Liver transplantation without immunosuppression: future perspectives.

G Selvaggi, C Ricordi, R Bottino, A G Tzakis
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Abstract

It has been hypothesized that a state of microchimerism in recipients of organ transplants may result in donor-specific tolerance to the graft. Numerous studies show that infusion of donor-derived bone marrow cells can, indeed, achieve systemic chimerism in the recipient and effectively prolong allograft survival. We have compared organ and patient survival in recipients of liver allografts alone (controls) or in combination with single or multiple infusions of donor bone marrow cells; recipients were infused either at day 0 (perioperatively) or at day 0 and 11 post-transplant. The incidence of rejection episodes and survival of the liver allograft were significantly reduced in recipients of two bone marrow infusions compared to controls; recipients of one infusion, conversely, experienced a higher number of rejection episodes when compared to controls, pointing to a possible sensitizing role of a single bone marrow infusion if administered perioperatively. Variables such as timing, number and composition of the bone marrow inocula still remain to be elucidated but may be of critical importance for the attainment of a state of donor-specific tolerance without the need for immunosuppressive therapy in recipients of organ allografts.

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无免疫抑制的肝移植:未来展望。
据推测,器官移植受者的微嵌合状态可能导致供者对移植物的特异性耐受。大量研究表明,输注供体来源的骨髓细胞确实可以在受体中实现全身嵌合,并有效延长同种异体移植物的存活时间。我们比较了单独接受同种异体肝脏移植(对照组)或与供体骨髓细胞单次或多次输注相结合的受者的器官和患者生存率;受者在移植后第0天(围手术期)或第0天和第11天进行输注。与对照组相比,两次骨髓输注受体的排斥事件发生率和同种异体肝脏移植的存活率显著降低;相反,与对照组相比,一次骨髓输注的受者经历了更多的排斥事件,这表明如果围手术期给予单次骨髓输注可能具有致敏作用。诸如骨髓接种的时间、数量和组成等变量仍有待阐明,但可能对异体器官移植受者在不需要免疫抑制治疗的情况下达到供者特异性耐受状态至关重要。
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