碍,目前急性体液异种移植排斥反应(AHXR)仍然是最重要的免疫障碍。在这个阶段,更好地控制引发的抗猪体液免疫反应和避免凝血障碍是为克服AHXR而正在推进的两个主要研究方向。尽管如此,令人鼓舞的是猪异种移植物能够维持非人类灵长类动物数月的生命。旨在开发更安全器官来源的前瞻性研究也在进行中。预计包括适应、耐受、免疫抑制和基因工程在内的多个领域的持续研究将进一步提高非人类灵长类动物的存活率。然而,在相关动物模型中建立令人信服的疗效数据和更有利的风险/效益比之前,不应将进入临床视为一种选择。