Heart xenograft survival with chimeric pig donors and modest immune suppression.
Heart xenograft survival with chimeric pig donors and modest immune suppression.
复制标题
嵌合猪供体和适度免疫抑制的心脏异种移植存活率。
DOI：
10.1097/01.sla.0000048456.81319.da
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
MatamorosJr,
中科院分区：
文献类型：
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作者：
Beschorner,WilliamE;Sudan,DebraL;Radio,StanleyJ;Yang,Tianyu;Franco,KennethL;Hill,ArthurC;Shearon,CCarson;Thompson,ScottC;Dixon,RobertS;Johnson,NoelD;Kuszynski,CharlesA;Rubocki,RonaldJ;Lechtenberg,KellyF;MatamorosJr,
目的 评估使用具有细胞嵌合状态的供体猪通过适度的免疫抑制来预防急性排斥反应。目前，猪器官异种移植物的临床使用因严重急性排斥反应而被排除，这种排斥反应抵抗标准的免疫抑制。背景数据摘要为了使猪器官异种移植物长期存活，目前需要比同种异体移植物使用明显更强的免疫抑制，从而使受体免疫缺陷，感染风险增加。诱导免疫耐受和组织适应可以提高异种移植物的存活率，但会导致并发症和频繁的移植物失败。然而，在供体猪内诱导细胞嵌合可以在移植前实现这些目标，从而显着降低风险。方法将绵羊的骨髓细胞注入胎猪体内。将嵌合或非嵌合猪的心脏异种移植物异位移植到受体羊体内，同时输注脾细胞。移植后抑制由环孢菌素和递减皮质类固醇组成，与同种异体移植相当。结果所有对照移植物（n = 12）在 4 至 8 天内因急性血管排斥而被排斥。相比之下，实验组仅观察到一次血管排斥反应（n=13）。 4 名实验受体出现中度弥漫性细胞排斥反应（3 级），1 名受试者出现中度局灶性细胞排斥反应（2 级）。每一次发作都对脉冲类固醇有反应。七个移植物没有表现出明显的排斥反应。几乎没有证据表明免疫缺陷、感染或毒性。结论 在大型动物模型中，急性血管排斥反应得到预防，无需严重的免疫抑制。
Objective To assess the use of donor pigs with cellular chimerism for prevention of acute rejection with modest immune suppression. The clinical use of pig organ xenografts is currently precluded by severe acute rejection, which resists standard immune suppression.Summary Background Data For long-term survival of pig organ xenografts, immune suppression significantly greater than used with allografts would currently be necessary, leaving the recipient immune deficient and at increased risk for infections. Induction of immune tolerance and tissue accommodation could enhance xenograft survival but would lead to complications and frequent graft failure. Induction of cellular chimerism within the donor pigs, however, could accomplish these goals before transplantation, significantly reducing the risk.Methods Marrow cells from sheep were infused into fetal pigs. Heart xenografts from chimeric or nonchimeric pigs were transplanted heterotopically into recipient sheep, simultaneous with infusion of splenocytes. Posttransplant suppression consisted of cyclosporine and tapered corticosteroids, comparable with allotransplants.Results All of the control grafts (n= 12) were rejected by acute vascular rejection in 4 to 8 days. In contrast, only one episode of vascular rejection was observed in the experimental group (n= 13). Four experimental recipients had an episode of moderate diffuse cellular rejection (grade 3) and one had moderate focal cellular rejection (grade 2). Each episode responded to pulse steroids. Seven grafts showed no significant rejection. There was little evidence of immune deficiency, infection, or toxicity.Conclusions Acute vascular rejection was prevented in a large animal model without the need for severe immune suppression.