Clinical aspects and perspectives in islet xenotransplantation.
Clinical aspects and perspectives in islet xenotransplantation.
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DOI：
10.1007/s005340070030
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发表时间：
2000-01-01
期刊：
影响因子：
--
通讯作者：
Korsgren, O
中科院分区：
文献类型：
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作者：
Groth, C G;Tibell, A;Korsgren, O
1990-1993年，8例糖尿病肾移植患者在斯德哥尔摩的Huddinge医院接受了猪胎胰岛门静脉内注射。4例患者有异种移植功能的证据，反映在少量猪C肽的排泄中。两名患者将猪胎儿胰岛置于同时移植的肾的包膜下。在这些患者中，移植后3周的移植物活检标本显示形态完整的上皮细胞胰岛素和胰高血糖素染色阳性。在所有情况下，胰岛素产量均不足以影响患者的胰岛素需求。所有患者均形成特异性异种抗体（主要是抗Gal）;据推测，大多数异种胰岛被排斥反应破坏。在异种移植后6-8年进行的随访研究中，大多数患者的异种抗体水平仍然高于移植前。没有证据表明猪内源性逆转录病毒传播给患者。所有患者均对使用动物组织治疗疾病表示积极态度，无患者后悔参加试验。细胞移植是目前临床异种移植的主要方法。补体抑制保护门静脉内注射的猪胰岛免受有害的不相容反应的发现为未来的临床应用提供了希望。使用来自表达人补体受体的转基因猪的胰岛可能实现类似的保护作用。
In 1990-1993, eight diabetic renal transplant patients had porcine fetal islets injected intraportally at Huddinge Hospital in Stockholm. Four of the patients had evidence of xenograft function reflected in the excretion of small amounts of porcine C-peptide. Two patients had the porcine fetal islets placed under the capsule of a simultaneously transplanted kidney. In one of these patients, a graft biopsy specimen taken 3 weeks after transplantation revealed morphologically intact epithelial cells staining positively for insulin and glucagon. The insulin production was in all instances insufficient to affect the patient's insulin requirements. All patients formed specific xenoantibodies (mostly anti-Gal); presumably, most of the xenoislets were destroyed by rejection. On follow-up studies carried out 6-8 years after xenotransplantation, most patients still had higher-than-pretransplant levels of xenoantibodies. There was no evidence of transmission of porcine endogeneous retroviruses to the patients. All patients expressed a positive attitude toward the use of animal tissue for treatment of disease, and none of the patients regretted participating in the trial. Cell transplantation is leading the way at present for clinical xenotransplantation. The finding that complement inhibition protects intraportally injected porcine islets from an injurious incompatibility reaction holds promise for future clinical application. A similar protective effect might be achievable with the use of islets from transgenic pigs expressing human complement receptors.