Apheresis of Deceased Donors as a New Source of Mobilized Peripheral Blood Hematopoietic Stem Cells for Transplant Tolerance.
Apheresis of Deceased Donors as a New Source of Mobilized Peripheral Blood Hematopoietic Stem Cells for Transplant Tolerance.
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已故捐献者的血浆分离术作为动员外周血造血干细胞的新来源以实现移植耐受。
DOI：
10.1097/tp.0000000000004288
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发表时间：
2023
期刊：
影响因子：
6.2
通讯作者：
Kogut,NeilM
中科院分区：
文献类型：
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作者：
Sosa,RebeccaA;Mone,Thomas;Naini,BitaV;Kohn,DonaldB;Reed,ElaineF;Wheeler,Kristina;Campo-Fernandez,Beatriz;Davila,Alejandra;Chaffin,DonaldJ;DiNorcia,Joseph;Kaldas,FadyM;Cohen,Aaron;Lum,ErikL;Veale,JeffreyL;Kogut,NeilM
背景：实体器官移植是许多终末期器官衰竭患者的首选治疗方法；然而，接受者必须终生接受免疫抑制，使他们容易感染和癌症。在没有免疫抑制的情况下延长移植物存活的移植耐受性研究仅限于活体供体移植的受者；然而，已故供者的数量明显多于活体供者。造血干细胞(HSCs)从骨髓到外周血(PB)的动员可以使PB-HSCs用于诱导已故供体肾移植受者的耐受；然而，一个主要的担忧是众所周知的伴随免疫细胞进入肝脏的动员。方法：我们使用2剂粒细胞集落刺激因子和1剂Plerxafor的方案将HSCs动员到PD，然后在3名已故供者中通过分离收集动员的细胞。在整个过程中监测生理、实验室和放射学参数。纵向活检评估了异位肝脏动员的可能性。结果：两种药物的使用都导致了外周血CD34+细胞的成功动员，证明了在移植耐受方案中使用的潜力。没有观察到免疫细胞转运到肝脏的增加，分离动员的细胞导致所有肝白细胞亚群的均匀下降。结论：可以从脑死亡供者的外周血中动员和收集HSCs。这一新方法可能有助于将免疫耐受试验从活体供肾移植推广到已故供体移植，而不会牺牲肝脏的可移植性。
Background.Solid organ transplantation is the therapy of choice for many patients with end-stage organ failure; however, recipients must remain on lifelong immunosuppression, leaving them susceptible to infections and cancer. The study of transplant tolerance to prolong graft survival in the absence of immunosuppression has been restricted to recipients of living donor allografts; however, deceased donors significantly outnumber living donors. Mobilization of hematopoietic stem cells (HSCs) from the bone marrow to peripheral blood (PB) could allow PB-HSCs to be used to induce tolerance in deceased donor kidney recipients; however, a major concern is the well-known concomitant mobilization of immune cells into the liver.Methods.We mobilized HSCs to the PD using a protocol of 2 doses of granulocyte colony-stimulating factor and 1 dose of plerixafor, followed by the collection of mobilized cells via apheresis in 3 deceased donors. The physiological, laboratory, and radiographic parameters were monitored throughout the procedure. Longitudinal biopsies were performed to assess the potential for ectopic liver mobilization.Results.The use of both agents led to the successful mobilization of peripheral blood CD34+ cells, demonstrating the potential for use in transplant tolerance protocols. Increased immune cell trafficking into the liver was not observed, and apheresis of mobilized cells resulted in a uniform decrease in all liver leukocyte subsets.Conclusions.HSCs can be mobilized and collected from the PB of brain-dead donors. This new approach may facilitate the dissemination of immune tolerance trials beyond living-donor kidney transplantation to deceased-donor transplantation, without sacrificing the transplantability of the liver.